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J	Shailasree, S; Venkataramana, M; Niranjana, SR; Prakash, HS				Shailasree, S.; Venkataramana, M.; Niranjana, S. R.; Prakash, H. S.			Cytotoxic Effect of p-Coumaric Acid on Neuroblastoma, N2a Cell via Generation of Reactive Oxygen Species Leading to Dysfunction of Mitochondria Inducing Apoptosis and Autophagy	MOLECULAR NEUROBIOLOGY			English	Article						p-Coumaric acid; Neuroblastoma N2a cells; Apoptosis; p53; Caspase-8; Autophagy; LC3-II	COLON-CANCER CELLS; IN-VITRO; ANTIOXIDANT ACTIONS; OXIDATIVE STRESS; DEATH; PATHWAYS; ACTIVATION; CASPASE-8; THERAPY; VIVO	p-Coumaric acid (p-CA), an ubiquitous plant phenolic acid, has been proven to render protection against pathological conditions. In the present study, p-CA was evaluated for its capacity to induce cytotoxic effect to neuroblastoma N2a cells and we report here the possible mechanism of its action. p-CA at a concentration of 150 mu mol/L, upon exposure for 72 h, stimulated 81.23 % of cells to apoptosis, as evidenced by flow cytometer studies mediated through elevated levels of ROS (7.5-fold over control). Excess ROS production activated structural injury to mitochondrial membrane, observed as dissipation of its membrane potential and followed by the release of cytochrome c (8.73-fold). Enhanced generation of intracellular ROS correlated well with the decreased levels (similar to 60 %) of intracellular GSH. Sensitizing neuroblastoma cells for induction of apoptosis by p-CA identified p53-mediated upregulated accumulation of caspase-8 messenger RNA (2.8-fold). Our data report on autophagy, representing an additional mechanism of p-CA to induce growth arrest, detected by immunoblotting and fluorescence, correlated with accumulation of elevated levels (1.2-fold) of the LC3-II protein and acridine orange-stained autophagosomes, both autophagy markers. The present study indicates p-CA was effective in production of ROS-dependent mitochondrial damage-induced cytotoxicity in N2a cells.	[Shailasree, S.] Univ Mysore, Inst Excellence, Mysore 570006, Karnataka, India; [Niranjana, S. R.; Prakash, H. S.] Univ Mysore, Dept Studies Biotechnol, Mysore 570006, Karnataka, India; [Venkataramana, M.] Bharathiar Univ, Def Res Dev Org, Coimbatore, Tamil Nadu, India		Prakash, HS (corresponding author), Univ Mysore, Dept Studies Biotechnol, Mysore 570006, Karnataka, India.	shailasree_s@yahoo.co.uk; srn@appbot.uni-mysore.ac.in; hsprakash55@yahoo.in		H S, Dr. Prakash/0000-0002-9973-7939	Ministry of Human Resource Development, Govt. of India through UGC [UOM/IOE/RESEARCH/1/2010-11]	The authors acknowledge the recognition of the University of Mysore as an Institution of Excellence and financial support from the Ministry of Human Resource Development, Govt. of India through UGC under UOM/IOE/RESEARCH/1/2010-11, dt 22-04-2010 project.	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Neurobiol.	FEB	2015	51	1					119	130		10.1007/s12035-014-8700-2			12	Neurosciences	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology	CA6FT	WOS:000349006200010	24760364				2022-04-25	
J	Ji, CX; Ju, S; Qiang, JW				Ji, Changxue; Ju, Shuai; Qiang, Jinwei			miR-212 and mTOR Form a Regulation Loop to Modulate Autophagy in Colorecta Adenoma HT-29 Cells	DISCOVERY MEDICINE			English	Article							INHIBITOR NVP-BEZ235; CANCER CELLS; IN-VIVO; PATHWAY; EXPRESSION; RAPAMYCIN; PROLIFERATION; TUMORIGENESIS; BIOGENESIS; MICRORNA	Autophagy is a conserved lysosomal degradation pathway that regulates cell survival and death in order to maintain cellular homeostasis. Dysfunctional autophagy is associated with different types of cancer, making it an attractive therapeutic target. Mammalian target of rapamycin (mTOR) signaling negatively regulates autophagy and suppresses the efficacy of certain cancer therapeutic agents. NVP-BEZ235 is a dual inhibitor of the P13K/mTOR signaling pathway and exhibits anticancer activities; it also induced autophagy and inhibited proliferation in colorectal adenoma HT-29 cells. Colorectal adenoma and colorectal cancer have been recently shown to have elevated levels of miR-212. In the current study, we examined the role of miR-212 in NVP-BEZ235-induced autophagy in HT-29 cells. NVP-BEZ235 at the concentration as low as of 1 nM effectively induced autophagy and dose-dependently inhibited the expression of microRNA-212 (miR-212) whereas mTOR activator MHY1485 elevated the milt-212 expression. Transfection of mi R-212 mimics inhibited autophagy whereas miR-212 inhibitors promoted autophagy as assessed by the LC3B-1 conversion to LC3B-II and the expression levels of beclin-1. Furthermore, miR-212 mimics activated mTOR whereas miR-212 inhibitors suppressed mTOR activation as shown by the levels of phospho-mTOR. miR-212 mimics further enhanced the effect of NVP-BEZ235 in reducing the viability of HT-29 cells. Our data support that miR-212 is a target of mTOR signaling as well as an activator of mTOR to negatively regulate autophagy. Thus, miR-212 and mTOR signalings may form a positive regulation loop in maintaining cellular homeostasis. This study warrants further investigation of miR-212 as an effective target of autophagy-based cancer therapeutic strategies.	[Qiang, Jinwei] Fudan Univ, Jinshan Hosp, Dept Radiol, Shanghai 201508, Peoples R China; Fudan Univ, Shanghai Med Coll, Shanghai 201508, Peoples R China		Qiang, JW (corresponding author), Fudan Univ, Jinshan Hosp, Dept Radiol, Shanghai 201508, Peoples R China.	dr.jinweiqiang@163.com	Ju, Shuai/AAE-5635-2019				Alemu EA, 2012, J BIOL CHEM, V287, DOI 10.1074/jbc.M112.378109; Bahrami A, 2018, J CELL BIOCHEM, V119, P2460, DOI 10.1002/jcb.25950; Bornachea O, 2012, SCI REP-UK, V2, DOI 10.1038/srep00434; Dunlop EA, 2014, SEMIN CELL DEV BIOL, V36, P121, DOI 10.1016/j.semcdb.2014.08.006; Ganley IG, 2009, J BIOL CHEM, V284, P12297, DOI 10.1074/jbc.M900573200; Go YM, 2015, AM J PHYSIOL-REG I, V308, pR62, DOI 10.1152/ajpregu.00278.2014; Gomes LR, 2016, PHARMACOL RES, V107, P300, DOI 10.1016/j.phrs.2016.03.031; Gozuacik D, 2017, FRONT ONCOL, V7, DOI 10.3389/fonc.2017.00065; Huang ZQ, 2017, J CELL MOL MED, V21, P467, DOI 10.1111/jcmm.12990; Hudder A, 2008, TOXICOL SCI, V103, P228, DOI 10.1093/toxsci/kfn033; Ji YH, 2015, CLIN LAB, V61, P1043, DOI 10.7754/Clin.Lab.2015.150144; Laplante M, 2009, J CELL SCI, V122, P3589, DOI 10.1242/jcs.051011; Lee IH, 2008, P NATL ACAD SCI USA, V105, P3374, DOI 10.1073/pnas.0712145105; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Lin F, 2017, CLIN CANCER RES, V23, P1286, DOI 10.1158/1078-0432.CCR-16-1276; Liu J, 2016, ADV CANCER RES, V130, P1, DOI 10.1016/bs.acr.2016.01.005; LoPiccolo J, 2008, DRUG RESIST UPDATE, V11, P32, DOI 10.1016/j.drup.2007.11.003; Maejima Y, 2016, J MOL CELL CARDIOL, V95, P19, DOI 10.1016/j.yjmcc.2015.10.032; Meng X, 2013, GASTROENTEROLOGY, V145; Mizushima N, 2011, ANNU REV CELL DEV BI, V27, P107, DOI 10.1146/annurev-cellbio-092910-154005; Mizushima N, 2010, CURR OPIN CELL BIOL, V22, P132, DOI 10.1016/j.ceb.2009.12.004; Park JK, 2011, BIOCHEM BIOPH RES CO, V406, P518, DOI 10.1016/j.bbrc.2011.02.065; Ramalinga M, 2015, ONCOTARGET, V6, P34446, DOI 10.18632/oncotarget.5920; Shukla U, 2013, DRUG METAB DISPOS, V41, P1769, DOI 10.1124/dmd.113.052860; Smith PY, 2015, HUM MOL GENET, V24, P6721, DOI 10.1093/hmg/ddv377; Song LL, 2016, TUMOR BIOL, V37, P12161, DOI 10.1007/s13277-016-5073-3; Totary-Jain H, 2013, J BIOL CHEM, V288, P6034, DOI 10.1074/jbc.M112.416446; Ucar A, 2012, NAT COMMUN, V3, DOI 10.1038/ncomms2090; Wada R, 2010, INT J CANCER, V127, P1106, DOI 10.1002/ijc.25126; Wanet A, 2012, NUCLEIC ACIDS RES, V40, P4742, DOI 10.1093/nar/gks151; Wang C, 2016, PHARMACOL RES, V105, P164, DOI 10.1016/j.phrs.2016.01.028; Weidberg H, 2011, DEV CELL, V20, P444, DOI 10.1016/j.devcel.2011.02.006; Wu ZR, 2017, CANCER BIOMARK, V18, P35, DOI 10.3233/CBM-160671; Xie GF, 2017, CANCER LETT, V388, P12, DOI 10.1016/j.canlet.2016.11.024; Yang XY, 2016, ONCOL LETT, V12, P102, DOI 10.3892/ol.2016.4590; Ye PY, 2015, MOL CELL, V57, P708, DOI 10.1016/j.molcel.2014.12.034; Yin Y, 2016, GENE, V578, P177, DOI 10.1016/j.gene.2015.12.015; Zhai HY, 2013, CELL CYCLE, V12, P246, DOI 10.4161/cc.23273; Zhang LD, 2016, INT J ONCOL, V49, P657, DOI 10.3892/ijo.2016.3557; Zhang YJ, 2017, CELL MOL LIFE SCI, V74, P2613, DOI 10.1007/s00018-017-2485-1	41	4	4	0	4	DISCOVERY MEDICINE	TIMONIUM	10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA	1539-6509	1944-7930		DISCOV MED	Discov. Med.	JUN	2018	25	140					265	275					11	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	GS4FN	WOS:000443593800001	30021100				2022-04-25	
J	Malarz, K; Zych, D; Gawecki, R; Kuczak, M; Musiol, R; Mrozek-Wilczkiewicz, A				Malarz, Katarzyna; Zych, Dawid; Gawecki, Robert; Kuczak, Michal; Musiol, Robert; Mrozek-Wilczkiewicz, Anna			New derivatives of 4 '-phenyl-2,2 ':6 ',2 ''-terpyridine as promising anticancer agents	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						Terpyridine; Anticancer activity; Metal chelators; Reactive oxygen species	CELL-PROLIFERATION; HEME OXYGENASE-1; ANTIPROLIFERATIVE ACTIVITY; TERPYRIDINE DERIVATIVES; POLYPYRIDYL COMPLEXES; CONFERS RESISTANCE; NUCLEASE ACTIVITY; METAL-COMPLEXES; CANCER-CELLS; DNA	Terpyridine derivatives are known from their broad application including anticancer properties. In this work we present the newly synthesized 4'-phenyl-2,2':6',2 ''-terpyridine group with high anti-proliferative activity. We suggest that these compounds influence cellular redox homeostasis. Cancer cells are particularly susceptible to any changes in the redox balance because of their handicapped and inefficient antioxidant cellular systems. The antiproliferative activity of the studied compounds was tested on five different cell lines that represent several types of tumours; glioblastoma, leukemia, breast, pancreatic and colon. Additionally, we also tested their selectivity towards normal cells. We performed molecular biology studies in order to detect the response of a cell to its treatment with the compounds that were tested. We looked at the in-depth changes in the proteins and cellular pathways that lead to cell cycle inhibition (G0/G1 and S), and consequently, death on the apoptosis and autophagy pathways. We proved that the studied compounds targeted DNA as well. Special attention was paid to the targets connected with ROS generation. (C) 2020 Elsevier Masson SAS. All rights reserved.	[Malarz, Katarzyna; Gawecki, Robert; Kuczak, Michal; Mrozek-Wilczkiewicz, Anna] Univ Silesia Katowice, A Chelkowski Inst Phys, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland; [Malarz, Katarzyna; Gawecki, Robert; Kuczak, Michal; Mrozek-Wilczkiewicz, Anna] Univ Silesia Katowice, Silesian Ctr Educ & Interdisciplinary Res, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland; [Zych, Dawid] Wroclaw Sch Informat Technol, Ks M Lutra 4, PL-54239 Wroclaw, Poland; [Kuczak, Michal; Musiol, Robert] Univ Silesia Katowice, Inst Chem, Szkolna 9, PL-40006 Katowice, Poland		Malarz, K; Mrozek-Wilczkiewicz, A (corresponding author), Univ Silesia Katowice, A Chelkowski Inst Phys, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland.; Malarz, K; Mrozek-Wilczkiewicz, A (corresponding author), Univ Silesia Katowice, Silesian Ctr Educ & Interdisciplinary Res, 75 Pulku Piechoty 1a, PL-41500 Chorzow, Poland.	katarzyna.malarz@us.edu.pl; anna.mrozek-wilczkiewicz@us.edu.pl	Gawecki, Robert/ABF-8021-2021; Zych, Dawid/Q-7629-2017	Zych, Dawid/0000-0002-7757-7321; Gawecki, Robert/0000-0002-7752-000X; Malarz, Katarzyna/0000-0003-4283-3126	National Science CentreNational Science Centre, Poland [2016/23/N/NZ7/00351, 2018/31/B/NZ7/02122]	The financial support of the National Science Centre grants; 2016/23/N/NZ7/00351 (K.M.) and 2018/31/B/NZ7/02122 (R.M.) is greatly appreciated.	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J. Med. Chem.	FEB 15	2021	212								113032	10.1016/j.ejmech.2020.113032		FEB 2021	14	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Pharmacology & Pharmacy	QX8WC	WOS:000629622800008	33261897				2022-04-25	
J	Maiese, K; Chong, ZZ; Shang, YC; Wang, SH				Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen; Wang, Shaohui			Targeting disease through novel pathways of apoptosis and autophagy	EXPERT OPINION ON THERAPEUTIC TARGETS			English	Review						beta-catenin; Akt; Alzheimer's disease; apoptosis; autophagy; Beclin 1; cancer; cardiovascular disease; caspase; CCN family; diabetes mellitus; erythropoietin; forkhead transcription factors; FoxO; glycogen synthase kinase-3 beta; mammalian target of rapamycin; neurodegenerative disease; oxidative stress; Parkinson's disease; phosphoinositide 3-kinase; programmed cell death; Wnt1-inducible signaling pathway protein 1	FOCAL CEREBRAL-ISCHEMIA; HUMAN COLORECTAL-CANCER; WNT SIGNALING PATHWAY; BETA-CATENIN LEVELS; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; CELL-SURVIVAL; PARKINSONS-DISEASE; MOUSE MODEL; CASPASE 3	Introduction: Apoptosis and autophagy impact cell death in multiple systems of the body. Development of new therapeutic strategies that target these processes must address their complex role during developmental cell growth as well as during the modulation of toxic cellular environments. Areas covered: Novel signaling pathways involving Wnt1-inducible signaling pathway protein 1 (WISP1), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), beta-catenin and mammalian target of rapamycin (mTOR) govern apoptotic and autophagic pathways during oxidant stress that affect the course of a broad spectrum of disease entities including Alzheimer's disease, Parkinson's disease, myocardial injury, skeletal system trauma, immune system dysfunction and cancer progression. Implications of potential biological and clinical outcome for these signaling pathways are presented. Expert opinion: The CCN family member WISP1 and its intimate relationship with canonical and non-canonical wingless signaling pathways of PI3K, Akt1, beta-catenin and mTOR offer an exciting approach for governing the pathways of apoptosis and autophagy especially in clinical disorders that are currently without effective treatments. Future studies that can elucidate the intricate role of these cytoprotective pathways during apoptosis and autophagy can further the successful translation and development of these cellular targets into robust and safe clinical therapeutic strategies.	[Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen; Wang, Shaohui] New Jersey Hlth Sci Univ, Canc Inst New Jersey, Lab Cellular & Mol Signaling, Newark, NJ 07101 USA		Maiese, K (corresponding author), New Jersey Hlth Sci Univ, Canc Inst New Jersey, Lab Cellular & Mol Signaling, F 1220,205 S Orange Ave, Newark, NJ 07101 USA.	wntin75@yahoo.com	Wang, Shaohui/G-7247-2012		American Diabetes AssociationAmerican Diabetes Association; American Heart Association (National)American Heart Association; Bugher Foundation AwardAmerican Heart Association; Janssen Neuroscience AwardJohnson & JohnsonJohnson & Johnson USAJanssen Biotech Inc; LEARN Foundation Award; NIH NIEHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS); NIH NIAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA); NIH NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS); NIH ARRAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NS059346-04, NS059346-03S1]; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS053946] Funding Source: NIH RePORTER	This research was supported by the following grants to K Maiese: American Diabetes Association, American Heart Association (National), Bugher Foundation Award, Janssen Neuroscience Award, LEARN Foundation Award, NIH NIEHS, NIH NIA, NIH NINDS and NIH ARRA (NS059346-04 and NS059346-03S1). The authors state no other conflicts of interest.	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Ther. Targets	DEC	2012	16	12					1203	1214		10.1517/14728222.2012.719499			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	039HM	WOS:000311235400006	22924465	Green Accepted			2022-04-25	
J	Shahzad, MMK; Felder, M; Ludwig, K; Van Gelder, HR; Anderson, ML; Kim, J; Cook, ME; Kapur, AK; Patankar, MS				Shahzad, Mian M. K.; Felder, Mildred; Ludwig, Kai; Van Gelder, Hannah R.; Anderson, Matthew L.; Kim, Jong; Cook, Mark E.; Kapur, Arvinder K.; Patankar, Manish S.			Trans10, cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src	PLOS ONE			English	Article							UNFOLDED-PROTEIN RESPONSE; COLON; APOPTOSIS; ISOMERS; KINASE; EXPRESSION; BREAST; DEPHOSPHORYLATION; ANTICARCINOGENS; DERIVATIVES	The goal of this study was to investigate the anti-cancer effects of Trans10, cis12 conjugated linoleic acid (t10, c12 CLA). MTT assays and QCM T chemotaxis 96-wells were used to test the effect of t10, c12 CLA on the proliferation and migration and invasion of cancer cells. qPCR and Western Blotting were used to determine the expression of specific factors. RNA sequencing was conducted using the Illumina platform and apoptosis was measured using a flow cytometry assay. t10, c12 CLA (IC50, 7 mu M) inhibited proliferation of ovarian cancer cell lines SKOV-3 and A2780. c9, t11 CLA did not attenuate the proliferation of these cells. Transcription of 165 genes was significantly repressed and 28 genes were elevated. Genes related to ER stress, ATF4, CHOP, and GADD34 were overexpressed whereas EDEM2 and Hsp90, genes required for proteasomal degradation of misfolded proteins, were downregulated upon treatment. While apoptosis was not detected, t10, c12 CLA treatment led to 9-fold increase in autophagolysosomes and higher levels of LC3-II. G1 cell cycle arrest in treated cells was correlated with phosphorylation of GSK3 beta and loss of beta-catenin. microRNA miR184 and miR215 were upregulated. miR184 likely contributed to G1 arrest by downregulating E2F1. miR215 upregulation was correlated with increased expression of p27/Kip-1. t10, c12 CLA-mediated inhibition of invasion and migration correlated with decreased expression of PTP1b and decreased Src activation by inhibiting phosphorylation at Tyr 416. Due to its ability to inhibit proliferation and migration, t10, c12 CLA should be considered for treatment of ovarian cancer.	[Shahzad, Mian M. K.; Felder, Mildred; Ludwig, Kai; Van Gelder, Hannah R.; Kapur, Arvinder K.; Patankar, Manish S.] Univ Wisconsin, Dept Obstet & Gynecol, Div Gynecol Oncol, Sch Med & Publ Hlth, Madison, WI 53706 USA; [Shahzad, Mian M. K.] H Lee Moffitt Canc Ctr & Res Inst, Dept Obstet & Gynecol, Tampa, FL USA; [Anderson, Matthew L.; Kim, Jong] Baylor Coll Med, Dept Obstet & Gynecol, Div Gynecol Oncol, Dan L Duncan Canc Ctr, Houston, TX 77030 USA; [Cook, Mark E.] Univ Wisconsin Sch Madison, Dept Anim Sci, Madison, WI USA		Kapur, AK; Patankar, MS (corresponding author), Univ Wisconsin, Dept Obstet & Gynecol, Div Gynecol Oncol, Sch Med & Publ Hlth, Madison, WI 53706 USA.	akapur@wisc.edu; patankar@wisc.edu	; Anderson, Matthew/C-4755-2019	Ludwig, Kai/0000-0001-9867-9346; Anderson, Matthew/0000-0002-2081-4672; Patankar, Manish/0000-0002-8205-6432	Department of Obstetrics and Gynecology at UW-Madison; NCI (T32 training grant) [CA 009614]; Cancer Prevention and Research Institute of Texas [RP11035]; Partnership for Baylor College of Medicine; Ovarian Cancer Research Fund; Young Texans Against Cancer; Cancer Fighters of Houston; Alkek Foundation; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [T32CA009614, T32CA009206] Funding Source: NIH RePORTER	This research was supported by an intramural grant from the Department of Obstetrics and Gynecology (MS, AK, and MSP) at UW-Madison, and a grant from the NCI (T32 training grant CA 009614) to MS. Additional support was provided by RP11035 from the Cancer Prevention and Research Institute of Texas (MLA), Partnership for Baylor College of Medicine (MLA), Ovarian Cancer Research Fund (MLA), Young Texans Against Cancer (MLA), Cancer Fighters of Houston (MLA) and the Alkek Foundation (MLA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; We thank Dr. Bilal Hafeez for providing helpful discussions. Author contributions: M.M.S., A. K.K., and M.S.P. designed the study. M.M.S., A.K.K., K.L., and H.R.V.G. performed all experiments, analyzed data, and helped prepare the manuscript. M.L.A., J.K. prepared small RNA sequencing libraries and performed small RNA sequencing. M.F. helped with flow cytometry and cell culture assays, K.L. and H.R.V.G helped with MTT assays,. M.E.C. provided expert and essential advice on CLA biochemistry and the CLA literature and M.S.P. designed and edited the manuscript. This research was supported by an intramural grants from the Department of Obstetrics and Gynecology (MS, AK, and MSP) at UW-Madison, and a grant from the NCI (T32 training grant CA 009614) to MS. Additional support was provided by RP11035 from the Cancer Prevention and Research Institute of Texas (MLA), Partnership for Baylor College of Medicine (MLA), Ovarian Cancer Research Fund (MLA), Young Texans Against Cancer (MLA), Cancer Fighters of Houston (MLA) and the Alkek Foundation (MLA).	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J	Lan, L; Liu, JJ; Xing, ML; Smith, AR; Wang, JA; Wu, XQ; Appelman, C; Li, K; Roy, A; Gowthaman, R; Karanicolas, J; Somoza, AD; Wang, CCC; Miao, YL; De Guzman, R; Oakley, BR; Neufeld, KL; Xu, L				Lan, Lan; Liu, Jiajun; Xing, Minli; Smith, Amber R.; Wang, Jinan; Wu, Xiaoqing; Appelman, Carl; Li, Ke; Roy, Anuradha; Gowthaman, Ragul; Karanicolas, John; Somoza, Amber D.; Wang, Clay C. C.; Miao, Yinglong; De Guzman, Roberto; Oakley, Berl R.; Neufeld, Kristi L.; Xu, Liang			Identification and Validation of anAspergillus nidulansSecondary Metabolite Derivative as an Inhibitor of the Musashi-RNA Interaction	CANCERS			English	Article						RNA-binding proteins; Musashi; drug discovery; Notch signaling; Wnt signaling; cancer therapy; fungi secondary metabolite derivative	BINDING PROTEIN MUSASHI1; SMALL-MOLECULE INHIBITORS; STEM-CELLS; THERAPEUTIC TARGET; MYELOID-LEUKEMIA; PROSTATE-CANCER; FAMILY; MARKER; EXPRESSION; SCLEROTIORIN	RNA-binding protein Musashi-1 (MSI1) is a key regulator of several stem cell populations. MSI1 is involved in tumor proliferation and maintenance, and it regulates target mRNAs at the translational level. The known mRNA targets of MSI1 includeNumb,APC, andP21(WAF-1), key regulators of Notch/Wnt signaling and cell cycle progression, respectively. In this study, we aim to identify small molecule inhibitors of MSI1-mRNA interactions, which could block the growth of cancer cells with high levels of MSI1. Using a fluorescence polarization (FP) assay, we screened small molecules from several chemical libraries for those that disrupt the binding of MSI1 to its consensus RNA. One cluster of hit compounds is the derivatives of secondary metabolites fromAspergillus nidulans. One of the top hits, Aza-9, from this cluster was further validated by surface plasmon resonance and nuclear magnetic resonance spectroscopy, which demonstrated that Aza-9 binds directly to MSI1, and the binding is at the RNA binding pocket. We also show that Aza-9 binds to Musashi-2 (MSI2) as well. To test whether Aza-9 has anti-cancer potential, we used liposomes to facilitate Aza-9 cellular uptake. Aza-9-liposome inhibits proliferation, induces apoptosis and autophagy, and down-regulates Notch and Wnt signaling in colon cancer cell lines. In conclusion, we identified a series of potential lead compounds for inhibiting MSI1/2 function, while establishing a framework for identifying small molecule inhibitors of RNA binding proteins using FP-based screening methodology.	[Lan, Lan; Liu, Jiajun; Smith, Amber R.; Wu, Xiaoqing; Appelman, Carl; Li, Ke; De Guzman, Roberto; Oakley, Berl R.; Neufeld, Kristi L.; Xu, Liang] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA; [Xing, Minli] Univ Kansas, Bio NMR Core Facil, Lawrence, KS 66045 USA; [Wang, Jinan; Gowthaman, Ragul; Miao, Yinglong] Univ Kansas, Ctr Computat Biol, Lawrence, KS 66045 USA; [Roy, Anuradha] Univ Kansas, High Throughput Screening Lab, Lawrence, KS 66045 USA; [Karanicolas, John] Fox Chase Canc Ctr, Program Mol Therapeut, 7701 Burholme Ave, Philadelphia, PA 19111 USA; [Somoza, Amber D.; Wang, Clay C. C.] Univ Southern Calif, Dept Chem, Los Angeles, CA 90007 USA; [Wang, Clay C. C.] Univ Southern Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90007 USA; [Neufeld, Kristi L.] Univ Kansas, Ctr Canc, Dept Canc Biol, Kansas City, KS 66160 USA; [Xu, Liang] Univ Kansas, Ctr Canc, Dept Radiat Oncol, Kansas City, KS 66160 USA		Xu, L (corresponding author), Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.; Xu, L (corresponding author), Univ Kansas, Ctr Canc, Dept Radiat Oncol, Kansas City, KS 66160 USA.	lan@ku.edu; gajun988@gmail.com; mlxing@umich.edu; arsmith1@stanford.edu; jawang@ku.edu; wuxq@ku.edu; carltonapps@gmail.com; lk_jzs@xiyi.edu.cn; anuroy@ku.edu; ragul@umd.edu; John.Karanicolas@fccc.edu; amber.somoza@gmail.com; clayw@usc.edu; miao@ku.edu; rdguzman@ku.edu; boakley@ku.edu; klneuf@ku.edu; xul@ku.edu	Wang, Clay/ABG-9056-2021	Neufeld, Kristi/0000-0003-3653-9385; LAN, LAN/0000-0002-8045-7654; Gowthaman, Ragul/0000-0002-0008-6401	National Institutes of Health from the National Institute of General Medical Science [R01 CA178831, CA191785, P01GM084077]; University of Kansas Bold Aspiration Strategic Initiative Award [P30 CA168524]; National Cancer Institute Cancer Center Support GrantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30 CA168524]; Kansas Bioscience Authority Rising Star Award; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AI074856]; NIH COBRE at KU CCET Pilot Project [P30 RR030926]; Irving S. Johnson Fund of the University of Kansas Endowment	This study was supported in part by National Institutes of Health grants R01 CA178831 and CA191785, P01GM084077 from the National Institute of General Medical Science (to B.R.O. and C.C.C.W.); the University of Kansas Bold Aspiration Strategic Initiative Award and National Cancer Institute Cancer Center Support Grant P30 CA168524 (to L.X., K.N.); Kansas Bioscience Authority Rising Star Award (to L.X.); NIH grant AI074856 (to R.N.D.); NIH COBRE at KU CCET Pilot Project (P30 RR030926 to K.N.) and the Irving S. Johnson Fund of the University of Kansas Endowment (to B.R.O.).	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J	Liu, YS; Chang, YC; Kuo, WW; Chen, MC; Hsu, HH; Tu, CC; Yeh, YL; Viswanadha, VP; Liao, PH; Huang, CY				Liu, Yi-Sheng; Chang, Yu-Chun; Kuo, Wei-Wen; Chen, Ming-Cheng; Hsu, Hsi-Hsien; Tu, Chuan-Chou; Yeh, Yu-Lan; Viswanadha, Vijaya Padma; Liao, Po-Hsiang; Huang, Chih-Yang			Inhibition of Protein Phosphatase 1 Stimulates Noncanonical ER Stress eIF2 alpha Activation to Enhance Fisetin-induced Chemosensitivity in HDAC Inhibitor-resistant Hepatocellular Carcinoma Cells	CANCERS			English	Article						hepatocellular carcinoma; fisetin; protein phosphatase 1; eIF2 alpha; chemosensitivity	HISTONE DEACETYLASE INHIBITORS; COLON-CANCER CELLS; ENDOPLASMIC-RETICULUM; SIGNALING PATHWAY; INDUCED APOPTOSIS; EXPRESSION; DEPHOSPHORYLATION; MIGRATION; TRANSCRIPTION; AUTOPHAGY	Hepatocellular carcinoma (HCC) is a common fatal type of malignant tumor that has highly metastatic and recurrent properties. Fisetin is a natural flavonoid found in various vegetables and fruits which exhibits anti-cancer and anti-inflammatory properties, as well as other effects. Thus, we hypothesized that fisetin can act as an adjuvant therapy in cancer or drug-resistant cancer cells, and further investigated the molecular mechanisms underlying the development of drug-resistance in HCC cells. We found that fisetin effectively inhibited the cell viability of not only parental cells but also histone deacetylase inhibitors-resistant (HDACis-R) cells and enhanced the chemosensitivity of HCC cells. Interestingly, fisetin did not induce cell apoptosis through the activation of the endoplasmic reticulum (ER) stress sensor of protein kinase R (PKR)-like endoplasmic reticulum kinase, but rather through the non-canonical pathway of the protein phosphatase 1 (PP1)-mediated suppression of eIF2 alpha phosphorylation. Moreover, fisetin-induced cell apoptosis was reversed by treatment with PP1 activator or eIF2 alpha siRNA in HCC cells. Based on these observations, we suggest that PP1-eIF2 alpha pathways are significantly involved in the effect of fisetin on HCC apoptosis. Thus, fisetin may act as a novel anticancer drug and new chemotherapy adjuvant which can improve the efficacy of chemotherapeutic agents and diminish their side-effects.	[Liu, Yi-Sheng] China Med Univ, Program Aging, Taichung 404, Taiwan; [Liu, Yi-Sheng] Kaohsiung Armed Forces Gen Hosp, Dept Med, Div Hematol & Oncol, Kaohsiung 802, Taiwan; [Chang, Yu-Chun] Natl Pingtung Univ Sci & Technol, Grad Dept Biol Sci & Technol, Pingtung 912, Taiwan; [Chang, Yu-Chun] China Med Univ, Sch Chinese Med, Taichung 404, Taiwan; [Kuo, Wei-Wen] China Med Univ, Dept Biol Sci & Technol, Taichung 404, Taiwan; [Chen, Ming-Cheng] Taichung Vet Gen Hosp, Dept Surg, Div Colorectal Surg, Taichung 407, Taiwan; [Chen, Ming-Cheng] Natl Yang Ming Univ, Fac Med, Taipei 112, Taiwan; [Hsu, Hsi-Hsien] MacKay Mem Hosp, Div Colorectal Surg, Taipei 104, Taiwan; [Hsu, Hsi-Hsien] MacKay Med Nursing & Management Coll, Taipei 112, Taiwan; [Tu, Chuan-Chou] Armed Force Taichung Gen Hosp, Dept Internal Med, Div Chest Med, Taichung 411, Taiwan; [Yeh, Yu-Lan] Changhua Christian Hosp, Dept Pathol, Changhua 500, Taiwan; [Yeh, Yu-Lan] Jen Teh Jr Coll Med Nursing & Management, Dept Med Technol, Miaoli 356, Taiwan; [Viswanadha, Vijaya Padma] Bharathiar Univ, Dept Biotechnol, Coimbatore 641046, Tamil Nadu, India; [Liao, Po-Hsiang] China Med Univ, Grad Inst Basic Med Sci, Taichung 404, Taiwan; [Liao, Po-Hsiang; Huang, Chih-Yang] Hualien Tzu Chi Hosp, Cardiovasc Res Ctr, Hualien 970, Taiwan; [Liao, Po-Hsiang; Huang, Chih-Yang] Tzu Chi Univ Sci & Technol, Buddhist Tzu Chi Med Fdn, Ctr Gen Educ, Hualien 970, Taiwan; [Huang, Chih-Yang] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 404, Taiwan; [Huang, Chih-Yang] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan		Liao, PH (corresponding author), China Med Univ, Grad Inst Basic Med Sci, Taichung 404, Taiwan.; Liao, PH; Huang, CY (corresponding author), Hualien Tzu Chi Hosp, Cardiovasc Res Ctr, Hualien 970, Taiwan.; Liao, PH; Huang, CY (corresponding author), Tzu Chi Univ Sci & Technol, Buddhist Tzu Chi Med Fdn, Ctr Gen Educ, Hualien 970, Taiwan.; Huang, CY (corresponding author), China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 404, Taiwan.; Huang, CY (corresponding author), Asia Univ, Dept Biotechnol, Taichung 413, Taiwan.	robert750927@hotmail.com; cyhuang@mail.cmu.edu.tw	Viswanadha, Vijaya Padma/ABG-4936-2020	Viswanadha, Vijaya Padma/0000-0001-9154-027X; Huang, Chih-Yang/0000-0003-2347-0411	Asia University, Taichung, Taiwan [ASIA-104-CMUH-08]; China Medical University Hospital, Taichung, Taiwan [DMR-108-169]	This work was supported by the Asia University, Taichung, Taiwan, Grant/Award Number: ASIA-104-CMUH-08 and China Medical University Hospital, Taichung, Taiwan, Grant/Award Number: DMR-108-169.	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J	Wu, SP; Zhang, YG; Lu, R; Xia, YL; Zhou, D; Petrof, EO; Claud, EC; Chen, D; Chang, EB; Carmeliet, G; Sun, J				Wu, Shaoping; Zhang, Yong-guo; Lu, Rong; Xia, Yinglin; Zhou, David; Petrof, Elaine O.; Claud, Erika C.; Chen, Di; Chang, Eugene B.; Carmeliet, Geert; Sun, Jun			Intestinal epithelial vitamin D receptor deletion leads to defective autophagy in colitis	GUT			English	Article							INFLAMMATORY-BOWEL-DISEASE; KAPPA-B ACTIVITY; COLON-CANCER CELLS; CROHNS-DISEASE; PANETH CELLS; 1,25-DIHYDROXYVITAMIN D-3; ULCERATIVE-COLITIS; GENE POLYMORPHISM; INNATE IMMUNITY; KNOCKOUT MICE	Objective Vitamin D and the vitamin D receptor (VDR) appear to be important immunological regulators of inflammatory bowel diseases (IBD). Defective autophagy has also been implicated in IBD, where interestingly, polymorphisms of genes such as ATG16L1 have been associated with increased risk. Although vitamin D, the microbiome and autophagy are all involved in pathogenesis of IBD, it remains unclear whether these processes are related or function independently. Design We investigated the effects and mechanisms of intestinal epithelial VDR in healthy and inflamed states using cell culture models, a conditional VDR knockout mouse model (VDR Delta IEC), colitis models and human samples. Results Absence of intestinal epithelial VDR affects microbial assemblage and increases susceptibility to dextran sulfate sodium-induced colitis. Intestinal epithelial VDR downregulates expressions of ATG16L1 and lysozyme, and impairs antimicrobial function of Paneth cells. Gain and loss-of-function assays showed that VDR levels regulate ATG16L1 and lysozyme at the transcriptional and translational levels. Moreover, low levels of intestinal epithelial VDR correlated with reduced ATG16L1 and representation by intestinal Bacteroides in patients with IBD. Administration of the butyrate (a fermentation product of gut microbes) increases intestinal VDR expression and suppresses inflammation in a colitis model. Conclusions Our study demonstrates fundamental relationship between VDR, autophagy and gut microbial assemblage that is essential for maintaining intestinal homeostasis, but also in contributing to the pathophysiology of IBD. These insights can be leveraged to define therapeutic targets for restoring VDR expression and function.	[Wu, Shaoping; Zhang, Yong-guo; Lu, Rong; Chen, Di; Sun, Jun] Rush Univ, Dept Biochem, Chicago, IL 60612 USA; [Xia, Yinglin] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA; [Zhou, David] Univ Rochester, Dept Pathol, Rochester, NY 14627 USA; [Petrof, Elaine O.] Queens Univ, Dept Med, GI Dis Res Unit, Kingston, ON K7L 3N6, Canada; [Petrof, Elaine O.] Queens Univ, Div Infect Dis, Kingston, ON, Canada; [Claud, Erika C.] Univ Chicago, Med Ctr, Dept Pediat, Chicago, IL 60637 USA; [Claud, Erika C.; Chang, Eugene B.] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA; [Carmeliet, Geert] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, Leuven, Belgium		Sun, J (corresponding author), Rush Univ, Dept Biochem, Cohn Res Bldg,1735 W Harrison St,506, Chicago, IL 60612 USA.	jun_sun@rush.edu	Chen, Di/AAJ-3665-2021; Sun, Jun/S-7440-2019	Sun, Jun/0000-0001-7465-3133	NIDDKUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [KO1 DK075386, 1R03DK089010-01]; American Cancer SocietyAmerican Cancer Society [RSG-09-075-01-MBC]; Swim Across America Cancer Research Award; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000430] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01AR055915, R01AR054465] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R37DK047722, R01DK047722, R01DK097268, K01DK075386, R03DK089010, P30DK042086] Funding Source: NIH RePORTER	We thank Liesbet Lieben for technical assistance with VDR.IEC mice. This work was supported by the NIDDK (KO1 DK075386 and 1R03DK089010-01), the American Cancer Society (RSG-09-075-01-MBC) and Swim Across America Cancer Research Award to JS. NIDDK DK42086 (DDRCC), DK097268 and DK47722 to EBC.	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J	Yu, C; Li, WB; Liu, JB; Lu, JW; Feng, JF				Yu, Chen; Li, Wei-bing; Liu, Jun-bao; Lu, Jian-wei; Feng, Ji-feng			Autophagy: novel applications of nonsteroidal anti-inflammatory drugs for primary cancer	CANCER MEDICINE			English	Review						Autophagy; nonsteroidal anti-inflammatory drugs; programmed cell death	ENDOPLASMIC-RETICULUM STRESS; COLORECTAL-CANCER; CELL-DEATH; HEPATOCELLULAR-CARCINOMA; CARDIOVASCULAR-DISEASE; REGULATES AUTOPHAGY; INHIBITOR CELECOXIB; MEDIATED CLEAVAGE; INDUCED APOPTOSIS; MAMMALIAN TARGET	In eukaryotic cells, autophagy is a process associated with programmed cell death. During this process, cytoplasmic proteins and organelles are engulfed by double-membrane autophagosomes, which then fuse with lysosomes to form autolysosomes. These autolysosomes then degrade their contents to recycle the cellular components. Autophagy has been implicated in a wide variety of physiological and pathological processes that are closely related to tumorigenesis. In recent years, an increasing number of studies have indicated that nonsteroidal anti-inflammatory drugs, such as celecoxib, meloxicam, sulindac, aspirin, sildenafil, rofecoxib, and sodium salicylate, have diverse effects in cancer that are mediated by the autophagy pathway. These nonsteroidal anti-inflammatory drugs can modulate tumor autophagy through the PI3K/Akt/mTOR, MAPK/ERK1/2, P53/DRAM, AMPK/mTOR, Bip/GRP78, CHOP/ GADD153, and HGF/MET signaling pathways and inhibit lysosome function, leading to p53-dependent G1 cell-cycle arrest. In this review, we summarize the research progress in autophagy induced by nonsteroidal anti-inflammatory drugs and the molecular mechanisms of autophagy in cancer cells to provide a reference for the potential benefits of nonsteroidal anti-inflammatory drugs in cancer chemotherapy.	[Yu, Chen; Li, Wei-bing] Nanjing Med Univ, Affiliated Canc Hosp, Jiangsu Inst Canc Res, Dept Integrated TCM & Western Med,Jiangsu Canc Ho, Nanjing 210000, Jiangsu, Peoples R China; [Liu, Jun-bao] Henan Prov Peoples Hosp, Dept Tradit Chinese Med, Zhengzhou, Henan, Peoples R China; [Lu, Jian-wei; Feng, Ji-feng] Nanjing Med Univ, Affiliated Canc Hosp, Jiangsu Inst Canc Res, Dept Med,Jiangsu Canc Hosp, Nanjing 210000, Jiangsu, Peoples R China		Lu, JW; Feng, JF (corresponding author), Nanjing Med Univ, Affiliated Canc Hosp, Jiangsu Inst Canc Res, Dept Med,Jiangsu Canc Hosp, Nanjing 210000, Jiangsu, Peoples R China.	lujw@medmail.com.cn; jifeng_feng@163.com			Jiangsu Cadre Health Care Research Project [BJ15028]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81503528]	This study was funded by grants from Jiangsu Cadre Health Care Research Project (BJ15028) and the National Natural Science Foundation of China (81503528).	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FEB	2018	7	2					471	484		10.1002/cam4.1287			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FV6TE	WOS:000424713800019	29282893	Green Published, gold			2022-04-25	
J	Zhao, H; Yang, MP; Zhao, B				Zhao, Hong; Yang, Maopeng; Zhao, Bin			Beclin 1 and LC3 as predictive biomarkers for metastatic colorectal carcinoma	ONCOTARGET			English	Article						colorectal carcinoma; beclin 1; LC3; metastasis; biomarker	AUTOPHAGY; CANCER; EXPRESSION; PROGNOSIS; SURVIVAL; SYSTEM; SENESCENCE; PROTEIN; GROWTH; CELLS	Autophagy is a highly conserved self-destructive process that disassembles dysfunctional or unnecessary cellular components. It plays an important role in cancer metastasis, which is of particular interest considering metastatic disease is the major cause of colorectal carcinoma (CRC) related mortality. Here, we investigated the immunohistochemical expression of autophagy-related protein Beclin 1 and Microtubule-associated protein 1A/1B-light chain 3 (LC3) within surgical CRC specimens, first in a training cohort (205 patients), then in an inner validation cohort (160 patients) and an independent cohort (161 patients). The expressions of Beclin 1 and LC3 were lower in metastatic CRC compared with non-metastatic CRC. Furthermore, we developed an autophagy-based classifier for metastatic prediction. This classifier, including Beclin 1, LC3 and carcinoembryonic antigen (CEA) level, resulted in 82.9% sensitivity and 89.8% specificity for metastatic detection in the training cohort. In the independent cohort, it achieved 77.9% sensitivity and 90.3% specificity in predicting the metastasis of CRC. These results suggested that low expression of Beclin 1 and LC3 contributed to a more aggressive cancer cell phenotype, and our autophagy-based classifier was a reliable tool for metastatic prediction in CRC.	[Zhao, Hong] Harbin Med Univ, Daqing, Heilongjiang, Peoples R China; [Zhao, Hong; Yang, Maopeng] Harbin Med Univ, Affiliated Hosp 3, Dept Med Oncol, Harbin, Heilongjiang, Peoples R China; [Zhao, Bin] Wenzhou Med Univ, Affiliated Hosp 2, Wenzhou, Peoples R China; [Zhao, Bin] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China		Zhao, H (corresponding author), Harbin Med Univ, Daqing, Heilongjiang, Peoples R China.; Zhao, H (corresponding author), Harbin Med Univ, Affiliated Hosp 3, Dept Med Oncol, Harbin, Heilongjiang, Peoples R China.; Zhao, B (corresponding author), Wenzhou Med Univ, Affiliated Hosp 2, Wenzhou, Peoples R China.; Zhao, B (corresponding author), Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China.	doctorhongzhao@126.com; doctorbinzhao@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31571417, 81502478]; Natural Science Foundation of Heilongjiang ProvinceNatural Science Foundation of Heilongjiang Province [H2016023]; Haiyan Foundation of The third Affiliated Hospital of Harbin Medical University [JJMS2014-06]	This work was funded by National Natural Science Foundation of China (No. 31571417 and No. 81502478), Natural Science Foundation of Heilongjiang Province (No. H2016023) and Haiyan Foundation of The third Affiliated Hospital of Harbin Medical University (No. JJMS2014-06).	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J	Sim, KH; Shu, MS; Kim, S; Kim, JY; Choi, BH; Lee, YJ				Sim, Kyeong Hwa; Shu, Mi-Sun; Kim, Soyoung; Kim, Jong-Yeon; Choi, Bo-Hyun; Lee, Youn Ju			Cilostazol Induces Apoptosis and Inhibits Proliferation of Hepatocellular Carcinoma Cells by Activating AMPK	BIOTECHNOLOGY AND BIOPROCESS ENGINEERING			English	Article						cilostazol; hepatocellular carcinoma; apoptosis; AMPK; ERK; AKT	LIVER-REGENERATION; SIGNALING PATHWAY; PROTEIN-KINASE; CANCER; MANAGEMENT; EXPRESSION; METASTASES; AUTOPHAGY; RESECTION; GROWTH	Hepatocellular carcinoma (HCC) is the most common primary liver cancer and one of the leading causes of cancer-related death. Cilostazol, an antiplatelet drug, elicits anticancer effects on human squamous cell carcinoma and colon cancer cells. We previously reported that cilostazol protects normal mature hepatocytes from alcohol-induced apoptotic cell death. In addition, cilostazol stimulates liver regeneration after hepatectomy. Therefore, this study evaluated whether cilostazol elicits pro- or anti-proliferative effects on HCC using Hep3B and SK-Hep1 cells. Cilostazol inhibited proliferation of HCC cells by inducing apoptosis. Additionally, cilostazol induced G(0)/G(1) cell cycle arrest and decreased expression of cyclin D1 and proliferating cell nuclear antigen. Activation of AMP-activated protein kinase (AMPK) and inhibition of extracellular signal-regulated kinase (ERK) and AKT signaling were associated with the anti-proliferative effect of cilostazol. LY294002 and PD98059, inhibitors of AKT and ERK, respectively, enhanced the anti-proliferative effect of cilostazol. By contrast, inhibition of AMPK using compound C or AMPK-targeting siRNA abolished the anti-proliferative effect of cilostazol. Moreover, AMPK inhibition reversed the down-regulation of AKT/EKR induced by cilostazol, indicating negative cross-talk between AMPK and AKT/ERK. These findings provide evidence that cilostazol exerts anti-tumor activity in HCC by counter-regulating AMPK and AKT/ERK signaling. Taken together, our findings suggest that cilostazol may provide clinical benefits in HCC patients by selectively targeting HCC cells without interfering with liver function.	[Sim, Kyeong Hwa; Choi, Bo-Hyun; Lee, Youn Ju] Catholic Univ Daegu, Sch Med, Dept Pharmacol, Daegu 42472, South Korea; [Shu, Mi-Sun; Kim, Jong-Yeon] Yeungnam Univ, Sch Med, Dept Physiol, Daegu 42415, South Korea; [Kim, Soyoung] Dongguk Univ, Sch Med, Dept Pharmacol, Gyeongju 38066, South Korea		Lee, YJ (corresponding author), Catholic Univ Daegu, Sch Med, Dept Pharmacol, Daegu 42472, South Korea.	whrytn4337@cu.ac.kr					Akula SM, 2019, EXPERT OPIN THER TAR, DOI 10.1080/14728222.2019.1685501; Cao W, 2019, BREAST CANCER RES, V21, DOI 10.1186/s13058-019-1107-2; Chan KM, 2017, LIVER INT, V37, P434, DOI 10.1111/liv.13280; Cheng JD, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0093256; Chiang PC, 2010, BIOCHEM PHARMACOL, V79, P162, DOI 10.1016/j.bcp.2009.08.022; Cordero MD, 2018, TRENDS ENDOCRIN MET, V29, P8, DOI 10.1016/j.tem.2017.10.009; Ferretti AC, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-39556-w; Fujii T, 2017, J SURG RES, V213, P207, DOI 10.1016/j.jss.2017.02.020; Gomez D, 2007, BRIT J SURG, V94, P1395, DOI 10.1002/bjs.5820; Grabinski N, 2012, MOL CANCER, V11, DOI 10.1186/1476-4598-11-85; He C, 2018, BIOCHEM BIOPH RES CO, V503, P3093, DOI 10.1016/j.bbrc.2018.08.098; Hoffmann K, 2011, ANTICANCER RES, V31, P3883; Huang J, 2018, MOL MED REP, V17, P5390, DOI 10.3892/mmr.2018.8522; Ishii H, 2016, J CARDIOL, V67, P199, DOI 10.1016/j.jjcc.2015.05.003; Ito Y, 1998, HEPATOLOGY, V27, P951, DOI 10.1002/hep.510270409; Jeon BH, 2015, METABOLISM, V64, P1444, DOI 10.1016/j.metabol.2015.07.014; Jiang X, 2019, CANCERS, V11, DOI 10.3390/cancers11050647; Jiao P, 2013, MOL CELL BIOCHEM, V382, P217, DOI 10.1007/s11010-013-1737-0; Kabil SL, 2018, CLIN EXP PHARMACOL P, V45, P1341, DOI 10.1111/1440-1681.13004; Kangawa Y, 2017, FOOD CHEM TOXICOL, V100, P103, DOI 10.1016/j.fct.2016.12.018; Kawaguchi T, 2015, INT J ONCOL, V46, P2216, DOI 10.3892/ijo.2015.2928; Kwon HY, 2018, ARCH TOXICOL, V92, P241, DOI 10.1007/s00204-017-2021-y; Lee CH, 2017, AM J PHYSIOL-RENAL, V312, pF398, DOI 10.1152/ajprenal.00258.2016; Lee YJ, 2019, PLOS ONE, V14, DOI 10.1371/journal.pone.0211415; Liu L, 2006, CANCER RES, V66, P11851, DOI 10.1158/0008-5472.CAN-06-1377; Matter MS, 2014, J HEPATOL, V60, P855, DOI 10.1016/j.jhep.2013.11.031; Merlen G, 2014, J HEPATOL, V60, P152, DOI 10.1016/j.jhep.2013.08.025; Mihaylova MM, 2011, NAT CELL BIOL, V13, P1016, DOI 10.1038/ncb2329; Nordlinger B, 2008, LANCET, V371, P1007, DOI 10.1016/S0140-6736(08)60455-9; Park SY, 2016, ONCOL REP, V35, P1566, DOI 10.3892/or.2015.4519; Poon RTP, 2002, J AM COLL SURGEONS, V195, P311, DOI 10.1016/S1072-7515(02)01226-7; Ratchford EV, 2017, J VASC SURG, V66, P275, DOI 10.1016/j.jvs.2017.02.040; Ruderman NB, 2013, J CLIN INVEST, V123, P2764, DOI 10.1172/JCI67227; Schulte L, 2019, LIVER INT, V39, P714, DOI 10.1111/liv.14048; Seo YS, 2016, MEDICINE, V95, DOI 10.1097/MD.0000000000003527; Shi JH, 2014, WORLD J GASTROENTERO, V20, P16167, DOI 10.3748/wjg.v20.i43.16167; Strowitzki MJ, 2014, CLIN EXP METASTAS, V31, P795, DOI 10.1007/s10585-014-9669-y; Tabrizian P, 2014, WORLD J GASTROENTERO, V20, P10223, DOI 10.3748/wjg.v20.i30.10223; Tejeda-Maldonado J, 2015, WORLD J HEPATOL, V7, P362, DOI 10.4254/wjh.v7.i3.362; Umezawa S, 2017, CURR PHARM DESIGN, V23, P3629, DOI 10.2174/0929867324666170713150440; Uzawa K, 2013, CANCER MED-US, V2, P40, DOI 10.1002/cam4.56; von Heesen M, 2015, LIVER TRANSPLANT, V21, P792, DOI 10.1002/lt.24114; Wang JC, 2019, J CELL PHYSIOL, V234, P6908, DOI 10.1002/jcp.27449; Wang SSS, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.18; Xie XH, 2018, CELL STRESS CHAPERON, V23, P203, DOI 10.1007/s12192-017-0828-3; Yang SF, 2017, ONCOL LETT, V13, P1041, DOI 10.3892/ol.2017.5557; Yoo AR, 2010, J ATHEROSCLER THROMB, V17, P1009, DOI 10.5551/jat.4309; Zheng LY, 2013, CLIN CANCER RES, V19, P5372, DOI 10.1158/1078-0432.CCR-13-0203	48	0	0	1	1	KOREAN SOC BIOTECHNOLOGY & BIOENGINEERING	SEOUL	KOREAN SCIENCE TECHNOLOGY CENTER, #704 YEOGSAM-DONG, KANGNAM-KU, SEOUL 135-703, SOUTH KOREA	1226-8372	1976-3816		BIOTECHNOL BIOPROC E	Biotechnol. Bioprocess Eng.	OCT	2021	26	5					776	785		10.1007/s12257-021-0002-8			10	Biotechnology & Applied Microbiology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology	WT4KR	WOS:000715835300008					2022-04-25	
J	Chen, Z; Gao, SH; Wang, DY; Song, DF; Feng, Y				Chen, Zhi; Gao, Shuohui; Wang, Dayv; Song, Defeng; Feng, Ye			Colorectal cancer cells are resistant to anti-EGFR monoclonal antibody through adapted autophagy	AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH			English	Article						Colorectal carcinoma (CRC); aEGFR; autophagy; Beclin-1; miR-216b	PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA; SIGNALING PATHWAY; INHIBITS GROWTH; MIR-216B; ACTIVATION; CRC; PATHOGENESIS; PROGRESSION; BIOMARKERS	The epidermal growth factor receptor (EGFR) signaling plays a key role in the initiation, progression, growth and metastases of colorectal carcinoma (CRC). Monoclonal antibody against EGFR (aEGFR; Cetuximab) has been used in treating CRC but some CRCs appeared to be resistant to aEGFR therapy, with undetermined mechanisms. Here, we studied the effects of aEGFR on CRC cells in vitro. We found that aEGFR dose-dependently activated Beclin-1 in 2 CRC cell lines, HT29 and SW480. Inhibition of autophagy significantly increased the aEGFR-induced CRC cell death in an CCK-8 assay. Moreover, microRNA (miR)-216b levels were significantly downregulated in aEGFR-treated CRC cells. Bioinformatics study showed that miR-216b targeted the 3'-UTR of Beclin-1 mRNA to inhibit its translation, which was confirmed by luciferase reporter assay. Together, these data suggest that aEGFR may decrease miR-216b levels in CRC cells, which subsequently upregulates Beclin-1 to increase CRC cell autophagy to antagonize aEGFR-induced cell death. Strategies that increase miR-216b levels or inhibit cell autophagy may improve the outcome of aEGFR treatment in CRC therapy.	[Chen, Zhi] Jilin Univ, Hosp 1, Dept Nephrol, Changchun 130021, Peoples R China; [Gao, Shuohui; Wang, Dayv; Song, Defeng; Feng, Ye] Jilin Univ, China Japan Union Hosp, Dept Gastrointestinal Colorectal & Anal Surg, 126 Xiantai St, Changchun 130033, Peoples R China		Feng, Y (corresponding author), Jilin Univ, China Japan Union Hosp, Dept Gastrointestinal Colorectal & Anal Surg, 126 Xiantai St, Changchun 130033, Peoples R China.	Fengye0431@163.com			Jilin province Natural Science Foundation of China [20160-101115JC]; provincal funds for health service of Jilin	This study was supported by Jilin province Natural Science Foundation of China 20160-101115JC, and the provincal funds for health service of Jilin.	Chen J, 2015, AM J TRANSL RES, V7, P1510; Chen YC, 2015, AM J TRANSL RES, V7, P1574; Coronnello C, 2013, NUCLEIC ACIDS RES, V41, pW159, DOI 10.1093/nar/gkt379; Dahabreh IJ, 2011, ANN INTERN MED, V154, P37, DOI 10.7326/0003-4819-154-1-201101040-00006; Dasari A, 2010, CLIN CANCER RES, V16, P3811, DOI 10.1158/1078-0432.CCR-09-2283; Deng M, 2011, J CELL SCI, V124, P2997, DOI 10.1242/jcs.085050; Di Leva G, 2013, CURR OPIN GENET DEV, V23, P3, DOI 10.1016/j.gde.2013.01.004; East JE, 2013, NAT REV GASTRO HEPAT, V10, P69, DOI 10.1038/nrgastro.2012.245; Farrow JM, 2014, NAT REV UROL, V11, P508, DOI 10.1038/nrurol.2014.196; Garza-Trevino EN, 2015, CANCER CELL INT, V15, DOI 10.1186/s12935-015-0163-7; Green DR, 2014, CELL, V157, P65, DOI 10.1016/j.cell.2014.02.049; Guo JY, 2013, CELL, V155, P1216, DOI 10.1016/j.cell.2013.11.019; Huang CY, 2015, SCI REP-UK, V5, DOI 10.1038/srep14045; Jean GW, 2008, PHARMACOTHERAPY, V28, P742, DOI 10.1592/phco.28.6.742; Jones C, 2013, HPB, V15, P11, DOI 10.1111/j.1477-2574.2012.00591.x; Kim SY, 2012, BIOCHEM BIOPH RES CO, V429, P173, DOI 10.1016/j.bbrc.2012.10.117; Labianca R, 2005, ANN ONCOL, V16, P37, DOI 10.1093/annonc/mdi906; LEIBOVITZ A, 1976, CANCER RES, V36, P4562; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Liu FY, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.46; Liu G, 2014, TUMOR BIOL, V35, P9801, DOI 10.1007/s13277-014-2273-6; Mei Q, 2014, CANCER SCI, V105, P755, DOI 10.1111/cas.12436; Nandi SS, 2015, AM J TRANSL RES, V7, P683; Patel DK, 2008, PHARMACOTHERAPY, V28, p31S, DOI 10.1592/phco.28.11-supp.31S; Pereira DM, 2013, DRUG DISCOV TODAY, V18, P282, DOI 10.1016/j.drudis.2012.10.002; Shi Y, 2013, MOL ENDOCRINOL, V27, P280, DOI 10.1210/me.2012-1260; Van Schaeybroeck S, 2011, NAT REV CLIN ONCOL, V8, P222, DOI 10.1038/nrclinonc.2011.15; von Kleist S, 1975, J Natl Cancer Inst, V55, P555; Wang F, 2014, TUMOR BIOL, V35, P8653, DOI 10.1007/s13277-014-2131-6; Wang F, 2015, ONCOTARGET, V6, P7899, DOI 10.18632/oncotarget.3219; White E, 2012, NAT REV CANCER, V12, P401, DOI 10.1038/nrc3262	31	26	28	0	3	E-CENTURY PUBLISHING CORP	MADISON	40 WHITE OAKS LN, MADISON, WI 53711 USA	1943-8141			AM J TRANSL RES	Am. J. Transl. Res.		2016	8	2					1190	1196					7	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	DJ1DR	WOS:000373944000082	27158405				2022-04-25	
J	Ren, LW; Yi, J; Li, W; Zheng, XJ; Liu, JY; Wang, JH; Du, GH				Ren, Liwen; Yi, Jie; Li, Wan; Zheng, Xiangjin; Liu, Jinyi; Wang, Jinhua; Du, Guanhua			Apolipoproteins and cancer	CANCER MEDICINE			English	Review						apolipoprotein; autophagy; cancer; drug resistance; oxidative stress	INHIBIT TUMOR-DEVELOPMENT; A-I; HEPATOCELLULAR-CARCINOMA; CLUSTERIN EXPRESSION; PROSTATE-CANCER; BREAST-CANCER; CLINICAL-SIGNIFICANCE; COLORECTAL-CANCER; POOR-PROGNOSIS; OVARIAN-CANCER	The role of apolipoproteins in cardiovascular disease has been well investigated, but their participation in cancer has only been explored in a few published studies which showed a close link with certain kinds of cancer. In this review, we focused on the function of different kinds of apolipoproteins in cancers, autophagy, oxidative stress, and drug resistance. The potential application of apolipoproteins as biomarkers for cancer diagnosis and prognosis was highlighted, together with an investigation of their potential as drug targets for cancer treatment. Many important roles of apolipoproteins and their mechanisms in cancers were reviewed in detail and future perspectives of apolipoprotein research were discussed.	[Ren, Liwen; Li, Wan; Zheng, Xiangjin; Liu, Jinyi; Wang, Jinhua; Du, Guanhua] State Key Lab Bioact Subst & Funct Nat Med, Beijing, Peoples R China; [Ren, Liwen; Li, Wan; Zheng, Xiangjin; Liu, Jinyi; Wang, Jinhua; Du, Guanhua] Chinese Acad Med Sci, Key Lab Drug Target Res & Drug Screen, Inst Mat Med, Beijing, Peoples R China; [Ren, Liwen; Li, Wan; Zheng, Xiangjin; Liu, Jinyi; Wang, Jinhua; Du, Guanhua] Peking Union Med Coll, Beijing, Peoples R China; [Yi, Jie] Peking Union Med Coll Hosp, Dept Clin Lab, Beijing, Peoples R China		Wang, JH; Du, GH (corresponding author), Peking Union Med Coll, Beijing, Peoples R China.; Wang, JH; Du, GH (corresponding author), Chinese Acad Med Sci, Inst Mat Med, Beijing, Peoples R China.	wjh@imm.ac.cn; dugh@imm.ac.cn			Beijing Natural Science FoundationBeijing Natural Science Foundation [7172142]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81573454]; Technology Major Projects for "Major New Drugs Innovation and Development" [2018ZX09711001-005-025]; 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NOV	2019	8	16					7032	7043		10.1002/cam4.2587		OCT 2019	12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	JM3TJ	WOS:000488691500001	31573738	gold, Green Published			2022-04-25	
J	Itabashi, M; Tsukamoto, C; Kurosaka, A; Krishnamurthy, P; Shin, TS; Yang, SH; Son, E; Chung, G				Itabashi, Mei; Tsukamoto, Chigen; Kurosaka, Ayaka; Krishnamurthy, Panneerselvam; Shin, Tai-Sun; Yang, Seung Hwan; Son, Eunho; Chung, Gyuhwa			Efficient method for large-scale preparation of two components H and I of Sg-6 saponins from whole seeds of wild soybean (Glycine soja Sieb. and Zucc.)	JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES			English	Article						Purification; saponins; separation; soybean; triterpene glycosides; wild soybean (Glycine soja)	COLON-CANCER CELLS; STRUCTURAL ELUCIDATION; SOYASAPONINS; MACROAUTOPHAGY; POLYMORPHISM; INHIBITION; INDUCTION; MICE; BB; AB	New saponin components, Sg-6 saponins, have been recently reported from the seeds of wild soybean (Glycine soja) which may have specific health benefits. To evaluate the possible health benefits, a large amount of Sg-6 saponins are needed, but general group A acetyl saponins and new Sg-6 saponins are eluted in overlapping peaks by ordinal preparative high-performance liquid chromatography and/or open column methods. A new method is proposed in this report. This method includes (1) deacetylation of group A acetyl saponins in alkali condition with KOH, (2) precipitation of Sg-6 saponins in acid condition with HCl, (3) recovery of Sg-6 saponins with aqueous methanol from the precipitate, and (4) elution of Sg-6 saponins by preparative reverse-phase open column. With this method, from 450g of wild soybean whole seed powder, about 1g of Sg-6 saponins (mixture of six components) was clearly separated from other saponins with 61% recovery. [GRAPHICS] .	[Itabashi, Mei; Kurosaka, Ayaka; Chung, Gyuhwa] Chonnam Natl Univ, Dept Biomed & Elect Engn, Yeosu 59626, Chonnam, South Korea; [Itabashi, Mei; Tsukamoto, Chigen; Kurosaka, Ayaka] Iwate Univ, Fac Agr, Morioka, Iwate, Japan; [Krishnamurthy, Panneerselvam] Natl Inst Agrobiol Sci, Soybean Appl Genom Res Unit, Tsukuba, Ibaraki, Japan; [Shin, Tai-Sun] Chonnam Natl Univ, Div Food & Nutr, Gwangju, South Korea; [Yang, Seung Hwan] Chonnam Natl Univ, Dept Biotechnol, Yeosu, Chonnam, South Korea; [Son, Eunho] RDA, Natl Inst Agr Sci, Natl Agrobiodivers Ctr, Jeonju, South Korea		Chung, G (corresponding author), Chonnam Natl Univ, Dept Biomed & Elect Engn, Yeosu 59626, Chonnam, South Korea.	chung@chonnam.ac.kr		Krishnamurthy, Panneerselvam/0000-0002-9045-430X	National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2015R1D1A1A09060925]; Revitalization Project for the Creation of Fisheries Research and Education Center in Sanriku under Ministry of Education, Culture, Sports, Science and Technology of Japan	This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A1A09060925) and was partly supported by the grant of the Revitalization Project for the Creation of Fisheries Research and Education Center in Sanriku under the aegis of the Ministry of Education, Culture, Sports, Science and Technology of Japan.	Berhow MA, 2000, MUTAT RES-FUND MOL M, V448, P11, DOI 10.1016/S0027-5107(99)00225-0; Chitisankul WT, 2015, LWT-FOOD SCI TECHNOL, V64, P197, DOI 10.1016/j.lwt.2015.05.023; Ellington AA, 2006, CARCINOGENESIS, V27, P298, DOI 10.1093/carcin/bgi214; Ellington AA, 2005, CARCINOGENESIS, V26, P159, DOI 10.1093/carcin/bgh297; Hirakawa T, 2000, CHEM PHARM BULL, V48, P286, DOI 10.1248/cpb.48.286; Honda N, 2009, P WORLD SOYB RES C 8; Hong SW, 2014, J AGR FOOD CHEM, V62, P2062, DOI 10.1021/jf4046528; Katano H, 2015, ANAL SCI, V31, P85, DOI 10.2116/analsci.31.85; Krishnamurthy P, 2014, BIOSCI BIOTECH BIOCH, V78, P1988, DOI 10.1080/09168451.2014.946389; Krishnamurthy P, 2014, GENET RESOUR CROP EV, V61, P1121, DOI 10.1007/s10722-014-0095-4; Krishnamurthy P, 2014, EUPHYTICA, V198, P413, DOI 10.1007/s10681-014-1118-0; KUDOU S, 1992, BIOSCI BIOTECH BIOCH, V56, P142, DOI 10.1271/bbb.56.142; KUDOU S, 1993, BIOSCI BIOTECH BIOCH, V57, P546, DOI 10.1271/bbb.57.546; OKUBO K, 1992, BIOSCI BIOTECH BIOCH, V56, P99, DOI 10.1271/bbb.56.99; TAKESHITA T, 1991, CHEM PHARM BULL, V39, P1908, DOI 10.1248/cpb.39.1908; TSUKAMOTO C, 1993, PHYTOCHEMISTRY, V34, P1351, DOI 10.1016/0031-9422(91)80028-Y; Tsukamoto C., 2005, SOY HLTH DIS PREVENT; Wang P, 2016, CHEM RES TOXICOL, V29, P406, DOI 10.1021/acs.chemrestox.5b00516; Yang SH, 2015, PHYTOTHER RES, V29, P281, DOI 10.1002/ptr.5252; YOSHIKI Y, 1995, BIOSCI BIOTECH BIOCH, V59, P1556, DOI 10.1271/bbb.59.1556	20	2	3	0	1	TAYLOR & FRANCIS INC	PHILADELPHIA	530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA	1082-6076	1520-572X		J LIQ CHROMATOGR R T	J. Liq. Chromatogr. Relat. Technol.		2016	39	14					640	646		10.1080/10826076.2016.1227991			7	Biochemical Research Methods; Chemistry, Analytical	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	EA8NH	WOS:000386891700002					2022-04-25	
J	Ono, A; Sano, O; Kazetani, K; Muraki, T; Imamura, K; Sumi, H; Matsui, J; Iwata, H				Ono, Akito; Sano, Osamu; Kazetani, Ken-ichi; Muraki, Takamichi; Imamura, Keisuke; Sumi, Hiroyuki; Matsui, Junji; Iwata, Hidehisa			Feedback activation of AMPK-mediated autophagy acceleration is a key resistance mechanism against SCD1 inhibitor-induced cell growth inhibition	PLOS ONE			English	Article							COA DESATURASE 1; IN-VITRO; HETEROGENEITY; CARBOXYLASE; LIPOGENESIS; EVOLUTION; DISCOVERY; CARCINOMA; TARGET; TUMORS	Elucidating the bioactive compound modes of action is crucial for increasing success rates in drug development. For anticancer drugs, defining effective drug combinations that overcome resistance improves therapeutic efficacy. Herein, by using a biologically annotated compound library, we performed a large-scale combination screening with Stearoyl-CoA desaturase-1 (SCD1) inhibitor, T-3764518, which partially inhibits colorectal cancer cell proliferation. T-3764518 induced phosphorylation and activation of AMPK in HCT-116 cells, which led to blockade of downstream fatty acid synthesis and acceleration of autophagy. Attenuation of fatty acid synthesis by small molecules suppressed the growth inhibitory effect of T-3764518. In contrast, combination of T-3764518 with autophagy flux inhibitors synergistically inhibited cellular proliferation. Experiments using SCD1 knock-out cells validated the results obtained with T-3764518. The results of our study indicated that activation of autophagy serves as a survival signal when SCD1 is inhibited in HCT-116 cells. Furthermore, these findings suggest that combining SCD1 inhibitor with autophagy inhibitors is a promising anticancer therapy.	[Ono, Akito; Sano, Osamu; Kazetani, Ken-ichi; Muraki, Takamichi; Matsui, Junji; Iwata, Hidehisa] Takeda Pharmaceut Co Ltd, Pharmaceut Res Div, Biomol Res Labs, Fujisawa, Kanagawa, Japan; [Imamura, Keisuke; Sumi, Hiroyuki] Takeda Pharmaceut Co Ltd, Pharmaceut Res Div, Oncol Drug Discovery Unit, Fujisawa, Kanagawa, Japan; [Sumi, Hiroyuki] Celgene KK, Med Affairs, Med Sci, Tokyo, Japan		Iwata, H (corresponding author), Takeda Pharmaceut Co Ltd, Pharmaceut Res Div, Biomol Res Labs, Fujisawa, Kanagawa, Japan.	hidehisa.iwata@takeda.com	Iwata, Hidehisa/K-7493-2019	Iwata, Hidehisa/0000-0002-0950-6388	Takeda Pharmaceutical Company LimitedTakeda Pharmaceutical Company Ltd	This study was financially supported by Takeda Pharmaceutical Company Limited. Employees of Takeda played roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Yu, XF; Shi, WN; Zhang, YH; Wang, XH; Sun, SY; Song, ZY; Liu, M; Zeng, Q; Cui, SX; Qu, XJ				Yu, Xinfeng; Shi, Wenna; Zhang, Yuhang; Wang, Xiaohui; Sun, Shiyue; Song, Zhiyu; Liu, Man; Zeng, Qiao; Cui, Shuxiang; Qu, Xianjun			CXCL12/CXCR4 axis induced miR-125b promotes invasion and confers 5-fluorouracil resistance through enhancing autophagy in colorectal cancer	SCIENTIFIC REPORTS			English	Article							EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELLS; BREAST-CANCER; CHEMOKINE RECEPTORS; TUMOR-SUPPRESSOR; BAK1 EXPRESSION; MICRORNAS; METASTASIS; CXCR4; CARCINOMA	The activation of CXCL12/CXCR4 axis is associated with potential progression of cancer, such as invasion, metastasis and chemoresistance. However, the underlying mechanisms of CXCL12/CXCR4 axis and cancer progression have been poorly explored. We hypothesized that miRNAs might be critical downstream mediators of CXCL12/CXCR4 axis involved in cancer invasion and chemoresistance in CRC. In human CRC cells, we found that the activation of CXCL12/CXCR4 axis promoted epithelialmesenchymal transition (EMT) and concurrent upregulation of miR-125b. Overexpression of miR-125b robustly triggered EMT and cancer invasion, which in turn enhanced the expression of CXCR4. Importantly, the reciprocal positive feedback loop between CXCR4 and miR-125b further activated the Wnt/beta-catenin signaling by targeting Adenomatous polyposis coli (APC) gene. There was a negative correlation of the expression of miR-125b with APC mRNA in paired human colorectal tissue specimens. Further experiments indicated a role of miR-125b in conferring 5-fluorouracil (5-FU) resistance in CRC probably through increasing autophagy both in vitro and in vivo. MiR-125b functions as an important downstream mediator upon the activation of CXCL12/CXCR4 axis that involved in EMT, invasion and 5-FU resistance of CRC. These findings shed a new insight into the role of miR-125b and provide a potential therapeutic target in CRC.	[Yu, Xinfeng; Shi, Wenna; Zhang, Yuhang; Sun, Shiyue; Song, Zhiyu; Liu, Man; Zeng, Qiao; Qu, Xianjun] Capital Med Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing, Peoples R China; [Wang, Xiaohui] Capital Med Univ, Xuan Wu Hosp, Dept Gen Surg, Beijing, Peoples R China; [Cui, Shuxiang] Capital Med Univ, Sch Publ Hlth, Dept Toxicol & Sanit Chem, Beijing Key Lab Environm Toxicol, Beijing, Peoples R China		Qu, XJ (corresponding author), Capital Med Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing, Peoples R China.	quxj@ccmu.edu.cn		Wang, Xiaohui/0000-0002-2299-3977	National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81201731, 81373435/6, 91229113]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7162024, 7142017]; Basic and Clinical grants of Capital Medical University [16JL56]	This study was supported by grants from the National Natural Science Foundation (81201731, 81373435/6 and 91229113), Beijing Natural Science Foundation (7162024, 7142017) and Basic and Clinical grants of Capital Medical University (16JL56). We thank Shandong Tumor Hospital for providing human colonic cancer tissues.	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J	Pagliero, RJ; D'Astolfo, DS; Lelieveld, D; Pratiwi, RD; Aits, S; Jaattela, M; Martin, NI; Klumperman, J; Egan, DA				Pagliero, Romina J.; D'Astolfo, Diego S.; Lelieveld, Daphne; Pratiwi, Riyona D.; Aits, Sonja; Jaattela, Marja; Martin, Nathaniel I.; Klumperman, Judith; Egan, David A.			Discovery of Small Molecules That Induce Lysosomal Cell Death in Cancer Cell Lines Using an Image-Based Screening Platform	ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES			English	Article						lysosomal cell dead; galectin-3 reporter; LMP phenotypic assay; high throughput screening	ACID SPHINGOMYELINASE; MEMBRANE PERMEABILIZATION; FUNCTIONAL INHIBITORS; CYSTEINE CATHEPSINS; OXIDATIVE STRESS; BREAST-CANCER; COLON-CANCER; LUNG-CANCER; APOPTOSIS; AUTOPHAGY	The lysosomal cell death (LCD) pathway is a caspase 3-independent cell death pathway that has been suggested as a possible target for cancer therapy, making the development of sensitive and specific high-throughput (HT) assays to identify LCD inducers highly desirable. In this study, we report a two-step HT screening platform to reliably identify such molecules. First, using a robust HT primary screen based on propidium iodide uptake, we identified compounds that kill through nonapoptotic pathways. A phenotypic image-based assay using a galectin-3 (Gal-3) reporter was then used to further classify hits based on lysosomal permeabilization, a hallmark of LCD. The identification of permeabilized lysosomes in our image-based assay is not affected by changes in the lysosomal pH, thus resolving an important limitation in currently used methods. We have validated our platform in a screen by identifying 24 LCD inducers, some previously known to induce LCD. Although most LCD inducers were cationic amphiphilic drugs (CADs), we have also identified a non-CAD LCD inducer, which is of great interest in the field. Our data also gave new insights into the biology of LCD, suggesting that lysosomal accumulation and acid sphingomyelinase inhibition are not sufficient or necessary for the induction of LCD. Overall, our results demonstrate a robust HT platform to identify novel LCD inducers that will also be very useful for gaining deeper insights into the molecular mechanism of LCD induction.	[Pagliero, Romina J.; D'Astolfo, Diego S.; Lelieveld, Daphne; Pratiwi, Riyona D.; Klumperman, Judith; Egan, David A.] UMCU, Dept Cell Biol, Heidelberglaan 100,Room H02-313, NL-3584 CX Utrecht, Netherlands; [D'Astolfo, Diego S.] KNAW Hubrecht Inst, Utrecht, Netherlands; [Aits, Sonja; Jaattela, Marja] Danish Canc Soc, Res Ctr, Ctr Autophagy Recycling & Dis, Cell Death & Metab Unit, Copenhagen, Denmark; [Martin, Nathaniel I.] Univ Utrecht, UIPS, Dept Chem Biol & Drug Discovery, Utrecht, Netherlands; [Pagliero, Romina J.] Genmab BV, Utrecht, Netherlands		Egan, DA (corresponding author), UMCU, Dept Cell Biol, Heidelberglaan 100,Room H02-313, NL-3584 CX Utrecht, Netherlands.	d.a.egan@umcutrecht.nl	Jäättelä, Marja/AAT-7932-2021; Aits, Sonja/D-1496-2011	Jäättelä, Marja/0000-0001-5950-7111; Aits, Sonja/0000-0002-1321-0678; Pratiwi, Riyona Desvy/0000-0003-3313-9909	UMCU; European Research CouncilEuropean Research Council (ERC)European Commission [AdG340751]; Danish National Research FoundationDanmarks Grundforskningsfond [DNRF125]; Danish Cancer SocietyDanish Cancer Society; Swedish Research CouncilSwedish Research CouncilEuropean Commission; The Danish Cancer SocietyDanish Cancer Society [R90-A5783] Funding Source: researchfish	The authors thank Dr. Harald Wodrich (Laboratoire de Microbiologie Fondamentale et Pathogenicite, Bordeaux, France) for kindly providing the U2OS-mCherry-Gal3 cells. This work was funded in part by the UMCU, the European Research Council (AdG340751), the Danish National Research Foundation (DNRF125), the Danish Cancer Society, the Swedish Research Council.	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TECHNOL.	OCT	2016	14	8			SI		489	510		10.1089/adt.2016.727			22	Biochemical Research Methods; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	DZ8MX	WOS:000386125600006	27732064	Green Accepted			2022-04-25	
J	Zhang, FF; Yang, QX; Meng, FJ; Shi, HJ; Li, H; Liang, YJ; Han, AJ				Zhang, Fenfen; Yang, Qingxu; Meng, Fengjiao; Shi, Huijuan; Li, Hui; Liang, Yingjie; Han, Anjia			Astrocyte Elevated Gene-1 Interacts With beta-Catenin and Increases Migration and Invasion of Colorectal Carcinoma	MOLECULAR CARCINOGENESIS			English	Article						astrocyte elevated gene-1; -catenin; colorectal carcinoma; migration; invasion	X-RECEPTOR-ALPHA; PROTECTIVE AUTOPHAGY; CANCER PROGRESSION; TUMOR PROGRESSION; BREAST-CANCER; METASTASIS; AEG-1; TRANSCRIPTION; PATHOGENESIS; SUPPRESSION	To investigate the astrocyte elevated gene-1 (AEG-1) expression and its relationship with the clinicopathological features of colorectal carcinoma (CRC) and -catenin signaling pathway. Real-time PCR, Western blot, immunohistochemistry, and immunofluorescence staining were performed to detect AEG-1 expression in CRC cell lines, 8 pairs of fresh CRC and adjacent nontumor tissues (ANT), 120 pairs of paraffin-embedded CRC specimens and ANT tissues, and 60 samples of lymph node metastatic CRC tissues. Scratch wound assay and transwell matrix penetration assay were performed to determine migration and invasion of SW480 cell lines with stable AEG-1 overexpression or SW620 cell lines with AEG-1 knockdown. AEG-1 expression was upregulated in CRC cell lines and tissues compared with ANT. Furthermore, AEG-1 expression level significantly correlated with UICC stage, and the N classification. AEG-1 overexpression significantly enhanced migration and invasion of SW480 cell lines. However, AEG-1 knockdown suppressed migration and invasion of SW620 cell lines. Meanwhile, there was a positive correlation between AEG-1 high expression and -catenin nuclear expression in CRC. AEG-1 overexpression increased nuclear -catenin accumulation in CRC cell lines. AEG-1 knockdown decreased nuclear -catenin accumulation in CRC cell lines. Moreover, we firstly found that AEG-1 interacted with -catenin in SW480 cell lines. Our results for the first time showed that AEG-1 interacted with -catenin in CRC cells and AEG-1 expression was closely associated with progression of CRC. AEG-1 might be a potential therapeutic target in CRC. (c) 2012 Wiley Periodicals, Inc.	[Zhang, Fenfen; Meng, Fengjiao; Shi, Huijuan; Li, Hui; Liang, Yingjie; Han, Anjia] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China; [Zhang, Fenfen; Meng, Fengjiao; Shi, Huijuan; Li, Hui; Liang, Yingjie; Han, Anjia] Sun Yat Sen Univ, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China; [Yang, Qingxu] Huizhou Municipal Cent Hosp, Dept Pathol, Huizhou, Peoples R China		Han, AJ (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, 58,Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China.				Guangdong Province Natural Science FoundationNational Natural Science Foundation of Guangdong Province [8151008901000125, S2011010004853]	We would like to thank Dr. Mengfeng Li, Jun Li, and Jueheng Wu for technical and reagent assistance. This study was supported by Guangdong Province Natural Science Foundation (8151008901000125; S2011010004853).	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Carcinog.	AUG	2013	52	8					603	610		10.1002/mc.21894			8	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	181LM	WOS:000321669100003	22431469				2022-04-25	
J	Huang, FC				Huang, Fu-Chen			The Role of Sphingolipids on Innate Immunity to Intestinal Salmonella Infection	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						sphingolipids; Salmonella; intestine epithelia; innate immunity	ENTERICA SEROVAR TYPHIMURIUM; NADPH PHAGOCYTE OXIDASE; RICH MEMBRANE RAFTS; COLON-CANCER CELLS; PROTEIN-KINASE-B; EPITHELIAL-CELLS; PSEUDOMONAS-AERUGINOSA; INTRACELLULAR TRAFFICKING; ANTIMICROBIAL ACTIONS; DIETARY GANGLIOSIDES	Salmonella spp. remains a major public health problem for the whole world. To reduce the use of antimicrobial agents and drug-resistant Salmonella, a better strategy is to explore alternative therapy rather than to discover another antibiotic. Sphingolipid- and cholesterol-enriched lipid microdomains attract signaling proteins and orchestrate them toward cell signaling and membrane trafficking pathways. Recent studies have highlighted the crucial role of sphingolipids in the innate immunity against infecting pathogens. It is therefore mandatory to exploit the role of the membrane sphingolipids in the innate immunity of intestinal epithelia infected by this pathogen. In the present review, we focus on the role of sphingolipids in the innate immunity of intestinal epithelia against Salmonella infection, including adhesion, autophagy, bactericidal effect, barrier function, membrane trafficking, cytokine and antimicrobial peptide expression. The intervention of sphingolipid-enhanced foods to make our life healthy or pharmacological agents regulating sphingolipids is provided at the end.	[Huang, Fu-Chen] Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung 833, Taiwan; [Huang, Fu-Chen] Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan		Huang, FC (corresponding author), Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung 833, Taiwan.; Huang, FC (corresponding author), Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan.	huang817@cgmh.org.tw		Huang, Fu-Chen/0000-0003-3702-6856	Ministry of Science and Technology [MOST 104-2314-B-182-057]	This work was supported, in part, by the Ministry of Science and Technology grant MOST 104-2314-B-182-057.	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J. Mol. Sci.	AUG	2017	18	8							1720	10.3390/ijms18081720			13	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	FF4HB	WOS:000408897400121	28783107	Green Submitted, Green Published, gold			2022-04-25	
J	Chuffa, LGD; Carvalho, RF; Justulin, LA; Cury, SS; Seiva, FRF; Jardim-Perassi, BV; Zuccari, DAPD; Reiter, RJ				Chuffa, Luiz Gustavo de Almeida; Carvalho, Robson Francisco; Justulin, Luis Antonio; Cury, Sarah Santiloni; Seiva, Fabio Rodrigues Ferreira; Jardim-Perassi, Bruna Victorasso; Zuccari, Debora Aparecida Pires de Campos; Reiter, Russel J.			A meta-analysis of microRNA networks regulated by melatonin in cancer: Portrait of potential candidates for breast cancer treatment	JOURNAL OF PINEAL RESEARCH			English	Review						cancer; melatonin; microRNA; miRNA regulatory network; target genes	EXPRESSION ANALYSIS; UP-REGULATION; TOOL; PROLIFERATION; TRANSCRIPTOME; ENVIRONMENT; INHIBITION; REPRESSION; RECEPTOR; HEALTH	Melatonin is a ubiquitous molecule with a broad spectrum of functions including widespread anti-cancer activities. Identifying how melatonin intervenes in complex molecular signaling at the gene level is essential to guide proper therapies. Using meta-analysis approach, herein we examined the role of melatonin in regulating the expression of 46 microRNAs (miRNAs) and their target genes in breast, oral, gastric, colorectal, and prostate cancers, and glioblastoma. The deregulated miRNA-associated target genes revealed their involvement in the regulation of cellular proliferation, differentiation, apoptosis, senescence, and autophagy. Melatonin changes the expression of miRNA-associated genes in breast, gastric, and oral cancers. These genes are associated with cellular senescence, the hedgehog signaling pathway, cell proliferation, p53 signaling, and the hippo signaling pathway. Conversely, colorectal and prostate cancers as well as glioblastoma and oral carcinoma present a clear pattern of less pronounced changes in the expression of miRNA-associated genes. Most notably, colorectal cancer displayed a unique molecular change in response to melatonin. Considering breast cancer network complexity, we compared the genes found during the meta-analysis with RNA-Seq data from breast cancer-bearing mice treated with melatonin. Mechanistically, melatonin upregulated genes associated with immune responses and apoptotic processes, whereas it downregulated genes involved in cellular aggressiveness/metastasis (eg, mitosis, telomerase activity, and angiogenesis). We further characterized the expression profile of our gene subsets with human breast cancer and found eight upregulated genes and 16 downregulated genes that were appositively correlated with melatonin. Our results pose a multi-dimension network of tumor-associated genes regulated by miRNAs potentially targeted by melatonin.	[Chuffa, Luiz Gustavo de Almeida; Carvalho, Robson Francisco; Justulin, Luis Antonio; Cury, Sarah Santiloni] UNESP Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP, Brazil; [Seiva, Fabio Rodrigues Ferreira] UENP CLM Univ Estadual Norte Parana, Dept Biol & Technol, Bandeirantes, Brazil; [Jardim-Perassi, Bruna Victorasso; Zuccari, Debora Aparecida Pires de Campos] Fac Med Sao Jose Do Rio Preto, Sao Jose Do Rio Preto, Brazil; [Reiter, Russel J.] UT Hlth, Dept Cell Syst & Anat, San Antonio, TX USA		Chuffa, LGD (corresponding author), UNESP Sao Paulo State Univ, Inst Biosci Botucatu, Dept Struct & Funct Biol, POB 18618-689,Rubiao Jr S-N, BR-510 Botucatu, SP, Brazil.	guchuffa@yahoo.com.br	Seiva, Fábio R.F./I-5452-2013; de Campos Zuccari, Debora Aparecida Pires/M-3560-2014; Justulin, Luis A/ABH-5494-2020; Chuffa, Luiz Gustavo/ABC-2781-2020; Justulin, Luis A/AAC-4000-2021; Carvalho, Robson Francisco/E-1161-2012	Seiva, Fábio R.F./0000-0002-7461-8773; de Campos Zuccari, Debora Aparecida Pires/0000-0002-0146-9041; Justulin, Luis A/0000-0001-6142-3515; Chuffa, Luiz Gustavo/0000-0002-0199-3396; Justulin, Luis A/0000-0001-6142-3515; Reis, AlessanRSS/0000-0001-8486-7469; Cury, Sarah/0000-0002-4803-0933; Carvalho, Robson Francisco/0000-0002-4901-7714	National Council for Scientific and Technological DevelopmentConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [CNPq 401040/2016-0, 311530/2019-2, 870415/1997-2]; Sao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2019/00906-6]	The following grants supported the development of this study: National Council for Scientific and Technological Development (CNPq 401040/2016-0, 311530/2019-2 to RFC and scholarship #870415/1997-2 to SSC) and Sao Paulo Research Foundation (FAPESP grants #2019/00906-6).	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Pineal Res.	NOV	2020	69	4							e12693	10.1111/jpi.12693		SEP 2020	19	Endocrinology & Metabolism; Neurosciences; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Endocrinology & Metabolism; Neurosciences & Neurology; Physiology	OI6LU	WOS:000570878100001	32910542	Bronze			2022-04-25	
J	Ragimbeau, R; El Kebriti, L; Sebti, S; Fourgous, E; Boulahtouf, A; Arena, G; Espert, L; Turtoi, A; Gongora, C; Houede, N; Pattingre, S				Ragimbeau, Romain; El Kebriti, Leila; Sebti, Salwa; Fourgous, Elise; Boulahtouf, Abdelhay; Arena, Giuseppe; Espert, Lucile; Turtoi, Andrei; Gongora, Celine; Houede, Nadine; Pattingre, Sophie			BAG6 promotes PINK1 signaling pathway and is essential for mitophagy	FASEB JOURNAL			English	Article						BAG6; mitophagy; receptor; signaling	QUALITY-CONTROL; PROTEIN; MITOCHONDRIA; PARKIN; DEGRADATION; ELIMINATION; APOPTOSIS; UBIQUITIN; RESOURCE; HUB	Bcl-2-associated athanogen-6 (BAG6) is a nucleocytoplasmic shuttling protein involved in protein quality control. We previously demonstrated that BAG6 is essential for autophagy by regulating the intracellular localization of the acetyltransferase EP300, and thus, modifying accessibility to its substrates (TP53 in the nucleus and autophagy-related proteins in the cytoplasm). Here, we investigated BAG6 localization and function in the cytoplasm. First, we demonstrated that BAG6 is localized in the mitochondria. Specifically, BAG6 is expressed in the mitochondrial matrix under basal conditions, and translocates to the outer mitochondrial membrane after mitochondrial depolarization with carbonyl cyanide m-chlorophenyl hydrazine, a mitochondrial uncoupler that induces mitophagy. In SW480 cells, the deletion of BAG6 expression abrogates its ability to induce mitophagy and PINK1 accumulation. On the reverse, its ectopic expression in LoVo colon cancer cells, which do not express endogenous BAG6, reduces the size of the mitochondria, induces mitophagy, leads to the activation of the PINK1/PARKIN pathway and to the phospho-ubiquitination of mitochondrial proteins. Finally, BAG6 contains two LIR (LC3-interacting Region) domains specifically found in receptors for selective autophagy and responsible for the interaction with LC3 and for autophagosome selectivity. Site-directed mutagenesis showed that BAG6 requires wild-type LIRs domains for its ability to stimulate mitophagy. In conclusion, we propose that BAG6 is a novel mitophagy receptor or adaptor that induces PINK1/PARKIN signaling and mitophagy in a LIR-dependent manner.	[Ragimbeau, Romain; El Kebriti, Leila; Fourgous, Elise; Boulahtouf, Abdelhay; Turtoi, Andrei; Gongora, Celine; Houede, Nadine; Pattingre, Sophie] Univ Montpellier, IRCM, Inst Reg Canc Montpellier, INSERM,U1194, F-34298 Montpellier, France; [El Kebriti, Leila; Houede, Nadine] CHU Nimes, Nimes, France; [Sebti, Salwa] Univ Texas Southwestern Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA; [Sebti, Salwa] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX USA; [Arena, Giuseppe] Univ Luxembourg, Luxembourg Ctr Syst Biomed LCSB, Belvaux, Luxembourg; [Espert, Lucile] Univ Montpellier, IRIM, UMR 9004, CNRS, Montpellier, France		Pattingre, S (corresponding author), Univ Montpellier, IRCM, Inst Reg Canc Montpellier, INSERM,U1194, F-34298 Montpellier, France.	sophie.pattingre@inserm.fr	Sebti, Salwa/AAB-3188-2020; Espert, Lucile/ABF-5614-2021; Arena, Giuseppe/ABE-8093-2021; Turtoi, Andrei/ABD-1271-2021	Arena, Giuseppe/0000-0003-2398-5503; Turtoi, Andrei/0000-0003-3813-6635; Sebti, Salwa/0000-0003-4327-1129; FOURGOUS, Elise/0000-0002-3626-250X			Bhujabal Z, 2017, EMBO REP, V18, P947, DOI 10.15252/embr.201643147; Che XQ, 2013, BIOCHEM BIOPH RES CO, V441, P488, DOI 10.1016/j.bbrc.2013.10.086; Chu CT, 2013, NAT CELL BIOL, V15, P1197, DOI 10.1038/ncb2837; Claessen JHL, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0028542; De Snoo ML, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-2132-x; Desmots F, 2005, MOL CELL BIOL, V25, P10329, DOI 10.1128/MCB.25.23.10329-10337.2005; Frezza C, 2007, NAT PROTOC, V2, P287, DOI 10.1038/nprot.2006.478; Gomes LC, 2013, BBA-MOL CELL RES, V1833, P205, DOI 10.1016/j.bbamcr.2012.02.012; Gomes LC, 2011, NAT CELL BIOL, V13, P589, DOI 10.1038/ncb2220; Hanna RA, 2012, J BIOL CHEM, V287, P19094, DOI 10.1074/jbc.M111.322933; Harbauer AB, 2014, CELL METAB, V19, P357, DOI 10.1016/j.cmet.2014.01.010; Hayashishita M, 2019, FEBS OPEN BIO, V9, P1281, DOI 10.1002/2211-5463.12677; Kalvari I, 2014, AUTOPHAGY, V10, P913, DOI 10.4161/auto.28260; Kawahara H, 2013, J BIOCHEM, V153, P147, DOI 10.1093/jb/mvs149; Kazlauskaite A, 2014, BIOCHEM J, V460, P127, DOI 10.1042/BJ20140334; Klionsky DJ, 2012, AUTOPHAGY, V8, P445, DOI 10.4161/auto.19496; Koyano F, 2014, NATURE, V510, P162, DOI 10.1038/nature13392; Lee JG, 2013, BIOESSAYS, V35, P377, DOI 10.1002/bies.201200159; Liu L, 2012, NAT CELL BIOL, V14, P177, DOI 10.1038/ncb2422; Montava-Garriga L, 2020, J MOL BIOL, V432, P206, DOI 10.1016/j.jmb.2019.06.032; Morita M, 2017, MOL CELL, V67, P922, DOI 10.1016/j.molcel.2017.08.013; Murakawa T, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms8527; Novak I, 2010, EMBO REP, V11, P45, DOI 10.1038/embor.2009.256; Okamoto K, 2009, DEV CELL, V17, P87, DOI 10.1016/j.devcel.2009.06.013; Qu DB, 2015, J BIOL CHEM, V290, P30441, DOI 10.1074/jbc.M115.677815; Rambold AS, 2011, CELL CYCLE, V10, P4032, DOI 10.4161/cc.10.23.18384; Saita S, 2016, GENES CELLS, V21, P408, DOI 10.1111/gtc.12351; Sebti S, 2014, AUTOPHAGY, V10, P1341, DOI 10.4161/auto.28979; Sebti S, 2014, P NATL ACAD SCI USA, V111, P4115, DOI 10.1073/pnas.1313618111; Stelzl U, 2005, CELL, V122, P957, DOI 10.1016/j.cell.2005.08.029; Tahrir FG, 2017, J CELL PHYSIOL, V232, P797, DOI 10.1002/jcp.25476; Twig G, 2008, EMBO J, V27, P433, DOI 10.1038/sj.emboj.7601963; Verma M, 2020, J BIOL CHEM, V295, P7865, DOI 10.1074/jbc.RA119.010474; Wai T, 2016, EMBO REP, V17, P1844, DOI 10.15252/embr.201642698; Wang XJ, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0086276; Wei YJ, 2017, CELL, V168, P224, DOI 10.1016/j.cell.2016.11.042; Wu W, 2012, J CELL SCI, V125, P4219, DOI 10.1242/jcs.086553; Yoshii SR, 2011, J BIOL CHEM, V286, P19630, DOI 10.1074/jbc.M110.209338; Zhu YY, 2013, J BIOL CHEM, V288, P1099, DOI 10.1074/jbc.M112.399345	39	6	6	2	5	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0892-6638	1530-6860		FASEB J	Faseb J.	FEB	2021	35	2							e21361	10.1096/fj.202000930R			14	Biochemistry & Molecular Biology; Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology	RY3BC	WOS:000647789600111	33522017	Green Submitted			2022-04-25	
J	Zhou, W; Yang, WL; Yang, J; Zhu, HJ; Duan, LL; Wang, XQ; Li, YD; Niu, LR; Xiao, S; Zhang, R; Yang, JJ; Hong, L				Zhou, Wei; Yang, Wanli; Yang, Jing; Zhu, Haijun; Duan, Lili; Wang, Xiaoqian; Li, Yiding; Niu, Liaoran; Xiao, Shuao; Zhang, Rui; Yang, Jianjun; Hong, Liu			miR-483 promotes the development of colorectal cancer by inhibiting the expression level of EI24	MOLECULAR MEDICINE REPORTS			English	Article						colorectal cancer; miR-483; EI24; proliferation; migration; invasion	METASTASIS; INVASION; ANGIOGENESIS; PROGRESSION; RESISTANCE; MICRORNAS; CARCINOMA; TARGETS; GROWTH	MicroRNAs (miRs) serve an important role in cell differentiation, proliferation and apoptosis by negatively regulating gene expression at the transcriptional or post-transcriptional level. EI24 autophagy associated transmembrane protein (EI24) is a tumor suppressor gene that serves an important role in the occurrence and development of digestive system tumors. However, little is known regarding the relationship between EI24 and the prognosis of patients with colorectal cancer (CRC). Our previous study confirmed EI24 as the target molecule of miR-483, using reporter gene detection. Thus, the aim of the present study was to elucidate the effect of the abnormal expression of miR-483 on the malignant phenotype of CRC through a series of cell function experiments and nude mice tumorigenicity experiments, and to determine the expression level of EI24, a downstream target gene of miR-483, in CRC and its relationship with patient prognosis. In CRC tissues and cells, the expression level of miR-483 was upregulated, while the expression level of EI24 was downregulated. Cell function tests such as MTT assay, cell cycle assay, colony formation assay, Migration and invasion assays and nude mice tumorigenicity experiments demonstrated that the overexpression of miR-483 promoted the proliferation, invasion and metastasis of CRC. Moreover, the reverse transcription-quantitative PCR results indicated that overexpression of miR-483 inhibited the expression level of EI24. The relationship between the clinical data and immunohistochemical results from 183 patients with CRC and survival was examined. It was found that the expression level of EI24 was positively associated with the prognosis of patients. As a cancer-promoting factor, miR-483 enhances the proliferation, migration and invasion of CRC cells by reducing the expression level of EI24.	[Zhou, Wei; Yang, Wanli; Duan, Lili; Wang, Xiaoqian; Li, Yiding; Niu, Liaoran; Xiao, Shuao; Zhang, Rui; Yang, Jianjun; Hong, Liu] Fourth Mil Med Univ, Xijing Hosp Digest Dis, Dept Gastrointestinal Surg, 127 Changle West Rd, Xian 710032, Shaanxi, Peoples R China; [Yang, Jing] Fourth Mil Med Univ, Xijing Hosp, Dept Emergency, Xian 710032, Shaanxi, Peoples R China; [Zhu, Haijun] Xian Cent Hosp, Dept Gen Surg, Xian 710003, Shaanxi, Peoples R China		Hong, L (corresponding author), Fourth Mil Med Univ, Xijing Hosp Digest Dis, Dept Gastrointestinal Surg, 127 Changle West Rd, Xian 710032, Shaanxi, Peoples R China.	hongliu1@fmmu.edu.cn					Allgayer H, 2020, SEMIN CANCER BIOL, V60, P1, DOI 10.1016/j.semcancer.2019.07.018; Brenner H, 2014, LANCET, V383, P1490, DOI 10.1016/S0140-6736(13)61649-9; Chen X, 2018, J TRANSL MED, V16, DOI 10.1186/s12967-018-1722-1; Chi SW, 2009, NATURE, V460, P479, DOI 10.1038/nature08170; Choi JM, 2015, LUNG CANCER, V90, P175, DOI 10.1016/j.lungcan.2015.08.019; Choi JM, 2013, ONCOTARGET, V4, P2383, DOI 10.18632/oncotarget.1434; Clark JAM, 2020, ANIM MODEL EXP MED, V3, P103, DOI 10.1002/ame2.12111; Cui HM, 2016, ONCOTARGET, V7, P48456, DOI 10.18632/oncotarget.10309; Dekker E, 2019, LANCET, V394, P1467, DOI 10.1016/S0140-6736(19)32319-0; Duan LL, 2020, FRONT ONCOL, V10, DOI 10.3389/fonc.2020.01570; Ferland-McCollough D, 2012, CELL DEATH DIFFER, V19, P1003, DOI 10.1038/cdd.2011.183; Haase G, 2016, CANCERS, V8, DOI 10.3390/cancers8050048; Huang DD, 2018, CANCER METAST REV, V37, P173, DOI 10.1007/s10555-017-9726-5; Huang SL, 2018, J CANCER, V9, P3867, DOI 10.7150/jca.28588; Kawaguchi Y, 2019, CLIN CANCER RES, V25, P5843, DOI 10.1158/1078-0432.CCR-19-0863; Leber MF, 2009, INT J ONCOL, V34, P881, DOI 10.3892/ijo_00000214; Li ZS, 2017, ONCOTARGET, V8, P19455, DOI 10.18632/oncotarget.14307; Liu X, 2015, FUTURE ONCOL, V11, P2911, DOI 10.2217/fon.15.235; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Loes IM, 2016, INT J CANCER, V139, P647, DOI 10.1002/ijc.30089; Ma JJ, 2016, CELL BIOL INT, V40, P448, DOI 10.1002/cbin.10585; Ma JJ, 2014, DIGEST DIS SCI, V59, P716, DOI 10.1007/s10620-013-2939-8; Malki A, 2021, INT J MOL SCI, V22, DOI 10.3390/ijms22010130; Mazumder D, 2011, INT J CANCER, V129, P1859, DOI 10.1002/ijc.25849; Mentz RJ, 2016, CIRCULATION, V133, P872, DOI 10.1161/CIRCULATIONAHA.115.019902; Nam TW, 2019, BIOCHEM BIOPH RES CO, V514, P1087, DOI 10.1016/j.bbrc.2019.04.186; Niu LR, 2021, MOL THER-NUCL ACIDS, V23, P42, DOI 10.1016/j.omtn.2020.10.030; Patterson EE, 2011, CANCER-AM CANCER SOC, V117, P1630, DOI 10.1002/cncr.25724; Qiao Y, 2011, FEBS LETT, V585, P3095, DOI 10.1016/j.febslet.2011.08.039; Shi L, 2015, REPROD BIOMED ONLINE, V31, P565, DOI 10.1016/j.rbmo.2015.06.023; Si YR, 2017, CELL PHYSIOL BIOCHEM, V42, P1670, DOI 10.1159/000479412; Song QC, 2014, CANCER RES, V74, P3031, DOI 10.1158/0008-5472.CAN-13-2193; Vu T, 2017, CANCERS, V9, DOI 10.3390/cancers9120171; Wang CR, 2015, ONCOTARGET, V6, P36231, DOI 10.18632/oncotarget.4740; Wang H, 2017, MOL THER, V25, P715, DOI 10.1016/j.ymthe.2016.12.020; Weidle UH, 2015, CLIN EXP METASTAS, V32, P623, DOI 10.1007/s10585-015-9732-3; Xiao Y, 2019, MOL MED REP, V20, P4558, DOI 10.3892/mmr.2019.10700; Xue LY, 2017, CANCER BIOMARK, V19, P193, DOI 10.3233/CBM-160506; Yang QQ, 2017, ONCOL LETT, V13, P1958, DOI 10.3892/ol.2017.5608; Yu X, 2016, TUMOR BIOL, V37, P1445, DOI 10.1007/s13277-015-4514-8; Zang Y, 2018, GASTROENT RES PRACT, V2018, DOI [10.1155/2018/2626545, 10.1080/00207543.2018.1471238]; Zhou W., 2016, J PREV MED CARE, V1, P9, DOI [10.14302/issn.2474-3585.jpmc-15-757, DOI 10.14302/ISSN.2474-3585.JPMC-15-757]; Zhou W, 2018, J CANCER, V9, P407, DOI 10.7150/jca.21394; Zhou Y, 2013, GENET TEST MOL BIOMA, V17, P470, DOI 10.1089/gtmb.2012.0518	44	0	0	0	5	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1791-2997	1791-3004		MOL MED REP	Mol. Med. Rep.	AUG	2021	24	2							567	10.3892/mmr.2021.12206			10	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	SS1SK	WOS:000661521400001	34109432				2022-04-25	
J	Huang, RH; Quan, YJ; Chen, JH; Wang, T; Xu, M; Ye, M; Yuan, H; Zhang, CJ; Liu, XJ; Min, ZJ				Huang, Ren-hong; Quan, Ying-jun; Chen, Jin-hong; Wang, Ting-feng; Xu, Ming; Ye, Min; Yuan, Hao; Zhang, Chong-jie; Liu, Xiao-jian; Min, Zhi-jun			Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway	CELLULAR PHYSIOLOGY AND BIOCHEMISTRY			English	Article						Osteopontin; Autophagy; Proliferation; Migration; Invasion; Apoptosis; Colorectal cancer; P38 MAPK pathway	BREAST-CANCER; CARCINOMA-CELLS; INTEGRIN; METASTASIS; GROWTH; PI3K/AKT/MTOR; PROGRESSION; RESISTANCE; EXPRESSION; BLOCKADE	Background: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms Methods: HCT116 cell proliferation, apoptosis, and wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared to investigate the formation of autophagosomes. Results: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. Conclusion: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC. (C) 2017 The Author(s) Published by S. Karger AG, Basel.	[Huang, Ren-hong; Quan, Ying-jun; Wang, Ting-feng; Xu, Ming; Ye, Min; Yuan, Hao; Zhang, Chong-jie; Min, Zhi-jun] Fudan Univ, Pudong Med Ctr, Shanghai Pudong Hosp, Dept Gastroenterol Surg, 2800 Gongwei Rd, Shanghai 201399, Peoples R China; [Chen, Jin-hong] Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai, Peoples R China; [Liu, Xiao-jian] Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, Shanghai 200032, Peoples R China		Min, ZJ (corresponding author), Fudan Univ, Pudong Med Ctr, Shanghai Pudong Hosp, Dept Gastroenterol Surg, 2800 Gongwei Rd, Shanghai 201399, Peoples R China.; Liu, XJ (corresponding author), Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, Shanghai 200032, Peoples R China.	lxj068@hotmail.com; minzhijun@126.com			Shanghai municipal Bureau of Health Fund [20134242]; Shanghai Committee of Science and Technology FundShanghai Science & Technology Committee [15ZR1437500]	This work were supported by Shanghai municipal Bureau of Health Fund (No. 20134242), Shanghai Committee of Science and Technology Fund (No. 15ZR1437500).	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Physiol. Biochem.		2017	41	5					1851	1864		10.1159/000471933			14	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	EY7LW	WOS:000404173800011	28376477	gold			2022-04-25	
J	Molinari, F; Pin, F; Gorini, S; Chiandotto, S; Pontecorvo, L; Penna, F; Rizzuto, E; Pisu, S; Musaro, A; Costelli, P; Rosano, G; Ferraro, E				Molinari, Francesca; Pin, Fabrizio; Gorini, Stefania; Chiandotto, Sergio; Pontecorvo, Laura; Penna, Fabio; Rizzuto, Emanuele; Pisu, Simona; Musaro, Antonio; Costelli, Paola; Rosano, Giuseppe; Ferraro, Elisabetta			The mitochondrial metabolic reprogramming agent trimetazidine as an 'exercise mimetic' in cachectic C26-bearing mice	JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE			English	Article						Cachexia; Atrophy; Metabolism; Mitochondria; Rehabilitation	FATTY-ACID OXIDATION; KINASE SIGNAL-TRANSDUCTION; SKELETAL-MUSCLE ATROPHY; COENZYME-A THIOLASE; CANCER CACHEXIA; TRANSCRIPTIONAL COACTIVATOR; HEART-FAILURE; FIBER-TYPE; MODULATOR TRIMETAZIDINE; GLUCOSE-OXIDATION	Background Cancer cachexia is characterized by muscle depletion and exercise intolerance caused by an imbalance between protein synthesis and degradation and by impaired myogenesis. Myofibre metabolic efficiency is crucial so as to assure optimal muscle function. Some drugs are able to reprogram cell metabolism and, in some cases, to enhance metabolic efficiency. Based on these premises, we chose to investigate the ability of the metabolic modulator trimetazidine (TMZ) to counteract skeletal muscle dysfunctions and wasting occurring in cancer cachexia. Methods For this purpose, we used mice bearing the C26 colon carcinoma as a model of cancer cachexia. Mice received 5 mg/kg TMZ (i.p.) once a day for 12 consecutive days. A forelimb grip strength test was performed and tibialis anterior, and gastrocnemius muscles were excised for analysis. Ex vivo measurement of skeletal muscle contractile properties was also performed. Results Our data showed that TMZ induces some effects typically achieved through exercise, among which is grip strength increase, an enhanced fast-to slow myofibre phenotype shift, reduced glycaemia, PGC1 alpha up-regulation, oxidative metabolism, and mitochondrial biogenesis. TMZ also partially restores the myofibre cross-sectional area in C26-bearing mice, while modulation of autophagy and apoptosis were excluded as mediators of TMZ effects. Conclusions In conclusion, our data show that TMZ acts like an 'exercise mimetic' and is able to enhance some mechanisms of adaptation to stress in cancer cachexia. This makes the modulation of the metabolism, and in particular TMZ, a suitable candidate for a therapeutic rehabilitative protocol design, particularly considering that TMZ has already been approved for clinical use.	[Molinari, Francesca; Gorini, Stefania; Pontecorvo, Laura; Rosano, Giuseppe; Ferraro, Elisabetta] IRCCS San Raffaele Pisana, Lab Pathophysiol Cachexia & Metab Skeletal Muscle, Via Val Cannuta, I-00166 Rome, Italy; [Pin, Fabrizio; Penna, Fabio; Costelli, Paola] Univ Turin, Dept Clin & Biol Sci, IIM, I-10125 Turin, Italy; [Chiandotto, Sergio] Sapienza Univ Rome, DMCM, Dept Surg Pietro Valdoni, Via Scarpa, I-00161 Rome, Italy; [Rizzuto, Emanuele] Sapienza Univ Rome, Dept Mech & Aerosp Engn, Via Eudossiana, I-00184 Rome, Italy; [Pisu, Simona; Musaro, Antonio] Sapienza Univ Rome, Inst Pasteur Cenci Bolognetti, DAHFMO Unit Histol & Med Embryol, IIM, Via Scarpa, I-00161 Rome, Italy; [Musaro, Antonio] Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, Viale Regina Elena, I-00161 Rome, Italy; [Rosano, Giuseppe] St Georges Univ London, Cardiovasc & Cell Sci Inst, Cranmer Terrace, London SW17, England		Ferraro, E (corresponding author), IRCCS San Raffaele Pisana, Lab Pathophysiol Cachexia & Metab Skeletal Muscle, Via Val Cannuta 247, I-00166 Rome, Italy.; Rosano, G (corresponding author), IRCCS San Raffaele, Ctr Vasc Physiol, 106 Harley St, London W1G 7JQ, England.	giuseppe.rosano@gmail.com; elisabetta.ferraro@sanraffaele.it	Musarò, Antonio/K-9598-2016; gorini, stefania/ABI-6853-2020; ferraro, elisabetta/K-3904-2016; Ferraro, Elisabetta/AAS-4975-2020; molinari, francesca/K-3862-2016; Musaro, Antonio/P-2953-2019; Rosano, Giuseppe M. C./K-8718-2018; Penna, Fabio/K-5090-2016	Musarò, Antonio/0000-0002-2944-9739; ferraro, elisabetta/0000-0002-9596-4624; molinari, francesca/0000-0003-0570-7438; Musaro, Antonio/0000-0002-2944-9739; Rosano, Giuseppe M. C./0000-0003-4023-2263; Pisu, Simona/0000-0002-8216-9090; Penna, Fabio/0000-0002-2774-6027	Italian Ministry of Health for Institutional ResearchMinistry of Health, Italy; grant Ricerca Finalizzata (RF) [2010-2318508]	This work was supported by the Italian Ministry of Health for Institutional Research and grant Ricerca Finalizzata (RF) 2010-2318508 to Elisabetta Ferraro.	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Caxhexia Sarcopenia Muscle	DEC	2017	8	6					954	973		10.1002/jcsm.12226			20	Geriatrics & Gerontology; Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	Geriatrics & Gerontology; General & Internal Medicine	FU4MP	WOS:000423827500009	29130633	Green Published, Green Accepted, gold			2022-04-25	
J	Wei, R; Xiao, YH; Song, Y; Yuan, HP; Luo, J; Xu, W				Wei, Ran; Xiao, Yuhong; Song, Yi; Yuan, Huiping; Luo, Jun; Xu, Wei			FAT4 regulates the EMT and autophagy in colorectal cancer cells in part via the PI3K-AKT signaling axis	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH			English	Article						Colorectal cancer; FAT4; PI3K; AKT; EMT; Proliferation; Autophagy	MESENCHYMAL TRANSITION; BETA-CATENIN; PATHWAY; PHOSPHORYLATION; COMPLEX; LC3; INHIBITION; EXPRESSION; GSK-3-BETA; INVASION	BackgroundFAT4 functions as a tumor suppressor, and previous findings have demonstrated that FAT4 can inhibit the epithelial-to-mesenchymal transition (EMT) and the proliferation of gastric cancer cells. However, few studies have investigated the role of FAT4 in the development of colorectal cancer (CRC). The current study aimed to detect the role of FAT4 in the invasion, migration, proliferation and autophagy of CRC and elucidate the probable molecular mechanisms through which FAT4 interacts with these processes.MethodsTranswell invasion assays, MTT assays, transmission electron microscopy, immunohistochemistry and western blotting were performed to evaluate the migration, invasion, proliferation and autophagy abilities of CRC cells, and the levels of active molecules involved in PI3K/AKT signaling were examined through a western blotting analysis. In addition, the function of FAT4 in vivo was assessed using a tumor xenograft model.ResultsFAT4 expression in CRC tissues was weaker than that in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation by promoting autophagy in vitro. Furthermore, the regulatory effects of FAT4 on autophagy and the EMT were partially attributed to the PI3K-AKT signaling pathway. The results in vivo also showed that FAT4 modulated CRC tumorigenesis.ConclusionFAT4 can regulate the activity of PI3K to promote autophagy and inhibit the EMT in part through the PI3K/AKT/mTOR and PI3K/AKT/GSK-3 signaling pathways.	[Xiao, Yuhong; Luo, Jun] Nanchang Univ, Affiliated Hosp 2, Dept Rehabil Med, Nanchang 330006, Jiangxi, Peoples R China; [Song, Yi; Yuan, Huiping; Xu, Wei] Nanchang Univ, Affiliated Hosp 2, Dept Gen Surg, Nanchang 330006, Jiangxi, Peoples R China; [Wei, Ran] Nanchang Univ, Clin Med Coll 1, Nanchang 330006, Jiangxi, Peoples R China		Luo, J (corresponding author), Nanchang Univ, Affiliated Hosp 2, Dept Rehabil Med, Nanchang 330006, Jiangxi, Peoples R China.; Xu, W (corresponding author), Nanchang Univ, Affiliated Hosp 2, Dept Gen Surg, Nanchang 330006, Jiangxi, Peoples R China.	luojun1786@163.com; xu_wei111@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81560365, 81760408, 81860435]	This work was supported by grants from the National Natural Science Foundation of China (Grant numbers 81560365, 81760408, and 81860435).	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J	Han, YH; Mun, JG; Jeon, HD; Kee, JY; Hong, SH				Han, Yo-Han; Mun, Jeong-Geon; Jeon, Hee Dong; Kee, Ji-Ye; Hong, Seung-Heon			Betulin Inhibits Lung Metastasis by Inducing Cell Cycle Arrest, Autophagy, and Apoptosis of Metastatic Colorectal Cancer Cells	NUTRIENTS			English	Article						betulin; colorectal metastasis; apoptosis; autophagy; cell cycle arrest	AMPK; INDUCTION; CARCINOMA; PATHWAYS; EXTRACT; INJURY; DEATH	Background: Colorectal cancer (CRC) is one of the diseases with high prevalence and mortality worldwide. In particular, metastatic CRC shows low probability of surgery and lacks proper treatment. In this study, we conducted experiments to investigate the inhibitory effect of betulin against metastatic CRC and related mechanisms. Methods: Water-soluble tetrazolium assay was used to determine the effect of betulin on metastatic CRC cell viability. Flow cytometry and TUNEL assay were performed to confirm whether betulin can induce apoptosis, autophagy, and cell cycle arrest. A lung metastasis mouse model was employed to estimate the anti-metastatic effect of betulin. Results: betulin decreased viability of metastatic CRC cells, including CT26, HCT116, and SW620 cell lines. Through PI3K/Akt/mTOR inactivation, betulin induced AMPK-mediated G0/G1 phase arrest and autophagy of CT26 and HCT116 cells. In addition, betulin occurred caspase-dependent apoptosis via the mitogen-activated protein kinase signaling pathway in metastatic CRC cells. Moreover, orally administered betulin significantly inhibited metastasis of CT26 cells to the lung. Conclusion: Our results demonstrate the anti-metastatic effect and therapeutic potential of betulin in metastatic CRC treatment.	[Han, Yo-Han; Mun, Jeong-Geon; Jeon, Hee Dong; Kee, Ji-Ye; Hong, Seung-Heon] Wonkwang Univ, Wonkwang Oriental Med Res Inst, Coll Pharm, Dept Oriental Pharm, 460 Iksandae Ro, Iksan 54538, Jeonbuk, South Korea		Kee, JY; Hong, SH (corresponding author), Wonkwang Univ, Wonkwang Oriental Med Res Inst, Coll Pharm, Dept Oriental Pharm, 460 Iksandae Ro, Iksan 54538, Jeonbuk, South Korea.	dygks1867@hanmail.net; wjdrjs92@daum.net; alen0707@naver.com; keejy@wku.ac.kr; jooklim@wku.ac.kr		Kee, Ji-Ye/0000-0002-9836-2127	Wonkwang University	This study was supported by Wonkwang University in 2017.	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J	Salgado-Garcia, R; Coronel-Hernandez, J; Delgado-Waldo, I; de Leon, DC; Garcia-Castillo, V; Lopez-Urrutia, E; Gutierrez-Ruiz, MC; Perez-Plasencia, C; Jacobo-Herrera, N				Salgado-Garcia, Rebeca; Coronel-Hernandez, Jossimar; Delgado-Waldo, Izamary; Cantu de Leon, David; Garcia-Castillo, Veronica; Lopez-Urrutia, Eduardo; Gutierrez-Ruiz, Ma. Concepcion; Perez-Plasencia, Carlos; Jacobo-Herrera, Nadia			Negative Regulation of ULK1 by microRNA-106a in Autophagy Induced by a Triple Drug Combination in Colorectal Cancer Cells In Vitro	GENES			English	Article						autophagy; miR-106a; ULK1; colorectal cancer; HCT116; SW480; metformin; doxorubicin; sodium oxamate		Colorectal cancer (CRC) is among the top three most deadly cancers worldwide. The survival rate for this disease has not been reduced despite the treatments, the reason why the search for therapeutic alternatives continues to be a priority issue in oncology. In this research work, we tested our successful pharmacological combination of three drugs, metformin, doxorubicin, and sodium oxamate (triple therapy, or TT), as an autophagy inducer. Firstly, we employed western blot (WB) assays, where we observed that after 8 h of stimulation with TT, the proteins Unc-51 like autophagy activating kinase 1(ULK1), becline-1, autophagy related 1 protein (Atg4), and LC3 increased in the CRC cell lines HCT116 and SW480 in contrast to monotherapy with doxorubicin. The overexpression of these proteins indicated the beginning of autophagy flow through the activation of ULK1 and the hyperlipidation of LC3 at the beginning of this process. Moreover, we confirm that ULK1 is a bona fide target of hsa-miR-106a-5p (referred to from here on as miR-106a) in HCT116. We also observed through the GFP-LC3 fusion protein that in the presence of miR-106a, the accumulation of autophagy vesicles in cells stimulated with TT is inhibited. These results show that the TT triggered autophagy to modulate miR-106a/ULK1 expression, probably affecting different cellular pathways involved in cellular proliferation, survivance, metabolic maintenance, and cell death. Therefore, considering the importance of autophagy in cancer biology, the study of miRNAs that regulate autophagy in cancer will allow a better understanding of malignant tumors and lead to the development of new disease markers and therapeutic strategies.	[Salgado-Garcia, Rebeca] Autonomous Metropolitan Univ Iztapalapa, Postgrad Expt Biol, DCBS, Mexico City 09340, DF, Mexico; [Salgado-Garcia, Rebeca; Coronel-Hernandez, Jossimar; Delgado-Waldo, Izamary; Perez-Plasencia, Carlos] Natl Canc Inst, Genom Lab, Mexico City 14080, DF, Mexico; [Coronel-Hernandez, Jossimar; Garcia-Castillo, Veronica; Lopez-Urrutia, Eduardo; Perez-Plasencia, Carlos] UNAM, Funct Genom Lab, Biomed Unit, FES IZTACALA, Tlalnepantla 54090, Mexico; [Cantu de Leon, David] Natl Canc Inst, Canc Biomed Res Unit, Genom Lab, Mexico City 14080, DF, Mexico; [Gutierrez-Ruiz, Ma. Concepcion] UNAM Natl Inst Cardiol Ignacio Chavez, Inst Biomed Res, Translat Med Unit, Expt Med Lab, Mexico City 14080, DF, Mexico; [Gutierrez-Ruiz, Ma. Concepcion] Autonomous Metropolitan Univ Iztapalapa, Dept Hlth Sci, Mexico City 09340, DF, Mexico; [Jacobo-Herrera, Nadia] Inst Med Sci & Nutr, Biochem Unit, Mexico City, DF 14080, Mexico		Perez-Plasencia, C (corresponding author), Natl Canc Inst, Genom Lab, Mexico City 14080, DF, Mexico.; Perez-Plasencia, C (corresponding author), UNAM, Funct Genom Lab, Biomed Unit, FES IZTACALA, Tlalnepantla 54090, Mexico.; Jacobo-Herrera, N (corresponding author), Inst Med Sci & Nutr, Biochem Unit, Mexico City, DF 14080, Mexico.	rebe_zoid92@hotmail.com; jossi_thunders@hotmail.com; izz.waldo11@gmail.com; dfcantu@gmail.com; garciaver@gmail.com; e_urrutia@unam.mx; mcgr@xanum.uam.mx; carlos.pplas@gmail.com; nadia.jacoboh@incmnsz.mx	Jacobo-Herrera, Nadia/AGG-8009-2022	Jacobo-Herrera, Nadia/0000-0002-1026-3774; Delgado-Waldo, Izamary/0000-0002-3688-9775; Salgado, Rebeca/0000-0002-1289-1213; Lopez-Urrutia, Eduardo/0000-0002-5307-2003; Gutierrez-Ruiz, Maria Concepcion/0000-0003-0501-7226	Consejo Nacional de Ciencia y Tecnologia (CONACYT), MexicoConsejo Nacional de Ciencia y Tecnologia (CONACyT) [285884]; UNAMUniversidad Nacional Autonoma de Mexico [PAPIIT-IN231420]	This research was funded by the Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico (grant number 285884); UNAM PAPIIT-IN231420.	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J	Zhang, CD; Wang, YL; Zhou, DM; Zhu, MY; Lv, Y; Hao, XQ; Qu, CF; Chen, Y; Gu, WZ; Wu, BQ; Chen, PC; Zhao, ZY				Zhang, Chu-di; Wang, Yi-long; Zhou, Dong-ming; Zhu, Meng-ying; Lv, Yao; Hao, Xiao-qiang; Qu, Chu-fan; Chen, Yi; Gu, Wei-zhong; Wu, Ben-qing; Chen, Pei-chun; Zhao, Zheng-yan			A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway	TRANSLATIONAL ONCOLOGY			English	Article						Colorectal cancer; Oncolytic measles virotherapy; Apoptosis; Autophagy; PI3K; AKT signaling pathway	ONCOLYTIC VIRUSES; UP-REGULATION; STEM-CELLS; RECEPTOR; THERAPY; MODEL; SLAM; AXIS	The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malig-nancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the anti-tumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro . In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective ther-apeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified.	[Zhang, Chu-di; Wang, Yi-long; Zhou, Dong-ming; Zhu, Meng-ying; Lv, Yao; Hao, Xiao-qiang; Qu, Chu-fan; Chen, Yi; Gu, Wei-zhong; Zhao, Zheng-yan] Zhejiang Univ, Sch Med, Childrens Hosp, Hangzhou 310052, Zhejiang, Peoples R China; [Zhang, Chu-di; Zhu, Meng-ying; Qu, Chu-fan; Chen, Yi; Zhao, Zheng-yan] Zhejiang Univ, Sch Med, Hangzhou 310000, Zhejiang, Peoples R China; [Wu, Ben-qing; Chen, Pei-chun] Univ Chinese Acad Sci, Shenzhen Hosp, Shenzhen 518000, Peoples R China		Zhao, ZY (corresponding author), Zhejiang Univ, Sch Med, Childrens Hosp, Hangzhou 310052, Zhejiang, Peoples R China.; Zhao, ZY (corresponding author), Zhejiang Univ, Sch Med, Hangzhou 310000, Zhejiang, Peoples R China.	21718442@zju.edu.cn; 11418155@zju.edu.cn; 21318243@zju.edu.cn; 11618182@zju.edu.cn; 21418068@zju.edu.cn; 11718196@zju.edu.cn; 21818469@zju.edu.cn; 21918473@zju.edu.cn; 6195013@zju.edu.cn; wubenqing783@126.com; 674870541@qq.com; zhaozy@zju.edu.cn		Wang, Yilong/0000-0002-7833-9990	Zhejiang Provincial Science technology research program [2017C33047]	This work was supported by the Zhejiang Provincial Science technology research program (2017C33047).	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Oncol.	JUL	2021	14	7							101091	10.1016/j.tranon.2021.101091		APR 2021	12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	SJ5PX	WOS:000655587700005	33848808	Green Published, gold			2022-04-25	
J	Huang, GN; Liu, ZM; He, LZ; Luk, KH; Cheung, ST; Wong, KH; Chen, TF				Huang, Guanning; Liu, Zumei; He, Lizhen; Luk, Kar-Him; Cheung, Siu-To; Wong, Ka-Hing; Chen, Tianfeng			Autophagy is an important action mode for functionalized selenium nanoparticles to exhibit anti-colorectal cancer activity	BIOMATERIALS SCIENCE			English	Article							REGULATES AUTOPHAGY; SURFACE DECORATION; PROTEIN COMPLEXES; CARCINOMA CELLS; CELLULAR UPTAKE; APOPTOSIS; INDUCTION; POLYSACCHARIDES; NANOTECHNOLOGY; EFFICACY	Selenium nanoparticles (SeNPs) have attracted much interest as potential anticancer nanodrugs. Our previous studies also demonstrated that SeNPs could be developed as carriers of clinically used anticancer drugs to achieve synergistic efficacy. Here, we describe the synthesis of Pleurotus tuber-regium (PTR)-conjugated SeNPs (PTR-SeNPs) and their application in the treatment of colorectal cancer (CRC), which is one of the principal causes of cancer morbidity and mortality in the world. PTR-SeNPs were absorbed by cancer cells via clathrin-mediated endocytosis into lysosomes and caveolae-mediated endocytosis into the Golgi apparatus. Internalized PTR-SeNPs trigger intracellular dose- and time-dependent G2/M phase arrest and apoptosis. Moreover, as shown by using a pEGFP-LC3 plasmid transfection model, PTR-SeNPs activate autophagy to promote the death of cancer cells via upregulation of beclin 1-related signaling pathways. In summary, this study demonstrates the high efficacy of functionalized SeNPs for therapy of colorectal cancer and reveals the important role of autophagy in promoting apoptosis and cell cycle arrest to induce cell death.	[Huang, Guanning; He, Lizhen; Chen, Tianfeng] Jinan Univ, Affiliated Hosp 1, Guangzhou 510632, Guangdong, Peoples R China; [Huang, Guanning; He, Lizhen; Chen, Tianfeng] Jinan Univ, Dept Chem, Guangzhou 510632, Guangdong, Peoples R China; [Liu, Zumei; Luk, Kar-Him; Cheung, Siu-To; Wong, Ka-Hing] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Hong Kong, Hong Kong, Peoples R China		Chen, TF (corresponding author), Jinan Univ, Affiliated Hosp 1, Guangzhou 510632, Guangdong, Peoples R China.; Chen, TF (corresponding author), Jinan Univ, Dept Chem, Guangzhou 510632, Guangdong, Peoples R China.; Wong, KH (corresponding author), Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Hong Kong, Hong Kong, Peoples R China.	kahing.wong@polyu.edu.hk; tchentf@jnu.edu.cn	Chen, Tianfeng/AAG-6123-2019; WONG, Ka Hing/AFW-2400-2022	WONG, Ka Hing/0000-0003-0286-4921	National High-level personnel of special support program [W02070191]; YangFan Innovative & Entrepreneurial Research Team Project [201312H05]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities; GRF/ECS 2017/18; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21701051]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2017A030313051]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2016M600705, 2018T110922]	This study was supported by the National High-level personnel of special support program (W02070191), YangFan Innovative & Entrepreneurial Research Team Project (201312H05), Fundamental Research Funds for the Central Universities, Internal Grant for Eligible PIs Whose Proposal Rated 3.5 in GRF/ECS 2017/18, Natural Science Foundation of China (21701051), Natural Science Foundation of Guangdong Province (2017A030313051), and China Postdoctoral Science Foundation (2016M600705, 2018T110922).	Bjorkoy G, 2009, METHOD ENZYMOL, V452, P181, DOI 10.1016/S0076-6879(08)03612-4; Brown NE, 2012, CANCER RES, V72, P6477, DOI 10.1158/0008-5472.CAN-11-4139; Canton I, 2012, CHEM SOC REV, V41, P2718, DOI 10.1039/c2cs15309b; Carew JS, 2007, BLOOD, V110, P313, DOI 10.1182/blood-2006-10-050260; Chan SL, 2006, LIFE SCI, V78, P2463, DOI 10.1016/j.lfs.2005.10.011; Chang YZ, 2017, ACS NANO, V11, P4848, DOI 10.1021/acsnano.7b01346; Decuypere Jean-Paul, 2012, Cells, V1, P284, DOI 10.3390/cells1030284; Farrell D, 2010, ACS NANO, V4, P589, DOI 10.1021/nn100073g; Feng YX, 2014, DALTON T, V43, P1854, DOI 10.1039/c3dt52468j; Guo WJ, 2013, AUTOPHAGY, V9, P996, DOI 10.4161/auto.24407; He LZ, 2014, ANGEW CHEM INT EDIT, V53, P12532, DOI 10.1002/anie.201407143; Heath JR, 2008, ANNU REV MED, V59, P251, DOI 10.1146/annurev.med.59.061506.185523; Huang H, 2018, BIOMATERIALS, V171, P12, DOI 10.1016/j.biomaterials.2018.04.022; Huang W, 2017, ADV FUNCT MATER, V27, DOI 10.1002/adfm.201701388; Huang YY, 2013, BIOMATERIALS, V34, P7106, DOI 10.1016/j.biomaterials.2013.04.067; Lefranc F, 2007, ONCOLOGIST, V12, P1395, DOI 10.1634/theoncologist.12-12-1395; Li YH, 2013, J MATER CHEM B, V1, P6365, DOI 10.1039/c3tb21168a; Liu T, 2015, NANOMED-NANOTECHNOL, V11, P947, DOI 10.1016/j.nano.2015.01.009; Liu W, 2012, ACS NANO, V6, P6578, DOI 10.1021/nn202452c; Ma XW, 2011, ACS NANO, V5, P8629, DOI 10.1021/nn202155y; Ma YT, 2016, J MOL MED, V94, P497, DOI 10.1007/s00109-016-1401-8; Maiuri MC, 2007, AUTOPHAGY, V3, P374, DOI 10.4161/auto.4237; Marchesi N, 2018, OXID MED CELL LONGEV, V2018, DOI 10.1155/2018/4956080; Mi FL, 2005, BIOMACROMOLECULES, V6, P975, DOI 10.1021/bm049335p; Musgrove EA, 2011, NAT REV CANCER, V11, P558, DOI 10.1038/nrc3090; Park SH, 2012, TOXICOL LETT, V212, P252, DOI 10.1016/j.toxlet.2012.06.007; Pattingre S, 2005, CELL, V122, P927, DOI 10.1016/j.cell.2005.07.002; Peer D, 2007, NAT NANOTECHNOL, V2, P751, DOI 10.1038/nnano.2007.387; Pimkina J, 2009, AUTOPHAGY, V5, P397, DOI 10.4161/auto.5.3.7782; Qu XP, 2007, CELL, V128, P931, DOI 10.1016/j.cell.2006.12.044; Schwarz-Schilling M, 2018, NANO LETT, V18, P2650, DOI 10.1021/acs.nanolett.8b00526; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Spyratou E, 2012, CANCER LETT, V327, P111, DOI 10.1016/j.canlet.2011.12.039; Wang JR, 2009, J BIOL CHEM, V284, P21412, DOI 10.1074/jbc.M109.026013; Wu HL, 2013, J AGR FOOD CHEM, V61, P9859, DOI 10.1021/jf403564s; Wu HL, 2012, J MATER CHEM, V22, P9602, DOI 10.1039/c2jm16828f; Yu B, 2015, J MATER CHEM B, V3, P2497, DOI 10.1039/c4tb02146k; Zeng HW, 2009, MOLECULES, V14, P1263, DOI 10.3390/molecules14031263; Zhang M, 2001, J AGR FOOD CHEM, V49, P5059, DOI 10.1021/jf010228l; Zhang WJ, 2011, COLLOID SURFACE B, V88, P196, DOI 10.1016/j.colsurfb.2011.06.031	40	31	35	5	84	ROYAL SOC CHEMISTRY	CAMBRIDGE	THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND	2047-4830	2047-4849		BIOMATER SCI-UK	Biomater. Sci.	SEP 1	2018	6	9					2508	2517		10.1039/c8bm00670a			10	Materials Science, Biomaterials	Science Citation Index Expanded (SCI-EXPANDED)	Materials Science	GS1GR	WOS:000443267300020	30091749				2022-04-25	
J	Mo, RH; Zaro, JL; Ou, JHJ; Shen, WC				Mo, Robert H.; Zaro, Jennica L.; Ou, Jing-Hsiung James; Shen, Wei-Chiang			Effects of Lipofectamine 2000/siRNA Complexes on Autophagy in Hepatoma Cells	MOLECULAR BIOTECHNOLOGY			English	Article						Autophagy; siRNA; Lipofectamine 2000; GFP-LC3; Autophagosomes; siRNA delivery	SMALL INTERFERING RNA; COLON-CANCER CELLS; MAMMALIAN-CELLS; PROTEASOME INHIBITOR; SIRNA DELIVERY; FLOW-CYTOMETRY; INDUCTION; LC3; NEURONS; PATHWAY	Lipofectamine 2000 is commonly used for siRNA transfections. However, few studies have examined cellular responses to this delivery system. The purpose of this study is to evaluate the effect of siRNA transfection using Lipofectamine 2000 on cellular autophagy. Huh7.5 cells, stably transfected to express GFP-LC3, were treated with Lipofectamine 2000/negative control siRNA (NC siRNA) complexes. At different time points after treatment, cells were lysed and analyzed by immunoblotting and fluorescence spectroscopy. Cells were also observed using confocal microscopy. An increase of endogenous LC3 lipidation, GFP-LC3 fluorescence, and autophagosomal puncta was observed in cells treated with Lipofectamine 2000/NC siRNA complexes. The kinetics of the increase of GFP-LC3 fluorescence correlated with the concentration of NC siRNA transfected, where 50, 100, and 200 nM NC siRNA caused a significant increase at 72, 48, and 24 h, respectively, after transfection. A similar effect on the GFP-LC3 signal was also observed for cells treated with Lipofectamine 2000 complexed with two other NC siRNAs. The effects were also confirmed in another hepatoma cell line, H4IIE, by immunoblotting. Lipofectamine 2000-mediated transport of NC siRNAs led to an increase of autophagosomes in a dose- and time-dependent manner. Thus, this effect on cells should be taken into consideration when using this approach for intracellular delivery of siRNA.	[Mo, Robert H.; Zaro, Jennica L.; Shen, Wei-Chiang] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90033 USA; [Ou, Jing-Hsiung James] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA		Shen, WC (corresponding author), Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, 1985 Zonal Ave,PSC 404B, Los Angeles, CA 90033 USA.	rmo@usc.edu; zaro@usc.edu; jamesou@hsc.usc.edu; weishen@usc.edu			NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM070777, AI083025]; American Foundation for Pharmaceutical Education; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [U19AI083025] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [P30DK048522] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM070777] Funding Source: NIH RePORTER	This research was supported in part by NIH GM070777 (W. C. S.) and AI083025 (J.J.O.). We thank Dr. Charles M. Rice, Rockefeller University, for providing us with the Huh7.5 cells. We also thank Cheng-Fu Kuo for his help with confocal microscopy and Michelle MacVeigh of the Confocal Microscopy Sub-Core at the USC Center for Liver Diseases (NIH P30 DK48522) for her assistance. R. H. M. is a recipient of the American Foundation for Pharmaceutical Education pre-doctoral fellowship.	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Biotechnol.	MAY	2012	51	1					1	8		10.1007/s12033-011-9422-6			8	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology	920CW	WOS:000302380500001	21660602	Green Accepted			2022-04-25	
J	Sumbul, AT; Gogebakan, B; Ergun, S; Yengil, E; Batmaci, CY; Tonyali, O; Yaldiz, M				Sumbul, Ahmet Taner; Gogebakan, Bulent; Ergun, Sercan; Yengil, Erhan; Batmaci, Celal Yucel; Tonyali, Onder; Yaldiz, Mehmet			miR-204-5p expression in colorectal cancer: an autophagy-associated gene	TUMOR BIOLOGY			English	Article						Colorectal cancer; miR-204-5p; LC3B-II; Bcl2; Clinicopathological factors	POOR-PROGNOSIS; MICRORNA; CELLS; OVEREXPRESSION; BIOGENESIS; TUMORS	MicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low-and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p=0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p=0.021 and p=0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-2045p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p=0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.	[Sumbul, Ahmet Taner; Tonyali, Onder] Mustafa Kemal Univ, Fac Med, Dept Med Oncol, Antakya, Turkey; [Gogebakan, Bulent] Mustafa Kemal Univ, Fac Med, Dept Med Biol & Genet, Antakya, Turkey; [Ergun, Sercan] Gaziantep Univ, Fac Med, Dept Med Biol, Antakya, Turkey; [Yengil, Erhan] Mustafa Kemal Univ, Fac Med, Dept Family Med, Antakya, Turkey; [Batmaci, Celal Yucel] Mustafa Kemal Univ, Fac Med, Dept Internal Med, Antakya, Turkey; [Yaldiz, Mehmet] Mustafa Kemal Univ, Fac Med, Dept Pathol, Antakya, Turkey		Sumbul, AT (corresponding author), Mustafa Kemal Univ, Fac Med, Dept Med Oncol, Antakya, Turkey.	drtanersu@yahoo.com	Sumbul, Ahmet T/D-4793-2014; Ergün, Sercan/I-8798-2019	Sumbul, Ahmet T/0000-0002-5573-906X; Ergün, Sercan/0000-0002-6733-9848	Turkish Medical Oncology Society	This study was performed with a grant taken from the Turkish Medical Oncology Society.	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DEC	2014	35	12					12713	12719		10.1007/s13277-014-2596-3			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AX3UI	WOS:000346863700120	25209181				2022-04-25	
J	Zhao, HB; Huang, CZ; Luo, YW; Yao, XY; Hu, Y; Wang, MQ; Chen, X; Zeng, J; Hu, WX; Wang, JJ; Li, RJ; Yao, XQ				Zhao, Haibi; Huang, Chengzhi; Luo, Yuwen; Yao, Xiaoya; Hu, Yong; Wang, Muqing; Chen, Xin; Zeng, Jun; Hu, Weixian; Wang, Junjiang; Li, Rongjiang; Yao, Xueqing			A Correlation Study of Prognostic Risk Prediction for Colorectal Cancer Based on Autophagy Signature Genes	FRONTIERS IN ONCOLOGY			English	Article						ARGs; prognostic indicator; CRC; nomogram; risk model	CELL-DEATH; PROMOTES; INFLAMMATION; INHIBITION; VALIDATION; ACTIVATION; RESISTANCE	Autophagy plays a complex role in tumors, sometimes promoting cancer cell survival and sometimes inducing apoptosis, and its role in the colorectal tumor microenvironment is controversial. The purpose of this study was to investigate the prognostic value of autophagy-related genes (ARGs) in colorectal cancer. We identified 37 differentially expressed autophagy-related genes by collecting TCGA colorectal tumor transcriptome data. A single-factor COX regression equation was used to identify 11 key prognostic genes, and a prognostic risk prediction model was constructed based on multifactor COX analysis. We classified patients into high and low risk groups according to prognostic risk parameters (p <0.001) and determined the prognostic value they possessed by survival analysis and the receiver operating characteristic (ROC) curve in the training and test sets of internal tests. In a multifactorial independent prognostic analysis, this risk value could be used as an independent prognostic indicator (HR=1.167, 95% CI=1.078-1.264, P<0.001) and was a robust predictor without any staging interference. To make it more applicable to clinical procedures, we constructed nomogram based on risk parameters and parameters of key clinical characteristics. The area under ROC curve for 3-year and 5-year survival rates were 0.735 and 0.718, respectively. These will better enable us to monitor patient prognosis, thus improve patient outcomes.	[Zhao, Haibi; Yao, Xiaoya; Hu, Yong; Yao, Xueqing] South China Univ Technol, Sch Biol & Biol Engn, Guangzhou, Peoples R China; [Zhao, Haibi; Huang, Chengzhi; Luo, Yuwen; Yao, Xiaoya; Hu, Yong; Wang, Muqing; Chen, Xin; Hu, Weixian; Wang, Junjiang; Yao, Xueqing] Guangdong Acad Med Sci, Dept Gastrointestinal Surg, Guangdong Prov Peoples Hosp, Guangzhou, Peoples R China; [Zhao, Haibi; Huang, Chengzhi; Luo, Yuwen; Yao, Xiaoya; Hu, Yong; Wang, Muqing; Chen, Xin; Yao, Xueqing] Guangdong Prov Peoples Hosp, Ganzhou Hosp, Ganzhou Municipal Hosp, Ganzhou, Peoples R China; [Huang, Chengzhi; Wang, Muqing; Wang, Junjiang; Yao, Xueqing] South China Univ Technol, Sch Med, Guangzhou, Peoples R China; [Luo, Yuwen; Wang, Junjiang; Yao, Xueqing] Southern Med Univ, Sch Clin Med 2, Guangzhou, Peoples R China; [Chen, Xin; Yao, Xueqing] Shantou Univ, Coll Med, Shantou, Peoples R China; [Zeng, Jun; Li, Rongjiang] Shen Zhen Univ, Affiliated Hosp 1, Baoan Cent Hosp, Dept Gen Surg, Shenzhen, Peoples R China		Yao, XQ (corresponding author), South China Univ Technol, Sch Biol & Biol Engn, Guangzhou, Peoples R China.; Yao, XQ (corresponding author), Guangdong Acad Med Sci, Dept Gastrointestinal Surg, Guangdong Prov Peoples Hosp, Guangzhou, Peoples R China.; Yao, XQ (corresponding author), Guangdong Prov Peoples Hosp, Ganzhou Hosp, Ganzhou Municipal Hosp, Ganzhou, Peoples R China.; Yao, XQ (corresponding author), South China Univ Technol, Sch Med, Guangzhou, Peoples R China.; Yao, XQ (corresponding author), Southern Med Univ, Sch Clin Med 2, Guangzhou, Peoples R China.; Yao, XQ (corresponding author), Shantou Univ, Coll Med, Shantou, Peoples R China.; Li, RJ (corresponding author), Shen Zhen Univ, Affiliated Hosp 1, Baoan Cent Hosp, Dept Gen Surg, Shenzhen, Peoples R China.	lirongjiang@163.com; syyaoxueqing@scut.edu.cn		CHEN, Xin/0000-0003-3561-2691	Science and Technology Planning Project of Guangdong Province, China [2017A030223006, 2016A020215128]; Science and Technology Planning Project of Guangzhou, China [201704020077]; Second Batch of Scientific Research Projects of Dengfeng Plan [DFJH201913]; Research Fund of CSCO-Roche Oncology [Y-2019Roche-190]; Research Fund of CSCO-Hansoh Oncology [Y-HS2019/2-050]; Research Fund of Guangdong General Hospital [y012015338]; Yuexiu Science and Information Center of Guangzhou Scientific Foundation [2012-GX-046]	This work was supported by grants from the Science and Technology Planning Project of Guangdong Province, China (No. 2017A030223006, 2016A020215128), the Science and Technology Planning Project of Guangzhou, China (No. 201704020077), the Second Batch of Scientific Research Projects of Dengfeng Plan (NO. DFJH201913), the Research Fund of CSCO-Roche Oncology (NO. Y-2019Roche-190) and the Research Fund of CSCO-Hansoh Oncology (NO. Y-HS2019/2-050), the Research Fund of Guangdong General Hospital (No. y012015338), the Yuexiu Science and Information Center of Guangzhou Scientific Foundation (No. 2012-GX-046).	Agarwal S, 2020, CANCERS, V12, DOI 10.3390/cancers12040772; Bae HR, 2020, J AUTOIMMUN, V111, DOI 10.1016/j.jaut.2020.102436; Barutcu SA, 2018, AUTOPHAGY, V14, P1586, DOI 10.1080/15548627.2018.1466013; Braden CR, 2016, FEBS J, V283, P3889, DOI 10.1111/febs.13906; Brown M, 2016, J CELL SCI, V129, P2317, DOI 10.1242/jcs.179127; Goruppi S, 2017, CELL REP, V20, P2468, DOI 10.1016/j.celrep.2017.08.048; Ishaq M, 2020, SEMIN CANCER BIOL, V66, P171, DOI 10.1016/j.semcancer.2020.03.010; Jiang YY, 2020, GASTROENTEROLOGY, V159, P1311, DOI 10.1053/j.gastro.2020.06.050; Jin P, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-1844-2; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Li YJ, 2017, CHIN J CANCER, V52, DOI 10.1186/s40880-017-0219-2; Liu M, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-12573-z; Lu XH, 2020, INT J BIOL SCI, V16, P1427, DOI 10.7150/ijbs.42962; Mao Z, 2019, INT J BIOL SCI, V15, P1310, DOI 10.7150/ijbs.32987; Matsuda Y, 2015, CANCER LETT, V357, P602, DOI 10.1016/j.canlet.2014.12.030; Perez-Hernandez M, 2019, CANCERS, V11, DOI 10.3390/cancers11101599; Polimeno L, 2020, MICROORGANISMS, V8, DOI 10.3390/microorganisms8040469; Qiu HD, 2020, FRONT GENET, V11, DOI 10.3389/fgene.2020.00012; Shi Y, 2020, ONCOTARGETS THER, V13, P2127, DOI 10.2147/OTT.S229913; Wang WJ, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1054-x; Wang ZH, 2019, AGING-US, V11, P12246, DOI 10.18632/aging.102566; Xie YH, 2020, SIGNAL TRANSDUCT TAR, V5, DOI 10.1038/s41392-020-0116-z; Yeh SJ, 2020, FRONT GENET, V11, DOI 10.3389/fgene.2020.00117; Yi M, 2020, CELL MOL LIFE SCI, V77, P4325, DOI 10.1007/s00018-020-03539-2; Yun CW, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19113466; Zhang ZOA, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1336-3; Zhao C, 2020, CANCER LETT, V481, P15, DOI 10.1016/j.canlet.2020.03.010	27	4	4	2	5	FRONTIERS MEDIA SA	LAUSANNE	AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND	2234-943X			FRONT ONCOL	Front. Oncol.	MAY 25	2021	11								595099	10.3389/fonc.2021.595099			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	SW0VJ	WOS:000664235200001	34168974	gold, Green Published			2022-04-25	
J	Shiratori, H; Kawai, K; Hata, K; Tanaka, T; Nishikawa, T; Otani, K; Sasaki, K; Kaneko, M; Murono, K; Emoto, S; Sonoda, H; Nozawa, H				Shiratori, Hiroshi; Kawai, Kazushige; Hata, Keisuke; Tanaka, Toshiaki; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Kaneko, Manabu; Murono, Koji; Emoto, Shigenobu; Sonoda, Hirofumi; Nozawa, Hiroaki			The combination of temsirolimus and chloroquine increases radiosensitivity in colorectal cancer cells	ONCOLOGY REPORTS			English	Article						colorectal cancer; radiosensitivity; mTOR; autophagy; temsirolimus; chloroquine	AUTOPHAGY INHIBITION; OVERCOMES RESISTANCE; MAMMALIAN TARGET; CARCINOMA-CELLS; RAPAMYCIN; APOPTOSIS; MTOR; PATHWAY; HYDROXYCHLOROQUINE; RADIORESISTANCE	The PI3K/AKT/mTOR pathway and autophagy are known to play important roles in cancer radioresistance. The aim of the present study was to investigate whether the combination of temsirolimus (TEM), an mTOR inhibitor, and chloroquine (CQ), an autophagy inhibitor, can increase radiosensitivity in colorectal cancer (CRC) cells. The efficacies of TEM and/or CQ as radiosensitizers were examined using clonogenic assays in CRC cell lines SW480 and HT-29. The expression levels of the phosphorylated isoforms of S6 and 4E-BP1, downstream proteins of mTOR, as well as the expression levels of p62 and LC3, autophagy-related proteins, were assessed by western blot analysis. The formation of acidic organelles was detected in acridine orange-stained cells. Apoptosis and caspase activity were assessed using flow cytometry. The results revealed that ionizing radiation (IR) activated the downstream proteins of mTOR and induced autophagy. In the clonogenic assays, neither TEM nor CQ influenced the efficacy of IR, whereas their combination significantly increased the dose-dependent efficacy of IR. TEM inhibited phosphorylation of the downstream proteins of mTOR and induced autophagy. CQ inhibited autophagy in the late phase and did not influence the downstream proteins of mTOR. TEM and CQ inhibited both the phosphorylation of downstream proteins of mTOR and autophagy. Cell death analysis revealed that the combination of TEM and CQ strongly induced apoptosis in cells exposed to IR. In conclusion, the combination of TEM and CQ increased radiosensitivity in CRC cells through co-inhibition of mTOR and autophagy.	[Shiratori, Hiroshi; Kawai, Kazushige; Hata, Keisuke; Tanaka, Toshiaki; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Kaneko, Manabu; Murono, Koji; Emoto, Shigenobu; Sonoda, Hirofumi; Nozawa, Hiroaki] Univ Tokyo, Fac Med, Dept Surg, Div Surg Oncol, Tokyo 1138655, Japan		Shiratori, H (corresponding author), Univ Tokyo, Fac Med, Dept Surg, Div Surg Oncol,Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.	tori.shior@gmail.com	Murono, Koji/AAC-3958-2020; Kawai, Kazushige/AAF-4334-2020	Kawai, Kazushige/0000-0002-5881-0036; Shiratori, Hiroshi/0000-0001-7404-7926; Sonoda, Hirofumi/0000-0003-3353-1783	Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [16K07143, 16K07161, 17K10620, 17K10621, 17K10623, 18K07194]; Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development (AMED)Japan Agency for Medical Research and Development (AMED) [18cm0106502h0003]	The present study was supported by Grants-in-Aid for Scientific Research (grant nos. 16K07143, 16K07161, 17K10620, 17K10621, 17K10623 and 18K07194) from the Japan Society for the Promotion of Science. This research was also supported by the Project for Cancer Research and Therapeutic Evolution (P-CREATE; grant no. 18cm0106502h0003) from the Japan Agency for Medical Research and Development (AMED).	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Rep.	JUL	2019	42	1					377	385		10.3892/or.2019.7134			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IH9EF	WOS:000474808700034	31059051	Bronze			2022-04-25	
J	Xia, D; Zhang, YT; Xu, GP; Yan, WW; Pan, XR; Tong, JH				Xia, Di; Zhang, Ying-Ting; Xu, Gui-Ping; Yan, Wei-Wei; Pan, Xiao-Rong; Tong, Jian-Hua			Sertraline exerts its antitumor functions through both apoptosis and autophagy pathways in acute myeloid leukemia cells	LEUKEMIA & LYMPHOMA			English	Article						Sertraline; apoptosis; autophagy; acute myeloid leukemia	SEROTONIN REUPTAKE INHIBITORS; TUMOR REVERSION; ANTIDEPRESSANT SERTRALINE; COLORECTAL-CANCER; LSD1 INHIBITORS; IN-VITRO; PHASE 1B; TARGET; BEVACIZUMAB; COMBINATION	It has been found that sertraline, a widely used antidepressant drug, possessed antitumor roles in a variety of cancers including liver cancer, colorectal cancer and lymphoma. In this study, we provided evidences that sertraline had potent antiproliferative activity not only in acute myeloid leukemia (AML) cell lines but also in the fresh leukemia cells from AML patients, and could induce cell death through both apoptosis and autophagy pathways. Moreover, we found that inhibiting autophagy pathway could partially attenuate sertraline-induced apoptosis and cell growth inhibition, indicating that sertraline-induced autophagy process could facilitate AML cell apoptosis to some degree. However, blocking apoptosis pathway seemed no obvious effects on sertraline-caused autophagy as well as cell growth inhibition. Our results suggested a potential application value of sertraline in the treatment of AML patients, furnishing some perspectives for novel therapeutic strategies in leukemia.	Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, State Key Lab Med Genom, Shanghai, Peoples R China; Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Fac Med Lab Sci, Shanghai, Peoples R China		Pan, XR; Tong, JH (corresponding author), Ruijin Hosp, 197 Ruijin Er Rd, Shanghai 200025, Peoples R China.	xrpan@126.com; jh_tong@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81470317, 81170508]; Shanghai Municipal Human Resources and Social Security Bureau	This work was supported in part by National Natural Science Foundation of China [81470317 and 81170508]; Leading Talent Program of Shanghai Municipal Human Resources and Social Security Bureau.	Acunzo J, 2014, CANCER TREAT REV, V40, P760, DOI 10.1016/j.ctrv.2014.02.007; Amit B, 2009, EUR NEUROPSYCHOPHARM, V19, P726, DOI 10.1016/j.euroneuro.2009.06.003; Amson R, 2013, CURR OPIN ONCOL, V25, P59, DOI 10.1097/CCO.0b013e32835b7d21; Baig S, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2015.275; Barbey JT, 1998, J CLIN PSYCHIAT, V59, P42; Brown LF, 2010, PSYCHO-ONCOLOGY, V19, P734, DOI 10.1002/pon.1627; Chen S, 2014, TOXICOL SCI, V137, P404, DOI 10.1093/toxsci/kft254; Fuchs Y, 2011, CELL, V147, P742, DOI 10.1016/j.cell.2011.10.033; Fulda S, 2015, ONCOGENE, V34, P5105, DOI 10.1038/onc.2014.458; Fulda S, 2015, SEMIN CANCER BIOL, V31, P84, DOI 10.1016/j.semcancer.2014.05.002; Gil-Ad I, 2008, INT J ONCOL, V33, P277, DOI 10.3892/ijo_00000007; Granata S, 2016, INT J MOL SCI, V17, DOI 10.3390/ijms17050735; Kaplan C, 2012, J MENT HEALTH POLICY, V15, P171; KERR JFR, 1972, BRIT J CANCER, V26, P239, DOI 10.1038/bjc.1972.33; Kim ES, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0118190; Lin CJ, 2010, CANCER RES, V70, P3199, DOI 10.1158/0008-5472.CAN-09-4072; Lockshin RA, 2016, CELL DEATH DIFFER, V23, P10, DOI 10.1038/cdd.2015.126; Maes T, 2015, CURR OPIN PHARMACOL, V23, P52, DOI 10.1016/j.coph.2015.05.009; Mandrioli R, 2013, EXPERT OPIN DRUG MET, V9, P1495, DOI 10.1517/17425255.2013.816675; Marino G, 2014, NAT REV MOL CELL BIO, V15, P81, DOI 10.1038/nrm3735; Mizushima N, 2010, CELL, V140, P313, DOI 10.1016/j.cell.2010.01.028; Mohammad HP, 2015, CANCER CELL, V28, P57, DOI 10.1016/j.ccell.2015.06.002; Ohsumi Y, 2014, CELL RES, V24, P9, DOI 10.1038/cr.2013.169; Rebecca VW, 2016, ONCOGENE, V35, P1, DOI 10.1038/onc.2015.99; SALETU B, 1986, J NEURAL TRANSM, V67, P241, DOI 10.1007/BF01243351; Sanchez C, 2014, INT CLIN PSYCHOPHARM, V29, P185, DOI 10.1097/YIC.0000000000000023; Saran U, 2015, CLIN SCI, V129, P895, DOI 10.1042/CS20150149; Schenk T, 2012, NAT MED, V18, P605, DOI 10.1038/nm.2661; Soria JC, 2010, J CLIN ONCOL, V28, P1527, DOI 10.1200/JCO.2009.25.4847; Telerman A, 2009, NAT REV CANCER, V9, P206, DOI 10.1038/nrc2589; Tuynder M, 2004, P NATL ACAD SCI USA, V101, P15364, DOI 10.1073/pnas.0406776101; Tzadok S, 2010, INT J ONCOL, V37, P1043, DOI 10.3892/ijo_00000756; Wainberg ZA, 2013, CLIN COLORECTAL CANC, V12, P248, DOI 10.1016/j.clcc.2013.06.002; Zheng YC, 2016, CURR TOP MED CHEM, V16, P2179, DOI 10.2174/1568026616666160216154042	34	17	17	3	8	TAYLOR & FRANCIS LTD	ABINGDON	2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND	1042-8194	1029-2403		LEUKEMIA LYMPHOMA	Leuk. Lymphoma		2017	58	9					2208	2217		10.1080/10428194.2017.1287358			10	Oncology; Hematology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Hematology	EY4FU	WOS:000403933700022	28278721				2022-04-25	
J	Nam, Y; Ryu, KD; Jang, C; Moon, YH; Kim, M; Ko, D; Chung, KS; Gandini, MA; Lee, KT; Zamponi, GW; Lee, JY				Nam, Yunchan; Ryu, Ki Deok; Jang, Changyoung; Moon, Yoon Hyoung; Kim, Misong; Ko, Dohyeong; Chung, Kyung-Sook; Gandini, Maria A.; Lee, Kyung-Tae; Zamponi, Gerald W.; Lee, Jae Yeol			Synthesis and cytotoxic effects of 2-thio-3,4-dihydroquinazoline derivatives as novel T-type calcium channel blockers	BIOORGANIC & MEDICINAL CHEMISTRY			English	Article						T-type calcium channel; 2-thio-3,4-dihydroquinazoline; Current inhibition; Cytotoxicity	CANCER-CELLS; A549 CELLS; APOPTOSIS; INHIBITION; EXPRESSION; AUTOPHAGY; ARREST; GROWTH	In our previous work, a series of 2-amino-3,4-dihydroquinazoline derivatives using an electron acceptor group was reported to be potent T-type calcium channel blockers and exhibit strong cytotoxic effects against various cancerous cell lines. To investigate the role of the guanidine moiety in the 2-amino-3,4-dihydroquinazoline scaffold as a pharmacophore for dual biological activity, a new series of 2-thio-3,4-dihydroquniazoline derivatives using an electron donor group at the C2-position was synthesized and evaluated for T-type calcium channel blocking activity and cytotoxic effects against two human cancerous cell lines (lung cancer A549 and colon cancer HCT-116). Among them, compound 6g showed potent inhibition of Ca(v)3.2 currents (83% inhibition) at 10 mu M concentrations. The compound also exhibited IC50 values of 5.0 and 6.4 mu M against A549 and HCT-116 cell lines, respectively, which are comparable to the parental lead compound KYS05090. These results indicate that the isothiourea moiety similar to the guanidine moiety of 2-amino-3,4-dihydroquinazoline derivatives may be an essential pharmacophore for the desired biological activities. Therefore, our preliminary work can provide the opportunity to expand a chemical repertoire to improve affinity and selectivity for T-type calcium channels.	[Nam, Yunchan; Ryu, Ki Deok; Jang, Changyoung; Moon, Yoon Hyoung; Kim, Misong; Ko, Dohyeong; Lee, Jae Yeol] Kyung Hee Univ, Coll Sci, Res Inst Basic Sci, Seoul 02447, South Korea; [Nam, Yunchan; Ryu, Ki Deok; Jang, Changyoung; Moon, Yoon Hyoung; Kim, Misong; Ko, Dohyeong; Lee, Jae Yeol] Kyung Hee Univ, Coll Sci, Dept Chem, Seoul 02447, South Korea; [Chung, Kyung-Sook; Lee, Kyung-Tae] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Coll Pharm, Seoul 02447, South Korea; [Gandini, Maria A.; Zamponi, Gerald W.] Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Dept Physiol & Pharmacol, Calgary, AB T2N 4N1, Canada; [Gandini, Maria A.; Zamponi, Gerald W.] Univ Calgary, Cumming Sch Med, Alberta Childrens Hosp Res Inst, Calgary, AB T2N 4N1, Canada; [Lee, Jae Yeol] Kyung Hee Univ, KHU KIST Dept Converging Sci & Technol, Seoul 02447, South Korea		Lee, KT; Zamponi, GW; Lee, JY (corresponding author), Kyung Hee Univ, Coll Sci, Res Inst Basic Sci, Seoul 02447, South Korea.; Lee, KT; Zamponi, GW; Lee, JY (corresponding author), Kyung Hee Univ, Coll Sci, Dept Chem, Seoul 02447, South Korea.	ktlee@khu.ac.kr; zamponi@ucalgary.ca; ljy@khu.ac.kr			National Research Foundation (NRF) - Korea government MISIT [2016R1D1A1B03936197]; National Research Foundation (NRF) grant - Korea government MIE [2019R1F1A1059332]; Canadian Institutes for Health Research (CIHR)Canadian Institutes of Health Research (CIHR); Alberta Innovates; CIHR FellowshipCanadian Institutes of Health Research (CIHR)	This work was supported by the National Research Foundation (NRF) grant funded by the Korea government MISIT (No. 2016R1D1A1B03936197) and MIE (No. 2019R1F1A1059332)/ The Canadian Institutes for Health Research (CIHR) and Alberta Innovates. GWZ is a Canada Research Chair. MAG holds a CIHR Fellowship.	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Med. Chem.	JUN 1	2020	28	11							115491	10.1016/j.bmc.2020.115491			9	Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry	LR6NF	WOS:000535808700014	32327350				2022-04-25	
J	Mbaveng, AT; Ndontsa, BL; Kuete, V; Nguekeu, YMM; Celik, I; Mbouangouere, R; Tane, P; Efferth, T				Mbaveng, Armelle T.; Ndontsa, Blanche L.; Kuete, Victor; Nguekeu, Yves M. M.; Celik, Ilhami; Mbouangouere, Roukayatou; Tane, Pierre; Efferth, Thomas			A naturally occuring triterpene saponin ardisiacrispin B displayed cytotoxic effects in multi-factorial drug resistant cancer cells via ferroptotic and apoptotic cell death	PHYTOMEDICINE			English	Article						Ardisiacrispin B; Cell cycle distribution; Cytotoxicity; Ferroptosis; Mitochondrial membrane potential; Saponin	LEUKEMIA-CELLS; BREAST-CANCER; TUMOR-CELLS; MODES; TRANSPORTER; FLAVONOIDS; AUTOPHAGY; PUSILLA; LINES	Introduction: Multidrug resistance of cancer cells constitutes a serious problem in chemotherapy and a challenging issue in the discovery of new cytotoxic drugs. Many saponins are known to display anti-cancer effects. In this study, the cytotoxicity and the modes of action of a naturally occuring oleanane-type tritepene saponin, ardisiacrispin B isolated from the fruit of Ardisia kivuensis Talon (Myrsinaceae) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant phenotypes. Methods: Resazurin reduction assay was used to evaluate cytotoxicity and ferroptotic cell death of samples; caspase-Glo assay was used to detect the activation of caspases in CCRF-CEM leukemia cells. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells by annexin V/PI staining, analysis of mitochondrial membrane potential (MMP) and measurement of reactive oxygen species (ROS). Results: Ardisiacrispin B displayed significant cytotoxic effects in the 9 tested cancer cell lines with IC 50 values below 10 mu M. The IC50 values ranges were 1.20 mu M (towards leukemia CCRF-CEM cells) to 6.76 mu M [against heptocarcinoma HepG2 cells] for ardisiacrispin B and 0.02 mu M (against CCRF-CEM cells) to 122.96 mu M (against resistant CEM/ADR5000 leukemia cells) for doxorubicin. Collateral sensitivity of resistant HCT116p53(-/-) colon adenocarcinoma cells to ardisiacripsin B was observed. Ardisiacrispin B induced apoptosis in CCRF-CEM cells via activation of inititator caspases 8 and 9 and effector caspase 3/7, alteration of MMP and increase in ROS production. Ferroptosis also contributed to the cytotoxicity of ardisiacrispin B. Conclusions: The studied oleanane-type triterpene saponin is a good cytotoxic molecule that deserve more detailed exploration in the future, to develop novel cytotoxic drugs to combat both sensitive and drug-resistant cancers.	[Mbaveng, Armelle T.; Kuete, Victor; Efferth, Thomas] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, Staudinger Weg 5, D-55128 Mainz, Germany; [Mbaveng, Armelle T.; Kuete, Victor] Univ Dschang, Dept Biochem, Fac Sci, Dschang, Cameroon; [Ndontsa, Blanche L.; Nguekeu, Yves M. M.; Mbouangouere, Roukayatou; Tane, Pierre] Univ Yaounde I, Dept Organ Chem, Fac Sci, Yaounde, Cameroon; [Celik, Ilhami] Anadolu Univ, Fac Sci, Dept Chem, TR-26470 Tepebasi, Eskisehir, Turkey		Efferth, T (corresponding author), Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, Staudinger Weg 5, D-55128 Mainz, Germany.	efferth@uni-mainz.de	Çelik, Ilhami/P-6075-2019	Çelik, Ilhami/0000-0002-5384-4755; Mbaveng, Armelle/0000-0003-4178-4967; Nguekeu Mba, Yves Martial/0000-0001-6543-2734; Efferth, Thomas/0000-0002-3096-3292	Alexander von Humboldt FoundationAlexander von Humboldt Foundation; International Foundation for Science (IFS)International Foundation for Science [F5543]; Organization for the Prohibition of Chemical Weapons (OPCW); Scientific Research Projects Commission of Anadolu University, Eskisehir, Turkey [1306F110]	ATM is thankful to Alexander von Humboldt Foundation for an 18 months fellowship in Prof. Dr. Thomas Efferth's laboratory in Mainz, Germany through the "Georg Foster Research Fellowship for Experienced Researcher'' program. VK is very grateful to the Alexander von Humboldt Foundation for the funding through the Linkage program (2015-2018). BLN grant (F5543) thanks the International Foundation for Science (IFS) and Organization for the Prohibition of Chemical Weapons (OPCW) for their financial supports. IC would like to thank the Scientific Research Projects Commission of Anadolu University, Eskisehir, Turkey for the funding grant (1306F110). Authors are also thankful to the Institute of Molecular Biology gGmbH (IMB) (Mainz, Germany) where the flow cytometry experiments were performed.	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J	Skrypek, N; Vasseur, R; Vincent, A; Duchene, B; Van Seuningen, I; Jonckheere, N				Skrypek, Nicolas; Vasseur, Romain; Vincent, Audrey; Duchene, Belinda; Van Seuningen, Isabelle; Jonckheere, Nicolas			The oncogenic receptor ErbB2 modulates gemcitabine and irinotecan/SN-38 chemoresistance of human pancreatic cancer cells via hCNT1 transporter and multidrug-resistance associated protein MRP-2	ONCOTARGET			English	Article						ErbB2; pancreatic cancer; gemcitabine; FOLFIRINOX; chemoresistance	TOPOISOMERASE-I INHIBITORS; MUCIN GENE; AUTOPHAGY; OVEREXPRESSION; COLON; HER2; ADENOCARCINOMA; CYTOTOXICITY; COMBINATION; ACTIVATION	Pancreatic adenocarcinoma (PDAC) is one of the most deadly cancers because of a lack of early diagnotic markers and efficient therapeutics. The fluorinated analog of deoxycytidine, gemcitabine and emerging FOLFIRINOX protocol (5-fluorouracil (5-FU), irinotecan/SN-38, oxaliplatin and leucovorin) are the main chemotherapies to treat PDAC. The ErbB2/HER2 oncogenic receptor is commonly overexpressed in PDAC. In this context, we aimed to decipher the ErbB2-mediated mechanisms of chemoresistance to the two main chemotherapy protocols used to treat PDAC. ErbB2 knocking down (KD) in CAPAN-1 and CAPAN-2 cells led to an increased sensitivity to gemcitabine and an increased resistance to irinotecan/SN-38 both in vitro and in vivo (subcuteanous xenografts) This was correlated to an increase of hCNT1 and hCNT3 transporters and ABCG2, MRP1 and MRP2 ATP-binding cassette transporters expression and resistance to cell death. We also show that MRP2 is repressed following activation of JNK, Erk1/2 and NF-kappa B pathways by ErbB2. Finally, in datasets of human PDAC samples, ErbB2 and MRP2 expression was conversely correlated. Altogether, we propose that ErbB2 mediates several intracellular mechanisms linked to PDAC cell chemoresistance that may represent potential targets in order to ameliorate chemotherapy response and allow stratification of patients eligible for either gemcitabine or FOLFIRINOX treatment.	[Skrypek, Nicolas; Vasseur, Romain; Vincent, Audrey; Duchene, Belinda; Van Seuningen, Isabelle; Jonckheere, Nicolas] INSERM, UMR S1172, Jean Pierre Aubert Res Ctr, Team Mucins Epithelial Differentiat & Carcinogene, F-59045 Lille, France; [Skrypek, Nicolas; Vasseur, Romain; Vincent, Audrey; Duchene, Belinda; Van Seuningen, Isabelle; Jonckheere, Nicolas] Univ Lille Nord France, F-59000 Lille, France; [Skrypek, Nicolas; Vasseur, Romain; Vincent, Audrey; Duchene, Belinda; Van Seuningen, Isabelle; Jonckheere, Nicolas] CHRU Lille, F-59037 Lille, France		Jonckheere, N (corresponding author), INSERM, UMR S1172, Jean Pierre Aubert Res Ctr, Team Mucins Epithelial Differentiat & Carcinogene, F-59045 Lille, France.	nicolas.jonckheere@inserm.fr	Jonckheere, Nicolas/J-6028-2013; Vincent, Audrey/I-2934-2016; VAN SEUNINGEN, Isabelle/N-6176-2016	Jonckheere, Nicolas/0000-0002-0496-0661; Vincent, Audrey/0000-0003-0058-2058; VAN SEUNINGEN, Isabelle/0000-0002-3131-2694; Vasseur, Romain/0000-0003-4179-9800; Duchene, Belinda/0000-0002-4810-4680	Centre Hospitalier Regional et Universitaire (CHRU) de Lille/region Nord-Pas de CalaisRegion Hauts-de-France; Universite de Lille 2; Fondation ARC; Region Nord-Pas de CalaisRegion Hauts-de-FranceEuropean Commission; la Ligue Nationale Contre le Cancer (Equipe Labellisee Ligue); SIRIC ONCOLille; Grant INCaDGOS-Inserm [6041]; "Contrat de Plan Etat Region" CPER Cancer	We thank MH Gevaert and R Siminsky (Department of Histology, Faculty of Medicine, University of Lille 2) for their technical help, the IFR114/IMPRT confocal microscopy platform (M. Tardivel), and animal facility (D. Taillieu). Nicolas Skrypek is the recipient of a PhD fellowship from the Centre Hospitalier Regional et Universitaire (CHRU) de Lille/region Nord-Pas de Calais. Romain Vasseur is a recipient of a PhD fellowship from the Universite de Lille 2. Audrey Vincent is the recipient of a postdoctoral fellowship from the Fondation ARC and Region Nord-Pas de Calais. Isabelle Van Seuningen. is the recipient of a "Contrat Hospitalier de Recherche Translationnelle"/CHRT 2010, AVIESAN. This work is supported by grants from la Ligue Nationale Contre le Cancer (Equipe Labellisee Ligue 2010, IVS), from SIRIC ONCOLille, Grant INCaDGOS-Inserm 6041 (IVS, NJ) and from "Contrat de Plan Etat Region" CPER Cancer 2007-2013 (IVS). The funders had no role in study design, data collection and interpretations, decision to publish, or preparation of the manuscript.	Candeil L, 2004, INT J CANCER, V109, P848, DOI 10.1002/ijc.20032; Catley L, 2004, CANCER RES, V64, P8746, DOI 10.1158/0008-5472.CAN-04-2894; Conroy T, 2011, NEW ENGL J MED, V364, P1817, DOI 10.1056/NEJMoa1011923; Davies BR, 2007, MOL CANCER THER, V6, P2209, DOI 10.1158/1535-7163.MCT-07-0231; Diamandis EP, 2010, J NATL CANCER I, V102, P1462, DOI 10.1093/jnci/djq306; Fiorini C, 2015, BBA-MOL CELL RES, V1853, P89, DOI 10.1016/j.bbamcr.2014.10.003; Fiorini C, 2013, APOPTOSIS, V18, P337, DOI 10.1007/s10495-012-0790-6; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Jonckheere N, 2004, ONCOGENE, V23, P5729, DOI 10.1038/sj.onc.1207769; Jonckheere N, 2009, BRIT J CANCER, V101, P637, DOI 10.1038/sj.bjc.6605190; Jonckheere N, 2014, CLIN RES HEPATOL GAS, V38, P423, DOI 10.1016/j.clinre.2014.04.009; Jonckheere N, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0032232; Kim HS, 2013, BIOMED RES INT, V2013, DOI 10.1155/2013/527534; Komoto M, 2009, CANCER SCI, V100, P1243, DOI 10.1111/j.1349-7006.2009.01176.x; LaBonte MJ, 2009, INT J CANCER, V125, P2957, DOI 10.1002/ijc.24658; Lee SH, 2012, PATHOL INT, V62, P167, DOI 10.1111/j.1440-1827.2011.02772.x; Lozy F, 2014, AUTOPHAGY, V10, P662, DOI 10.4161/auto.27867; Lu CR, 2006, MOL CELL, V23, P121, DOI 10.1016/j.molcel.2006.05.023; Maciejczyk A, 2012, PATHOL ONCOL RES, V18, P331, DOI 10.1007/s12253-011-9449-9; Mazard T, 2013, MOL CANCER THER, V12, P2121, DOI 10.1158/1535-7163.MCT-12-0966; Mishra Alok, 2010, Cancers (Basel), V2, P190, DOI 10.3390/cancers2010190; Moasser MM, 2007, ONCOGENE, V26, P6469, DOI 10.1038/sj.onc.1210477; Mohelnikova-Duchonova B, 2013, PANCREAS, V42, P707, DOI 10.1097/MPA.0b013e318279b861; O'Reilly Eileen M, 2009, Gastrointest Cancer Res, V3, pS11; Piessen G, 2007, BIOCHEM J, V402, P81, DOI 10.1042/BJ20061461; Pommier Y, 2006, NAT REV CANCER, V6, P789, DOI 10.1038/nrc1977; Pommier Y, 2009, CHEM REV, V109, P2894, DOI 10.1021/cr900097c; Rahib L, 2014, CANCER RES, V74, P2913, DOI 10.1158/0008-5472.CAN-14-0155; Rosenfeldt MT, 2013, NATURE, V504, P296, DOI 10.1038/nature12865; Rosner GL, 2008, CLIN PHARMACOL THER, V84, P393, DOI 10.1038/clpt.2008.63; Sharom FJ, 2008, PHARMACOGENOMICS, V9, P105, DOI 10.2217/14622416.9.1.105; Skrypek N, 2013, ONCOGENE, V32, P1714, DOI 10.1038/onc.2012.179; Stoecklein NH, 2004, J CLIN ONCOL, V22, P4737, DOI 10.1200/JCO.2004.05.142; Szakacs G, 2006, NAT REV DRUG DISCOV, V5, P219, DOI 10.1038/nrd1984; Torrisani J, 2009, HUM GENE THER, V20, P831, DOI 10.1089/hum.2008.134; van der Sluis M, 2004, BIOCHEM BIOPH RES CO, V325, P952, DOI 10.1016/j.bbrc.2004.10.108; Van Seuningen I, 2000, BIOCHEM J, V348, P675; Vannini I, 2009, ANTI-CANCER DRUG, V20, P918, DOI 10.1097/CAD.0b013e32833179bf; Vincent A, 2011, LANCET, V378, P607, DOI 10.1016/S0140-6736(10)62307-0; Wagner EF, 2009, NAT REV CANCER, V9, P537, DOI 10.1038/nrc2694; Yamade M, 2012, ANTICANCER RES, V32, P105; Yu H, 2012, CANCER RES TREAT, V44, P195, DOI 10.4143/crt.2012.44.3.195; Zhang L, 2009, CANCER LETT, V285, P58, DOI 10.1016/j.canlet.2009.04.041	43	29	32	0	9	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA		1949-2553		ONCOTARGET	Oncotarget	MAY 10	2015	6	13					10853	10867		10.18632/oncotarget.3414			15	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	CO2SH	WOS:000359006400016	25890497	Green Submitted, gold, Green Published			2022-04-25	
J	Kranz, P; Sanger, C; Wolf, A; Baumann, J; Metzen, E; Baumann, M; Gopelt, K; Brockmeier, U				Kranz, Philip; Saenger, Christopher; Wolf, Alexandra; Baumann, Jennifer; Metzen, Eric; Baumann, Melanie; Goepelt, Kirsten; Brockmeier, Ulf			Tumor cells rely on the thiol oxidoreductase PDI for PERK signaling in order to survive ER stress	SCIENTIFIC REPORTS			English	Article							PROTEIN DISULFIDE-ISOMERASE; ENDOPLASMIC-RETICULUM STRESS; INHIBITOR; DISCOVERY; RADIATION; AUTOPHAGY; KINASE; FAMILY; DEATH	Upon ER stress cells activate the unfolded protein response through PERK, IRE1 and ATF6. Remarkable effort has been made to delineate the downstream signaling of these three ER stress sensors after activation, but upstream regulation at the ER luminal site still remains mostly undefined. Here we report that the thiol oxidoreductase PDI is mandatory for activation of the PERK pathway in HEK293T as well as in human pancreatic, lung and colon cancer cells. Under ER stress, depletion of PDI selectively abrogated eIF2 alpha phosphorylation, induction of ATF4, CHOP and even BiP. Furthermore, we could demonstrate that PDI prevented degradation of activated PERK by the 26S proteasome and therefore contributes to maintained PERK signaling. As a result of decreased PERK activity, PDI depleted cells showed an increased vulnerability to ER stress induced by chemicals or ionizing radiation in 2D as well as in 3D culture models. We conclude that PDI is an obligatory regulator of the PERK pathway with future therapy implications.	[Kranz, Philip; Saenger, Christopher; Wolf, Alexandra; Baumann, Jennifer; Metzen, Eric; Baumann, Melanie; Goepelt, Kirsten; Brockmeier, Ulf] Univ Duisburg Essen, Inst Physiol, Duisburg, Germany; [Brockmeier, Ulf] Univ Duisburg Essen, Univ Hosp Essen, Dept Neurol, Duisburg, Germany		Brockmeier, U (corresponding author), Univ Duisburg Essen, Inst Physiol, Duisburg, Germany.; Brockmeier, U (corresponding author), Univ Duisburg Essen, Univ Hosp Essen, Dept Neurol, Duisburg, Germany.	ulf.brockmeier@uni-due.de			IFORES program of the Universitatsklinik Essen; research training group GRK1739 of the Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG)	This study was funded by the IFORES program of the Universitatsklinik Essen and the research training group GRK1739 of the Deutsche Forschungsgemeinschaft. We are indebted to George Iliakis, Institut fur Strahlenbiologie, Universitat Duisburg-Essen, for providing radiation equipment.	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J	Nasef, NA; Mehta, S; Ferguson, LR				Nasef, Noha Ahmed; Mehta, Sunali; Ferguson, Lynnette R.			Dietary interactions with the bacterial sensing machinery in the intestine: the plant polyphenol case	FRONTIERS IN GENETICS			English	Review							CATECHOL-O-METHYLTRANSFERASE; VITAMIN-E SUPPLEMENTATION; CORONARY-HEART-DISEASE; TOLL-LIKE RECEPTORS; COLON-CANCER CELLS; NF-KAPPA-B; BETA-CAROTENE; IN-VITRO; PHYTOCHEMICAL VARIATION; CARDIOVASCULAR EVENTS	There are millions of microbes that live in the human gut. These are important in digestion as well as defense. The host immune system needs to be able to distinguish between the harmless bacteria and pathogens. The initial interaction between bacteria and the host happen through the pattern recognition receptors (PRRs). As these receptors are in direct contact with the external environment, this makes them important candidates for regulation by dietary components and therefore potential targets for therapy. 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[Nasef, Noha Ahmed; Mehta, Sunali; Ferguson, Lynnette R.] Univ Auckland, Dept Nutr, Fac Med & Hlth Sci, Auckland 1023, New Zealand		Ferguson, LR (corresponding author), Univ Auckland, Dept Nutr, Fac Med & Hlth Sci, 85 Pk Rd, Auckland 1023, New Zealand.	l.ferguson@auckland.ac.nz	Mehta, Sunali/O-8459-2019	Mehta, Sunali/0000-0002-1777-1245			Abbas AK, 2012, CELLULAR MOL IMMUNOL; Abreu MT, 2010, NAT REV IMMUNOL, V10, P131, DOI 10.1038/nri2707; Aharoni A, 2005, TRENDS PLANT SCI, V10, P594, DOI 10.1016/j.tplants.2005.10.005; Aherne SA, 2002, NUTRITION, V18, P75, DOI 10.1016/S0899-9007(01)00695-5; Albert A, 2009, OECOLOGIA, V160, P1, DOI 10.1007/s00442-009-1277-1; Alexopoulou L, 2001, NATURE, V413, P732, DOI 10.1038/35099560; Ban H, 2004, INT J MOL MED, V13, P537; Bernales S, 2006, PLOS BIOL, V4, P2311, DOI 10.1371/journal.pbio.0040423; Beutler B, 2009, IMMUNOL REV, V227, P248, DOI 10.1111/j.1600-065X.2008.00733.x; Bielig H, 2010, CHEMMEDCHEM, V5, P2065, DOI 10.1002/cmdc.201000320; Binns SE, 2002, J AGR FOOD CHEM, V50, P3673, DOI 10.1021/jf011439t; 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Genet.	APR 4	2014	5								64	10.3389/fgene.2014.00064			14	Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Genetics & Heredity	AX6LP	WOS:000347034100001	24772116	Green Published, gold			2022-04-25	
J	Zhu, B; Li, SX; Yu, L; Hu, W; Sheng, DD; Hou, J; Zhao, NP; Hou, XJ; Wu, YC; Han, ZP; Wei, LX; Zhang, L				Zhu, Bing; Li, Shanxin; Yu, Lei; Hu, Wei; Sheng, Dandan; Hou, Jing; Zhao, Naping; Hou, Xiaojuan; Wu, Yechen; Han, Zhipeng; Wei, Lixin; Zhang, Li			Inhibition of Autophagy with Chloroquine Enhanced Sinoporphyrin Sodium Mediated Photodynamic Therapy-induced Apoptosis in Human Colorectal Cancer Cells	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES			English	Article						sinoporphyin sodium; photodynamic therapy; colorectal cancer; apoptosis; autophagy; chloroquine	BREAST-CANCER; IN-VITRO; SENSITIZER; STATISTICS; RESISTANCE; MITOCHONDRIAL; RESPONSES	To evaluate the antitumor effect of sinoporphyrin sodium mediated photodynamic therapy (DVDMS-PDT) against human colorectal cancer (CRC) and to investigate the role of autophagy in its effect. Shrunken cells, condensed nuclei and increased levels of cleaved caspase-3 and Bax were observed in DVDMS-PDT treated HCT116 cells, reminiscent of apoptosis. DVDMS-PDT showed better antitumor efficiency in HCT116 cells than Photofrin mediated photodynamic therapy (PF-PDT) both in vitro and in vivo. And DVDMS-PDT caused autophagic characteristics: double membrane autophagosome structures and changes in autophagy-related protein expression (ATG7, P62, Bcl-2 and LC3-II). In addition, inhibition of autophagy by chloroquine (CQ) promoted apoptosis, suggesting a possible protective role of autophagy in DVDMS-PDT-treated HCT116 cells, which was proved by flow cytometry and western blotting. The results of xenograft mouse model showed markedly increased apoptosis and significantly reduced tumor size in DVDMS-PDT treated group than Control, and DVDMS-PDT exhibited better antitumor efficiency than PF-PDT. Further, no visible tumor was observed in the CQ+DVDMS-PDT group at the end of the xenograft mouse experiment, which confirmed the hypothesis that autophagy was protective to DVDMS-PDT treated HCT116 cells. Our findings suggest that DVDMS is a promising photosensitizer and the combined use of autophagy inhibitor can remarkably enhance the DVDMS-PDT mediated anti-cancer efficiency in HCT116 cells both in vitro and in vivo.	[Zhu, Bing; Li, Shanxin; Zhao, Naping; Zhang, Li] Second Mil Med Univ, Changhai Hosp, Dept Pharm, Shanghai, Peoples R China; [Sheng, Dandan; Hou, Xiaojuan; Wu, Yechen; Han, Zhipeng; Wei, Lixin] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Tumor Immunol & Gene Therapy Ctr, Shanghai, Peoples R China; [Yu, Lei] Second Mil Med Univ, Changzheng Hosp, Dept Informat, Shanghai, Peoples R China; [Hu, Wei; Zhang, Li] Anhui Med Univ, Dept Pharm, Hosp 2, Hefei, Anhui, Peoples R China; [Hou, Jing] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, GCP Off, Shanghai, Peoples R China		Zhang, L (corresponding author), Second Mil Med Univ, Changhai Hosp, Dept Pharm, Shanghai, Peoples R China.; Wei, LX (corresponding author), Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Tumor Immunol & Gene Therapy Ctr, Shanghai, Peoples R China.; Zhang, L (corresponding author), Anhui Med Univ, Dept Pharm, Hosp 2, Hefei, Anhui, Peoples R China.	weilixin_smmu@163.com; chyyzhl@163.com	cai, yuanyuan/C-6301-2014		National Key Research and Development Program of China [2018YFA0107503]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472846]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [GK201502009]	This research was supported by the National Key Research and Development Program of China (2018YFA0107503), the National Natural Science Foundation of China (No. 81472846) and the Fundamental Research Funds for the Central Universities (GK201502009). The authors thank department of biophysics (College of Basic Medical Sciences, Second Military Medical University) for performing the TEM imaging. The authors thank Qinglong Hi-tech Co., Ltd for providing the novel sensitizer DVDMS.	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J. Biol. Sci.		2019	15	1					12	23		10.7150/ijbs.27156			12	Biochemistry & Molecular Biology; Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics	HE3LU	WOS:000453258300002	30662343	Green Published, gold, Green Submitted			2022-04-25	
J	Dalla Pozza, M; Orvain, C; Brustolin, L; Pettenuzzo, N; Nardon, C; Gaiddon, C; Fregona, D				Dalla Pozza, Maria; Orvain, Christophe; Brustolin, Leonardo; Pettenuzzo, Nicolo; Nardon, Chiara; Gaiddon, Christian; Fregona, Dolores			Gold(III) to Ruthenium(III) Metal Exchange in Dithiocarbamato Complexes Tunes Their Biological Mode of Action for Cytotoxicity in Cancer Cells	MOLECULES			English	Article						gastric cancer; metal complexes; chemotherapy; dithiocarbamates; drug mechanism of action; ER stress; p53; autophagy	CURRENT CLINICAL-USES; ANTICANCER AGENTS; MTT ASSAY; PLATINUM; APOPTOSIS; THERAPY; LOCALIZATION; PERSPECTIVES; MECHANISMS; EXPRESSION	Malignant tumors have affected the human being since the pharaoh period, but in the last century the incidence of this disease has increased due to a large number of risk factors, including deleterious lifestyle habits (i.e., smoking) and the higher longevity. Many efforts have been spent in the last decades on achieving an early stage diagnosis of cancer, and more effective cures, leading to a decline in age-standardized cancer mortality rates. In the last years, our research groups have developed new metal-based complexes, with the aim to obtain a better selectivity for cancer cells and less side effects than the clinically established reference drug cisplatin. This work is focused on four novel Au(III) and Ru(III) complexes that share the piperidine dithiocarbamato (pipe-DTC) as the ligand, in a different molar ratio. The compounds [AuCl2(pipeDTC)], [Au(pipeDTC)(2)]Cl, [Ru(pipeDTC)(3)] and beta-[Ru-2(pipeDTC)(5)] have been synthesized and fully characterized by several chemical analyses. We have then investigated their biological properties in two different cell lines, namely, AGS (gastric adenocarcinoma) and HCT116 (colon carcinomas), showing significant differences among the four compounds. First, the two gold-based compounds and beta-[Ru-2(pipeDTC)(5)] display IC50 in the mu M range, significantly lower than cisplatin. Second, we showed that [AuCl2(pipeDTC)] and beta-[Ru-2(pipeDTC)(5)]Cl drive different molecular mechanisms. The first was able to induce the protein level of the DNA damage response factor p53 and the autophagy protein p62, in contrast to the second that induced the ATF4 protein level, but repressed p62 expression. This study highlights that the biological activity of different complexes bringing the same organic ligand depends on the electronic and structural properties of the metal, which are able to fine tune the biological properties, giving us precious information that can help to design more selective anticancer drugs.	[Dalla Pozza, Maria; Brustolin, Leonardo; Pettenuzzo, Nicolo; Nardon, Chiara; Fregona, Dolores] Univ Padua, Dept Chem Sci, Via F Marzolo 1, I-35131 Padua, Italy; [Orvain, Christophe; Gaiddon, Christian] Univ Strasbourg, INSERM, UMR S 1113, Interface Rech Fondamentale Cancerol, 3 Av Moliere, F-67200 Strasbourg, France		Fregona, D (corresponding author), Univ Padua, Dept Chem Sci, Via F Marzolo 1, I-35131 Padua, Italy.; Gaiddon, C (corresponding author), Univ Strasbourg, INSERM, UMR S 1113, Interface Rech Fondamentale Cancerol, 3 Av Moliere, F-67200 Strasbourg, France.	maria.dalla-pozza@chimieparistech.psl.eu; orvain@unistra.fr; leo.brus90@gmail.com; nicolo.pettenuzzo.np@gmail.com; chiara.nardon@unipd.it; Gaiddon@unistra.fr; dolores.fregona@unipd.it	Gaiddon, Christian/F-7321-2012	Gaiddon, Christian/0000-0003-4315-3851	Ligue contre le CancerLigue nationale contre le cancer; IDEX from Strasbourg University; Interdisciplinary Thematic Institute InnoVec	This research was funded by Ligue contre le Cancer, IDEX from Strasbourg University, Interdisciplinary Thematic Institute InnoVec.	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J	Issman-Zecharya, N; Schuldiner, O				Issman-Zecharya, Noa; Schuldiner, Oren			The PI3K Class III Complex Promotes Axon Pruning by Downregulating a Ptc-Derived Signal via Endosome-Lysosomal Degradation	DEVELOPMENTAL CELL			English	Article							MICROSATELLITE INSTABILITY; COLON-CANCER; DROSOPHILA; UVRAG; EXPRESSION; AUTOPHAGY; RECEPTOR; PROTEIN; TRAFFICKING; HEDGEHOG	Developmental axon pruning is essential for wiring the mature nervous system, but its regulation remains poorly understood. Here we show that the endosomal-lysosomal pathway regulates developmental pruning of Drosophila mushroom body gamma neurons. We demonstrate that the UV radiation resistance-associated gene (UVRAG) functions together with all core components of the phosphatidylinositol 3-kinase class Ill (PI3K-cIII) complex to promote pruning via the endocytic pathway. By studying several PI(3)P binding proteins, we found that Hrs, a subunit of the ESCRT-0 complex, required for multivesicular body (MVB) maturation, is essential for normal pruning progression. Thus, we hypothesized the existence of an inhibitory signal that needs to be downregulated. Finally, our data suggest that the Hedgehog receptor, Patched, is the source of this inhibitory signal likely functioning in a Smo-independent manner. Taken together, our in vivo study demonstrates that the PI3K-cIII complex is essential for downregulating Patched via the endosomal-lysosomal pathway to execute axon pruning.	[Issman-Zecharya, Noa; Schuldiner, Oren] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel		Schuldiner, O (corresponding author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.	oren.schuldiner@weizmann.ac.il	Schuldiner, Oren/K-1353-2012	Schuldiner, Oren/0000-0002-7350-9380	Israeli Cancer Research Fund (ICRF) [11-711-RCDA]; Minerva foundation	We thank E. Arama, E.H. Baehrecke, H. Bellen, Y. Chou, J. Chung, S. Eaton, F.B. Gao, L. Gilboa, M. Gonzalez-Gaitan, I. Guerrero, H. Kramer, T. Neufeld, A. Rodal, J. Rubin, F. Tina, F. Tokunaga, F. Yu, and the Bloomington Stock Center for reagents; E.H. Baehrecke for providing reagents prior to publication; F. Yu and S. Zhu for discussing experiments prior to publication; Ron Rotkopf for statistical analyses; and E.H Baehrecke, A. Yaron, M. Schuldiner, S.P. Yaniv, and members of the O.S. lab for discussions and critical readings of the manuscript. The Fasll (1D4) and EcR-B1 (AD4.4) monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa. This work was supported by the Israeli Cancer Research Fund (ICRF) grant #11-711-RCDA and the Minerva foundation. The Zeiss LSM710 microscope was purchased with the help of the Adelis foundation. O.S. is the incumbent of the Rothstein Career Development Chair of Genetic Diseases.	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Cell	NOV 24	2014	31	4					461	473		10.1016/j.devcel.2014.10.013			13	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	AU3UZ	WOS:000345540200011	25458013	Bronze			2022-04-25	
J	Liu, Z; Xiong, L; Ouyang, GQ; Ma, L; Sahi, S; Wang, KP; Lin, LW; Huang, H; Miao, XY; Chen, W; Wen, Y				Liu, Zhipeng; Xiong, Li; Ouyang, Guoqing; Ma, Lun; Sahi, Sunil; Wang, Kunpeng; Lin, Liangwu; Huang, He; Miao, Xiongying; Chen, Wei; Wen, Yu			Investigation of Copper Cysteamine Nanoparticles as a New Type of Radiosensitiers for Colorectal Carcinoma Treatment	SCIENTIFIC REPORTS			English	Article							PHOTODYNAMIC THERAPY; SINGLET OXYGEN; CANCER; RADIOTHERAPY; CELLS; SENSITIZERS; RADIATION	Copper Cysteamine (Cu-Cy) is a new photosensitizer and a novel radiosensitizer that can be activated by light, X-ray and microwave to produce singlet oxygen for cancer treatment. However, the killing mechanism of Cu-Cy nanoparticles on cancer cells is not clear yet and Cu-Cy nanoparticles as novel radiosensitizers have never been tested on colorectal cancers. Here, for the first time, we investigate the treatment efficiency of Cu-Cy nanoparticles on SW620 colorectal cells and elucidate the underlying mechanisms of the effects. The results show that X-ray activated Cu-Cy nanoparticles may kill SW620 cancerscells is in a dose-dependent manner. The JC-1 staining shows the mitochondrial membrane potential is decreased after the treatment. The observations confirm that Cu-Cy nanoparticles may improve X-ray radiotherapy on cancer treatment and X-ray activated Cu-Cy nanoparticles can be efficiently destroy colorectal cancer cells by inducing apoptosis as well as autophagy. As a new type of radiosensitizers and photosensitizers, Cu-Cy nanoparticles have a good potential for colorectal cancer treatment and the discovery of autophagy induced by X-ray irradiated Cu-Cy nanoparticles sheds a good insight to the mechanism of Cu-Cy for cancer treatment as a new radiosensitizers.	[Liu, Zhipeng; Xiong, Li; Ouyang, Guoqing; Wang, Kunpeng; Miao, Xiongying; Wen, Yu] Cent South Univ Changsha, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China; [Ma, Lun; Sahi, Sunil; Chen, Wei] Univ Texas Arlington, Dept Phys, Arlington, TX 76019 USA; [Ma, Lun; Sahi, Sunil; Chen, Wei] Univ Texas Arlington, SAVANT Ctr, Arlington, TX 76019 USA; [Lin, Liangwu] Cent South Univ, State Key Lab Powder Met, Changsha 410083, Hunan, Peoples R China; [Huang, He] Cent South Univ, Xiangya Sch Med, Dept Histol & Embryol, Changsha 410078, Hunan, Peoples R China		Wen, Y (corresponding author), Cent South Univ Changsha, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China.; Chen, W (corresponding author), Univ Texas Arlington, Dept Phys, Arlington, TX 76019 USA.; Chen, W (corresponding author), Univ Texas Arlington, SAVANT Ctr, Arlington, TX 76019 USA.	weichen@uta.edu; 1850129046@qq.com			Development and Reform Commission of Hunan the Fundamental Research Funds for the Central South University [201583, 2016zzts537]; Furong Scholarship from Central South University; U.S. Army Medical Research Acquisition Activity (USAMRAA) [W81XWH-10-1-0279, W81XWH-10-1-0234]; Science and Technology Department of Nanning [20151266]	This work was supported by the Development and Reform Commission of Hunan (Grant 201583) the Fundamental Research Funds for the Central South University (grant 2016zzts537), the Furong Scholarship from Central South University as well as the support from the U.S. Army Medical Research Acquisition Activity (USAMRAA) under Contracts of W81XWH-10-1-0279 and W81XWH-10-1-0234, and a grant from the Science and Technology Department of Nanning (grant no. 20151266).	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J	Kukcinaviciute, E; Sasnauskiene, A; Dabkeviciene, D; Kirveliene, V; Jonusiene, V				Kukcinaviciute, E.; Sasnauskiene, A.; Dabkeviciene, D.; Kirveliene, V.; Jonusiene, V.			Effect of mTHPC-mediated photodynamic therapy on 5-fluorouracil resistant human colorectal cancer cells	PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES			English	Article							APOPTOSIS; ACTIVATION; AUTOPHAGY; MCF-7; DEATH	The primary or acquired cancer chemoresistance is a major problem in the treatment of cancer patients. It could be overcome by non-overlapping treatment regimens such as photodynamic therapy (PDT). PDT is based on the oxidation of cellular components which occurs when a light-excited photosensitizer generates reactive oxygen species (ROS). In this study the effect of mTHPC mediated PDT (mTHPC-PDT) on 5-FU resistant colorectal cancer (CRC) cells HCT116 was investigated. The results show that mTHPC-PDT overcomes 5-FU resistance and is effective against chemoresistant colorectal carcinoma cells.	[Kukcinaviciute, E.; Sasnauskiene, A.; Dabkeviciene, D.; Kirveliene, V.; Jonusiene, V.] Vilnius Univ, Life Sci Ctr, Inst Biosci, Vilnius, Lithuania		Jonusiene, V (corresponding author), Vilnius Univ, Life Sci Ctr, Inst Biosci, Vilnius, Lithuania.	violeta.jonusiene@gf.vu.lt			EEA grant of the Norwegian financial mechanism [2004-LT0057-IP-1NOR]	This project was supported by the EEA grant of the Norwegian financial mechanism, No. 2004-LT0057-IP-1NOR.	Celli JP, 2011, LASER SURG MED, V43, P565, DOI 10.1002/lsm.21093; Chiu SM, 2005, APOPTOSIS, V10, P1357, DOI 10.1007/s10495-005-2217-0; Dallas NA, 2009, CANCER RES, V69, P1951, DOI 10.1158/0008-5472.CAN-08-2023; Ferlay J, 2012, CANC INCIDENCE MORTA; Francois A, 2011, INT J ONCOL, V39, P1537, DOI 10.3892/ijo.2011.1174; Goler-Baron V, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0035487; Holohan C, 2013, NAT REV CANCER, V13, P714, DOI 10.1038/nrc3599; ITO M, 1984, J INTERFERON RES, V4, P603, DOI 10.1089/jir.1984.4.603; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Kessel D, 2016, PHOTOCHEM PHOTOBIOL, V92, P620, DOI 10.1111/php.12592; Kessel D, 2015, AUTOPHAGY, V11, P1941, DOI 10.1080/15548627.2015.1078960; Kulbacka J, 2010, EXP BIOL MED, V235, P98, DOI 10.1258/ebm.2009.009162; Longley DB, 2003, NAT REV CANCER, V3, P330, DOI 10.1038/nrc1074; Marchal S, 2007, BRIT J CANCER, V96, P944, DOI 10.1038/sj.bjc.6603631; Oleinick NL, 2002, PHOTOCH PHOTOBIO SCI, V1, P1, DOI 10.1039/b108586g; Saif MW, 2010, CANCER J, V16, P196, DOI 10.1097/PPO.0b013e3181e076af; Sasnauskiene A, 2009, APOPTOSIS, V14, P276, DOI 10.1007/s10495-008-0292-8; Senge MO, 2011, PHOTOCHEM PHOTOBIOL, V87, P1240, DOI 10.1111/j.1751-1097.2011.00986.x; Spring BQ, 2015, PHOTOCH PHOTOBIO SCI, V14, P1476, DOI 10.1039/c4pp00495g; Tsai T, 2004, LASER SURG MED, V34, P62, DOI 10.1002/lsm.10246; Weyergang A, 2015, PHOTOCH PHOTOBIO SCI, V14, P1465, DOI 10.1039/c5pp00029g; White E, 2012, NAT REV CANCER, V12, P401, DOI 10.1038/nrc3262; Yao CW, 2017, BIOMOL THER, V25, P315, DOI 10.4062/biomolther.2016.069; Yu CS, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0099368; Zuluaga MF, 2008, CURR MED CHEM, V15, P1655, DOI 10.2174/092986708784872401	25	5	6	0	10	SPRINGERNATURE	LONDON	CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND	1474-905X	1474-9092		PHOTOCH PHOTOBIO SCI	Photochem. Photobiol. Sci.	JUL 1	2017	16	7					1063	1070		10.1039/c7pp00014f			8	Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics; Chemistry	FA4RV	WOS:000405431800006	28509917				2022-04-25	
J	Wang, ZY; Wang, N; Wang, Q; Peng, C; Zhang, J; Liu, PX; Ou, AH; Zhong, SW; Cordero, MD; Lin, Y				Wang Zhiyu; Wang, Neng; Wang, Qi; Peng, Cheng; Zhang, Jin; Liu, Pengxi; Ou, Aihua; Zhong, Shaowen; Cordero, Mario D.; Lin, Yi			The inflammasome: an emerging therapeutic oncotarget for cancer prevention	ONCOTARGET			English	Review						inflammasome; nod-like receptors; inflammation; cancer prevention; IL-1 beta/IL-18	NF-KAPPA-B; NLRP3 INFLAMMASOME; NALP3 INFLAMMASOME; CASPASE-1 ACTIVATION; OXIDATIVE STRESS; INNATE IMMUNITY; LISTERIA-MONOCYTOGENES; FRANCISELLA-TULARENSIS; COLON INFLAMMATION; AIM2 INFLAMMASOME	Deregulated inflammation is considered to be one of the hallmarks of cancer initiation and development regulation. Emerging evidence indicates that the inflammasome plays a central role in regulating immune cells and cytokines related to cancer. The inflammasome is a multimeric complex consisting of Nod-like receptors (NLRs) and responds to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli. Several lines of evidence suggests that in cancer the inflammasome is positively associated with characteristics such as elevated levels of IL-1 beta and IL-18, activation of NF-kappa B signaling, enhanced mitochondrial oxidative stress, and activation of autophagic process. A number of NLRs, such as NLRP3 and NLRC4 are also highlighted in carcinogenesis and closely correlate to chemoresponse and prognosis. Although conflicting evidence suggested the duplex role of inflammasome in cancer development, the phenomenon might be attributed to NLRs difference, cell and tissue type, cancer stage, and specific experimental conditions. Given the promising role of inflammasome in mediating cancer development, precise elucidation of its signaling network and pathological significance may lead to novel therapeutic options for malignancy therapy and prevention.	[Wang Zhiyu; Liu, Pengxi; Ou, Aihua; Zhong, Shaowen; Lin, Yi] Guangdong Prov Hosp Chinese Med, Dept Mammary Dis, Guangzhou, Guangdong, Peoples R China; [Wang, Neng] Sun Yat Sen Univ, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Dept Breast Oncol,Canc Ctr, Guangzhou, Guangdong, Peoples R China; [Wang, Qi] Inst Clin Pharmacol, Guangzhou, Guangdong, Peoples R China; [Peng, Cheng] Chengdu Univ Tradit Chinese Med, State Key Lab Breeding Base Systemat Res Dev & Ut, Coll Pharm, Chengdu, Peoples R China; [Zhang, Jin] Guangzhou Univ Chinese Med, Coll Basic Med, Guangzhou, Guangdong, Peoples R China; [Cordero, Mario D.] Univ Seville, Dept Oral Med, Res Lab, Seville, Spain		Wang, ZY (corresponding author), Guangdong Prov Hosp Chinese Med, Dept Mammary Dis, Guangzhou, Guangdong, Peoples R China.	wangzhiyu976@126.com	wang, zhiyu/K-5255-2016	wang, zhiyu/0000-0002-5299-8410	National Natural science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402173, 81573651]; Pearl River S&T Nova Program of Guangzhou [201506010098]; Combined Scientific Project - Guangdong Provincial Science and Technology Agency; Guangdong Provincial Academy of Traditional Chinese Medicine [2014A020221047]	This work was supported by the National Natural science Foundation of China (81402173, 81573651), Pearl River S&T Nova Program of Guangzhou (201506010098) and Combined Scientific Project Funded by Guangdong Provincial Science and Technology Agency and Guangdong Provincial Academy of Traditional Chinese Medicine (2014A020221047).	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J	Ma, Z; Lou, SP; Jiang, Z				Ma, Zhan; Lou, Shuping; Jiang, Zheng			PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway	AGING-US			English	Article						PHLDA2; colorectal cancer; autophagy; apoptosis; tumorigenesis	EPITHELIAL-MESENCHYMAL TRANSITION; DOWN-REGULATION; PROSTATE-CANCER; GENE; CELLS; EXPRESSION; MODULATION; APOPTOSIS	High levels of the imprinted gene pleckstrin homology like domain family A member 2 (PHLDA2) correlate with tumor progression in several malignancies. Here, we investigated the effects of PHDLDA2 expression in CRC through assays of cellular proliferation, invasion, migration, and apoptosis. We also screened for possible mechanisms of action. Our results show that PHLDA2 was upregulated in CRC tissues. Knockdown of PHLDA2 inhibited cellular proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) in vitro. Knockout of PHLDA2 promoted cellular apoptosis, in part by activating autophagy. PHLDA2 knockout also inhibited tumorigenesis and expression of KI67 protein in vivo. The effects of PHLDA2 on autophagy and EMT were mediated in part via the PI3K/AKT signaling pathway. Taken together, these results suggest that downregulation of PHLDA2 inhibits tumor growth and PI3K, thereby promoting autophagy and inhibiting EMT, in part through the PI3K/AKT/mTOR and PI3K/AKT/GSK-3 beta signaling pathways.	[Ma, Zhan; Jiang, Zheng] Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Lou, Shuping] Huazhong Univ Sci & Technol, Sch Publ Hlth, Dept Maternal & Child Hlth, Tongji Med Coll, Wuhan 430030, Peoples R China		Jiang, Z (corresponding author), Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 1, Chongqing 400016, Peoples R China.	jiangz1753@163.com					Baran Y, 2015, GENOME RES, V25, P927, DOI 10.1101/gr.192278.115; Bianchini F, 2002, LANCET ONCOL, V3, P565, DOI 10.1016/S1470-2045(02)00849-5; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Cohen JH, 2000, JNCI-J NATL CANCER I, V92, P61, DOI 10.1093/jnci/92.1.61; Ding XF, 2017, AM J HYPERTENS, V30, P1211, DOI 10.1093/ajh/hpx117; Durbas M, 2016, INT J ONCOL, V49, P823, DOI 10.3892/ijo.2016.3572; FRIEDRICHS K, 1993, CANCER, V72, P3641, DOI 10.1002/1097-0142(19931215)72:12<3641::AID-CNCR2820721215>3.0.CO;2-8; GOLDGAR DE, 1994, J NATL CANCER I, V86, P1600, DOI 10.1093/jnci/86.21.1600; Heras-Sandoval D, 2014, CELL SIGNAL, V26, P2694, DOI 10.1016/j.cellsig.2014.08.019; Huber MA, 2005, CURR OPIN CELL BIOL, V17, P548, DOI 10.1016/j.ceb.2005.08.001; Idichi T, 2018, CANCER SCI, V109, P2013, DOI 10.1111/cas.13610; Jiang JY, 2019, ONCOL REP, V41, P3281, DOI 10.3892/or.2019.7126; Jung CH, 2010, FEBS LETT, V584, P1287, DOI 10.1016/j.febslet.2010.01.017; Kim YC, 2015, J CLIN INVEST, V125, P25, DOI 10.1172/JCI73939; Kolonel LN, 2004, NAT REV CANCER, V4, P519, DOI 10.1038/nrc1389; Kroemer G, 2010, MOL CELL, V40, P280, DOI 10.1016/j.molcel.2010.09.023; Kwon YJ, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0151598; Lamouille S, 2014, NAT REV MOL CELL BIO, V15, P178, DOI 10.1038/nrm3758; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Li YJ, 2017, CHIN J CANCER, V52, DOI 10.1186/s40880-017-0219-2; Liu GB, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18020367; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Lu Z, 2008, J CLIN INVEST, V118, P3917, DOI 10.1172/JCI35512; Lv YF, 2016, CANCER LETT, V373, P164, DOI 10.1016/j.canlet.2016.01.046; Lv YF, 2015, SCI REP-UK, V5, DOI 10.1038/srep12999; Meng Y, 2008, MOL CANCER THER, V7, P2192, DOI 10.1158/1535-7163.MCT-08-0333; Mizushima N, 2008, NATURE, V451, P1069, DOI 10.1038/nature06639; Moad AIH, 2013, CELL BIOCHEM BIOPHYS, V66, P567, DOI 10.1007/s12013-012-9504-5; Mohindra V, 2014, J BIOSCIENCES, V39, P433, DOI 10.1007/s12038-014-9426-z; Moon HG, 2015, BREAST CANCER RES TR, V154, P13, DOI 10.1007/s10549-015-3585-y; Osaki M, 2004, APOPTOSIS, V9, P667, DOI 10.1023/B:APPT.0000045801.15585.dd; Simon K, 2016, CLIN INTERV AGING, V11, DOI 10.2147/CIA.S109285; Takao T, 2012, J BIOL CHEM, V287, P42685, DOI 10.1074/jbc.M112.388777; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; Vara JAF, 2004, CANCER TREAT REV, V30, P193, DOI 10.1016/j.ctrv.2003.07.007; Wei R, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1043-0; White E, 2009, CLIN CANCER RES, V15, P5308, DOI 10.1158/1078-0432.CCR-07-5023; Xiong Y, 2020, OXID MED CELL LONGEV, V2020, DOI 10.1155/2020/4909103; Yang J, 2008, DEV CELL, V14, P818, DOI 10.1016/j.devcel.2008.05.009; Yang W, 2007, J BIOL CHEM, V282, P3799, DOI 10.1074/jbc.M610185200; Ying L, 2013, MOL BIOSYST, V9, P407, DOI 10.1039/c2mb25386k; Zhao GS, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0856-6; Zhou BHP, 2001, NAT CELL BIOL, V3, P245, DOI 10.1038/35060032; Zhu L, 2016, J CELL BIOCHEM, V117, P1187, DOI 10.1002/jcb.25402	44	13	13	2	12	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA	1945-4589			AGING-US	Aging-US	MAY 15	2020	12	9					7985	8000		10.18632/aging.103117			16	Cell Biology; Geriatrics & Gerontology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Geriatrics & Gerontology	LN7ZB	WOS:000533150800025	32385195	Green Published, gold			2022-04-25	
J	Bahrami, A; Bianconi, V; Pirro, M; Orafai, HM; Sahebkar, A				Bahrami, Afsane; Bianconi, Vanessa; Pirro, Matteo; Orafai, Hossein M.; Sahebkar, Amirhossein			The role of TFEB in tumor cell autophagy: Diagnostic and therapeutic opportunities	LIFE SCIENCES			English	Review						TFEB; CLEAR network; MALAT1; MiT family; Traslocation renal cell carcinoma	TRANSCRIPTION FACTOR GENE; LYSOSOMAL BIOGENESIS; COLORECTAL-CANCER; CLINICOPATHOLOGICAL FEATURES; TRANSLOCATION CARCINOMA; REGULATES AUTOPHAGY; PHYTOSOMAL CURCUMIN; SUPPRESSOR GENE; RENAL TUMOR; FACTOR EB	Autophagy is a conserved "self-eating" recycling process which removes aggregated or misfolded proteins, or defective organelles, to maintain cellular hemostasis. In the autophagy-lysosome pathway (ALP), clearance of unwanted debris and materials occurs through the generation of the autophagosome, a complex of double-membrane bounded vesicles that form around cytosolic cargos and catabolize their contents by fusion to lysosomes. In tumors, autophagy has dichotomous functions via preventing tumor initiation but promoting tumor progression. The basic helix-loop-helix leucine zipper transcription factor EB (TFEB) activates the promoters of genes encoding for proteins, which participate in this cellular degradative system by regulating lysosomal biogenesis, lysosomal acidification, lysosomal exocytosis and autophagy. In humans, disturbances of ALP are related to various pathological conditions. Recently, TFEB dysregulation was found to have a crucial pathogenic role in different tumors by modulating tumor cell autophagy. Notably, in renal cell carcinomas, different TFEB gene fusions were reported to promote oncogenic features. In this review, we discuss the role of TFEB in human cancers with a special focus on potential diagnostic and therapeutic implications.	[Bahrami, Afsane] Birjand Univ Med Sci, Cellular & Mol Res Ctr, Birjand, Iran; [Bianconi, Vanessa; Pirro, Matteo] Univ Perugia, Dept Med, Unit Internal Med, Perugia, Italy; [Orafai, Hossein M.] Univ Ahl Al Bayt, Fac Pharm, Dept Pharmaceut, Karbala, Iraq; [Orafai, Hossein M.] Al Zahraa Univ, Fac Pharm, Dept Pharmaceut, Karbala, Iraq; [Sahebkar, Amirhossein] FDA, Halal Res Ctr IRI, Tehran, Iran; [Sahebkar, Amirhossein] Mashhad Univ Med Sci, Biotechnol Res Ctr, Pharmaceut Technol Inst, Mashhad, Razavi Khorasan, Iran; [Sahebkar, Amirhossein] Mashhad Univ Med Sci, Neurogen Inflammat Res Ctr, Mashhad, Razavi Khorasan, Iran		Sahebkar, A (corresponding author), Mashhad Univ Med Sci, Sch Med, Dept Med Biotechnol, POB 91779-48564, Mashhad, Razavi Khorasan, Iran.	sahebkara@mums.ac.ir	Pirro, Matteo/AAC-2318-2022; Sahebkar, Amirhossein/B-5124-2018		Cancer Research Center of Cancer Institute of Iran (Shams cancer charity) [37312-202-01-97, 960206]; Biotechnology Development Council of the Islamic Republic of Iran	This study has been conducted by a grant from Cancer Research Center of Cancer Institute of Iran (Shams cancer charity, Grant No: 37312-202-01-97). This study was also financially supported by grant No. 960206 of the Biotechnology Development Council of the Islamic Republic of Iran.	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MAR 1	2020	244								117341	10.1016/j.lfs.2020.117341			12	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	KK8OT	WOS:000512996400024	31972208				2022-04-25	
J	Zhang, RJ; Yu, QY; Lu, WQ; Shen, J; Zhou, DQ; Wang, YJ; Gao, SR; Wang, ZJ				Zhang, Ruijuan; Yu, Qianyun; Lu, Wenqiang; Shen, Jun; Zhou, Dongqing; Wang, Yingjue; Gao, Shurong; Wang, Zhijun			Grape seed procyanidin B2 promotes the autophagy and apoptosis in colorectal cancer cells via regulating PI3K/Akt signaling pathway	ONCOTARGETS AND THERAPY			English	Article						colorectal cancer; grape seed procyanidin extract; autophagy; apoptosis; PI3K/Akt/mTOR dsignaling pathway	ENDOPLASMIC-RETICULUM STRESS; INHIBITION; EXTRACT	Aim: Colorectal cancer (CRC) is a major malignancy in China, which is the critical risk of people health. Many natural herbs extracts have been found to exhibit good therapeutic effect on CRC. Our previous study found that grape seed procyanidins B2 (PB2) would induce CRC cell death. However, the molecular mechanism underlying its anti-tumor effect on CRC remains unclear. Thereby, this study aimed to investigate the anti-tumor mechanism of PB2 on CRC. Methods: CCK-8, western blotting, flow cytometry, qRT-PCR and animal study were used in the current study. Results: The in vitro and in vivo data demonstrated that PB2 could promote the apoptosis of CRC cells in a dose-dependent manner, which was significantly reversed by caspase 3 inhibitor. Meanwhile, PB2 dose-dependently induced autophagy in CRC cells, which was markedly attenuated by autophagy inhibitor 3-MA. In addition, PB2 dose-dependently inhibited the expressions of p-PI3K, p-Akt and p-mTOR in the cells. Conclusion: PB2 dose-dependently induced apoptosis and autophagy in CRC cells via downregulation of PI3K/Akt pathway. This study provided the experimental basis for further development of PB2 as a new effective anticancer drug for the patients with CRC.	[Zhang, Ruijuan; Lu, Wenqiang; Shen, Jun; Zhou, Dongqing; Wang, Yingjue; Gao, Shurong; Wang, Zhijun] Shanghai Putuo Dist Peoples Hosp, Dept TCM, 1291 Jiangning Rd, Shanghai 200060, Peoples R China; [Yu, Qianyun] Shanghai Huangpu Dist Wuliqiao Community Hlth Ctr, Dept TCM, Shanghai 200023, Peoples R China		Gao, SR; Wang, ZJ (corresponding author), Shanghai Putuo Dist Peoples Hosp, Dept TCM, 1291 Jiangning Rd, Shanghai 200060, Peoples R China.	shuronggao@yandex.com; zhijunwang90@126.com			independent innovation research fund of Shanghai Putuo District health system [KW15204]	This work was supported by Project supported by independent innovation research fund of Shanghai Putuo District health system (No. KW15204).	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J	Ge, J; Liu, Y; Li, Q; Guo, X; Gu, L; Ma, ZG; Zhu, YP				Ge Jiao; Liu Yan; Li Qiang; Guo Xia; Gu Ling; Ma Zhi Gui; Zhu Yi Ping			Resveratrol Induces Apoptosis and Autophagy in T-cell Acute Lymphoblastic Leukemia Cells by Inhibiting Akt/mTOR and Activating p38-MAPK	BIOMEDICAL AND ENVIRONMENTAL SCIENCES			English	Article						Resveratrol; Apoptosis; Autophagy; T-cell acute lymphoblastic leukemia; Akt/mTOR; p38-MAPK	PI3K/AKT/MTOR PATHWAY; MULTITARGETED AGENT; COLON-CANCER; CYCLE ARREST; IN-VITRO; CROSSTALK; BECLIN-1; TARGET; MCF-7	Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MU test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin-dependent kinase (CDK) inhibitors p21 and p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3-1 and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.	[Ge Jiao; Liu Yan; Li Qiang; Guo Xia; Gu Ling; Ma Zhi Gui; Zhu Yi Ping] Sichuan Univ, West China Univ Hosp 2, Dept Pediat Hematol Oncol, Chengdu 610041, Sichuan, Peoples R China		Li, Q (corresponding author), Sichuan Univ, West China Univ Hosp 2, Dept Pediat Hematol Oncol, Chengdu 610041, Sichuan, Peoples R China.	lqcm2000@yahoo.com.cn		Gu, Ling/0000-0002-2410-1696	Department of Science and Technology of Sichuan Province, China [2008JY0029-1, 07FG002-024]; Program for Changjiang Scholars and Innovative-Research Team in UniversityProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT0935]	This study was supported by grants from the Department of Science and Technology of Sichuan Province, China (No. 2008JY0029-1 and No. 07FG002-024) and research funds from the Program for Changjiang Scholars and Innovative-Research Team in University (No. IRT0935).	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Environ. Sci.	NOV	2013	26	11					902	911		10.3967/bes2013.019			10	Environmental Sciences; Public, Environmental & Occupational Health	Science Citation Index Expanded (SCI-EXPANDED)	Environmental Sciences & Ecology; Public, Environmental & Occupational Health	AA2HW	WOS:000330916700005	24331535				2022-04-25	
J	McMahon, KM; Volpato, M; Chi, HY; Musiwaro, P; Poterlowicz, K; Peng, Y; Scally, AJ; Patterson, LH; Phillips, RM; Sutton, CW				McMahon, K. M.; Volpato, M.; Chi, H. Y.; Musiwaro, P.; Poterlowicz, K.; Peng, Y.; Scally, A. J.; Patterson, L. H.; Phillips, R. M.; Sutton, C. W.			Characterization of Changes in the Proteome in Different Regions of 3D Multicell Tumor Spheroids	JOURNAL OF PROTEOME RESEARCH			English	Article						cancer; spheroids; proteomics; autophagy; necrosis; hypoxia; metabolic processes; lipid metabolism	CYCLE INHIBITOR P27(KIP1); BIOREDUCTIVE DRUGS; CELL-CULTURE; EXPRESSION; HYPOXIA; MONOLAYER; CARCINOMA; NECROSIS; GLUCOSE; MODELS	Three dimensional multicell tumor spheroids (MCTS) provide an experimental model where the influence of microenvironmental conditions on protein expression can be determined. Sequential trypsin digestion of HT29 colon carcinoma MCTS enabled segregation into four populations comprising proliferating cells from the surface (SL), an intermediate region (IR), nonproliferating hypoxic cells from the perinecrotic region (PN), and a necrotic core (NC). Total protein was extracted from each population and subjected to iTRAQ-based quantitative proteomics analysis. From a total of 887 proteins identified, 209 were observed to be up-regulated and 114 were down-regulated in the PN and NC regions relative to the SL. Among the up-regulated proteins, components of glycolysis, TCA cycle, lipid metabolism, and steroid biosynthesis increased progressively toward the PN and NC regions. Western blotting, immunohistochemistry, and enzyme assays confirmed that significant changes in the expression of proteins involved in cellular metabolism occur in the nonproliferating fraction of cells within the viable rim. The presence of full length, functional proteins within the NC was unexpected, and further analysis demonstrated that this region contains cells that are undergoing autophagy. This study has identified possible targets that may be suitable for therapeutic intervention, and further studies to validate these are required.	[McMahon, K. M.; Volpato, M.; Chi, H. Y.; Musiwaro, P.; Patterson, L. H.; Phillips, R. M.; Sutton, C. W.] Univ Bradford, Inst Canc Therapeut, Bradford BD7 1DP, W Yorkshire, England; [Poterlowicz, K.; Peng, Y.] Univ Bradford, Dept Comp, Bradford BD7 1DP, W Yorkshire, England; [Scally, A. J.] Univ Bradford, Sch Hlth Studies, Bradford BD7 1DP, W Yorkshire, England		Phillips, RM (corresponding author), Univ Bradford, Inst Canc Therapeut, Bradford BD7 1DP, W Yorkshire, England.	r.m.phillips@Bradford.ac.uk; c.w.sutton@bradford.ac.uk	Poterlowicz, Krzysztof/AAS-2395-2020; Peng, Yonghong/A-5778-2013; Phillips, Roger M/I-5803-2017; Peng, Yonghong/ABD-5633-2021	Poterlowicz, Krzysztof/0000-0001-6173-5674; Peng, Yonghong/0000-0002-8806-2075; Phillips, Roger M/0000-0003-3504-177X; Sutton, Chris/0000-0002-1548-5093; Scally, Andy/0000-0002-6189-2247	Agilent Technologies UK; EPSRCUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC); Yorkshire Cancer Research	We thank Sham Naal and Agilent Technologies UK for their cosponsorship, with the EPSRC grant awarding body, for the support of KM. and Yorkshire Cancer Research for the support of C.S. Thanks to Tavga Mohammed, Hajer Omar, Asma Omar and Rafiqul Fysal for their technical support.	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Proteome Res.	MAY	2012	11	5					2863	2875		10.1021/pr2012472			13	Biochemical Research Methods	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	935BM	WOS:000303492100020	22416669				2022-04-25	
J	Wang, HY; Wang, X; Zhang, HY; Deng, T; Liu, R; Liu, Y; Li, HL; Bai, M; Ning, T; Wang, JY; Ge, SH; Ba, Y				Wang, Huiya; Wang, Xia; Zhang, Haiyang; Deng, Ting; Liu, Rui; Liu, Ying; Li, Hongli; Bai, Ming; Ning, Tao; Wang, Junyi; Ge, Shaohua; Ba, Yi			The HSF1/miR-135b-5p axis induces protective autophagy to promote oxaliplatin resistance through the MUL1/ULK1 pathway in colorectal cancer	ONCOGENE			English	Article							ADJUVANT CHEMOTHERAPY; OPEN-LABEL; CELLS; CHEMORESISTANCE; MIR-135B-5P; MICRORNAS; TUMORIGENESIS; FLUOROURACIL; LEUCOVORIN; MECHANISM	Oxaliplatin (oxa) is widely used in the treatment of colorectal cancer (CRC), but the development of oxaliplatin resistance is a major obstacle to the therapeutic efficacy in patients. MicroRNAs (miRNAs), endogenous noncoding RNAs measuring between 22 and 24 nucleotides, have been shown to be involved in the development of CRC drug resistance. However, the mechanism by which differentially expressed miRNAs induce chemotherapy resistance in CRC has not been fully elucidated to date. Here, we showed the differentially expressed miRNAs in oxaliplatin-sensitive and oxaliplatin-resistant CRC cells through miRNA microarray technology and found that miR-135b-5p was significantly increased in oxaliplatin-resistant cells. And miR-135b-5p was increased in the serum of colorectal cancer patients. More importantly, the miR-135b-5p level in the serum of oxaliplatin-resistant patients was further increased compared to that of oxaliplatin-sensitive patients. Recent studies have shown that protective autophagy is an important mechanism that promotes drug resistance in tumors. The potential role of miR-135b-5p in inducing protective autophagy and promoting oxaliplatin resistance was evaluated in two stable oxaliplatin-resistant CRC cell lines and their parental cells. We further identified MUL1 as a direct downstream target of miR-135b-5p and showed that MUL1 could degrade the key molecule of autophagy, ULK1, through ubiquitination. Mouse xenograft models were adopted to evaluate the correlation between miR-135b-5p and oxaliplatin-induced autophagy in vivo. Furthermore, we also investigated the regulatory factors for the upregulation of miR-135b-5p in CRC cells under oxaliplatin chemotoxicity. These results indicated that miR-135b-5p upregulation in colorectal cancer could induce protective autophagy through the MUL1/ULK1 signaling pathway and promote oxaliplatin resistance. Targeting miR-135b-5p may provide a new treatment strategy for reversing oxaliplatin resistance in CRC.	[Wang, Huiya; Wang, Xia; Zhang, Haiyang; Deng, Ting; Liu, Rui; Liu, Ying; Li, Hongli; Bai, Ming; Ning, Tao; Wang, Junyi; Ge, Shaohua; Ba, Yi] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjins Clin Res Ctr Canc, Tianjin, Peoples R China		Ba, Y (corresponding author), Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjins Clin Res Ctr Canc, Tianjin, Peoples R China.	bayi@tjmuch.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82072664, 81772629, 81802363, 81702431, 81772843, 81974374]; Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs [2018ZX09201015]; Tianjin Science FoundationNatural Science Foundation of Tianjin [18JCQNJC81900, 18JCYBJC92000, 18JCYBJC25400, 18JCYBJC92900, 20JCYBJC00100]; Science & Technology Development Fund of the Tianjin Education Commission for Higher Education [2018KJ046, 2017KJ227]	This work was supported by grants from the National Natural Science Foundation of China (Nos. 82072664, 81772629, 81802363, 81702431, 81772843, 81974374) and the Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs (No. 2018ZX09201015). This work was also supported by the Tianjin Science Foundation (Nos. 18JCQNJC81900, 18JCYBJC92000, 18JCYBJC25400, 18JCYBJC92900, 20JCYBJC00100) and the Science & Technology Development Fund of the Tianjin Education Commission for Higher Education (2018KJ046, 2017KJ227). The funders had no role in the study design, the data collection and analysis, the interpretation of the data, the writing of the report, and the decision to submit this article for publication.	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J	Feng, J; Li, Z; Li, L; Xie, HB; Lu, QC; He, XZ				Feng, Jin; Li, Zhong; Li, Ling; Xie, Haibin; Lu, Qicheng; He, Xiaozhou			Hypoxia-induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR-3140/autophagy pathway	INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE			English	Article						colorectal cancer; circCCDC66; microRNA-3140; autophagy; hypoxia	GENE-EXPRESSION; PROGRESSION; INVASION; PROLIFERATION; MIGRATION; MIRNAS; GROWTH	Circular RNAs (circRNAs) have been reported to be involved in the progression of colorectal cancer (CRC). However, the biological role of circCCDC66 in CRC remains unclear. Therefore, the present study aimed to elucidate the mechanisms through which circCCDC66 affects the hypoxia-induced progression of CRC. It was found that hypoxia promoted the progression of CRC and upregulated the expression of circCCDC66. Furthermore, circCCDC66-knockdown reduced viability, migration and invasion, and enhanced the apoptosis of hypoxia-exposed CRC cells. Using the starBase database, it was identified that circCCDC66 may bind to miR-3140. Subsequently, it was confirmed that circCCDC66 serves as a sponge of miR-3140 and the depletion of miR-3140 partly abolished the effects of circCCDC66 on the phenotype of hypoxia-exposed CRC cells. In addition, miR-3140 was validated to inhibit the autophagy pathway. The use of an autophagy inducer partially reversed the miR-3140 overexpression-induced inhibition of the viability and invasion, and the promotion of the apoptosis of hypoxia-exposed CRC cells. In summary, the findings of the present study demonstrated that circCCDC66 facilitates the development of CRC cells under hypoxic conditions via regulation of miR-3140/autophagy. These findings may provide a novel therapeutic option for patients with CRC.	[Feng, Jin; Li, Zhong; Li, Ling; Xie, Haibin; Lu, Qicheng] First Peoples Hosp Changzhou, Dept Gastrointestinal Surg, 185 Juqian St, Changzhou 213029, Jiangsu, Peoples R China; [He, Xiaozhou] First Peoples Hosp Changzhou, Dept Urol Surg, 185 Juqian St, Changzhou 213029, Jiangsu, Peoples R China		Lu, QC (corresponding author), First Peoples Hosp Changzhou, Dept Gastrointestinal Surg, 185 Juqian St, Changzhou 213029, Jiangsu, Peoples R China.; He, XZ (corresponding author), First Peoples Hosp Changzhou, Dept Urol Surg, 185 Juqian St, Changzhou 213029, Jiangsu, Peoples R China.	qichenglu666@126.com; xiaozhouhe59@163.com			Applied Basic Research Project of Changzhou Science and Technology Bureau [J20180070]; Changzhou High-Level Medical Talents Training Project [2016-CZBJ046]	This work was supported by the Applied Basic Research Project of Changzhou Science and Technology Bureau (no.C J20180070) and Changzhou High-Level Medical Talents Training Project (no. 2016-CZBJ046).	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J. Mol. Med.	DEC	2020	46	6					1973	1982		10.3892/ijmm.2020.4747			10	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	OU2PZ	WOS:000591376800004	33125087	hybrid, Green Published			2022-04-25	
J	Usman, RM; Razzaq, F; Akbar, A; Farooqui, AA; Iftikhar, A; Latif, A; Hassan, H; Zhao, JJ; Carew, JS; Nawrocki, ST; Anwer, F				Usman, Rana Muhammad; Razzaq, Faryal; Akbar, Arshia; Farooqui, Arafat Ali; Iftikhar, Ahmad; Latif, Azka; Hassan, Hamza; Zhao, Jianjun; Carew, Jennifer S.; Nawrocki, Steffan T.; Anwer, Faiz			Role and mechanism of autophagy-regulating factors in tumorigenesis and drug resistance	ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY			English	Review						Autophagy-related genes; autophagy; drug resistance; hydroxychloroquine; tumorigenesis	MIGRATION INHIBITORY FACTOR; OVARIAN-CANCER CELLS; BREAST-CANCER; FACTOR MIF; THERAPEUTIC TARGET; SIGNALING PATHWAY; INDUCED APOPTOSIS; TUMOR-SUPPRESSOR; OVER-EXPRESSION; POOR-PROGNOSIS	A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance includingBeclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAFandc-MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.	[Usman, Rana Muhammad] Univ Tennessee, Dept Med, Hlth Sci Ctr, Memphis, TN USA; [Razzaq, Faryal] Fdn Univ Med Coll, Islamabad, Pakistan; [Akbar, Arshia] Holy Family Hosp, Dept Med Intens Care, Rawalpindi, Pakistan; [Farooqui, Arafat Ali] King Edward Med Univ, Dept Med, Lahore, Pakistan; [Iftikhar, Ahmad; Carew, Jennifer S.; Nawrocki, Steffan T.] Univ Arizona, Dept Med, Tucson, AZ USA; [Latif, Azka] Crieghton Univ, Dept Med, Omaha, NE USA; [Hassan, Hamza] Boston Univ, Med Ctr, Dept Hematol & Med Oncol, Boston, MA USA; [Zhao, Jianjun; Anwer, Faiz] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA		Anwer, F (corresponding author), Cleveland Clin, Taussig Canc Ctr, Multiple Myeloma Program, Hematol,Oncol,Stem Cell Transplantat, Cleveland, OH 44195 USA.	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J	Goder, A; Nagel, G; Kraus, A; Dorsam, B; Seiwert, N; Kaina, B; Fahrer, J				Goeder, Anja; Nagel, Georg; Kraus, Alexander; Doersam, Bastian; Seiwert, Nina; Kaina, Bernd; Fahrer, Jorg			Lipoic acid inhibits the DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) and triggers its depletion in colorectal cancer cells with concomitant autophagy induction	CARCINOGENESIS			English	Article							BASE-EXCISION-REPAIR; AGE-RELATED LOSS; TUMOR-CELLS; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ALKYLATING-AGENTS; INDUCED APOPTOSIS; OXIDATIVE STRESS; KAPPA-B; ALPHA; P53	Alkylating agents are present in food and tobacco smoke, but are also used in cancer chemotherapy, inducing the DNA lesion O-6-methylguanine. This critical adduct is repaired by O-6-methylguanine-DNA methyltransferase (MGMT), resulting in MGMT inactivation and degradation. In the present study, we analyzed the effects of the natural disulfide compound lipoic acid (LA) on MGMT in vitro and in colorectal cancer cells. We show that LA, but not its reduced form dihydrolipoic acid, potently inhibits the activity of recombinant MGMT by interfering with its catalytic Cys-145 residue, which was partially reversible by N-acetyl cysteine. Incubation of HCT116 colorectal cancer cells with LA altered their glutathione pool and caused a decline in MGMT activity. This was mirrored by LA-induced depletion of MGMT protein, which was not attributable to changes in MGMT messenger RNA levels. Loss of MGMT protein coincided with LA-induced autophagy, a process resulting in lysosomal degradation of proteins, including presumably MGMT. LA-stimulated autophagy in a p53-independent manner as revealed by the response of isogenic HCT116 cell lines. Knockdown of the crucial autophagy component beclin-1 and chemical inhibitors blocked LA-induced autophagy, but did not abrogate LA-triggered MGMT degradation. Concomitant with MGMT depletion, LA pretreatment resulted in enhanced O-6-methylguanine levels in DNA. It also increased the cytotoxicity of the alkylating anticancer drug temozolomide in temozolomide-resistant colorectal cancer cells. Taken together, our study showed that the natural compound LA inhibits MGMT and induces autophagy. Furthermore, LA enhanced the cytotoxic effects of temozolomide, which makes it a candidate for a supplement in cancer therapy.	[Goeder, Anja; Nagel, Georg; Kraus, Alexander; Doersam, Bastian; Seiwert, Nina; Kaina, Bernd; Fahrer, Jorg] Univ Med Ctr Mainz, Dept Toxicol, D-55131 Mainz, Germany		Fahrer, J (corresponding author), Univ Med Ctr Mainz, Dept Toxicol, Obere Zahlbacher Str 67, D-55131 Mainz, Germany.	fahrer@uni-mainz.de	Seiwert, Nina/ABD-2627-2020; Kaina, Bernd/AAE-4692-2020	Seiwert, Nina/0000-0003-2169-3670; Goder, Anja/0000-0001-9743-1656	University of Mainz (Stufe I) [973 8549]; University Medical Center Mainz (MAIFOR) [972 8716]; German Research FoundationGerman Research Foundation (DFG) [DFG-FA1034, DFG-KA724]	University of Mainz (Stufe I, grant # 973 8549), University Medical Center Mainz (MAIFOR, grant # 972 8716), and the German Research Foundation (DFG-FA1034 and DFG-KA724).	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J	Jin, L; Chen, YH; Cheng, D; He, ZK; Shi, XY; Du, BY; Xi, XY; Gao, YJ; Guo, Y				Jin, Lan; Chen, Yunhe; Cheng, Dan; He, Zhikai; Shi, Xinyi; Du, Boyu; Xi, Xueyan; Gao, Yujing; Guo, Yang			YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression	CELL DEATH & DISEASE			English	Article							YES-ASSOCIATED PROTEIN; CELL-DEATH; HIPPO PATHWAY; PROLIFERATION; GROWTH; CHEMORESISTANCE; BIOLOGY	Colorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.	[Jin, Lan; Chen, Yunhe; Cheng, Dan; He, Zhikai; Du, Boyu; Xi, Xueyan; Guo, Yang] Hubei Univ Med, Sch Basic Med Sci, Dept Immunol, Shiyan 442000, Hubei, Peoples R China; [Jin, Lan; Chen, Yunhe; Guo, Yang] Hubei Univ Med, Hubei Key Lab Embryon Stem Cell Res, Shiyan 442000, Hubei, Peoples R China; [Shi, Xinyi; Gao, Yujing] Ningxia Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Key Lab Fertil Preservat & Maintenance,Minist Edu, Yinchuan, Ningxia, Peoples R China		Guo, Y (corresponding author), Hubei Univ Med, Sch Basic Med Sci, Dept Immunol, Shiyan 442000, Hubei, Peoples R China.; Guo, Y (corresponding author), Hubei Univ Med, Hubei Key Lab Embryon Stem Cell Res, Shiyan 442000, Hubei, Peoples R China.; Gao, YJ (corresponding author), Ningxia Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Key Lab Fertil Preservat & Maintenance,Minist Edu, Yinchuan, Ningxia, Peoples R China.	gaoyujing2004@126.com; guoyang_hbmu@foxmail.com		Gao, yujing/0000-0003-0718-4992; Guo, Yang/0000-0002-4763-0072	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81702930, 81872395, 81660486]; Hubei Provincial Natural Science Foundation [2019CFB424]; Biomedical Research Foundation, Hubei University of Medicine [PI201804]	This study was supported by the National Natural Science Foundation of China (81702930, 81872395, 81660486), Hubei Provincial Natural Science Foundation (2019CFB424), and the Biomedical Research Foundation, Hubei University of Medicine (PI201804).	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MAY 7	2021	12	5							457	10.1038/s41419-021-03722-8			10	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	SK5LQ	WOS:000656257100003	33963173	gold, Green Published			2022-04-25	
J	Tsai, WL; Wang, CY; Lee, YC; Tang, WC; Anuraga, G; Ta, HDK; Wu, YF; Lee, KH				Tsai, Wei-Lun; Wang, Chih-Yang; Lee, Yu-Cheng; Tang, Wan-Chun; Anuraga, Gangga; Ta, Hoang Dang Khoa; Wu, Yung-Fu; Lee, Kuen-Haur			A New Light on Potential Therapeutic Targets for Colorectal Cancer Treatment	BIOMEDICINES			English	Article						colorectal cancer; CRNDE; MiR-29b-3p; ANGPTL4; autophagy; lipid metabolism	NONCODING RNA CRNDE; EPITHELIAL-MESENCHYMAL TRANSITION; ANGIOPOIETIN-LIKE 4; LIPID-ACCUMULATION; AUTOPHAGY; EXPRESSION; AMPK; CELLS; AXIS; PROLIFERATION	The development and progression of colorectal cancer (CRC) involve changes in genetic and epigenetic levels of oncogenes and/or tumor suppressors. In spite of advances in understanding of the molecular mechanisms involved in CRC, the overall survival rate of CRC still remains relatively low. Thus, more research is needed to discover and investigate effective biomarkers and targets for diagnosing and treating CRC. The roles of long non-coding RNAs (lncRNAs) participating in various aspects of cell biology have been investigated and potentially contribute to tumor development. Our recent study also showed that CRNDE was among the top 20 upregulated genes in CRC clinical tissues compared to normal colorectal tissues by analyzing a Gene Expression Omnibus (GEO) dataset (GSE21815). Although CRNDE is widely reported to be associated with different types of cancer, most studies of CRNDE were limited to examining regulation of its transcription levels, and in-depth mechanistic research is lacking. In the present study, CRNDE was found to be significantly upregulated in CRC patients at an advanced TNM stage, and its high expression was correlated with poor outcomes of CRC patients. In addition, we found that knocking down CRNDE could reduce lipid accumulation through the miR-29b-3p/ANGPTL4 axis and consequently induce autophagy of CRC cells.</p>	[Tsai, Wei-Lun; Anuraga, Gangga; Ta, Hoang Dang Khoa] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Mol Biol & Drug Discovery, Taipei 11031, Taiwan; [Tsai, Wei-Lun; Anuraga, Gangga; Ta, Hoang Dang Khoa] Acad Sinica, Taipei 11031, Taiwan; [Wang, Chih-Yang; Tang, Wan-Chun; Lee, Kuen-Haur] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Mol Biol & Drug Discovery, Taipei 11031, Taiwan; [Wang, Chih-Yang; Tang, Wan-Chun; Anuraga, Gangga; Ta, Hoang Dang Khoa; Lee, Kuen-Haur] Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery, Taipei 11031, Taiwan; [Lee, Yu-Cheng] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei 11031, Taiwan; [Anuraga, Gangga] Univ PGRI Adi Buana, Fac Sci & Technol, Dept Stat, Surabaya 60234, East Java, Indonesia; [Wu, Yung-Fu] Triserv Gen Hosp, Sch Med, Dept Med Res, Natl Def Med Ctr, Taipei 11490, Taiwan; [Lee, Kuen-Haur] Taipei Med Univ, Wan Fang Hosp, Canc Ctr, Taipei 11031, Taiwan		Lee, KH (corresponding author), Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Mol Biol & Drug Discovery, Taipei 11031, Taiwan.; Lee, KH (corresponding author), Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery, Taipei 11031, Taiwan.; Lee, KH (corresponding author), Taipei Med Univ, Wan Fang Hosp, Canc Ctr, Taipei 11031, Taiwan.	mebar1995@gmail.com; chihyang@tmu.edu.tw; yclee0212@tmu.edu.tw; yeas0310@hotmail.com; g.anuraga@unipasby.ac.id; d621109004@tmu.edu.tw; qrince@yahoo.com.tw; khlee@tmu.edu.tw	Anuraga, Gangga/AAE-8623-2021; Anuraga, Gangga/ABE-1220-2021	Anuraga, Gangga/0000-0002-0902-3968; Lee, Kuen-Haur/0000-0002-6354-3315; , Khoa/0000-0001-8809-239X	Health and Welfare Surcharge of Tobacco Product of Taiwan (Wan-Fang Hospital) [MOHW110-TDU-B-212-144020]; Health and Welfare Surcharge of Tobacco Product of Taiwan (Chi-Mei Medical Center) [MOHW110-TDU-B-212-144020]; Health and Welfare Surcharge of Tobacco Product of Taiwan (Hualien Tzu-Chi Hospital Joint Cancer Center Grant-Focus on Colon Cancer Research) [MOHW110-TDU-B-212-144020]; Ministry of Education of TaiwanMinistry of Education, Taiwan [DP2-110-21121-03-C-03-03]; Chi-Mei Medical Center [110CM-TMU-16]; "TMU Research Center of Cancer Translational Medicine" from The Featured Areas Research Center Program within the Ministry of Education (MOE) in Taiwan	This research was funded by the Health and Welfare Surcharge of Tobacco Products of Taiwan (Wan-Fang Hospital, Chi-Mei Medical Center, and Hualien Tzu-Chi Hospital Joint Cancer Center Grant-Focus on Colon Cancer Research; grant no.: MOHW110-TDU-B-212-144020, awarded to K-H.L.), Ministry of Education of Taiwan (grant no.: DP2-110-21121-03-C-03-03), Chi-Mei Medical Center (grant no.: 110CM-TMU-16 to K.-H.L.), and the "TMU Research Center of Cancer Translational Medicine" from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.	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J	Li, HY; Gao, CD; Liu, C; Liu, LJ; Zhuang, J; Yang, J; Zhou, C; Feng, FB; Sun, CG; Wu, JB				Li, Huayao; Gao, Chundi; Liu, Cun; Liu, Lijuan; Zhuang, Jing; Yang, Jing; Zhou, Chao; Feng, Fubin; Sun, Changgang; Wu, Jibiao			A review of the biological activity and pharmacology of cryptotanshinone, an important active constituent in Danshen	BIOMEDICINE & PHARMACOTHERAPY			English	Review						Cryptotanshinone; Biological activity; Pharmacological; Anti-cancer; Anti-inflammatory	SALVIA-MILTIORRHIZA; CANCER-CELLS; IN-VITRO; COLON-CANCER; LUNG-CANCER; APOPTOSIS; GROWTH; INHIBITION; EXPRESSION; ANTITUMOR	Cryptotanshinone (IUPAC name: (R)-1,2,6,7,8,9-hexahydro-1,6,6-trimethyl-phenanthro(1,2-b)furan-10,11dione), a biologically active constituent extracted from the roots and rhizomes of the plant Salvia miltiorrhiza, has been studied in depth as a medicinally active compound and shown to have efficacy in the treatment of numerous diseases and disorders. In this review, we describe in detail the current status of cryptotanshinone research, including findings relating to the structure, pharmacokinetics, pharmacological activity, and derivatives of this compound. Cryptotanshinoneh as a diverse range of pharmacological effects, including anticancer, anti-inflammatory, immune regulatory, neuroprotective, and anti-fibrosis activities. Studies on the molecular mechanisms underlying the activities of cryptotanshinone have established that the JAK2/STAT3, PI3K/AKT, NF-kappa B, AMPK, and cell cycle pathways are involved in the inhibitory and pro-apoptotic effects of cryptotanshinone on different tumor cell lines, these molecular pathways interact in a coordinated manner to inhibit cell proliferation, migration and invasion,and induce transformation, autophagy, necrosis, and cellular immunity. The anti-inflammatory mechanisms of cryptotanshinone have been found to be associated with the TLR4MyD88/PI3K/Nrf2 and TLR4-MyD88/NF-kappa B/MAPK pathways, whereasthe Hedgehog, NF-kappa B, and Nrf-2/HO-1 pathways are regulated by cryptotanshinone to reduce organ fibrosis, and its inhibitory effects on the PI3K/ AKT-eNOS pathway have been linked to neuroprotective effects. Given the potential medicinal utility of cryptotanshinone, further research is needed to verify the efficacy and safety of this compound in clinical use, evaluate its pharmacological activity, and identify molecular targets.	[Li, Huayao; Wu, Jibiao] Shandong Univ Tradit Chinese Med, Coll Chinese Med, Jinan 250014, Shandong, Peoples R China; [Gao, Chundi; Liu, Cun; Zhou, Chao] Shandong Univ Tradit Chinese Med, Coll Clin Med 1, Jinan 250014, Shandong, Peoples R China; [Liu, Lijuan; Zhuang, Jing; Yang, Jing; Zhou, Chao; Feng, Fubin; Sun, Changgang] Weifang Tradit Chinese Hosp, Dept Oncol, Weifang 261041, Shandong, Peoples R China; [Zhuang, Jing] Shandong Univ Chinese Med, Qingdao Acad Chinese Med Sci, Qingdao 266112, Shandong, Peoples R China; [Liu, Cun; Feng, Fubin] Qingdao Univ, Dept Basic Med Sci, Qingdao 266071, Peoples R China; [Sun, Changgang] Shandong Univ Tradit Chinese Med, Chinese Med Innovat Inst, Jinan 250014, Shandong, Peoples R China		Sun, CG; Wu, JB (corresponding author), 4655 Univ Rd,Univ Sci Pk, Jinan 250355, Shandong, Peoples R China.	lhy126913@163.com; gaochundi2017@163.com; 18763678002@163.com; hxdhxd19852003@163.com; 13963676719@163.com; xyjf63@163.com; 285758078@163.com; wfffb0618@163.com; scgdoctor@126.com; wujibiao1963@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81673799, 81973677, 81703915]	This work is supported by the grants from National Natural Science Foundation of China (81673799, 81973677, 81703915) .	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Pharmacother.	MAY	2021	137								111332	10.1016/j.biopha.2021.111332		FEB 2021	12	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	RC2UF	WOS:000632659500001	33548911	gold			2022-04-25	
J	Olszewski, U; Deally, A; Tacke, M; Hamilton, G				Olszewski, Ulrike; Deally, Anthony; Tacke, Matthias; Hamilton, Gerhard			Alterations of Phosphoproteins in NCI-H526 Small Cell Lung Cancer Cells Involved in Cytotoxicity of Cisplatin and Titanocene Y	NEOPLASIA			English	Article							N-TERMINAL KINASE; CASPASE-DEPENDENT APOPTOSIS; OVARIAN-CANCER; ANTITUMOR-ACTIVITY; ANTICANCER DRUGS; IN-VITRO; ACTIVATION; RESISTANCE; INHIBITION; PATHWAY	First-line treatment of small cell lung cancer (SCLC) with combination chemotherapy consisting of cis-diamminedichloroplatinum(II) (cisplatin) and etoposide is frequently followed by early relapses and a dismal prognosis. Survival of a fraction of tumor cells and development of chemoresistance may be influenced by an initial cellular stress response against the administered xenobiotics. Therefore, we compared the short-term effects of cisplatin and non-cross-resistant bis-[(p-methoxybenzyl) cyclopentadienyl] titanium(IV) dichloride (Titanocene Y) on phosphorylation of 46 sites of a total of 38 signaling proteins in tumor suppressor protein 53 (p53)-wild-type NCI-H526 SCLC cells. The functional significance of selected kinases for the cytotoxicity of both drugs was tested using specific inhibitors and an activator. The cisplatin-induced cellular stress response involved activation of p38 alpha mitogen-activated protein kinase, whereas Titanocene Y-triggered signaling affected c-Jun N-terminal kinase. Phosphorylation of adenosine monophosphate (AMP)-activated protein kinase alpha 1 (AMPK alpha 1) was increased by both drugs, which promoted cell survival, as indicated by results obtained using AMPK inhibitor compound C and AMPK activator 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside. This is in good agreement with previous reports, where AMPK alpha 1 was demonstrated to represent an important factor for the sensitivity to cisplatin in colon and ovarian cancers, most likely by induction of autophagy. Thus, AMPK alpha 1 constitutes a potential target to be exploited for chemotherapeutic treatment of SCLC to circumvent resistance to metal-based compounds. Neoplasia (2012) 14, 813-822	[Olszewski, Ulrike; Hamilton, Gerhard] Ludwig Boltzmann Soc, Vienna, Austria; [Deally, Anthony; Tacke, Matthias] Univ Coll Dublin, Sch Chem & Chem Biol, Dublin 2, Ireland; [Hamilton, Gerhard] Med Univ Vienna, Dept Surg, Vienna, Austria		Olszewski, U (corresponding author), Ludwig Boltzmann Cluster Translat Oncol, Balderichgasse 26A-7-8, A-1170 Vienna, Austria.	ulrike.olszewski@toc.lbg.ac.at		Tacke, Matthias/0000-0002-8903-3137	Higher Education Authority (HEA) [PRTLI4]; Medical Scientific Fund of the Mayor of the City of Vienna [11016]	This project was funded in part (in Ireland) by the Higher Education Authority (HEA) through a PRTLI4 grant and the Medical Scientific Fund of the Mayor of the City of Vienna (No. 11016). The authors declare that they have no conflict of interest.	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J	Wang, KL; Chen, Q; Shao, YY; Yin, SS; Liu, CY; Liu, YM; Wang, R; Wang, T; Qiu, YL; Yu, HY				Wang, Kailong; Chen, Qian; Shao, Yingying; Yin, Shuangshuang; Liu, Caiyan; Liu, Yiman; Wang, Rui; Wang, Tao; Qiu, Yuling; Yu, Haiyang			Anticancer activities of TCM and their active components against tumor metastasis	BIOMEDICINE & PHARMACOTHERAPY			English	Review						Cancer metastasis; Traditional Chinese medicine (TCM); TCM prescription; Chinese patent medicine; TCM monomer compound	EPITHELIAL-MESENCHYMAL TRANSITION; LUNG-CANCER CELLS; TRADITIONAL CHINESE MEDICINE; NF-KAPPA-B; HUMAN HEPATOCELLULAR-CARCINOMA; HUMAN GASTRIC ADENOCARCINOMA; BREAST-CANCER; IN-VITRO; COLORECTAL-CANCER; INHIBITS METASTASIS	Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, slight side effects and good therapeutic effects. Good anti-tumor effects are shown by Traditional Chinese Medicine prescription, Chinese patent medicine, single Traditional Chinese Medicine and Traditional Chinese medicine monomer compound. Clinically, TCM prolonged the survival time of patients and improved the life quality of patients, due to less side effects. Cancer metastasis is a complex process involving numerous steps, multiple genes and their products. During the process of tumor metastasis, firstly, cancer cell increases its proliferative capacity by reducing autophagy and apoptosis, and then the cancer cell capacity is stimulated by increasing the ability of tumors to absorb nutrients from the outside through angiogenesis. Both of the two steps can increase tumor migration and invasion. Finally, the purpose of tumor metastasis is achieved. By inhibiting autophagy and apoptosis of tumor cells, angiogenesis and EMT outside the tumor can inhibit the invasion and migration of cancer, and consequently achieve the purpose of inhibiting tumor metastasis. This review explores the research achievements of Traditional Chinese Medicine on breast cancer, lung cancer, hepatic carcinoma, colorectal cancer, gastric cancer and other cancer metastasis in the past five years, summarizes the development direction of TCM on cancer metastasis research in the past five years and makes a prospect for the future.	[Wang, Kailong; Chen, Qian; Shao, Yingying; Yin, Shuangshuang; Liu, Caiyan; Liu, Yiman; Wang, Rui; Wang, Tao; Yu, Haiyang] Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Modern Chinese Med, Tianjin 301617, Peoples R China; [Qiu, Yuling] Tianjin Med Univ, Sch Pharm, Tianjin 300070, Peoples R China		Yu, HY (corresponding author), Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Modern Chinese Med, Tianjin 301617, Peoples R China.; Qiu, YL (corresponding author), Tianjin Med Univ, Sch Pharm, Tianjin 300070, Peoples R China.	qiuyuling@tmu.edu.cn; hyyu@tjutcm.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81873089, 81603253, 81973570]; Important Drug Development Fund, Ministry of Science and Technology of China [2018ZX09735-002, 2018ZX092011]	This work was supported by grants from National Natural Science Foundation of China (Nos. 81873089 and 81603253 to H. Yu, No. 81973570 to Y. Qiu), Important Drug Development Fund, Ministry of Science and Technology of China (2018ZX09735-002 to T. Wang, No. 2018ZX092011 to Z. Li).	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Pharmacother.	JAN	2021	133								111044	10.1016/j.biopha.2020.111044			17	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	PN6JO	WOS:000604583500002	33378952	gold	Y	N	2022-04-25	
J	Yang, B; Zang, J; Yuan, WL; Jiang, XJ; Zhang, F				Yang, Bo; Zang, Jian; Yuan, Weili; Jiang, Xuejun; Zhang, Fang			The miR-136-5p/ROCK1 axis suppresses invasion and migration, and enhances cisplatin sensitivity in head and neck cancer cells	EXPERIMENTAL AND THERAPEUTIC MEDICINE			English	Article						cell invasion; cell migration; cisplatin sensitivity; laryngeal squamous cell carcinoma; hypopharyngeal squamous cell carcinoma; microRNA-136-5p; Rho-associated coiled-coil containing protein kinase 1	PROTEIN-KINASE; COLON-CANCER; RHO; MIR-136; PROLIFERATION; METASTASIS; EXPRESSION; ROCK; RESISTANCE; CARCINOMA	Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) are two types of head and neck cancers with high incidence rates and relatively poor prognoses. The aim of the present study was to determine the effects of microRNA (miR/miRNA)-136-5p and its downstream target, Rho-associated coiled-coil containing protein kinase 1 (ROCK1), on LSCC and HPSCC progression and cisplatin sensitivity. The miRNA and protein expression levels in head and neck cancer cell lines were evaluated using reverse transcription-quantitative PCR and western blotting, respectively. MTT, wound healing assays, transwell assays and flow cytometry analysis were performed to measure cell properties. The binding between miR-136-5p and ROCK1 was detected using a dual-luciferase reporter assay. Autophagy double-labeled adenoviral infection assays were used to assess cell autophagy. The results showed that miR-136-5p was expressed in LSCC and HPSCC cells. Functional experiments showed that the expression of miR-136-5p in LSCC and HPSCC cells was negatively correlated with cell viability, invasion and migration. Additionally, miR-136-5p overexpression inhibited epithelial-mesenchymal transition, whereas miR-136-5p knockdown had the opposite effect. Dual-luciferase reporter assays confirmed the targeting relationship between miR-136-5p and ROCK1. miR-136-5p overexpression increased the cisplatin sensitivity of LSCC and HPSCC cells by reducing cell viability, as well as promoting cell apoptosis and autophagy. miR-136-5p overexpression decreased the expression levels of its downstream target ROCK1 and attenuated activity of the Akt/mTOR signaling pathway in cisplatin-treated LSCC and HPSCC cells. Conversely, miR-136-5p knockdown increased ROCK1 levels and decreased cisplatin sensitivity of the LSCC and HPSCC cells by increasing cell viability and inhibiting cell apoptosis, which was reversed by ROCK1 inhibition using the ROCK1 inhibitor, Y27632. Taken together, the results showed that the miR-136-5p/ROCK1 axis inhibits cell invasion and migration, and increases the sensitivity of LSCC and HPSCC cells to cisplatin.	[Yang, Bo; Zang, Jian; Jiang, Xuejun] China Med Univ, Hosp 1, Dept Otorhinolaryngol Head & Neck Surg, Shenyang 110001, Liaoning, Peoples R China; [Yuan, Weili] China Med Univ, Affiliated Hosp 4, Dept Oral & Maxillofacial Surg, Shenyang 110032, Liaoning, Peoples R China; [Zhang, Fang] China Med Univ, Affiliated Hosp 4, Dept Otorhinolaryngol Head & Neck Surg, 4 East Chongshan Rd, Shenyang 110032, Liaoning, Peoples R China		Zhang, F (corresponding author), China Med Univ, Affiliated Hosp 4, Dept Otorhinolaryngol Head & Neck Surg, 4 East Chongshan Rd, Shenyang 110032, Liaoning, Peoples R China.	zhangfang_cmu4h@163.com					Amable L, 2016, PHARMACOL RES, V106, P27, DOI 10.1016/j.phrs.2016.01.001; Azoulay-Alfaguter I, 2015, ONCOGENE, V34, P4613, DOI 10.1038/onc.2014.390; Bhowmick NA, 2001, MOL BIOL CELL, V12, P27, DOI 10.1091/mbc.12.1.27; Bishop AL, 2000, BIOCHEM J, V348, P241, DOI 10.1042/0264-6021:3480241; Bjorkoy G, 2005, J CELL BIOL, V171, P603, DOI 10.1083/jcb.200507002; Bushati N, 2007, ANNU REV CELL DEV BI, V23, P175, DOI 10.1146/annurev.cellbio.23.090506.123406; 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Ther. Med.	APR	2021	21	4							317	10.3892/etm.2021.9748			10	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	QI4EW	WOS:000618933600001	33717260	gold, Green Published			2022-04-25	
J	Smith, EL; Schuchman, EH				Smith, Eric L.; Schuchman, Edward H.			Acid sphingomyelinase overexpression enhances the antineoplastic effects of irradiation in vitro and in vivo	MOLECULAR THERAPY			English	Article							NIEMANN-PICK-DISEASE; RENAL-CELL CARCINOMA; RADIATION-INDUCED APOPTOSIS; HUMAN COLON-CANCER; PROSTATE-CANCER; GLUCOSYLCERAMIDE SYNTHASE; ADRIAMYCIN RESISTANCE; GLIOMA-CELLS; HUMAN-TUMORS; CERAMIDE	Exposure of cells or animals to stress frequently induces acid sphingomyelinase (ASM)-mediated ceramide production that leads to cell death. Consistent with this, overexpression of ASM in subcutaneous B16-F10 mouse melanomas, in combination with irradiation, resulted in tumors that were up to 12-fold smaller than irradiated control melanomas. Similarly, when irradiated melanomas were pretreated with a single, peritumoral injection of recombinant ASM (rhASM), the tumors were up to threefold smaller. The in vivo effect of ASM was likely due to enhanced cell death of the tumor cells themselves, as well as the surrounding microvascular endothelial cells. In vitro, rhASM had little or no effect on the growth of tumor cells, even in combination with irradiation. However, when the culture media was acidified to mimic the acidic microenvironment of solid tumors, rhASM-mediated cell death was markedly enhanced when combined with irradiation. Microscopic analysis suggested that this was associated with an increase in autophagy. rhASM has been produced for the treatment of the lysosomal storage disorder, type B Niemann-Pick disease, and is currently being evaluated in a phase-1 clinical trial. Based on the data presented in this article, we propose that further investigation of this protein and gene as antineoplastic agents also is warranted.	[Smith, Eric L.; Schuchman, Edward H.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA		Schuchman, EH (corresponding author), Mt Sinai Sch Med, Dept Genet & Genom Sci, 1425 Madison Ave,Room 14-20A, New York, NY 10029 USA.	edward.schuchman@mssm.edu			NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [2 R01 HD28607, 5 T32 GM007280]; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENTUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01HD028607] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [T32GM007280] Funding Source: NIH RePORTER	We thank Xingxuan He and Chien-Ling Huang for help with the ceramide quantification assay, and Yu Zhou for help with bioluminescent imaging. We also thank John Martignetti and Goutham Narla for careful reading of the manuscript. This research was supported by a grant from the NIH (2 R01 HD28607) to E. H. S. E. L. S. was supported, in part, by a Medical Scientist Training Program Grant from the NIH (5 T32 GM007280).	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J	Mathieu, V; Le Mercier, M; De Neve, N; Sauvage, S; Gras, T; Roland, I; Lefranc, F; Kiss, R				Mathieu, Veronique; Le Mercier, Marie; De Neve, Nancy; Sauvage, Sebastien; Gras, Thierry; Roland, Isabelle; Lefranc, Florence; Kiss, Robert			Galectin-1 knockdown increases sensitivity to temozolomide in a B16F10 mouse metastatic melanoma model	JOURNAL OF INVESTIGATIVE DERMATOLOGY			English	Article							LYSOSOMAL MEMBRANE PERMEABILIZATION; MALIGNANT GLIOMA-CELLS; INDUCED CYTOTOXICITY; TUMOR ANGIOGENESIS; FUTURE-ISSUES; CANCER-CELLS; COLON-CANCER; IN-VITRO; APOPTOSIS; RESISTANCE	The rapid increase in the incidence of malignant melanomas has not been associated with improved therapeutic options over the years. Indeed melanomas have proven resistant to apoptosis ( type I programmed cell death ( PCD)) and consequently to most chemotherapy and immunotherapy. It is believed that this resistance can be partly overcome by proautophagic drugs inducing type II ( autophagy) PCD. Change at the genomic, transcriptional, and post- translational level of G- proteins and protein kinases, including Ras, plays an important role in the ability of melanomas to resist apoptosis. Ras transformation itself requires membrane anchorage and the overexpression of galectin- 1 increases membrane- associated Ras. In this study, it has been found that decreasing galectin- 1 expression in B16F10 mouse melanoma cells in vitro by means of an antigalectin-1 small interfering RNA approach does not modify their sensitivity to type I and type II PCD. However, it does induce heat shock protein 70- mediated lysosomal membrane permeabilization, a process associated with cathepsin B release into the cytosol, which in turn is believed to sensitize the cells to the proautophagic effects of temozolomide when grafted in vivo. Furthermore, temozolomide when compared to the proapoptotic drug cisplatin, significantly increased the survival times of mice in the B16F10 melanoma model.	Free Univ Brussels, Inst Pharm, Toxicol Lab, B-1050 Brussels, Belgium; Unibioscreen SA, Brussels, Belgium; Univ Libre Bruxelles, Erasmus Univ Hosp, Dept Neurosurg, Brussels, Belgium		Kiss, R (corresponding author), Free Univ Brussels, Inst Pharm, Toxicol Lab, Campus Plaine,CP205-1,Blvd Triomphe, B-1050 Brussels, Belgium.	rkiss@ulb.ac.be					Atallah Ehab, 2005, Curr Treat Options Oncol, V6, P185; Branle F, 2002, CANCER-AM CANCER SOC, V95, P641, DOI 10.1002/cncr.10710; Camby I, 2002, J NEUROPATH EXP NEUR, V61, P585, DOI 10.1093/jnen/61.7.585; Camby I, 2006, GLYCOBIOLOGY, V16, p137R, DOI 10.1093/glycob/cwl025; Cheng Z, 2005, CANCER RES, V65, P4979, DOI 10.1158/0008-5472.CAN-03-3093; Danguy A, 2002, BBA-GEN SUBJECTS, V1572, P285, DOI 10.1016/S0304-4165(02)00315-X; Darro F, 2005, INT J ONCOL, V27, P607; Debeir O, 2005, IEEE T MED IMAGING, V24, P697, DOI 10.1109/TMI.2005.846851; Decaestecker C, 2007, MED RES REV, V27, P149, DOI 10.1002/med.20078; DELBELLO B, ONCOGENE; Douma S, 2004, NATURE, V430, P1034, DOI 10.1038/nature02765; Eskelinen Eeva-Liisa, 2006, Molecular Aspects of Medicine, V27, P495, DOI 10.1016/j.mam.2006.08.005; Fehrenbacher N, 2005, CANCER RES, V65, P2993, DOI 10.1158/0008-5472.CAN-05-0476; Glinsky GV, 1996, CANCER LETT, V101, P43, DOI 10.1016/0304-3835(96)04112-2; He SJ, 2005, MOL CANCER THER, V4, P996, DOI 10.1158/1535-7163.MCT-04-0252; Hersey P, 2006, CURR OPIN ONCOL, V18, P189, DOI 10.1097/01.cco.0000208794.24228.9f; Ingrassia L, 2006, CURR MED CHEM, V13, P3513, DOI 10.2174/092986706779026219; Ivanov VN, 2003, ONCOGENE, V22, P3152, DOI 10.1038/sj.onc.1206456; Kageshita T, 2002, INT J CANCER, V99, P809, DOI 10.1002/ijc.10436; Kanzawa T, 2004, CELL DEATH DIFFER, V11, P448, DOI 10.1038/sj.cdd.4401359; Kondo Y, 2005, NAT REV CANCER, V5, P726, DOI 10.1038/nrc1692; Kroemer G, 2005, NAT REV CANCER, V5, P886, DOI 10.1038/nrc1738; Kuwada SK, 2005, J BIOL CHEM, V280, P19027, DOI 10.1074/jbc.M410540200; Lefranc F, 2005, J CLIN ONCOL, V23, P2411, DOI 10.1200/JCO.2005.03.089; Lefranc F, 2004, CLIN CANCER RES, V10, P8250, DOI 10.1158/1078-0432.CCR-04-0343; Lefranc F, 2006, EXPERT REV ANTICANC, V6, P719, DOI 10.1586/14737140.6.5.719; Liu FT, 2005, NAT REV CANCER, V5, P29, DOI 10.1038/nrc1527; Maecker HL, 2000, CANCER RES, V60, P4638; Mathieu A, 2005, MODERN PATHOL, V18, P1264, DOI 10.1038/modpathol.3800416; Mathieu V, 2005, NEOPLASIA, V7, P930, DOI 10.1593/neo.05379; Mijatovic T, 2006, NEOPLASIA, V8, P402, DOI 10.1593/neo.05850; Miller AJ, 2006, NEW ENGL J MED, V355, P51, DOI 10.1056/NEJMra052166; Na KY, 2003, J AM SOC NEPHROL, V14, P283, DOI 10.1097/01.ASN.0000045050.19544.B2; Nylandsted J, 2004, J EXP MED, V200, P425, DOI 10.1084/jem.20040531; Ozawa K, 2001, CANCER RES, V61, P4206; Pattingre S, 2006, CANCER RES, V66, P2885, DOI 10.1158/0008-5472.CAN-05-4412; Paz A, 2001, ONCOGENE, V20, P7486, DOI 10.1038/sj.onc.1204950; PERILLO NL, 1995, NATURE, V378, P736, DOI 10.1038/378736a0; Roos WP, 2007, ONCOGENE, V26, P186, DOI 10.1038/sj.onc.1209785; Rubinstein N, 2004, CANCER CELL, V5, P241, DOI 10.1016/S1535-6108(04)00024-8; Schmitt E, 2006, CANCER RES, V66, P4191, DOI 10.1158/0008-5472.CAN-05-3778; Schmitt E, 2003, CANCER RES, V63, P8233; Smalley KSM, 2006, MOL CANCER THER, V5, P1136, DOI 10.1158/1535-7163.MCT-06-0084; Stillman BN, 2006, J IMMUNOL, V176, P778, DOI 10.4049/jimmunol.176.2.778; Stillman BN, 2005, BRAIN PATHOL, V15, P124; Tas F, 2005, MELANOMA RES, V15, P543, DOI 10.1097/00008390-200512000-00010; Thijssen VLJL, 2006, P NATL ACAD SCI USA, V103, P15975, DOI 10.1073/pnas.0603883103; Tinari N, 2001, INT J CANCER, V91, P167, DOI 10.1002/1097-0215(200002)9999:9999<::AID-IJC1022>3.3.CO;2-Q; Toker A, 2006, CANCER RES, V66, P3963, DOI 10.1158/0008-5472.CAN-06-0743; Walzel H, 2002, CELL SIGNAL, V14, P861, DOI 10.1016/S0898-6568(02)00035-9; Zubieta MR, 2006, AM J PATHOL, V168, P1666, DOI 10.2353/ajpath.2006.050971	51	80	82	1	5	ELSEVIER SCIENCE INC	NEW YORK	360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA	0022-202X	1523-1747		J INVEST DERMATOL	J. Invest. Dermatol.	OCT	2007	127	10					2399	2410		10.1038/sj.jid.5700869			12	Dermatology	Science Citation Index Expanded (SCI-EXPANDED)	Dermatology	217FF	WOS:000249933100018	17495956	Bronze			2022-04-25	
J	Divya, D; Nagarajaprakash, R; Vidhyapriya, P; Sakthivel, N; Manimaran, B				Divya, Dhanaraj; Nagarajaprakash, Ramamurthy; Vidhyapriya, Pitchavel; Sakthivel, Natarajan; Manimaran, Bala			Single-Pot Self-Assembly of Heteroleptic Mn(I)-Based Aminoquinonato-Bridged Ester/Amide-Functionalized Dinuclear Metallastirrups: Potential Anticancer and Visible-Light-Triggered CORMs	ACS OMEGA			English	Article							CO-RELEASING MOLECULES; MANGANESE(I) TRICARBONYL COMPLEX; CARBON-MONOXIDE RELEASE; STRUCTURAL-CHARACTERIZATION; METAL COORDINATION; EXCITED-STATE; RECTANGLES; RHENIUM(I); LIGAND; PHOTOCORMS	Multicomponent self-assembly of Mn-2(CO)(10), a bis-chelating aminoquinonato (ON boolean AND ON) bridge (L), and an ester/amide-functionalized flexible neutral ditopic linker (L') has resulted into the formation of M2LL'-type manganese(I)-based dinuclear metallastirrups of general formula [{(CO)(3)Mn(mu-eta(4)-L) Mn(CO)(3)}(mu-L')] (1-10). Compounds 1-10 were accomplished via orthogonal bonding of the aminoquinone ligand (2,5-bis(n-butylamino)-1,4-benzoquinone/2,5-bis(phenethylamino)-1,4-benzoquinone) and ditopic pyridyl ligand to manganese carbonyl. The resultant metal-lastirrups were characterized using elemental analyses and IR, UV-vis, H-1 NMR, and electrospray ionization-mass spectroscopic techniques. The molecular structure of 6 was confirmed by single-crystal X-ray diffraction methods. Furthermore, molecular recognition capabilities of 1, 5, 7, and 9 were evaluated with aromatic compounds containing hydroxy/amine functionalities. Anticancer activities of compounds 1-3, 5-7, 9, and 10 were investigated against three cancer cell lines, that is, lung (A549), colon (HCT-15), and cervical (HeLa) as well as on normal cells (HEK 293). Compound 9 showed a broad-spectrum inhibition toward these cancer cells upon exposure to visible light. The myoglobin assay was performed using UV-vis absorption spectroscopy to investigate the visible-light-triggered CO release from 5 and 9 that could be related to their ability to effectively inhibit cancer cells. In addition, morphological studies confirmed the induction of autophagy due to the treatment of cancer cells using compound 9.	[Divya, Dhanaraj; Manimaran, Bala] Pondicherry Univ, Dept Chem, Pondicherry 605014, India; [Vidhyapriya, Pitchavel; Sakthivel, Natarajan] Pondicherry Univ, Dept Biotechnol, Pondicherry 605014, India; [Nagarajaprakash, Ramamurthy] Lovely Profess Univ, Div Res & Dev, Chem Sci Res Grp, Phagwara 144411, Punjab, India		Manimaran, B (corresponding author), Pondicherry Univ, Dept Chem, Pondicherry 605014, India.; Sakthivel, N (corresponding author), Pondicherry Univ, Dept Biotechnol, Pondicherry 605014, India.	manimaran.che@pondiuni.edu.in		Manimaran, Bala./0000-0002-2974-4949; D, Divya/0000-0002-8127-2678	Department of Science and Technology, Government of IndiaDepartment of Science & Technology (India); Council of Scientific and Industrial Research, Government of IndiaCouncil of Scientific & Industrial Research (CSIR) - India; CSIR, Government of IndiaCouncil of Scientific & Industrial Research (CSIR) - India; DBTDepartment of Biotechnology (DBT) India; DST-FIST ProgramDepartment of Science & Technology (India); UGC-SAPUniversity Grants Commission, India	We thank the Department of Science and Technology, Government of India, and Council of Scientific and Industrial Research, Government of India, for financial support. D. D. gratefully acknowledges CSIR, Government of India, for the award of Senior Research Fellowship and financial assistance. P. V. gratefully acknowledges DBT for the award of Senior Research Fellowship. We are grateful to the Central Instrumentation Facility, Pondicherry University, for providing spectral data. We are also thankful to the DST-FIST Program sponsored ESI-MS facility at the Department of Chemistry, Pondicherry University, and UGC-SAP-funded cell culture facility at the Department of Biotechnology, Pondicherry University. The authors thank the SAIF, IIT-Madras, Chennai, for providing single-crystal X-ray diffraction data.	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Ustun E, 2017, TRANSIT METAL CHEM, V42, P331, DOI 10.1007/s11243-017-0136-x; Wahler K, 2014, EUR J INORG CHEM, V2014, P807; Woessner SM, 1998, INORG CHEM, V37, P5406, DOI 10.1021/ic9805168; Wu JY, 2008, ORGANOMETALLICS, V27, P2141, DOI 10.1021/om700873x; Yang QZ, 2005, CHEM-EUR J, V11, P7237, DOI 10.1002/chem.200500704; Yang SH, 2016, DALTON T, V45, P3727, DOI 10.1039/c5dt04479k; Zeng Q, 2014, ORGANOMETALLICS, V33, P5002, DOI 10.1021/om500389y; Zobi F, 2012, DALTON T, V41, P370, DOI 10.1039/c1dt10649j; Zobi F, 2011, DALTON T, V40, P4994, DOI 10.1039/c1dt10110b; Zobi F, 2010, INORG CHEM, V49, P7313, DOI 10.1021/ic100458j; Zobi F, 2009, INORG CHEM, V48, P8965, DOI 10.1021/ic901031x	99	7	7	2	10	AMER CHEMICAL SOC	WASHINGTON	1155 16TH ST, NW, WASHINGTON, DC 20036 USA	2470-1343			ACS OMEGA	ACS Omega	JUL	2019	4	7					12790	12802		10.1021/acsomega.9b01438			13	Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	IS5FB	WOS:000482176800170	31460403	Green Published, gold			2022-04-25	
J	Zhang, X; Huang, QB; Wang, XH; Xu, YY; Xu, R; Han, MZ; Huang, B; Chen, AJ; Qiu, C; Sun, T; Wang, F; Li, XG; Wang, J; Zhao, P; Wang, XY				Zhang, Xin; Huang, Qibing; Wang, Xuehai; Xu, Yangyang; Xu, Ran; Han, Mingzhi; Huang, Bin; Chen, Anjing; Qiu, Chen; Sun, Tao; Wang, Feng; Li, Xingang; Wang, Jian; Zhao, Peng; Wang, Xinyu			Bufalin enhances radiosensitivity of glioblastoma by suppressing mitochondrial function and DNA damage repair	BIOMEDICINE & PHARMACOTHERAPY			English	Article						Bufalin; Glioblastoma; Mitochondria; RAD51; Radiosensitivity	LUNG-CANCER CELLS; PHASE-II; RADIATION; AUTOPHAGY; INHIBITION; RAD51; RADIOTHERAPY; ACTIVATION; INDUCTION; APOPTOSIS	Bufalin, a cardiotonic steroid found in the venom of the Chinese toad Bufo gargarizan, has been shown to inhibit the growth of human cancers, such as colon and bladder. Here, we investigated the response of U251 and U87MG glioblastoma (GBM) cell lines to bufalin in vitro and found that bufalin impaired several biological processes. First, in both U251 and U87 MG, bufalin reduced cell proliferation and induced a G2/M cell cycle arrest (similar to 10% vs similar to 30%, untreated vs treated cells, respectively). Second, bufalin disrupted the mitochondrial membrane potential, leading to reduced oxygen consumption and ATP production. Third, homologous recombination (HR) efficiency was reduced by similar to 40% in both cell lines in the presence of bufalin. At the molecular level, bufalin led to decreased RAD51 protein, a central player in HR, and increased gamma-H2AX, a marker for the presence of DNA double strand breaks. Finally, bufalin was additive with radiation in the treatment of GBM cells in vitro. Cell death increased significantly under combination treatment compared to radiation treatment alone. Our findings indicated that bufalin led to reduced mitochondrial and DNA repair function and therefore, might be a promising therapeutic drug to increase the sensitivity of GBM cells to radiotherapy. (C) 2017 Published by Elsevier Masson SAS.	[Zhang, Xin; Xu, Yangyang; Xu, Ran; Han, Mingzhi; Huang, Bin; Chen, Anjing; Li, Xingang; Wang, Jian; Zhao, Peng; Wang, Xinyu] Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan 250012, Shandong, Peoples R China; [Zhang, Xin; Xu, Yangyang; Xu, Ran; Han, Mingzhi; Huang, Bin; Chen, Anjing; Li, Xingang; Wang, Jian; Zhao, Peng; Wang, Xinyu] Shandong Univ, Brain Sci Res Inst, Jinan 250012, Shandong, Peoples R China; [Huang, Qibing] Shandong Univ, Qilu Hosp, Dept Emergency Surg, Jinan 250012, Shandong, Peoples R China; [Wang, Xuehai] Weihai Municipal Hosp, Dept Otolaryngol, Weihai 264200, Shandong, Peoples R China; [Qiu, Chen] Shandong Univ, Qilu Hosp, Dept Radiat Oncol, Jinan 250012, Shandong, Peoples R China; [Sun, Tao; Wang, Feng] Ningxia Med Univ, Incubat Base Natl Key Lab, Ningxia Key Lab Craniocerebral Dis, Yinchuan 750004, Peoples R China; [Wang, Jian] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway		Zhao, P; Wang, XY (corresponding author), Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan 250012, Shandong, Peoples R China.; Zhao, P; Wang, XY (corresponding author), Shandong Univ, Brain Sci Res Inst, Jinan 250012, Shandong, Peoples R China.	zhaopengqilu@163.com; sjwwxy@126.com	Huang, Bin/AAT-4514-2021	Han, Mingzhi/0000-0001-8357-5974	Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572487, 81402060]; Special Foundation for Taishan Scholars [tshw201502056]; Department of Science & Technology of Shandong Province [2015ZDXX0801A01, 2014kjhm0101]; Shandong Provincial Outstanding Medical Academic Professional Program; Fundamental Research Funds of Shandong University [2016JC019]; Stiftelsen Kristian Gerhard Jebsen; Norwegian Cancer SocietyNorwegian Cancer Society; Norwegian Research CouncilResearch Council of NorwayEuropean Commission; Norwegian Centre for International Cooperation in Education (SIU) [UTF-2014/10047]; Helse-Vest; Haukeland Hospital	This work was supported by the Natural Science Foundation of China Grant (81572487 and 81402060), the Special Foundation for Taishan Scholars (No. tshw201502056), the Department of Science & Technology of Shandong Province (2015ZDXX0801A01 and 2014kjhm0101), the Shandong Provincial Outstanding Medical Academic Professional Program, Fundamental Research Funds of Shandong University (2016JC019), Stiftelsen Kristian Gerhard Jebsen, Helse-Vest, Haukeland Hospital, the Norwegian Cancer Society, the Norwegian Research Council and the Norwegian Centre for International Cooperation in Education (SIU) (UTF-2014/10047).	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Pharmacother.	OCT	2017	94						627	635		10.1016/j.biopha.2017.07.136			9	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	FP6MU	WOS:000417741000069	28787697				2022-04-25	
J	Masuelli, L; Benvenuto, M; Izzi, V; Zago, E; Mattera, R; Cerbelli, B; Potenza, V; Fazi, S; Ciuffa, S; Tresoldi, I; Lucarelli, E; Modesti, A; Bei, R				Masuelli, Laura; Benvenuto, Monica; Izzi, Valerio; Zago, Erika; Mattera, Rosanna; Cerbelli, Bruna; Potenza, Vito; Fazi, Sara; Ciuffa, Sara; Tresoldi, Ilaria; Lucarelli, Enrico; Modesti, Andrea; Bei, Roberto			In vivo and in vitro inhibition of osteosarcoma growth by the pan Bcl-2 inhibitor AT-101	INVESTIGATIONAL NEW DRUGS			English	Article						AT-101; Bcl-2 inhibitor; Osteosarcoma; Apoptosis; Polyphenol	HIGH-GRADE OSTEOSARCOMA; CARCINOMA CELL-LINES; PHASE-II TRIAL; INDUCED APOPTOSIS; BREAST-CANCER; BECLIN 1; AUTOPHAGY; GOSSYPOL; CURCUMIN; CISPLATIN	Osteosarcoma (OS) is the most common primary malignant bone tumor and mainly affects children and adolescents. The OS five-year survival rate remains very low. Thus, novel therapeutic protocols for the treatment of OS are needed. Several approaches targeting deregulated signaling pathways have been proposed. The antitumoral effects of polyphenols, which are naturally occurring compounds with potent antioxidant and anti-inflammatory activity, have been investigated in different tumors. Gossypol, which is a natural polyphenolic aldehyde isolated from the seeds of the cotton plant, has been shown to exert antitumoral activity in leukemia and lymphoma and in breast, head and neck, colon and prostate cancers. Therefore, in this study, we evaluated the effect of AT-101, which is the (-) enantiomer and more active form of gossypol, on the growth of human and murine OS cells in vitro and in vivo. Several clinical trials employing AT-101 have been performed, and some clinical trials are ongoing. Our results showed for the first time that AT-101 significantly inhibits OS cell growth in a dose- and time-dependent manner, inducing apoptosis and necrosis and partially activating autophagy. Our results demonstrated that AT-101 inhibits prosurvival signaling pathways depending on Akt, p38 MAPK and JNK. In addition, treatment with AT-101 increases the survival of OS-bearing mice. Overall, these results suggest that AT-101 is a candidate chemo-supportive molecule for the development of novel chemotherapeutic protocols for the treatment of OS.	[Masuelli, Laura; Zago, Erika; Fazi, Sara] Univ Rome Sapienza, Dept Expt Med, I-00164 Rome, Italy; [Benvenuto, Monica; Mattera, Rosanna; Potenza, Vito; Ciuffa, Sara; Tresoldi, Ilaria; Modesti, Andrea; Bei, Roberto] Univ Roma Tor Vergata, Dept Clin Sci & Translat Med, I-00133 Rome, Italy; [Izzi, Valerio] Univ Oulu, Oulu Ctr Cell Matrix Res, FIN-90014 Oulu, Finland; [Cerbelli, Bruna] Polo Pontino Sapienza Univ, Dept Medicosurg Sci & Biotechnol, I-04100 Latina, Italy; [Lucarelli, Enrico] IRCCS, Ist Ortoped Rizzoli, Osteoarticolar Regenerat Lab, I-40136 Bologna, Italy		Masuelli, L (corresponding author), Univ Rome Sapienza, Dept Expt Med, I-00164 Rome, Italy.	laura.masuelli@uniromal.it	Bei, Roberto/W-8023-2019; Enrico, Lucarelli/G-3588-2015; Masuelli, Laura/AGW-4259-2022; Benvenuto, Monica/K-2685-2016	Enrico, Lucarelli/0000-0002-6681-6374; Benvenuto, Monica/0000-0002-2520-1306; MASUELLI, Laura/0000-0001-8174-8034; Izzi, Valerio/0000-0002-9960-4917			Abdullah LN, 2013, CLIN TRANSL MED, V2, DOI 10.1186/2001-1326-2-3; 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New Drugs	JUN	2020	38	3					675	689		10.1007/s10637-019-00827-y			15	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	LK9XS	WOS:000531213000011	31264066				2022-04-25	
J	Nguyen, CB; Kotturi, H; Waris, G; Mohammed, A; Chandrakesan, P; May, R; Sureban, S; Weygant, N; Qu, DF; Rao, CV; Dhanasekaran, DN; Bronze, MS; Houchen, CW; Ali, N				Nguyen, Charles B.; Kotturi, Hari; Waris, Gulam; Mohammed, Altaf; Chandrakesan, Parthasarathy; May, Randal; Sureban, Sripathi; Weygant, Nathaniel; Qu, Dongfeng; Rao, Chinthalapally V.; Dhanasekaran, Danny N.; Bronze, Michael S.; Houchen, Courtney W.; Ali, Naushad			(Z)-3,5,4'-Trimethoxystilbene Limits Hepatitis C and Cancer Pathophysiology by Blocking Microtubule Dynamics and Cell-Cycle Progression	CANCER RESEARCH			English	Article							DOUBLECORTIN-LIKE KINASE; RESVERATROL ANALOG (Z)-3,5,4'-TRIMETHOXYSTILBENE; ADVANCED HEPATOCELLULAR-CARCINOMA; GENOTYPE 1 INFECTION; MESENCHYMAL TRANSITION; STEM-CELLS; TUMOR; GROWTH; INHIBITION; MECHANISM	Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Chronic hepatitis C virus (HCV) infection causes induction of several tumors/cancer stem cell (CSC) markers and is known to be a major risk factor for development of HCC. Therefore, drugs that simultaneously target viral replication and CSC properties are needed for a risk-free treatment of advanced stage liver diseases, including HCC. Here, we demonstrated that (Z)-3,5,4'-trimethoxystilbene (Z-TMS) exhibits potent antitumor and anti-HCV activities without exhibiting cytotoxicity to human hepatocytes in vitro or in mice livers. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl4) extensively induced expression of DCLK1 (a CSC marker) in the livers of C57BL/6 mice following hepatic injury. Z-TMS exhibited hepatoprotective effects against DEN/CCl4-induced injury by reducing DCLK1 expression and improving histologic outcomes. The drug caused bundling of DCLK1 with microtubules and blocked cell-cycle progression at G(2)-M phase in hepatoma cells via downregulation of CDK1, induction of p21(cip1/waf1) expression, and inhibition of Akt (Ser(473)) phosphorylation. Z-TMS also inhibited proliferation of erlotinib-resistant lung adenocarcinoma cells (H1975) bearing the T790M EGFR mutation, most likely by promoting autophagy and nuclear fragmentation. In conclusion, Z-TMS appears to be a unique therapeutic agent targeting HCV and concurrently eliminating cells with neoplastic potential during chronic liver diseases, including HCC. It may also be a valuable drug for targeting drug-resistant carcinomas and cancers of the lungs, pancreas, colon, and intestine, in which DCLK1 is involved in tumorigenesis. (C) 2016 AACR.	[Nguyen, Charles B.; Mohammed, Altaf; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Oklahoma City, OK 73190 USA; [Kotturi, Hari] Univ Cent Oklahoma, Dept Biol, Edmond, OK USA; [Waris, Gulam] Rosalind Franklin Univ Med & Sci, Dept Microbiol & Immunol, N Chicago, IL USA; [Mohammed, Altaf; Chandrakesan, Parthasarathy; Sureban, Sripathi; Rao, Chinthalapally V.; Dhanasekaran, Danny N.; Houchen, Courtney W.; Ali, Naushad] Univ Oklahoma, Hlth Sci Ctr, Peggy & Charles Stephenson Canc Ctr, Oklahoma City, OK 73190 USA; [Mohammed, Altaf; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, Hematol Oncol Sect, Oklahoma City, OK USA; [Chandrakesan, Parthasarathy; May, Randal; Sureban, Sripathi; Weygant, Nathaniel; Qu, Dongfeng; Bronze, Michael S.; Houchen, Courtney W.; Ali, Naushad] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Sect Digest Dis & Nutr, Oklahoma City, OK 73190 USA; [Chandrakesan, Parthasarathy; May, Randal; Sureban, Sripathi; Qu, Dongfeng; Houchen, Courtney W.; Ali, Naushad] Dept Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA; [Dhanasekaran, Danny N.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA		Houchen, CW (corresponding author), Univ Oklahoma, Hlth Sci Ctr, Peggy & Charles Stephenson Canc Ctr, Oklahoma City, OK 73190 USA.; Houchen, CW (corresponding author), Univ Oklahoma, Hlth Sci Ctr, Dept Med, Sect Digest Dis & Nutr, Oklahoma City, OK 73190 USA.; Houchen, CW (corresponding author), Dept Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA.; Ali, N (corresponding author), Univ Oklahoma, Hlth Sci Ctr, 975 NE 10th St BRC1266, Oklahoma City, OK 73104 USA.	Courtney-houchen@ouhsc.edu; naushad-ali@ouhsc.edu	Sureban, Sripathi/Q-8232-2019; Chandrakesan, Parthasarathy/AAB-9136-2020	Weygant, Nathaniel/0000-0001-7861-6532; Sureban, Sripathi/0000-0001-5476-9593	NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P20GM103639] Funding Source: NIH RePORTER; NIGMS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P20 GM103639] Funding Source: Medline		Afdhal N, 2014, NEW ENGL J MED, V370, P1889, DOI 10.1056/NEJMoa1402454; Afdhal N, 2014, NEW ENGL J MED, V370, P1483, DOI 10.1056/NEJMoa1316366; Ali N, 2015, ONCOTARGET, V6, P20327, DOI 10.18632/oncotarget.3972; Ali N, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0080304; Ali N, 2011, J VIROL, V85, P12292, DOI 10.1128/JVI.05920-11; Bartosch B, 2009, J HEPATOL, V51, P810, DOI 10.1016/j.jhep.2009.05.008; Baur JA, 2006, NATURE, V444, P337, DOI 10.1038/nature05354; Bertino G, 2014, BIOMED RES INT, V2014, DOI 10.1155/2014/203693; Borriello A, 2014, CANCER TREAT RES, V159, P167, DOI 10.1007/978-3-642-38007-5_10; Caviglia Jorge Matias, 2015, Methods Mol Biol, V1267, P165, DOI 10.1007/978-1-4939-2297-0_8; Chabert P, 2006, BIOFACTORS, V27, P37, DOI 10.1002/biof.5520270104; Chen KF, 2011, J PHARMACOL EXP THER, V337, P155, DOI 10.1124/jpet.110.175786; Chow AKM, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0078675; Dapito DH, 2012, CANCER CELL, V21, P504, DOI 10.1016/j.ccr.2012.02.007; Diao JY, 2012, J VIROL, V86, P10935, DOI 10.1128/JVI.00750-12; El-Serag HB, 2012, GASTROENTEROLOGY, V142, P1264, DOI 10.1053/j.gastro.2011.12.061; Gauthier A, 2013, HEPATOL RES, V43, P147, DOI 10.1111/j.1872-034X.2012.01113.x; Guo JT, 2001, J VIROL, V75, P8516, DOI 10.1128/JVI.75.18.8516-8523.2001; Iqbal J, 2013, J BIOL CHEM, V288, P36994, DOI 10.1074/jbc.M113.492314; Jung Y, 2015, ARCH PHARM RES, V38, P414, DOI 10.1007/s12272-015-0570-2; Kandel ES, 2002, MOL CELL BIOL, V22, P7831, DOI 10.1128/MCB.22.22.7831-7841.2002; Kao CL, 2009, INT J RADIAT ONCOL, V74, P219, DOI 10.1016/j.ijrobp.2008.12.035; Kasai T, 2014, J STEM CELLS REGEN, V10, pP2; Kavallaris M, 2010, NAT REV CANCER, V10, P194, DOI 10.1038/nrc2803; Kim MH, 2003, NAT STRUCT BIOL, V10, P324, DOI 10.1038/nsb918; Lai CK, 2008, J VIROL, V82, P8838, DOI 10.1128/JVI.00398-08; Li JP, 2014, MOL MED REP, V10, P1717, DOI 10.3892/mmr.2014.2417; Lin HS, 2010, J PHARMACEUT BIOMED, V53, P693, DOI 10.1016/j.jpba.2010.03.028; Lin PT, 2000, J NEUROSCI, V20, P9152; Liu B, 2014, MOL MED REP, V10, P1697, DOI 10.3892/mmr.2014.2406; Llovet JM, 2008, NEW ENGL J MED, V359, P378, DOI 10.1056/NEJMoa0708857; Lupberger J, 2011, NAT MED, V17, P589, DOI 10.1038/nm.2341; MACRAE WD, 1984, J ETHNOPHARMACOL, V12, P75, DOI 10.1016/0378-8741(84)90088-6; Majumdar A, 2012, NAT REV GASTRO HEPAT, V9, P530, DOI 10.1038/nrgastro.2012.114; Nelson HB, 2006, J VIROL, V80, P1181, DOI 10.1128/JVI.80.3.1181-1190.2006; Novelle MG, 2015, AGEING RES REV, V21, P1, DOI 10.1016/j.arr.2015.01.002; Padhya KT, 2013, CURR OPIN GASTROEN, V29, P285, DOI 10.1097/MOG.0b013e32835ff1cf; Schneider Y, 2003, INT J CANCER, V107, P189, DOI 10.1002/ijc.11344; Singh CK, 2013, ANN NY ACAD SCI, V1290, P113, DOI 10.1111/nyas.12160; Souza GR, 2010, NAT NANOTECHNOL, V5, P291, DOI 10.1038/nnano.2010.23; Sureban SM, 2015, ONCOTARGET, V6, P37200, DOI 10.18632/oncotarget.5808; Tresguerres IF, 2014, REJUV RES, V17, P439, DOI 10.1089/rej.2014.1551; Uehara T, 2013, TOXICOL SCI, V132, P53, DOI 10.1093/toxsci/kfs342; Weygant N, 2014, MOL CANCER, V13, DOI 10.1186/1476-4598-13-103; Yamashita T, 2013, J CLIN INVEST, V123, P1911, DOI 10.1172/JCI66024; Yang HL, 2010, J BIOL CHEM, V285, P32242, DOI 10.1074/jbc.M110.160820; Yang JD, 2010, NAT REV GASTRO HEPAT, V7, P448, DOI 10.1038/nrgastro.2010.100; Zhou BBS, 2009, NAT REV DRUG DISCOV, V8, P806, DOI 10.1038/nrd2137	48	15	15	1	6	AMER ASSOC CANCER RESEARCH	PHILADELPHIA	615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA	0008-5472	1538-7445		CANCER RES	Cancer Res.	AUG 15	2016	76	16					4887	4896		10.1158/0008-5472.CAN-15-2722			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DU6BI	WOS:000382297700029	27287718	Green Accepted, hybrid			2022-04-25	
J	Khan, MZI; Tam, SY; Law, HKW				Khan, Md Zahirul Islam; Tam, Shing Yau; Law, Helen Ka Wai			Autophagy-Modulating Long Non-coding RNAs (LncRNAs) and Their Molecular Events in Cancer	FRONTIERS IN GENETICS			English	Review						autophagy; long non-coding RNAs; cancer; therapy; biomarkers	PROMOTES CELL-PROLIFERATION; HEPATOCELLULAR-CARCINOMA; GASTRIC-CANCER; ACTIVATES AUTOPHAGY; COLORECTAL-CANCER; PANCREATIC-CANCER; TUMOR-SUPPRESSOR; PROSTATE-CANCER; CISPLATIN SENSITIVITY; GROWTH ARREST	Cancer is a global threat of health. Cancer incidence and death is also increasing continuously because of poor understanding of diseases. Although, traditional treatments (surgery, radiotherapy, and chemotherapy) are effective against primary tumors, death rate is increasing because of metastasis development where traditional treatments have failed. Autophagy is a conserved regulatory process of eliminating proteins and damaged organelles. Numerous research revealed that autophagy has dual sword mechanisms including cancer progressions and suppressions. In most of the cases, it maintains homeostasis of cancer microenvironment by providing nutritional supplement under starvation and hypoxic conditions. Over the past few decades, stunning research evidence disclosed significant roles of long non-coding RNAs (lncRNAs) in the regulation of autophagy. LncRNAs are RNA containing more than 200 nucleotides, which have no protein-coding ability but they are found to be expressed in most of the cancers. It is also proved that, autophagy-modulating lncRNAs have significant impacts on pro-survival or pro-death roles in cancers. In this review, we highlighted the recently identified autophagy-modulating lncRNAs, their signaling transduction in cancer and mechanism in cancer. This review will explore newly emerging knowledge of cancer genetics and it may provide novel targets for cancer therapy.	[Khan, Md Zahirul Islam; Tam, Shing Yau; Law, Helen Ka Wai] Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Hlth Technol & Informat, Hong Kong, Peoples R China		Law, HKW (corresponding author), Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Hlth Technol & Informat, Hong Kong, Peoples R China.	hthelen@polyu.edu.hk	Tam, Shing Yau/AAZ-1345-2020; Tam, Shing Yau/AAN-4109-2020; Khan, Zahirul Islam/AAV-4254-2020	Tam, Shing Yau/0000-0002-5899-1041; Islam Khan, Md Zahirul/0000-0001-7048-2613	Hong Kong Polytechnic UniversityHong Kong Polytechnic University	This work was supported by Departmental Start-up and Seed Funding for HL, and Departmental Postgraduate Funds for MK and ST, The Hong Kong Polytechnic University.	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Genet.	JAN 14	2019	9								750	10.3389/fgene.2018.00750			11	Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Genetics & Heredity	HH4DN	WOS:000455671000001	30693021	Green Published, gold			2022-04-25	
J	Buzzai, M; Jones, RG; Amaravadi, RK; Lum, JJ; DeBerardinis, RJ; Zhao, FP; Viollet, B; Thompson, CB				Buzzai, Monica; Jones, Russell G.; Amaravadi, Ravi K.; Lum, Julian J.; DeBerardinis, Ralph J.; Zhao, Fangping; Viollet, Benoit; Thompson, Craig B.			Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth	CANCER RESEARCH			English	Article							ACTIVATED PROTEIN-KINASE; CREB COACTIVATOR TORC2; AUTOPHAGY; APOPTOSIS; METABOLISM; MECHANISM; SURVIVAL; RESPIRATION; REGULATOR; PATHWAYS	The effect of the antidiabetic drug metformin on tumor growth was investigated using the paired isogenic colon cancer cell lines HCT116 p53(+/+) and HCT116 p53(-/-) . Treatment with metformin selectively suppressed the tumor growth of HCT116 p53(-/-) xenografts. Following treatment with metformin, we detected increased apoptosis in p53(-/-) tumor sections and an enhanced susceptibility of p53(-/-) cells to undergo apoptosis in vitro when subject to nutrient deprivation. Metformin is proposed to function in diabetes treatment as an indirect activator of AIMP-activated protein kinase (AMPK). Treatment with AICAR, another AMPK activator, also showed a selective ability to inhibit p53(-/-) tumor growth in vivo. In the presence of either of the two drugs, HCT116 P53(+/+) cells, but not HCT116 p53(-/-) cells, activated autophagy. A similar p53-dependent induction of autophagy was observed when nontransformed mouse embryo fibroblasts were treated. Treatment with either metformin or AICAR also led to enhanced fatty acid beta-oxidation in p53(+/+) MEFs but not in p53(-/-) MEFs. However, the magnitude of induction was significantly lower in metformin-treated cells, as metformin treatment also suppressed mitochondrial electron transport. Metformin-treated cells compensated for this suppression of oxidative phosphorylation by increasing their rate of glycolysis in a p53-dependent manner. Together, these data suggest that metformin treatment forces a metabolic conversion that p53(-/-) cells are unable to execute. Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin.	Univ Penn, Dept Canc Biol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA; Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA; Childrens Hosp Philadelphia, Div Child Dev Rehabil Med & Metab Dis, Philadelphia, PA 19104 USA; Univ Paris 05, Inst Cochin Genet Mol, CNRS, UMR 8104, Paris, France; INSERM, U567, Paris, France		Thompson, CB (corresponding author), Univ Penn, Dept Canc Biol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.	craig@mail.med.upenn.edu	Jones, Russell Graham/ABD-5261-2021; Viollet, Benoit/O-6927-2017; Viollet, Benoit/N-2397-2019; Jones, Russell/AAC-2861-2022	Jones, Russell Graham/0000-0003-2250-4675; Viollet, Benoit/0000-0002-0121-0224; Viollet, Benoit/0000-0002-0121-0224; Lum, Julian/0000-0002-5624-3541			Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; Bensaad K, 2006, CELL, V126, P107, DOI 10.1016/j.cell.2006.05.036; Bowker SL, 2006, DIABETES CARE, V29, P254, DOI 10.2337/diacare.29.02.06.dc05-1558; Buzzai M, 2005, ONCOGENE, V24, P4165, DOI 10.1038/sj.onc.1208622; Carling D, 2004, TRENDS BIOCHEM SCI, V29, P18, DOI 10.1016/j.tibs.2003.11.005; Crighton D, 2006, CELL, V126, P121, DOI 10.1016/j.cell.2006.05.034; DeBerardinis RJ, 2006, J BIOL CHEM, V281, P37372, DOI 10.1074/jbc.M608372200; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; El-Mir MY, 2000, J BIOL CHEM, V275, P223, DOI 10.1074/jbc.275.1.223; Evans JMM, 2005, BMJ-BRIT MED J, V330, P1304, DOI 10.1136/bmj.38415.708634.F7; Fang YM, 2001, SCIENCE, V294, P1942, DOI 10.1126/science.1066015; Feng ZH, 2005, P NATL ACAD SCI USA, V102, P8204, DOI 10.1073/pnas.0502857102; Fryer LGD, 2002, J BIOL CHEM, V277, P25226, DOI 10.1074/jbc.M202489200; Hawley SA, 2002, DIABETES, V51, P2420, DOI 10.2337/diabetes.51.8.2420; HUNDAL HS, 1992, ENDOCRINOLOGY, V131, P1165, DOI 10.1210/en.131.3.1165; James F, 1996, BIOCHEM J, V320, P283, DOI 10.1042/bj3200283; Jones RG, 2005, MOL CELL, V18, P283, DOI 10.1016/j.molcel.2005.03.027; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Kahn BB, 2005, CELL METAB, V1, P15, DOI 10.1016/j.cmet.2004.12.003; Koo SH, 2005, NATURE, V437, P1109, DOI 10.1038/nature03967; Laderoute KR, 2006, MOL CELL BIOL, V26, P5336, DOI 10.1128/MCB.00166-06; Lam E, 2004, NAT REV MOL CELL BIO, V5, P305, DOI 10.1038/nrm1358; LILLY K, 1992, BIOCHEM PHARMACOL, V43, P353, DOI 10.1016/0006-2952(92)90298-W; Lum JJ, 2005, CELL, V120, P237, DOI 10.1016/j.cell.2004.11.046; Matoba S, 2006, SCIENCE, V312, P1650, DOI 10.1126/science.1126863; Melendez A, 2003, SCIENCE, V301, P1387, DOI 10.1126/science.1087782; Mizushima N, 2004, INT J BIOCHEM CELL B, V36, P2491, DOI 10.1016/j.biocel.2004.02.005; SCHAFER G, 1983, DIABETES METAB, V9, P148; SCHUMACKER PT, 1993, AM J PHYSIOL, V265, P395; Screaton RA, 2004, CELL, V119, P61, DOI 10.1016/j.cell.2004.09.015; Shaw RJ, 2005, SCIENCE, V310, P1642, DOI 10.1126/science.1120781; STUMVOLL M, 1995, NEW ENGL J MED, V333, P550, DOI 10.1056/NEJM199508313330903; Warburg O., 1924, BIOCHEM Z, V152, P319; Witters LA, 2001, J CLIN INVEST, V108, P1105, DOI 10.1172/JCI14178; Zhou GC, 2001, J CLIN INVEST, V108, P1167, DOI 10.1172/JCI200113505	35	726	752	1	93	AMER ASSOC CANCER RESEARCH	PHILADELPHIA	615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA	0008-5472			CANCER RES	Cancer Res.	JUL 15	2007	67	14					6745	6752		10.1158/0008-5472.CAN-06-4447			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	194BN	WOS:000248319000028	17638885				2022-04-25	
J	Hao, M; Kong, CF; Jiang, CW; Hou, RZ; Zhao, XM; Li, J; Wang, YQ; Gao, YY; Zhang, H; Yang, B; Jiang, JL				Hao, Miao; Kong, Chenfei; Jiang, Chengwei; Hou, Ruizhi; Zhao, Xiaoming; Li, Jing; Wang, Yuqian; Gao, Yiyao; Zhang, Hao; Yang, Bai; Jiang, Jinlan			Polydopamine-coated Au-Ag nanoparticle-guided photothermal colorectal cancer therapy through multiple cell death pathways	ACTA BIOMATERIALIA			English	Article						Photothermal therapy; Nanoparticles; Lysosomal membrane permeability; Autophagy; Caspase-independent apoptosis	LYSOSOMAL MEMBRANE PERMEABILIZATION; HEAT-SHOCK PROTEINS; NANOMEDICINE; EXPRESSION; APOPTOSIS	Nanoparticles are emerging as a new therapeutic modality due to their high stability, precise targeting, and high biocompatibility. Branched Au-Ag nanoparticles with polydopamine coating (Au-Ag@PDA) have strong near-infrared absorbance and no cytotoxicity but high photothermal conversion efficiency. However, the photothermal activity of Au-Ag@PDA in vivo and in vitro has not been reported yet, and the mechanism underlying the effects of photothermal nanomaterials is not clear. Therefore, in this study, the colorectal cancer cell line HCT-116 and nude mice xenografts were used to observe the photothermal effects of Au-Ag@PDA in vivo and in vitro. The results suggest that Au-Ag@PDA NPs significantly inhibited cell proliferation and induced apoptosis in colorectal cancer cells. Moreover, Au-Ag@PDA NP mediated photothermal therapy inhibited the growth of tumors at doses of 50 and 100 mu g in vivo. The mechanisms through which Au-Ag@PDA NPs induced colorectal cancer cell death involved multiple pathways, including caspase-dependent and -independent apoptosis, mitochondrial damage, lysosomal membrane permeability, and autophagy. Thus, our findings suggest that Au-Ag@PDA NPs could be used as potential antitumor agents for photothermal ablation of colorectal cancer cells. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.	[Hao, Miao; Kong, Chenfei; Zhao, Xiaoming; Li, Jing; Wang, Yuqian; Gao, Yiyao; Jiang, Jinlan] Jilin Univ, China Japan Union Hosp, Sci Res Ctr, Changchun 130033, Jilin, Peoples R China; [Jiang, Chengwei] Jilin Univ, China Japan Union Hosp, Dept Pathol, Changchun 130033, Jilin, Peoples R China; [Hou, Ruizhi] Jilin Univ, China Japan Union Hosp, Gastrointestinal Colorectal & Anal Surg, Changchun 130033, Jilin, Peoples R China; [Zhang, Hao; Yang, Bai] Jilin Univ, Coll Chem, State Key Lab Supramol Struct & Mat, Changchun 130000, Jilin, Peoples R China		Jiang, JL (corresponding author), Jilin Univ, China Japan Union Hosp, Sci Res Ctr, Changchun 130033, Jilin, Peoples R China.	jiangjinlan@jlu.edu.cn	guo, min/AAI-2966-2021; Yang, Bai/F-6483-2012		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81401966]; Bethune plan of Jilin University [2015332]; Jilin Provincial Health Project [sczsy201614, sczsy201716]; Jilin Province Health Service Capacity Improvement Project [2017F014]	This work was supported by the National Natural Science Foundation of China (Grant No. 81401966), the research project of Bethune plan of Jilin University (No. 2015332), Jilin Provincial Health Project (No. sczsy201614 and sczsy201716) and Jilin Province Health Service Capacity Improvement Project (No. 2017F014). We would like to thank Peize Optoelectronics Technology Co., Ltd (Nanjing, China) for technical service, and Editage [www.editage.cn] for English language editing.	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JAN 1	2019	83						414	424		10.1016/j.actbio.2018.10.032			11	Engineering, Biomedical; Materials Science, Biomaterials	Science Citation Index Expanded (SCI-EXPANDED)	Engineering; Materials Science	HG6CP	WOS:000455068900036	30366131				2022-04-25	
J	Jalota-Badhwar, A; Bhatia, DR; Boreddy, S; Joshi, A; Venkatraman, M; Desai, N; Chaudhari, S; Bose, J; Kolla, LS; Deore, V; Yewalkar, N; Kumar, S; Sharma, R; Damre, A; More, A; Sharma, S; Agarwal, VR				Jalota-Badhwar, Archana; Bhatia, Dimple R.; Boreddy, Srinivas; Joshi, Asavari; Venkatraman, Magesh; Desai, Nikesh; Chaudhari, Sarika; Bose, Julie; Kolla, Lakshmi S.; Deore, Vijaykumar; Yewalkar, Nilambari; Kumar, Sanjay; Sharma, Rajiv; Damre, Anagha; More, Avinash; Sharma, Somesh; Agarwal, Veena R.			P7170: A Novel Molecule with Unique Profile of mTORC1/C2 and Activin Receptor-like Kinase 1 Inhibition Leading to Antitumor and Antiangiogenic Activity	MOLECULAR CANCER THERAPEUTICS			English	Article							MONOCLONAL-ANTIBODY; CELL-PROLIFERATION; TARGET; CANCER; RAPAMYCIN; PATHWAY; GROWTH; ACTIVATION; NVP-BEZ235; GENERATION	The mTOR pathway is often upregulated in cancer and thus intensively pursued as a target to design novel anticancer therapies. Approved and emerging drugs targeting the mTOR pathway have positively affected the clinical landscape. Recently, activin receptor-like kinase 1 (ALK1), belonging to the TGF beta receptor family, has been reported as an emerging target for antiangiogenic cancer therapy. Here, we describe a novel orally efficacious compound, P7170, that inhibits mTORC1/mTORC2/ALK1 activity with a potent cell growth inhibition. In cell-based assays, P7170 strongly inhibited (IC50 < 10 nmol/L) the phosphorylation of p70S6K (T389) and pAKT (S473). In many cancer cell lines, such as prostate, ovarian, colon, and renal, P7170 treatment resulted in marked cell growth inhibition. Furthermore, it induced G(1)-S cell-cycle arrest and autophagy. In vitro HUVEC tube formation, in vivo Matrigel plug, and rat aorta ring assays demonstrated that P7170 exhibited significant antiangiogenic activity. In addition, ALK1 knockdown studies in HUVEC confirmed that the antiangiogenic activity of P7170 was primarily due to ALK1 inhibition. Strong inhibition of ALK1 in addition to mTORC1/mTORC2 differentiates P7170 in its mechanism of action in comparison with existing inhibitors. In vivo mouse xenograft studies revealed P7170 to exhibit a significant dose-dependent tumor growth inhibition in a broad range of human tumor types when administered orally at 10 to 20 mg/kg doses. The distinctive pharmacological profile with favorable pharmacokinetic parameters and in vivo efficacy makes P7170 an attractive candidate for clinical development. It is currently being tested in phase I clinical studies. (C) 2015 AACR.	[Jalota-Badhwar, Archana; Bhatia, Dimple R.; Boreddy, Srinivas; Joshi, Asavari; Venkatraman, Magesh; Desai, Nikesh; Chaudhari, Sarika; Bose, Julie; Kolla, Lakshmi S.; Sharma, Somesh; Agarwal, Veena R.] Piramal Enterprises Ltd, Dept Pharmacol, Bombay 400063, Maharashtra, India; [Deore, Vijaykumar; Yewalkar, Nilambari; Kumar, Sanjay; Sharma, Rajiv] Piramal Enterprises Ltd, Dept Med Chem, Bombay 400063, Maharashtra, India; [Damre, Anagha; More, Avinash] Piramal Enterprises Ltd, Dept Pharmacokinet & Drug Metab, Bombay 400063, Maharashtra, India		Agarwal, VR (corresponding author), Piramal Enterprises Ltd, 1-Nirlon Complex,Western Express Highway, Bombay 400063, Maharashtra, India.	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J	Mishra, SK; Gao, YG; Zou, XQ; Stephenson, DJ; Malinina, L; Hinchcliffe, EH; Chalfant, CE; Brown, RE				Mishra, Shrawan K.; Gao, Yong-Guang; Zou, Xianqiong; Stephenson, Daniel J.; Malinina, Lucy; Hinchcliffe, Edward H.; Chalfant, Charles E.; Brown, Rhoderick E.			Emerging roles for human glycolipid transfer protein superfamily members in the regulation of autophagy, inflammation, and cell death	PROGRESS IN LIPID RESEARCH			English	Review						Glycolipid transfer protein superfamily; Sphingolipid homeostasis; Autophagy; Inflammasomes; Necroptosis; Eicosanoids; Cytokines; Sphingolipid rheostat; Phosphoglyceride regulatory binding	MEMBRANE CONTACT SITES; CERAMIDE-1-PHOSPHATE TRANSFER PROTEIN; CERAMIDE 1-PHOSPHATE; STRUCTURAL BASIS; NONVESICULAR TRAFFICKING; SPHINGOLIPID METABOLISM; PLASMA-MEMBRANE; GD3 GANGLIOSIDE; TRYPTOPHAN FLUORESCENCE; MEDIATED TRANSFER	Glycolipid transfer proteins (GLTPs) were first identified over three decades ago as similar to 24kDa, soluble, amphitropic proteins that specifically accelerate the intermembrane transfer of glycolipids. Upon discovery that GLTPs use a unique, all-alpha-helical, two-layer 'sandwich' architecture (GLTP-fold) to bind glycosphingolipids (GSLs), a new protein superfamily was born. Structure/function studies have provided exquisite insights defining features responsible for lipid headgroup selectivity and hydrophobic 'pocket' adaptability for accommodating hydrocarbon chains of differing length and unsaturation. In humans, evolutionarily-modified GLTP-folds have been identified with altered sphingolipid specificity, e. g. ceramide-1-phosphate transfer protein (CPTP), phosphatidylinositol 4-phosphate adaptor protein-2 (FAPP2) which harbors a GLTP-domain and GLTPD2. Despite the wealth of structural data (> 40 Protein Data Bank deposits), insights into the in vivo functional roles of GLTP superfamily members have emerged slowly. In this review, recent advances are presented and discussed implicating human GLTP superfamily members as important regulators of: i) pro-inflammatory eicosanoid production associated with Group-IV cytoplasmic phospholipase A(2); ii) autophagy and inflammasome assembly that drive surveillance cell release of interleukin-1 beta and interleukin-18 inflammatory cytokines; iii) cell cycle arrest and necroptosis induction in certain colon cancer cell lines. The effects exerted by GLTP superfamily members appear linked to their ability to regulate sphingolipid homeostasis by acting in either transporter and/or sensor capacities. These timely findings are opening new avenues for future cross-disciplinary, translational medical research involving GLTP-fold proteins in human health and disease. Such avenues include targeted regulation of specific GLTP superfamily members to alter sphingolipid levels as a therapeutic means for combating viral infection, neurodegenerative conditions and circumventing chemo-resistance during cancer treatment.	[Mishra, Shrawan K.; Gao, Yong-Guang; Zou, Xianqiong; Malinina, Lucy; Hinchcliffe, Edward H.; Brown, Rhoderick E.] Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA; [Stephenson, Daniel J.] Virginia Commonwealth Univ, Med Ctr, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA; [Stephenson, Daniel J.; Chalfant, Charles E.] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA; [Chalfant, Charles E.] James A Haley Vet Hosp, Res Serv, Tampa, FL 33612 USA; [Chalfant, Charles E.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33620 USA; [Mishra, Shrawan K.] WuXi AppTec Inc, 2540 Execut Dr, St Paul, MN 55120 USA; [Zou, Xianqiong] Guilin Med Univ, Coll Biotechnol, Guilin 541100, Guangxi, Peoples R China		Brown, RE (corresponding author), UMN Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA.	reb@umn.edu	Mishra, Shrawan K/J-7972-2013; Gao, Yongguang/B-8546-2012	Gao, Yongguang/0000-0002-9359-4252; Brown, Rhoderick/0000-0002-7337-3604	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RO1-GM45928]; Southern Minnesota Paint-the-Town-Pink Grant Awards; Hormel Foundation;  [RO1-CA121493];  [RO1-HL125353]	We are grateful to Xin Lin, Taeowan Chung, and Helen Pike for their pioneering molecular biological and cell biological studies of GLTP and CPTP as members of the REB lab. Our studies also benefited from collaborative research on the plant CPTP orthologue, ACD11, with the John Mundy lab via Nikolaj Petersen, Daniel Hofius, and David Munch. We are thankful for biophysical studies carried out by Xiuhong Zhai, Dhirendra Simanshu, Ivan Boldyrev, Ravi-Kanth Kamlekar, Roop Kenoth, Margarita Malakhova, Chetan Rao, Xin-Min Li, and Peter Mattjus as well as to other long-standing collaborators (Julian G. Molotkovsky and Dinshaw J. Patel) who played key roles in elucidating GLTP-fold structure/function relationships. We especially appreciate the long-term interest and support of GLTP superfamily research by Dr. Jean Chin while administering NIH RO1-GM45928 and also are grateful for support received from RO1-CA121493, RO1-HL125353, Southern Minnesota Paint-the-Town-Pink Grant Awards, and the Hormel Foundation.	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Lipid Res.	APR	2020	78								101031	10.1016/j.plipres.2020.101031			18	Biochemistry & Molecular Biology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Nutrition & Dietetics	LO3CZ	WOS:000533508000005	32339554	Green Accepted			2022-04-25	
J	Sorokina, IV; Denisenko, TV; Imreh, G; Tyurin-Kuzmin, PA; Kaminskyy, VO; Gogvadze, V; Zhivotovsky, B				Sorokina, Irina V.; Denisenko, Tatiana V.; Imreh, Gabriela; Tyurin-Kuzmin, Pyotr A.; Kaminskyy, Vitaliy O.; Gogvadze, Vladimir; Zhivotovsky, Boris			Involvement of autophagy in the outcome of mitotic catastrophe	SCIENTIFIC REPORTS			English	Article							CELL-CYCLE CHECKPOINT; DNA-DAMAGE; IMMUNE-RESPONSES; DEATH; CANCER; APOPTOSIS; 14-3-3-SIGMA; MITOCHONDRIA; DISRUPTION; ACTIVATION	Evading cell death is a major driving force for tumor progression that is one of the main problems in current cancer research. Mitotic catastrophe (MC) represents attractive platform compromising tumor resistance to current therapeutic modalities. MC appeared as onco-suppressive mechanism and is defined as a stage driving the cell to an irreversible destiny, i.e. cell death via apoptosis or necrosis. Our study highlights that MC induction in colorectal carcinoma cell lines ultimately leads to the autophagy followed by apoptosis. We show that autophagy suppression in Atg 13 knockout non-small cell lung carcinoma cells lead to the dramatic decrease of MC rate. Furthermore, mitochondria-linked antiapoptotic proteins Mcl-1 and Bcl-xL play a crucial role in the duration of MC and a cross-talk between autophagy and apoptosis. Thus, the suppression of apoptosis by overexpression of Mcl-1 or Bcl-xL affected MC and lead to a significant induction of autophagy in HCT116 wt and HCT116 14-3-3 sigma(-/-)cells. Our data demonstrate that MC induction is a critical stage, in which a cell decides how to die, while mitochondria are responsible for the maintaining the balance between MC - autophagy - apoptosis.	[Sorokina, Irina V.; Denisenko, Tatiana V.; Tyurin-Kuzmin, Pyotr A.; Gogvadze, Vladimir; Zhivotovsky, Boris] Moscow MV Lomonosov State Univ, Fac Fundamental Med, Moscow 119992, Russia; [Imreh, Gabriela; Kaminskyy, Vitaliy O.; Gogvadze, Vladimir; Zhivotovsky, Boris] Karolinska Inst, Inst Environm Med, Div Toxicol, Box 210, S-17177 Stockholm, Sweden; [Imreh, Gabriela] Karolinska Inst, Dept Biosci & Nutr, S-17177 Stockholm, Sweden		Zhivotovsky, B (corresponding author), Moscow MV Lomonosov State Univ, Fac Fundamental Med, Moscow 119992, Russia.; Zhivotovsky, B (corresponding author), Karolinska Inst, Inst Environm Med, Div Toxicol, Box 210, S-17177 Stockholm, Sweden.	Boris.Zhivotovsky@ki.se	Tyurin-Kuzmin, Pyotr A./A-8193-2014; Gogvadze, Vladimir/A-4392-2014; Zhivotovsky, Boris/A-4346-2014; Denisenko, Tatyana/U-9986-2018	Tyurin-Kuzmin, Pyotr A./0000-0002-1901-1637; Zhivotovsky, Boris/0000-0002-2238-3482; Kaminskyy, Vitaliy/0000-0002-8151-5270	Russian Science FoundationRussian Science Foundation (RSF) [14-25-00056]; Stockholm Cancer Society [161292]; Swedish Cancer SocietySwedish Cancer Society [160733]; Swedish Childhood Cancer FoundationEuropean Commission [PR2016-0090]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [521-2014-2258];  [NSH-7082.2016]; Russian Science FoundationRussian Science Foundation (RSF) [17-25-00012] Funding Source: Russian Science Foundation	We thank Prof. Bert Vogelstein for HCT116 cells, Prof. Fazoil Ataullakhanov and Dr. Pyotr Makhov for plasmid containing LC3-GFP. This work was supported by Russian Science Foundation (grant number 14-25-00056). The work in the authors' laboratories is being supported from Russian President Fund (grant number NSH-7082.2016), as well as the Stockholm (grant number 161292) and Swedish (grant number 160733) Cancer Societies, the Swedish Childhood Cancer Foundation (grant number PR2016-0090), the Swedish Research Council (grant number 521-2014-2258).	Abedin MJ, 2007, CELL DEATH DIFFER, V14, P500, DOI 10.1038/sj.cdd.4402039; Allavena G, 2016, AUTOPHAGY, V12, P2085, DOI 10.1080/15548627.2016.1226733; Castedo M, 2004, ONCOGENE, V23, P4353, DOI 10.1038/sj.onc.1207573; Chan TA, 1999, NATURE, V401, P616, DOI 10.1038/44188; Chopra P, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0014305; Cook K. 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J	Gerada, C; Ryan, KM				Gerada, Chelsea; Ryan, Kevin M.			Autophagy, the innate immune response and cancer	MOLECULAR ONCOLOGY			English	Review						autophagy; cancer; immunotherapy; innate immune response; tumour microenvironment	INFLAMMATORY-BOWEL-DISEASE; LYMPH-NODE METASTASIS; TUMOR-CELLS; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; NK CELLS; SUSCEPTIBILITY; INHIBITION; SENESCENCE; INVASION	Autophagy is a cellular degradation and recycling system, which can interact with components of innate immune signalling pathways to enhance pathogen clearance, in both immune and nonimmune cells. Whilst this interaction is often beneficial for pathogen clearance, it can have varying outcomes in regard to tumorigenesis. Autophagy and the innate immune response can have both pro- and antitumorigenic effects at different stages of tumorigenesis due to the plastic nature of the tumour microenvironment (TME). Although both of these components have been studied in isolation as potential therapeutic targets, there has been less research concerning the interaction between autophagy and the innate immune response within the TME. As the innate immune response is critical for the formation of an effective antitumour adaptive immune response, targeting autophagy pathways in both tumour cells and innate immune cells could enhance tumour clearance. Within tumour cells, autophagy pathways are intertwined with pattern recognition receptor (PRR), inflammatory and cell death pathways, and therefore can alter the immunogenicity of the TME and development of the antitumour immune response. In innate immune cells, autophagy components can have autophagy-independent roles in functional pathways, and therefore could be valuable targets for enhancing immune cell function in the TME and immunotherapy. This review highlights the individual importance of autophagy and the innate immune response to tumorigenesis, and also explains the complex interactions between these pathways in the TME.	[Gerada, Chelsea; Ryan, Kevin M.] Canc Res UK Beatson Inst, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland; [Ryan, Kevin M.] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland		Ryan, KM (corresponding author), Canc Res UK Beatson Inst, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.	k.ryan@beatson.gla.ac.uk	Gerada, Chelsea/AAD-7063-2021	Ryan, Kevin M./0000-0002-1059-9681; Gerada, Chelsea/0000-0001-8491-2506	Cancer Research UKCancer Research UK [A22903, A17196]	Work in the Tumour Cell Death Laboratory is supported by grants from Cancer Research UK (A22903 and A17196). Thanks to Dr. Victoria Wang for reading and providing suggestions for the manuscript.	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Oncol.	SEP	2020	14	9					1913	1929		10.1002/1878-0261.12774		AUG 2020	17	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NH8GM	WOS:000563745600001	32745353	Green Published, gold			2022-04-25	
J	Fu, ZQ; Luo, WZ; Wang, JT; Peng, T; Sun, GF; Shi, JY; Li, ZH; Zhang, BA				Fu, Zhenqiang; Luo, Wenzheng; Wang, Jingtao; Peng, Tao; Sun, Guifang; Shi, Jingyu; Li, Zhihong; Zhang, Boai			Malatl activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Glioma; The long noncoding RNA Malat1; Autophagy; Proliferation; miR-101	HEPATOCELLULAR-CARCINOMA CELLS; INHIBITS AUTOPHAGY; COLORECTAL-CANCER; POOR-PROGNOSIS; TUMOR-GROWTH; METASTASIS; OSTEOSARCOMA; APOPTOSIS	The long noncoding RNA Malati has been reported to be an oncogene that promotes tumor progress and correlates with prognosis in glioma. Growing evidence shows that autophagy plays a very important role in tumorigenesis and tumor cell survival, but whether Malatl regulates autophagy in glioma is still unclear. In this study, we found that Malatl expression and autophagy activity were significantly increased in glioma tissues compared with adjacent normal tissues. Additionally, Malatl level was positively correlated with the expression of LC3-II (autophagy marker) mRNA in vivo. In vitro assays revealed that Malatl significantly promoted autophagy activation and cell proliferation in glioma cells. More importantly, inhibition of autophagy by 3-MA relieved Malatl-induced cell proliferation. These data demonstrated that Malatl activates autophagy and increases cell proliferation in glioma. We further investigated the molecular mechanisms whereby Malatl functioned on glioma cell autophagy and proliferation. We found that Malati served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malati abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D. Overall, our study elucidated a novel Malatl-miR-101-STMN1/RAB5A/ATG4D regulatory network that Malatl activates autophagy and promotes cell proliferation by sponging miR101 and upregulating STMN1, RAB5A and ATG4D expression in glioma cells. (C) 2017 Elsevier Inc. All rights reserved.	[Fu, Zhenqiang; Wang, Jingtao; Peng, Tao; Sun, Guifang; Zhang, Boai] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurol, Jianshe Dong Rd 1, Zhengzhou 450000, Henan, Peoples R China; [Luo, Wenzheng] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurosurg, Zhengzhou, Henan, Peoples R China; [Shi, Jingyu] Luoyang Cent Hosp, Dept Neurol, Luoyang, Peoples R China; [Li, Zhihong] Zhengzhou Cent Hosp, Dept Neurol, Zhengzhou, Henan, Peoples R China		Zhang, BA (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Neurol, Jianshe Dong Rd 1, Zhengzhou 450000, Henan, Peoples R China.	zbadoctor@163.com					Betin VMS, 2009, AUTOPHAGY, V5, P1057, DOI 10.4161/auto.5.7.9684; Chang Y, 2012, GASTROENTEROLOGY, V143, P177, DOI 10.1053/j.gastro.2012.04.009; Chang Z., 2014, SCI WORLD J; Dong YQ, 2015, TUMOR BIOL, V36, P1477, DOI 10.1007/s13277-014-2631-4; Fan Y, 2014, CLIN CANCER RES, V20, P1531, DOI 10.1158/1078-0432.CCR-13-1455; Frankel LB, 2011, EMBO J, V30, P4628, DOI 10.1038/emboj.2011.331; Hu YL, 2012, CANCER RES, V72, P1773, DOI 10.1158/0008-5472.CAN-11-3831; Ji Q, 2014, BRIT J CANCER, V111, P736, DOI 10.1038/bjc.2014.383; Kyostila K, 2015, PLOS GENET, V11, DOI 10.1371/journal.pgen.1005169; Li H, 2014, ONCOTARGET, V5, P2318, DOI 10.18632/oncotarget.1913; Li J, 2009, BMC CANCER, V9, DOI 10.1186/1471-2407-9-215; Li L, 2016, MOL CANCER THER, V15, P2232, DOI 10.1158/1535-7163.MCT-16-0008; Li YJ, 2013, AUTOPHAGY, V9, P150, DOI 10.4161/auto.22742; Lu YY, 2014, AUTOPHAGY, V10, P1895, DOI 10.4161/auto.32200; Ma KX, 2015, TUMOR BIOL, V36, P3355, DOI 10.1007/s13277-014-2969-7; Ostrom QT, 2014, NEURO-ONCOLOGY, V16, P1, DOI 10.1093/neuonc/nou223; Pennati M, 2014, BIOCHEM PHARMACOL, V87, P579, DOI 10.1016/j.bcp.2013.12.009; Smits M, 2010, ONCOTARGET, V1, P710, DOI 10.18632/oncotarget.205; Wang YW, 2014, BIOCHEM PHARMACOL, V88, P322, DOI 10.1016/j.bcp.2014.01.041; Wang Z., 1899, ONCOL LETT, V13, P3465; Wu H, 2006, CANCER RES, V66, P3015, DOI 10.1158/0008-5472.CAN-05-1554; Xu T, 2015, AM J TRANSL RES, V7, P1172; Xu YH, 2013, ONCOL REP, V29, P2019, DOI 10.3892/or.2013.2338; Yao YL, 2015, CNS NEUROSCI THER, V21, P40, DOI 10.1111/cns.12321; Yuan P, 2016, BIOCHEM BIOPH RES CO, V478, P1067, DOI 10.1016/j.bbrc.2016.08.065; Zhang HH, 2015, CANCER LETT, V356, P781, DOI 10.1016/j.canlet.2014.10.029; Zhao HX, 2016, AM J TRANSL RES, V8, P3503	27	64	66	1	16	ACADEMIC PRESS INC ELSEVIER SCIENCE	SAN DIEGO	525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA	0006-291X	1090-2104		BIOCHEM BIOPH RES CO	Biochem. Biophys. Res. Commun.	OCT 21	2017	492	3					480	486		10.1016/j.bbrc.2017.08.070			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	FH8EJ	WOS:000411424300031	28834690				2022-04-25	
J	Paillas, S; Boudousq, V; Piron, B; Kersual, N; Bardies, M; Chouin, N; Bascoul-Mollevi, C; Arnaud, FX; Pelegrin, A; Navarro-Teulon, I; Pouget, JP				Paillas, Salome; Boudousq, Vincent; Piron, Berengere; Kersual, Nathalie; Bardies, Manuel; Chouin, Nicolas; Bascoul-Mollevi, Caroline; Arnaud, Francois-Xavier; Pelegrin, Andre; Navarro-Teulon, Isabelle; Pouget, Jean-Pierre			Apoptosis and p53 are not involved in the anti-tumor efficacy of I-125-labeled monoclonal antibodies targeting the cell membrane	NUCLEAR MEDICINE AND BIOLOGY			English	Article						Radioimmunotherapy; Auger electrons; p53; Apoptosis; I-125-mAbs	MAMMALIAN-CELLS; COLON-CANCER; RADIOIMMUNOTHERAPY; DEATH; RADIOTOXICITY; THERAPY; LINES; DNA	Introduction: I-125-labeled monoclonal antibodies (I-125-mAbs) can efficiently treat small solid tumors. Here, we investigated the role of apoptosis, autophagy and mitotic catastrophe in I-125-mAb toxicity in p53(-/-) and p53(+/+) cancer cells. Methods: We exposed p53(-/-) and p53(+/+) HCT116 cells to increasing activities of internalizing (cytoplasmic location) anti-HER1 I-125-mAbs, or non-internalizing (cell surface location) anti-CEA I-125-mAbs. For each targeting model we established the relationship between survival and mean nucleus absorbed dose using the MIRD formalism. Results: In both p53(-/-) and p53(+/+) HCT116 cells, anti-CEA I-125-mAbs were more cytotoxic per Gy than anti-HER1 I-125-mAbs. Sensitivity to anti-CEA I-125-mAbs was p53-independent, while sensitivity to anti-HER1 I-125-mAbs was higher in p53(-/-) HCT116 cells, suggesting that they act through different signaling pathways. Apoptosis was only induced in p53(+/+) HCT116 cells and could not explain cell membrane radiation sensitivity. Inhibition of autophagy did not modify the cell response to I-125-mAbs. By contrast, mitotic death was similarly induced in both p53(-/-) and p53(+/+) HCT116 cells by the two types of I-125-mAbs. We also showed using medium transfer experiments that gamma-H2AX foci were produced in bystander cells. Conclusion: Cell membrane sensitivity to I-125-mAbs is not mediated by apoptosis and is p53-independent. Bystander effects-mediated mitotic death could be involved in the efficacy of I-125-mAbs binding cell surface receptors. (C) 2013 Elsevier Inc. All rights reserved.	[Paillas, Salome; Boudousq, Vincent; Piron, Berengere; Kersual, Nathalie; Pelegrin, Andre; Navarro-Teulon, Isabelle; Pouget, Jean-Pierre] Inst Rech Cancerol Montpellier, IRCM, F-34298 Montpellier, France; [Paillas, Salome; Boudousq, Vincent; Piron, Berengere; Kersual, Nathalie; Pelegrin, Andre; Navarro-Teulon, Isabelle; Pouget, Jean-Pierre] INSERM, U896, F-34298 Montpellier, France; [Paillas, Salome; Boudousq, Vincent; Piron, Berengere; Kersual, Nathalie; Pelegrin, Andre; Navarro-Teulon, Isabelle; Pouget, Jean-Pierre] Univ Montpellier I, F-34298 Montpellier, France; [Paillas, Salome; Boudousq, Vincent; Piron, Berengere; Kersual, Nathalie; Bascoul-Mollevi, Caroline; Pelegrin, Andre; Navarro-Teulon, Isabelle; Pouget, Jean-Pierre] CRLC Val dAurelle Paul Lamarque, F-34298 Montpellier, France; [Bardies, Manuel] INSERM UPS, UMR 1037, Toulouse, France; [Chouin, Nicolas] LUNAM Univ, Oniris, AMaROC, F-44307 Nantes, France; [Arnaud, Francois-Xavier] Univ Toulouse, Lab Laplace, UMR 5213, F-31400 Toulouse, France		Pouget, JP (corresponding author), CRLC Val dAurelle, Inst Rech Cancerol Montpellier, F-34298 Montpellier 5, France.	jean-pierre.pouget@inserm.fr	Pèlegrin, André/J-3167-2016; Chouin, Nicolas/M-7914-2016; Mollevi, Caroline/AAA-6839-2019; Bardies, Manuel/L-3136-2014	Chouin, Nicolas/0000-0003-1489-4351; Mollevi, Caroline/0000-0003-4827-3684; Bardies, Manuel/0000-0002-1766-727X; POUGET, Jean-Pierre/0000-0001-8551-2029; Pelegrin, Andre/0000-0001-9254-2648	Institut National du CancerInstitut National du Cancer (INCA) France [R09080FF/RPT09005FFA]	The authors would like to thank Dr Jean-Marc Brondello, Dr Maguy Del Rio and Dr Celine Gongora for helpful discussions. This work was supported by the Institut National du Cancer, grant R09080FF/RPT09005FFA.	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J	Zhu, Y; Cheng, J; Min, ZL; Yin, TZ; Zhang, R; Zhang, W; Hu, L; Cui, ZW; Gao, CZ; Xu, SQ; Zhang, CX; Hu, XM				Zhu, Yue; Cheng, Jing; Min, Zhenli; Yin, Tingzi; Zhang, Rong; Zhang, Wei; Hu, Ling; Cui, Zhiwen; Gao, Chengzhi; Xu, Shiqiang; Zhang, Chunxiang; Hu, Xiamin			Effects of fucoxanthin on autophagy and apoptosis in SGC-7901cells and the mechanism	JOURNAL OF CELLULAR BIOCHEMISTRY			English	Article						apoptosis; autophagy; fucoxanthin; SGC-7901 cells	CANCER-CELLS; PI3K/AKT/MTOR PATHWAY; SIGNALING PATHWAYS; COLORECTAL-CANCER; BECLIN 1; MACROAUTOPHAGY; INHIBITION; INDUCTION; INVASION; DISEASE	Autophagy and apoptosis are involved in the development of a variety of cancers. Fucoxanthin is a natural compound known to have antitumor effects, so we aimed to explore its effects on autophagy and apoptosis in gastric cancer SGC7901 cells. Specifically, we performed methyl thiazolyl tetrazolium assay, transmission electron microscopy, real-time polymerase chain reaction, Western blot analysis, immunofluorescence assay, and cell apoptosis analysis to clarify the role of fucoxanthin in SGC-7901 cells. Our results indicate that fucoxanthin significantly inhibits the viability of SGC-7901 cells, effectively inducing both autophagy and apoptosis by up-regulating the expressions of beclin-1, LC3, and cleaved caspase-3 (CC3), and by down regulating Bcl-2. Fucoxanthin-induced autophagy also seems to occur before, and may promote apoptosis.	[Zhu, Yue; Cheng, Jing; Min, Zhenli; Yin, Tingzi; Zhang, Rong; Hu, Ling; Cui, Zhiwen; Gao, Chengzhi; Xu, Shiqiang; Zhang, Chunxiang; Hu, Xiamin] Wuhan Univ Sci & Technol, Hubei Prov Key Lab Occupat Hazard Identificat & C, Wuhan 430065, Hubei, Peoples R China; [Zhu, Yue; Cheng, Jing; Min, Zhenli; Yin, Tingzi; Zhang, Rong; Hu, Ling; Cui, Zhiwen; Gao, Chengzhi; Zhang, Chunxiang] Univ Alabama Birmingham, Dept Biomed Engn, Sch Med, Birmingham, AL 35294 USA; [Zhu, Yue; Cheng, Jing; Min, Zhenli; Yin, Tingzi; Zhang, Rong; Hu, Ling; Cui, Zhiwen; Gao, Chengzhi; Zhang, Chunxiang] Univ Alabama Birmingham, Dept Biomed Engn, Sch Engn, Birmingham, AL 35294 USA; [Zhang, Wei] China Resources & WISCO Gen Hosp, Dept Rehabil Med, Wuhan, Hubei, Peoples R China; [Hu, Xiamin] Shanghai Univ Med & Hlth Sci, Dept Pharm, Shanghai, Peoples R China		Hu, XM (corresponding author), Wuhan Univ Sci & Technol, Hubei Prov Key Lab Occupat Hazard Identificat & C, Wuhan 430065, Hubei, Peoples R China.	huxm@sumhs.edu.cn					Antoine F, 2013, SAGE OPEN MED, V1, DOI 10.1177/2050312113488104; Brech A, 2009, MOL ONCOL, V3, P366, DOI 10.1016/j.molonc.2009.05.007; Campbell Frederick C, 2005, Future Oncol, V1, P405, DOI 10.1517/14796694.1.3.405; Che JB, 2017, CARDIOVASC PATHOL, V31, P57, DOI 10.1016/j.carpath.2017.08.001; Ciechomska IA, 2009, ONCOGENE, V28, P2128, DOI 10.1038/onc.2009.60; Djavaheri-Mergny M, 2010, ONCOGENE, V29, P1717, DOI 10.1038/onc.2009.519; Geng JF, 2008, EMBO REP, V9, P859, DOI 10.1038/embor.2008.163; Hara T, 2006, NATURE, V441, P885, DOI 10.1038/nature04724; Hayashi-Nishino M, 2009, NAT CELL BIOL, V11, P1433, DOI 10.1038/ncb1991; He CC, 2009, ANNU REV GENET, V43, P67, DOI 10.1146/annurev-genet-102808-114910; Hou LL, 2013, ACTA PHARMACOL SIN, V34, P1403, DOI 10.1038/aps.2013.90; Huang ZQ, 2015, MOL MED REP, V11, P4678, DOI 10.3892/mmr.2015.3322; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Kuma A, 2004, NATURE, V432, P1032, DOI 10.1038/nature03029; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Liu YG, 2016, NEUROCHEM RES, V41, P2728, DOI 10.1007/s11064-016-1989-7; Luo C, 2017, FRONT CELL NEUROSCI, V11, DOI 10.3389/fncel.2017.00197; Miracco C, 2007, INT J ONCOL, V30, P429; Nakatogawa H, 2009, NAT REV MOL CELL BIO, V10, P458, DOI 10.1038/nrm2708; O'Sullivan-Coyne G, 2009, BRIT J CANCER, V101, P1585, DOI 10.1038/sj.bjc.6605308; Pattingre S, 2008, BIOCHIMIE, V90, P313, DOI 10.1016/j.biochi.2007.08.014; Ravikumar B, 2010, PHYSIOL REV, V90, P1383, DOI 10.1152/physrev.00030.2009; Rubinsztein DC, 2010, EMBO REP, V11, P3, DOI 10.1038/embor.2009.253; Ryan KM, 2011, EUR J CANCER, V47, P44, DOI 10.1016/j.ejca.2010.10.020; Shinojima N, 2007, AUTOPHAGY, V3, P635, DOI 10.4161/auto.4916; Su JN, 2016, AM J CANCER RES, V6, P1949; Wang J, 2012, MAR DRUGS, V10, P2055, DOI 10.3390/md10092055; Yang ZF, 2009, CURR TOP MICROBIOL, V335, P1, DOI 10.1007/978-3-642-00302-8_1; Ye GL, 2014, TUMOR BIOL, V35, P11261, DOI 10.1007/s13277-014-2337-7; Yu RX, 2011, EUR J PHARMACOL, V657, P10, DOI 10.1016/j.ejphar.2010.12.006; Yuan Q, 2016, CAN J PHYSIOL PHARM, V94, P929, DOI 10.1139/cjpp-2015-0530; Zhang JQ, 2011, ONCOL REP, V26, P115, DOI 10.3892/or.2011.1277; Zhang LL, 2017, EUR J PHARMACOL, V797, P1, DOI 10.1016/j.ejphar.2017.01.008	34	19	19	4	18	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0730-2312	1097-4644		J CELL BIOCHEM	J. Cell. Biochem.	SEP	2018	119	9					7274	7284		10.1002/jcb.27022			11	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	GU3OB	WOS:000445187800016	29761894				2022-04-25	
J	Zheng, NN; Wang, K; He, JJ; Qiu, YP; Xie, GX; Su, MM; Jia, W; Li, HK				Zheng, Ningning; Wang, Ke; He, Jiaojiao; Qiu, Yunping; Xie, Guoxiang; Su, Mingming; Jia, Wei; Li, Houkai			Effects of ADMA on gene expression and metabolism in serum-starved LoVo cells	SCIENTIFIC REPORTS			English	Article							STARVATION-INDUCED APOPTOSIS; ASYMMETRIC DIMETHYLARGININE; AUTOPHAGY; PROTEIN; DAMAGE; GROWTH; HOMOCYSTEINE; DEPRIVATION; P62/SQSTM1; CARCINOMA	Serum starvation is a typical way for inducing tumor cell apoptosis and stress. Asymmetric dimethylarginine (ADMA) is an endogenous metabolite. Our previous study reveals the plasma ADMA level is elevated in colon cancer patients, which can attenuate serum starvation-induced apoptosis in LoVo cells. In current study, we evaluated the effects of ADMA on gene expression and metabolism in serum-starved LoVo cells with gene microarray and metabolomic approaches. Our results indicated that 96 h serum starvation induced comprehensive alterations at transcriptional level, and most of them were restored by ADMA. The main signaling pathways induced by serum starvation included cancers-related pathways, pathways in cell death, apoptosis, and cell cycle etc. Meanwhile, the metabolomic data showed serum-starved cells were clearly separated with control cells, but not with ADMA-treated cells in PCA model. The identified differential metabolites indicated serum starvation significantly suppressed TCA cycle, altered glucose and fatty acids metabolism, as well as nucleic acids metabolism. However, very few differential metabolites were identified between ADMA and serum-starved cells. In summary, our current results indicated serum starvation profoundly altered the gene expression and metabolism of LoVo cells, whereas ADMA could restore most of the changes at transcriptional level, but not at metabolic level.	[Zheng, Ningning; He, Jiaojiao; Jia, Wei; Li, Houkai] Shanghai Univ Tradit Chinese Med, Ctr Chinese Med Therapy & Syst Biol, Shanghai 201203, Peoples R China; [Wang, Ke] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Lab Integrat Med Surg, Shanghai 201203, Peoples R China; [Qiu, Yunping] Albert Einstein Coll Med, Ctr Diabet, Stable Isotope & Metabol Core Facil, 1300 Morris Part Ave, Bronx, NY 10461 USA; [Xie, Guoxiang; Su, Mingming; Jia, Wei] Univ Hawaii, Ctr Canc, Cancer Epidemiol Program, Honolulu, HI 96813 USA; [Jia, Wei] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Ctr Translat Med, Shanghai 200233, Peoples R China; [Jia, Wei] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai Key Lab Diabet Mellitus, Shanghai 200233, Peoples R China		Li, HK (corresponding author), Shanghai Univ Tradit Chinese Med, Ctr Chinese Med Therapy & Syst Biol, Shanghai 201203, Peoples R China.	houkai1976@126.com	Qiu, Yunping/AAO-5200-2021; li, houkai/S-6785-2019; Xie, Guoxiang/F-3022-2016; Jia, Wei/AAN-5102-2020	li, houkai/0000-0003-2846-7895; Xie, Guoxiang/0000-0002-0951-4150; Jia, Wei/0000-0002-3739-8994; Qiu, Yunping/0000-0003-1039-5264	Shanghai Municipal Education CommissionShanghai Municipal Education Commission (SHMEC); Shanghai Pujiang Program from the Science and Technology Commission of Shanghai Municipality [14PJD031]; Shanghai Creative Research Fund of Higher Education [ZYX-CXYJ-017]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA071789] Funding Source: NIH RePORTER	This work was financially supported by The Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning from Shanghai Municipal Education Commission, Shanghai Pujiang Program (14PJD031) from the Science and Technology Commission of Shanghai Municipality, and the Shanghai Creative Research Fund (ZYX-CXYJ-017) of Higher Education.	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J	Janicke, P; Lennicke, C; Meister, A; Seliger, B; Wessjohann, LA; Kaluderovic, GN				Jaenicke, Paul; Lennicke, Claudia; Meister, Annette; Seliger, Barbara; Wessjohann, Ludger A.; Kaluderovic, Goran N.			Fluorescent spherical mesoporous silica nanoparticles loaded with emodin: Synthesis, cellular uptake and anticancer activity	MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS			English	Article						Emodin; Spherical mesoporous silica; Apoptosis; Anticancer drugs; Drug targeting; Tumor cells; Autophagy	POROUS SILICON; DRUG-DELIVERY; ALOE EMODIN; CONTROLLED-RELEASE; CANCER CELLS; GROWTH; PATHWAY; SBA-15; DIFFERENTIATION; APOPTOSIS	The natural product emodin (EO) exhibits anti-inflammatory, antiangiogenesis and antineoplastic properties in vitro and in vivo. Due to its biological properties as well as its fluorescence, EO can be useful in pharmacology and pharmacokinetics. To enhance its selectivity to cancer cells, EO was loaded into non-fluorescent and novel fluorescent spherical mesoporous nanoparticles bearing N-methyl isatoic anhydride (SNM similar to M) or lissamine rhodamine B sulfonyl moieties (SNM similar to L). The propylamine functionalized mesoporous silica nanomaterial (SNM) were characterized by powder X-ray diffraction (XRD), nitrogen gas sorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), fluorescence spectroscopy, thermogravimetric analysis (TGA) and UV spectroscopy. The cytotoxicity of EO-loaded nanoparticles was tested against the human colon carcinoma cell line HT-29. Non-loaded SNM did not affect cell proliferation, whereas those loaded with EO were at least as efficient as EO alone. It could be shown by fluorescence microscopy that the uptake of silica nano material by the tumor cells occurred within 2 h and the release of EO occurred within 48 h of treatment. Flow cytometry and Western blot analysis showed that SNM containing EO induced apoptosis in HT-29 cells.	[Jaenicke, Paul; Wessjohann, Ludger A.; Kaluderovic, Goran N.] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany; [Lennicke, Claudia; Seliger, Barbara] Martin Luther Univ Halle Wittenberg, Inst Med Immunol, Magdeburger Str 2, D-06112 Halle, Saale, Germany; [Meister, Annette] Martin Luther Univ Halle Wittenberg, Inst Chem Phys & Theoret Chem, D-06099 Halle, Saale, Germany; [Kaluderovic, Goran N.] Univ Appl Sci Merseburg, Dept Engn & Nat Sci, Eberhard Leibnitz Str 2, D-06217 Merseburg, Germany		Kaluderovic, GN (corresponding author), Univ Appl Sci Merseburg, Dept Engn & Nat Sci, Eberhard Leibnitz Str 2, D-06217 Merseburg, Germany.	goran.kaluderovic@hs-merseburg.de	Wessjohann, Ludger/AAZ-3838-2021; Kaluderovic, Goran/AAR-7347-2021	Kaluderovic, Goran/0000-0001-5168-1000; Wessjohann, Ludger A./0000-0003-2060-8235			Ahn HJ, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0086173; Amann T, 2010, ONCOL REP, V23, P1669, DOI 10.3892/or_00000810; Anglin EJ, 2008, ADV DRUG DELIVER REV, V60, P1266, DOI 10.1016/j.addr.2008.03.017; Bulatovic MZ, 2014, ANGEW CHEM INT EDIT, V53, P5982, DOI 10.1002/anie.201400763; CANHAM LT, 1994, ADV MATER, V6, P865, DOI 10.1002/adma.19940061115; Cao Y.-Y., 2012, J TRADIT CHIN MED, V9, P81; Chang CH, 1996, AM J CHINESE MED, V24, P139, DOI 10.1142/S0192415X96000189; Chen M, 2017, PROSTATE, V77, P489, DOI 10.1002/pros.23287; Chipuk JE, 2006, CELL DEATH DIFFER, V13, P1396, DOI 10.1038/sj.cdd.4401963; CORY AH, 1991, CANCER COMMUN, V3, P207, DOI 10.3727/095535491820873191; Coti KK, 2009, NANOSCALE, V1, P16, DOI 10.1039/b9nr00162j; CRABTREE EV, 1978, J ORG CHEM, V43, P268, DOI 10.1021/jo00396a019; Crawford ED, 2011, ANNU REV BIOCHEM, V80, P1055, DOI 10.1146/annurev-biochem-061809-121639; Crowell JA, 2005, EUR J CANCER, V41, P1889, DOI 10.1016/j.ejca.2005.04.016; Deng G., 2015, MOL MED REPORTS; Dong MH, 2014, BIOMED REP, V2, P250, DOI 10.3892/br.2014.226; Drury LJ, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0012895; Duronio V, 2008, BIOCHEM J, V415, P333, DOI 10.1042/BJ20081056; Dutta D, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2055-1; Edeler D., 2014, THESIS; Edeler D, 2019, MAT SCI ENG C-MATER, V100, P315, DOI 10.1016/j.msec.2019.03.010; Feng Y, 2010, BRIT J PHARMACOL, V161, P113, DOI 10.1111/j.1476-5381.2010.00826.x; FERRARI M, 1990, J IMMUNOL METHODS, V131, P165, DOI 10.1016/0022-1759(90)90187-Z; Foraker AB, 2003, PHARMACEUT RES, V20, P110, DOI 10.1023/A:1022211127890; Franke TF, 1997, CELL, V88, P435, DOI 10.1016/S0092-8674(00)81883-8; Fruman DA, 2014, NAT REV DRUG DISCOV, V13, P140, DOI 10.1038/nrd4204; Hamanaka RB, 2009, ONCOGENE, V28, P910, DOI 10.1038/onc.2008.428; Heo SK, 2008, J CELL BIOCHEM, V105, P70, DOI 10.1002/jcb.21805; HUANG HC, 1992, EUR J PHARMACOL, V211, P359, DOI 10.1016/0014-2999(92)90393-I; Huang Q, 2007, MED RES REV, V27, P609, DOI 10.1002/med.20094; Iyer AK, 2006, DRUG DISCOV TODAY, V11, P812, DOI 10.1016/j.drudis.2006.07.005; Josse C., AM J PHYSL GASTROINT, V306; KAWAI K, 1984, TOXICOL LETT, V20, P155, DOI 10.1016/0378-4274(84)90141-3; Klarner T, 2014, BIOSYST BIOROBOT, V7, P479, DOI 10.1007/978-3-319-08072-7_71; Ko JC, 2010, BIOCHEM PHARMACOL, V79, P655, DOI 10.1016/j.bcp.2009.09.024; Krajnovic T, 2018, NANOMATERIALS-BASEL, V8, DOI 10.3390/nano8050322; Kumar R, 2008, ACS NANO, V2, P449, DOI 10.1021/nn700370b; KUPCHAN SM, 1976, LLOYDIA, V39, P223; KUROBANE I, 1979, J ANTIBIOT, V32, P1256, DOI 10.7164/antibiotics.32.1256; Lee CH, 2009, ADV FUNCT MATER, V19, P215, DOI 10.1002/adfm.200800753; Lee HZ, 2001, BRIT J PHARMACOL, V134, P11, DOI 10.1038/sj.bjp.0704205; Lien GS, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0104891; Lindqvist LM, 2014, P NATL ACAD SCI USA, V111, P8512, DOI 10.1073/pnas.1406425111; Liong M, 2008, ACS NANO, V2, P889, DOI 10.1021/nn800072t; Liu A, 2011, ONCOL REP, V26, P81, DOI 10.3892/or.2011.1257; Luna-Vargas MPA, 2016, FEBS J, V283, P2676, DOI 10.1111/febs.13624; Ma L, 2014, EXP THER MED, V8, P1225, DOI 10.3892/etm.2014.1900; Maksimovic-Ivanic D, 2019, J BIOL INORG CHEM, V24, P223, DOI 10.1007/s00775-019-01640-x; Malinowsky K, 2014, BRIT J CANCER, V110, P2081, DOI 10.1038/bjc.2014.100; Mellaerts R, 2007, CHEM COMMUN, P1375, DOI 10.1039/b616746b; Meng HA, 2010, J AM CHEM SOC, V132, P12690, DOI 10.1021/ja104501a; Mijatovic S, 2005, CELL MOL LIFE SCI, V62, P589, DOI 10.1007/s00018-005-4425-8; Mishra BB, 2011, EUR J MED CHEM, V46, P4769, DOI 10.1016/j.ejmech.2011.07.057; Mombeini M, 2018, MEDICINA-LITHUANIA, V54, DOI 10.3390/medicina54010001; Murai S, 2017, ANTICANCER RES, V37, P436, DOI 10.21873/anticanres.11335; Nuvoli B, 2014, MOL CANCER, V13, DOI 10.1186/1476-4598-13-69; Parish C. 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Sci. Eng. C-Mater. Biol. Appl.	FEB	2021	119								111619	10.1016/j.msec.2020.111619			10	Materials Science, Biomaterials	Science Citation Index Expanded (SCI-EXPANDED)	Materials Science	PI1PP	WOS:000600871200006	33321661				2022-04-25	
J	Schmitz, KJ; Ademi, C; Bertram, S; Schmid, KW; Baba, HA				Schmitz, Klaus Juergen; Ademi, Ceflije; Bertram, Stefanie; Schmid, Kurt Werner; Baba, Hideo Andreas			Prognostic relevance of autophagy-related markers LC3, p62/sequestosome 1, Beclin-1 and ULK1 in colorectal cancer patients with respect to KRAS mutational status	WORLD JOURNAL OF SURGICAL ONCOLOGY			English	Article						Colorectal cancer; Autophagy; p62; Beclin-1; LC3; ULK1	PROTEIN EXPRESSION; POOR-PROGNOSIS; P62; HYDROXYCHLOROQUINE; MTOR; PHOSPHORYLATION; TEMOZOLOMIDE; INHIBITION; P62/SQSTM1; KINASE	Background: Autophagy is a cellular pathway that regulates transportation of cytoplasmic macromolecules and organelles to lysosomes for degradation. Autophagy is involved in both tumorigenesis and tumour suppression. Here we investigated the potential prognostic value of the autophagy-related proteins Beclin-1, p62, LC3 and uncoordinated (UNC) 51-like kinase 1 (ULK1) in a cohort of colorectal cancer (CRC) specimens. Methods: In this study, we analysed the immunoexpression of the autophagy-related proteins p62, LC3, Beclin-1 and ULK1 in 127 CRC patients with known KRAS mutational status and detailed clinical follow-up. Results: Survival analysis of p62 staining showed a significant correlation of cytoplasmic (not nuclear) p62 expression with a favourable tumour-specific overall survival (OS). The prognostic power of cytoplasmic p62 was found in the KRAS-mutated subgroup but was lost in the KRAS wildtype subgroup. Survival analysis of Beclin-1 staining did not show an association with OS in the complete cohort. LC3 overexpression demonstrated a slight, though not significant, association with decreased OS. Upon stratifying cases by KRAS mutational status, nuclear (not cytoplasmic) Beclin-1 staining was associated with a significantly decreased OS in the KRAS-mutated subgroup but not in the KRAS wildtype CRCs. In addition, LC3 overexpression was significantly associated with decreased OS in the KRAS-mutated CRC subgroup. ULK1 expression was not correlated to survival. Conclusions: Immunohistochemical analyses of LC3, p62 and Beclin-1 may constitute promising novel prognostic markers in CRC, especially in KRAS-mutated CRCs. This strategy might help in identifying high-risk patients who would benefit from autophagy-related anticancer drugs.	[Schmitz, Klaus Juergen] Inst Pathol, Muhlenstr 31, D-45659 Recklinghausen, Germany; [Schmitz, Klaus Juergen; Bertram, Stefanie; Schmid, Kurt Werner; Baba, Hideo Andreas] Univ Duisburg Essen, Univ Hosp Essen, Inst Pathol, Hufelandstr 55, D-45147 Essen, Germany; [Ademi, Ceflije] Prosper Hosp Recklinghausen, Dept Senol, Muhlenstr 27, D-45659 Recklinghausen, Germany		Schmitz, KJ (corresponding author), Inst Pathol, Muhlenstr 31, D-45659 Recklinghausen, Germany.; Schmitz, KJ (corresponding author), Univ Duisburg Essen, Univ Hosp Essen, Inst Pathol, Hufelandstr 55, D-45147 Essen, Germany.	kjschmitz@pathologie-re.de					Adams O, 2016, ONCOTARGET, V7, P39241, DOI 10.18632/oncotarget.9649; Avalos Y, 2014, BIOMED RES INT, V2014, DOI 10.1155/2014/603980; Carew JS, 2007, BLOOD, V110, P313, DOI 10.1182/blood-2006-10-050260; Cerami E, 2012, CANCER DISCOV, V2, P401, DOI 10.1158/2159-8290.CD-12-0095; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Dong LW, 2011, AUTOPHAGY, V7, P1222, DOI 10.4161/auto.7.10.16610; Duffy A, 2015, CANCER CHEMOTH PHARM, V75, P439, DOI 10.1007/s00280-014-2637-z; Duran A, 2008, CANCER CELL, V13, P343, DOI 10.1016/j.ccr.2008.02.001; Egan DF, 2011, AUTOPHAGY, V7, P645, DOI 10.4161/auto.7.6.15123; Fei BY, 2016, ONCOL LETT, V11, P2271, DOI 10.3892/ol.2016.4183; Fullgrabe J, 2014, NAT REV MOL CELL BIO, V15, P65, DOI 10.1038/nrm3716; Gao C, 2010, NAT CELL BIOL, V12, P781, DOI 10.1038/ncb2082; Gao JJ, 2013, SCI SIGNAL, V6, DOI 10.1126/scisignal.2004088; Guo JY, 2011, GENE DEV, V25, P460, DOI 10.1101/gad.2016311; Han J, 2008, J BIOL CHEM, V283, P19665, DOI 10.1074/jbc.M710169200; Huang SB, 2011, J BIOL CHEM, V286, P40002, DOI 10.1074/jbc.M111.297432; Inoue D, 2012, CANCER SCI, V103, P760, DOI 10.1111/j.1349-7006.2012.02216.x; Inui T, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0074398; Jin ZY, 2009, CELL, V137, P721, DOI 10.1016/j.cell.2009.03.015; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Kim HS, 2011, PATHOL RES PRACT, V207, P247, DOI 10.1016/j.prp.2011.02.007; Klionsky DJ, 2008, AUTOPHAGY, V4, P740, DOI 10.4161/auto.6398; Klionsky DJ, 2012, AUTOPHAGY, V8, P445, DOI 10.4161/auto.19496; Ko YH, 2013, PANCREAS, V42, P829, DOI 10.1097/MPA.0b013e318279d0dc; Koukourakis MI, 2010, BRIT J CANCER, V103, P1209, DOI 10.1038/sj.bjc.6605904; Laddha SV, 2014, MOL CANCER RES, V12, P485, DOI 10.1158/1541-7786.MCR-13-0614; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Linares JF, 2011, MOL CELL BIOL, V31, P105, DOI 10.1128/MCB.00620-10; Liu JL, 2014, BRIT J CANCER, V111, P944, DOI 10.1038/bjc.2014.355; Lock R, 2011, MOL BIOL CELL, V22, P165, DOI 10.1091/mbc.E10-06-0500; Luo Rong-Zhen, 2013, Onco Targets Ther, V6, P883, DOI 10.2147/OTT.S46222; Mahalingam D, 2014, AUTOPHAGY, V10, P1403, DOI 10.4161/auto.29231; Masuda G, 2016, ANTICANCER RES, V36, P129; Mohamed A, 2015, FRONT ONCOL, V5, DOI [10.3389/fonc.2015.00070, 10.1158/1541-7786.MCR-06-0182]; Moscat J, 2012, TRENDS BIOCHEM SCI, V37, P230, DOI 10.1016/j.tibs.2012.02.008; Park JM, 2013, CANCER BIOL THER, V14, P100, DOI 10.4161/cbt.22954; Pattingre S, 2008, BIOCHIMIE, V90, P313, DOI 10.1016/j.biochi.2007.08.014; Rabinowitz JD, 2010, SCIENCE, V330, P1344, DOI 10.1126/science.1193497; Rangwala R, 2014, AUTOPHAGY, V10, P1369, DOI 10.4161/auto.29118; Rosenfeld MR, 2014, AUTOPHAGY, V10, P1359, DOI 10.4161/auto.28984; Sahni S, 2014, J CLIN PATHOL, V67, P656, DOI 10.1136/jclinpath-2014-202356; Schlafli AM, 2015, EUR J HISTOCHEM, V59, P137, DOI 10.4081/ejh.2015.2481; Schmitz KJ, 2007, VIRCHOWS ARCH, V450, P151, DOI 10.1007/s00428-006-0342-y; Wu SH, 2015, INT J CLIN EXP PATHO, V8, P3882; Yuan N, 2015, HAEMATOLOGICA, V100, P345, DOI 10.3324/haematol.2014.113324; Zou YF, 2015, ONCOL LETT, V10, P1583, DOI 10.3892/ol.2015.3417	46	65	71	1	5	BMC	LONDON	CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	1477-7819			WORLD J SURG ONCOL	World J. Surg. Oncol.	JUL 22	2016	14								189	10.1186/s12957-016-0946-x			13	Oncology; Surgery	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Surgery	DR9SB	WOS:000380235300001	27444698	Green Published, gold			2022-04-25	
J	Yang, XY; Niu, BX; Wang, LB; Chen, ML; Kang, XC; Wang, LN; Ji, YH; Zhong, JT				Yang, Xiaoyu; Niu, Bingxuan; Wang, Libo; Chen, Meiling; Kang, Xiaochun; Wang, Luonan; Ji, Yinghua; Zhong, Jiateng			Autophagy inhibition enhances colorectal cancer apoptosis induced by dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235	ONCOLOGY LETTERS			English	Article						NVP-BEZ235; autophagy; apoptosis; colorectal cancer; phosphatidylinositol 3-kinase/mammalian target of rapamycin	PI3K/MTOR INHIBITOR; BREAST-CANCER; CELL-LINES; PATHWAY; GROWTH; ANTICANCER; ACTIVATION; MECHANISM; THERAPY; STRESS	Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway performs a central role in tumorigenesis and is constitutively activated in many malignancies. As a novel dual PI3K/mTOR inhibitor currently undergoing evaluation in a phase I/II clinical trial, NVP-BEZ235 indicates a significant antitumor efficacy in diverse solid tumors, including colorectal cancer (CRC). Autophagy is a catabolic process that maintains cellular homeostasis and reduces diverse stresses through lysosomal recycling of the unnecessary and damaged cell components. This process is also observed to antagonize the antitumor efficacy of PI3K/mTOR inhibitor agents such as NVP-BEZ235, via apoptosis inhibition. In the present study, we investigated anti-proliferative and apoptosis-inducing ability of NVP-BEZ235 in SW480 cells and the crosstalk between autophagy and apoptosis in SW480 cells treated with NVP-BEZ235 in combination with an autophagy inhibitor. The results revealed that, NVP-BEZ235 effectively inhibit the growth of SW480 cells by targeting the PI3K/mTOR signaling pathway and induced apoptosis. The inhibition of autophagy with 3-methyladenine or chloroquine inhibitors in combination with NVP-BEZ235 in SW480 cells enhanced the apoptotic rate as componets to NVP-BEZ235 alone. In conclusion, the findings provide a rationale for chemotherapy targeting the PI3K/mTOR signaling pathway presenting a potential therapeutic strategy to enhance the efficacy of dual PI3K/mTOR inhibitor NVP-BEZ235 in combination with an autophagy inhibitor in CRC treatment and treatment of other tumors.	[Yang, Xiaoyu; Zhong, Jiateng] Xinxiang Med Univ, Dept Pathol, 96 Xinfei St, Xinxiang 453003, Henan, Peoples R China; [Niu, Bingxuan] Xinxiang Med Univ, Coll Pharm, Xinxiang 453003, Henan, Peoples R China; [Wang, Libo] Jilin Univ, Affiliated Hosp 1, Dept Gastroenterol, Changchun 130021, Jilin, Peoples R China; [Chen, Meiling; Kang, Xiaochun; Wang, Luonan; Ji, Yinghua] Xinxiang Med Univ, Affiliated Hosp 1, Dept Oncol, Xinxiang 453100, Henan, Peoples R China		Zhong, JT (corresponding author), Xinxiang Med Univ, Dept Pathol, 96 Xinfei St, Xinxiang 453003, Henan, Peoples R China.	si148w@163.com					Atkin WS, 2010, LANCET, V375, P1624, DOI 10.1016/S0140-6736(10)60551-X; Brachmann SM, 2009, P NATL ACAD SCI USA, V106, P22299, DOI 10.1073/pnas.0905152106; Carpten JD, 2007, NATURE, V448, P439, DOI 10.1038/nature05933; Carracedo A, 2008, J CLIN INVEST, V118, P3065, DOI [10.1172/jCI34739, 10.1172/JCI34739]; Cerniglia GJ, 2012, MOL PHARMACOL, V82, P1230, DOI 10.1124/mol.112.080408; Chen HY, 2011, CANCER PREV RES, V4, P973, DOI 10.1158/1940-6207.CAPR-10-0387; Denton D, 2012, CELL DEATH DIFFER, V19, P87, DOI 10.1038/cdd.2011.146; Eisenberg-Lerner A, 2009, CELL DEATH DIFFER, V16, P966, DOI 10.1038/cdd.2009.33; Engelman JA, 2006, NAT REV GENET, V7, P606, DOI 10.1038/nrg1879; Fan QW, 2006, CANCER CELL, V9, P341, DOI 10.1016/j.ccr.2006.03.029; Filomeni G, 2015, CELL DEATH DIFFER, V22, P377, DOI 10.1038/cdd.2014.150; Fujiwara K, 2007, INT J ONCOL, V31, P753; Generali D, 2008, CLIN CANCER RES, V14, P2673, DOI 10.1158/1078-0432.CCR-07-1046; Ghadimi MP, 2012, MOL CANCER THER, V11, P1758, DOI 10.1158/1535-7163.MCT-12-0015; Herrera VA, 2011, ANTICANCER RES, V31, P849; Janku F, 2011, NAT REV CLIN ONCOL, V8, P528, DOI 10.1038/nrclinonc.2011.71; Kurtz JE, 2012, ANTICANCER RES, V32, P2463; Lao VV, 2011, NAT REV GASTRO HEPAT, V8, P686, DOI 10.1038/nrgastro.2011.173; Li MX, 2014, INT J CANCER, V134, P2403, DOI 10.1002/ijc.28536; Li QG, 2011, BMC CANCER, V11, DOI 10.1186/1471-2407-11-277; Liu TJ, 2009, MOL CANCER THER, V8, P2204, DOI 10.1158/1535-7163.MCT-09-0160; Maira SM, 2008, MOL CANCER THER, V7, P1851, DOI 10.1158/1535-7163.MCT-08-0017; Markman B, 2010, ONCOTARGET, V1, P530, DOI 10.18632/oncotarget.188; Masuda M, 2011, ONCOL REP, V26, P1273, DOI 10.3892/or.2011.1370; Mathur A, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0098515; McMillin DW, 2009, CANCER RES, V69, P5835, DOI 10.1158/0008-5472.CAN-08-4285; Mirzoeva OK, 2011, J MOL MED, V89, P877, DOI 10.1007/s00109-011-0774-y; Murrow L, 2013, ANNU REV PATHOL-MECH, V8, P105, DOI 10.1146/annurev-pathol-020712-163918; Ogino S, 2008, J MOL DIAGN, V10, P13, DOI 10.2353/jmoldx.2008.070082; Potter DS, 2014, NEOPLASIA, V16, P147, DOI 10.1593/neo.131376; Prevo R, 2008, CANCER RES, V68, P5915, DOI 10.1158/0008-5472.CAN-08-0757; Rubinsztein DC, 2012, NAT REV DRUG DISCOV, V11, P709, DOI 10.1038/nrd3802; Samuels Y, 2005, CANCER CELL, V7, P561, DOI 10.1016/j.ccr.2005.05.014; Samuels Y, 2004, SCIENCE, V304, P554, DOI 10.1126/science.1096502; Scarlatti F, 2009, CELL DEATH DIFFER, V16, P12, DOI 10.1038/cdd.2008.101; Wan X, 2007, ONCOGENE, V26, P1932, DOI 10.1038/sj.onc.1209990; Xu CX, 2011, CANCER BIOL THER, V12, P549, DOI 10.4161/cbt.12.6.16397; Yang F, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0059879; Yang SJ, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0026343; Yang Y, 2010, BIOCHEM BIOPH RES CO, V395, P190, DOI 10.1016/j.bbrc.2010.03.155; Zimonin F S, 1973, Veterinariia, V8, P69; Zoncu R, 2011, NAT REV MOL CELL BIO, V12, P21, DOI 10.1038/nrm3025	42	19	21	0	5	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	JUL	2016	12	1					102	106		10.3892/ol.2016.4590			5	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DR5RN	WOS:000379960200018	27347108	Green Published, gold, Green Submitted			2022-04-25	
J	He, C; Fu, Y; Chen, Y; Li, XQ				He, Chi; Fu, Yi; Chen, Yan; Li, Xiquan			Long non-coding RNA SNHG8 promotes autophagy as a ceRNA to upregulate ATG7 by sponging microRNA-588 in colorectal cancer	ONCOLOGY LETTERS			English	Article						SNHG8; autophagy; CRC; ATG7; microRNA-588	CELL-PROLIFERATION; LUNG-CANCER; MIGRATION; INVASION; PROGRESSION; METASTASIS; STATISTICS; APOPTOSIS	Colorectal cancer (CRC) is the third most common cancer worldwide. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 8 (SNHG8) acts as an oncogene in different types of cancer, including prostate, breast and ovarian cancer. SNHG8 promotes the tumorigenesis of CRC; however, its underlying molecular mechanism remains unclear. The present study aimed to explore the mechanism of SNHG8 on CRC development via various assays, including western blot, pull-down, PCR and immunofluorescence assays. The results of the present study demonstrated that SNHG8 expression was substantially upregulated in primary tumor tissues from The Cancer Genome Atlas dataset. Western blot and immunofluorescence analyses demonstrated that SNHG8 facilitated cell proliferation and autophagy in CRC cells. Notably, the function of SNHG8 in enhancing autophagy was dependent on autophagy-related gene 7 (ATG7). In addition, western blot analysis indicated that the effect of SNHG8 on autophagy in CRC cells was dependent on the miR-588/ATG7 axis. Taken together, the results of the present study suggest that SNHG8 promotes autophagy in CRC cells.	[He, Chi; Li, Xiquan] Shenyang Anorectal Hosp, Dept Gen Surg, 9 Nanjingbei St, Shenyang 110054, Liaoning, Peoples R China; [Fu, Yi] Dalian Med Univ, Dept Gen Surg, Hosp 2, Dalian 116000, Liaoning, Peoples R China; [Chen, Yan] Daqing Oilfield Gen Hosp, Dept Gen Surg, Daqing 163000, Heilongjiang, Peoples R China		Li, XQ (corresponding author), Shenyang Anorectal Hosp, Dept Gen Surg, 9 Nanjingbei St, Shenyang 110054, Liaoning, Peoples R China.	shenyang_xiquan@126.com					Amaravadi R, 2016, GENE DEV, V30, P1913, DOI 10.1101/gad.287524.116; Cao QH, 2016, AM J TRANSL RES, V8, P3831; Dikic I, 2018, NAT REV MOL CELL BIO, V19, P349, DOI 10.1038/s41580-018-0003-4; Fan D, 2020, EUR REV MED PHARMACO, V24, P11639, DOI 10.26355/eurrev_202011_23808; Guo CT, 2020, ONCOL LETT, V20, DOI 10.3892/ol.2020.12139; Jin KT, 2021, BIOMED PHARMACOTHER, V134, DOI 10.1016/j.biopha.2020.110932; Kang Y, 2019, ONCOTARGETS THER, V12, P10787, DOI 10.2147/OTT.S226044; Kohlhapp FJ, 2015, ONCOGENE, V34, P5857, DOI 10.1038/onc.2015.89; Kroemer G, 2015, J CLIN INVEST, V125, P1, DOI 10.1172/JCI78652; Li CF, 2018, CELL PHYSIOL BIOCHEM, V50, P196, DOI 10.1159/000493968; Li C, 2015, AM J TRANSL RES, V7, P1747; Li HR, 2004, CANCER RES, V64, P4760, DOI 10.1158/0008-5472.CAN-04-0975; Li XM, 2020, ONCOL LETT, V20, DOI 10.3892/ol.2020.12219; Li XY, 2019, BIOMED PHARMACOTHER, V119, DOI 10.1016/j.biopha.2019.109415; Lin LQ, 2021, J CELL MOL MED, V25, P61, DOI 10.1111/jcmm.15759; Liu AH, 2019, AM J TRANSL RES, V11, P5240; Liu JY, 2019, BIOMED PHARMACOTHER, V114, DOI 10.1016/j.biopha.2019.108847; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Luo M, 2013, CANCER LETT, V333, P213, DOI 10.1016/j.canlet.2013.01.033; Ma HB, 2018, J CELL BIOCHEM, V119, P8325, DOI 10.1002/jcb.26883; Masters JR, 2001, P NATL ACAD SCI USA, V98, P8012, DOI 10.1073/pnas.121616198; Miao Wei, 2020, Cancer Biomark, V28, P459, DOI 10.3233/CBM-190640; Mukhopadhyay S, 2021, P NATL ACAD SCI USA, V118, DOI 10.1073/pnas.2021475118; Qian L, 2016, MOL MED REP, V14, P3021, DOI 10.3892/mmr.2016.5643; Qu XH, 2020, J CELL BIOCHEM, V121, P4120, DOI 10.1002/jcb.29646; Shi ZF, 2021, J GENE MED, V23, DOI 10.1002/jgm.3309; Shukla Girish C, 2011, Mol Cell Pharmacol, V3, P83; Si YR, 2019, CELL MOL BIOL LETT, V24, DOI 10.1186/s11658-019-0175-8; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Tang B, 2019, GENE, V686, P56, DOI 10.1016/j.gene.2018.10.059; Xu JL, 2020, FRONT CELL DEV BIOL, V8, DOI 10.3389/fcell.2020.621428; Yan XH, 2015, CANCER CELL, V28, P529, DOI 10.1016/j.ccell.2015.09.006; Yang L, 2019, GENE, V697, P94, DOI 10.1016/j.gene.2019.02.036; Ying SY, 2008, MOL BIOTECHNOL, V38, P257, DOI 10.1007/s12033-007-9013-8; Yu M, 2017, MED SCI MONITOR, V23, P5690, DOI 10.12659/MSM.905126; Yu XZ, 2020, ONCOTARGETS THER, V13, P11645, DOI 10.2147/OTT.S271955; Yun CW, 2021, INT J MOL SCI, V22, DOI 10.3390/ijms22010179; Zhang PG, 2020, HUM CELL, V33, P123, DOI 10.1007/s13577-019-00290-0	39	2	2	2	7	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	AUG	2021	22	2							577	10.3892/ol.2021.12838			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	SP6VU	WOS:000659805500001	34122628	Green Published, gold			2022-04-25	
J	Noble, CL; Abbas, AR; Lees, CW; Cornelius, J; Toy, K; Modrusan, Z; Clark, HF; Arnott, ID; Penman, ID; Satsangi, J; Diehl, L				Noble, Colin L.; Abbas, Alexander R.; Lees, Charles W.; Cornelius, Jennine; Toy, Karen; Modrusan, Zora; Clark, Hilary F.; Arnott, Ian D.; Penman, Ian D.; Satsangi, Jack; Diehl, Lauri			Characterization of Intestinal Gene Expression Profiles in Crohn's Disease by Genome-wide Microarray Analysis	INFLAMMATORY BOWEL DISEASES			English	Article						genome-wide microarray analysis; Crohn's disease; gene expression; Th17 signalling; autophagy	INFLAMMATORY-BOWEL-DISEASE; COLONIC EPITHELIAL-CELLS; ULCERATIVE-COLITIS; SUSCEPTIBILITY; ASSOCIATION; CHEMOKINES; CANCERS; FAT10; HOMEOSTASIS; CYTOKINES	Background: Genome-wide microarray expression analysis creates a comprehensive picture of gene expression at the cellular level. The aim of this study was to investigate differential intestinal gene expression in patients with Crohn's disease (CD) and controls with subanalysis of confirmed CD susceptibility genes, associated pathways, and cell lineage. Methods: In all, 172 biopsies from 53 CD and 31 control subjects were studied. Paired endoscopic biopsies were taken at ileo-colonoscopy from five specific anatomical locations including the terminal ileum (TI) for RNA extraction and histology. The 41,058 expression sequence tags were analyzed using the Agilent platform. Results: Analysis of all CD biopsies versus controls showed 259 sequences were upregulated and 87 sequences were downregulated. Upregulated genes in CD included SAA1 (fold change [FC] +7.5, P = 1.47 x 10(-41)) and REGL (FC +7.3, P = 2.3 x 10(-16)), whereas cellular detoxification genes including-SLC14A2 (FC-2.49, P = 0.00002) were downregulated. In the CD TI biopsies diubiquitin (FC+11.3, P < 1 x 10(-45)), MMP3 (FC+7.4, P = 1.3 x 10(-11)), and IRTA1 (FC-11.4, P = 4.7 x 10(-12)) were differentially expressed compared to controls. In the colon SAA1 (FC+6.3, P = 5.3 x 10(-8)) was upregulated and thymic stromal lymphopoietin (TSLP) (FC-2.3, P = 2.7 x 10(-6)) was downregulated comparing noninflamed CD and control biopsies, and the colonic inflammatory CD signature was characterized by downregulation of the organic solute carriers-SLC38A4, SLC26A2, and OST alpha. Of CD susceptibility genes identified by genome-wide association scan IL-23A, JAK2, and STAT3 were upregulated in the CD group, confirming the dysregulation of Th17 signaling. Conclusions: These data characterize the dysregulation of a series of specific inflammatory pathways highlighting potential pathogenic mechanisms as well as areas for translation to therapeutic targets.	[Noble, Colin L.] Univ Edinburgh, Western Gen Hosp, Gastrointestinal Unit, Mol Med Ctr,MRCP, Edinburgh EH4 2XU, Midlothian, Scotland; [Noble, Colin L.; Cornelius, Jennine; Diehl, Lauri] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA; [Abbas, Alexander R.; Clark, Hilary F.] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA; [Toy, Karen; Modrusan, Zora] Genentech Inc, Microarray Dept, San Francisco, CA 94080 USA		Noble, CL (corresponding author), Univ Edinburgh, Western Gen Hosp, Gastrointestinal Unit, Mol Med Ctr,MRCP, Edinburgh EH4 2XU, Midlothian, Scotland.	noblecolin@hotmail.com		Lees, Charlie/0000-0002-0732-8215	Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [G0800675, G0600329, G0800759] Funding Source: Medline; Chief Scientist Office [CZB/4/540] Funding Source: Medline; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [G0600329, G0800759, G0800675] Funding Source: UKRI		Al-Shami A, 2005, J EXP MED, V202, P829, DOI 10.1084/jem.20050199; Aldhous MC, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0006285; Banks C, 2003, J PATHOL, V199, P28, DOI 10.1002/path.1245; Barrett JC, 2008, NAT GENET, V40, P955, DOI 10.1038/ng.175; Burton PR, 2007, NATURE, V447, P661, DOI 10.1038/nature05911; Cho JH, 2007, GASTROENTEROLOGY, V133, P1327, DOI 10.1053/j.gastro.2007.08.032; Costello CM, 2005, PLOS MED, V2, P771, DOI 10.1371/journal.pmed.0020199; Duerr RH, 2006, SCIENCE, V314, P1461, DOI 10.1126/science.1135245; Dwinell MB, 2001, GASTROENTEROLOGY, V120, P49, DOI 10.1053/gast.2001.20914; Fan WF, 1996, IMMUNOGENETICS, V44, P97, DOI 10.1007/BF02660056; Gaya DR, 2006, LANCET, V367, P1271, DOI 10.1016/S0140-6736(06)68345-1; Gutfeld O, 2006, J HISTOCHEM CYTOCHEM, V54, P63, DOI 10.1369/jhc.5A6645.2005; Hugot JP, 2001, NATURE, V411, P599, DOI 10.1038/35079107; Kwon JH, 2002, GUT, V51, P818, DOI 10.1136/gut.51.6.818; Lawrance IC, 2001, HUM MOL GENET, V10, P445, DOI 10.1093/hmg/10.5.445; Lee CGL, 2003, ONCOGENE, V22, P2592, DOI 10.1038/sj.onc.1206337; Lee JW, 2008, J IMMUNOL, V181, P6536, DOI 10.4049/jimmunol.181.9.6536; LEES CW, 2009, INFLAMM BOWEL DIS MO, V9; LENNARDJONES JE, 1989, SCAND J GASTROENTERO, V24, P2, DOI 10.3109/00365528909091339; Lukasiak S, 2008, ONCOGENE, V27, P6068, DOI 10.1038/onc.2008.201; Madsen L, 2007, BMC BIOCHEM, V8, DOI 10.1186/1471-2091-8-S1-S1; Maloy KJ, 2008, MUCOSAL IMMUNOL, V1, P339, DOI 10.1038/mi.2008.28; Noble CL, 2008, GUT, V57, P1398, DOI 10.1136/gut.2008.148395; Ogura Y, 2001, NATURE, V411, P603, DOI 10.1038/35079114; Puleston J, 2005, ALIMENT PHARM THER, V21, P109, DOI 10.1111/j.1365-2036.2004.02262.x; Ren JW, 2006, J BIOL CHEM, V281, P11413, DOI 10.1074/jbc.M507218200; Sandborn WJ, 2008, GASTROENTEROLOGY, V135, P1130, DOI 10.1053/j.gastro.2008.07.014; Sanjuan MA, 2007, NATURE, V450, P1253, DOI 10.1038/nature06421; Simms LA, 2008, GUT, V57, P903, DOI 10.1136/gut.2007.142588; Storey JD, 2003, P NATL ACAD SCI USA, V100, P9440, DOI 10.1073/pnas.1530509100; Strober W, 2007, J CLIN INVEST, V117, P514, DOI 10.1172/JCI30587; Travassos LH, 2010, NAT IMMUNOL, V11, P55, DOI 10.1038/ni.1823; Wehkamp J, 2005, P NATL ACAD SCI USA, V102, P18129, DOI 10.1073/pnas.0505256102; Yang SK, 1997, GASTROENTEROLOGY, V113, P1214, DOI 10.1053/gast.1997.v113.pm9322516; Zaph C, 2007, NATURE, V446, P552, DOI 10.1038/nature05590; Zhang DW, 2006, ONCOGENE, V25, P2318, DOI 10.1038/sj.onc.1209220	36	60	60	0	2	OXFORD UNIV PRESS INC	CARY	JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA	1078-0998	1536-4844		INFLAMM BOWEL DIS	Inflamm. Bowel Dis.	OCT	2010	16	10					1717	1728		10.1002/ibd.21263			12	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	660EV	WOS:000282623700016	20848455				2022-04-25	
J	Yan, SY; Yuan, DD; Li, QQ; Li, S; Zhang, F				Yan, Siyuan; Yuan, Dongdong; Li, Qianqian; Li, Shi; Zhang, Fan			AICAR enhances the cytotoxicity of PFKFB3 inhibitor in an AMPK signaling-independent manner in colorectal cancer cells	MEDICAL ONCOLOGY			English	Article						PFKFB3; Cell viability; AICAR; AMPK signaling; Colorectal cancer	UBIQUITIN-PROTEASOME SYSTEM; AUTOPHAGIC DEGRADATION; PROTEIN-KINASE; PHOSPHORYLATION; AKT; COORDINATE; PATHWAY; DEATH; ULK1	Numerous studies have shown that 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), a pivotal enzyme in modulating glycolysis, plays vital roles in various physiological processes. PFKFB3 activity could be regulated by several factors, such as hypoxia and AMPK signaling; however, it could also function as upstream of AMPK signaling. Here, we showed that PFKFB3 inhibitor PFK-15 induced cell viability loss and apoptosis. Deprivation of PFKFB3 inhibited autophagy, while enhanced the ubiquitin-proteasome degradation pathway. Furthermore, PFK-15 reduced both the AMPK and AKT-mTORC1 signaling pathways, as the attenuated phosphorylation level of kinases themselves and their substrates. The addition of AICAR rescued the AMPK activity and autophagy, but enhanced PFK-15-induced cell viability loss. In fact, AICAR promoted the cytotoxicity of PFK-15 even in the AMPK alpha 1/2-silenced cells, indicating AICAR might function in an AMPK-independent manner. Nevertheless, AICAR further reduced the AKT-mTORC1 activity down-regulated by PFK-15. Moreover, it failed to enhance PFK-15's cytotoxicity in the AKT1/2-silenced cells, indicating AKT-mTORC1 participated during these processes. Collectively, the presented data demonstrated that PFK-15 inhibited cell viability, AMPK, and AKT-mTORC1 signaling, and AICAR probably enhanced the cell viability loss aroused by PFK-15 in an AKT-dependent and AMPK-independent manner, thereby revealing a more intimate relationship among PFKFB3, AMPK, and AKT-mTORC1 signaling pathways.	[Yan, Siyuan; Li, Qianqian; Li, Shi] Jining Med Univ, Key Lab Precis Oncol Univ Shandong, Inst Precis Med, Jining 272067, Peoples R China; [Yuan, Dongdong] Shandong Acad Pharmaceut Sci, Jinan 250101, Peoples R China; [Zhang, Fan] Zhengzhou Univ, Dept Bone & Soft Tissue Oncol, Affiliated Canc Hosp, Zhengzhou 450008, Peoples R China		Yan, SY (corresponding author), Jining Med Univ, Key Lab Precis Oncol Univ Shandong, Inst Precis Med, Jining 272067, Peoples R China.; Zhang, F (corresponding author), Zhengzhou Univ, Dept Bone & Soft Tissue Oncol, Affiliated Canc Hosp, Zhengzhou 450008, Peoples R China.	yansy@mail.jnmc.edu.cn; zhangfan_1109@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31801169]; Miaopu Funds from Henan Cancer Hospital; Jining Medical University; Teacher Research Support Foundation in Jining Medical University [JYFC2018KJ065]	This work was supported by Grants from the National Natural Science Foundation of China (31801169), the Miaopu Funds from Henan Cancer Hospital (to Fan Zhang), the Faculty Start-up Funds from Jining Medical University (to Yan S.), and the Teacher Research Support Foundation in Jining Medical University (JYFC2018KJ065).	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Oncol.	JAN	2022	39	1							10	10.1007/s12032-021-01601-y			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	WV0QY	WOS:000716943200004	34761330				2022-04-25	
J	Lee, YC; Lee, CH; Tsai, HP; An, HW; Lee, CM; Wu, JC; Chen, CS; Huang, SH; Hwang, J; Cheng, KT; Leiw, PL; Chen, CL; Lin, CM				Lee, Yu-Chieh; Lee, Chii-Hong; Tsai, Hsiang-Ping; An, Herng-Wei; Lee, Chi-Ming; Wu, Jen-Chine; Chen, Chien-Shu; Huang, Shih-Hao; Hwang, Jaulang; Cheng, Kur-Ta; Leiw, Phui-Ly; Chen, Chi-Long; Lin, Chun-Mao			Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer	PLOS ONE			English	Article							CYCLIN D1; COLORECTAL-CANCER; CARCINOMA-CELLS; EVODIAMINE; APOPTOSIS; INHIBITION; TUMORS; EXPRESSION; AUTOPHAGY; VITRO	DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers.	[Lee, Yu-Chieh; An, Herng-Wei; Lee, Chi-Ming] Taipei Med Univ, Grad Inst Med Sci, Coll Med, Taipei, Taiwan; [Lee, Chii-Hong; Leiw, Phui-Ly] Taipei Med Univ, Shuang Ho Hosp, Dept Pathol, New Taipei City, Taiwan; [Tsai, Hsiang-Ping; Hwang, Jaulang; Cheng, Kur-Ta; Lin, Chun-Mao] Taipei Med Univ, Sch Med, Dept Biochem, Taipei, Taiwan; [Wu, Jen-Chine] Chang Gung Mem Hosp, Ctr Stem Cells & Translat Canc Res, Gueishan, Taoyuan County, Taiwan; [Chen, Chien-Shu] China Med Univ, Sch Pharm, Taichung, Taiwan; [Huang, Shih-Hao] Taipei Coll Maritime Technol, Dept Food & Beverage Management, Taipei, Taiwan; [Chen, Chi-Long] Taipei Med Univ, Dept Pathol, Coll Med, Taipei, Taiwan; [Chen, Chi-Long] Taipei Med Univ Hosp, Dept Pathol, Taipei, Taiwan		Lin, CM (corresponding author), Taipei Med Univ, Sch Med, Dept Biochem, Taipei, Taiwan.	cmlin@tmu.edu.tw		Lin, Chun-Mao/0000-0002-8366-4026	National Science Council, TaiwanMinistry of Science and Technology, Taiwan [NSC101-2320-B-038-023]; Ministry of Health Welfare [MOHW104-TDU-B-212-113001]; Taipei Medical University-Shuang Ho Hospital [101TMU-SHH-10]	This study was supported by grants from the National Science Council, Taiwan (NSC101-2320-B-038-023), the Ministry of Health & Welfare (MOHW104-TDU-B-212-113001), and Taipei Medical University-Shuang Ho Hospital (101TMU-SHH-10).	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J	Foerster, EG; Mukherjee, T; Cabral-Fernandes, L; Rocha, JDB; Girardin, SE; Philpott, DJ				Foerster, Elisabeth G.; Mukherjee, Tapas; Cabral-Fernandes, Liliane; Rocha, Juliana D. B.; Girardin, Stephen E.; Philpott, Dana J.			How autophagy controls the intestinal epithelial barrier	AUTOPHAGY			English	Review						Autophagy; Crohn disease; IBD; intestinal epithelium; intestinal stem cells; MTOR	INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; ER STRESS; COLORECTAL-CANCER; GENE ATG16L1; SUSCEPTIBILITY LOCI; PANETH CELLS; STEM-CELLS; SELECTIVE AUTOPHAGY	Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well as the destruction of intracellular pathogens. Its role in the maintenance of the intestinal epithelium is of particular interest, as several autophagy-related genes have been associated with intestinal disease. Autophagy and its regulatory mechanisms are involved in both homeostasis and repair of the intestine, supporting intestinal barrier function in response to cellular stress through tight junction regulation and protection from cell death. Furthermore, a clear role has emerged for autophagy not only in secretory cells but also in intestinal stem cells, where it affects their metabolism, as well as their proliferative and regenerative capacity. Here, we review the physiological role of autophagy in the context of intestinal epithelial maintenance and how genetic mutations affecting autophagy contribute to the development of intestinal disease.	[Foerster, Elisabeth G.; Mukherjee, Tapas; Rocha, Juliana D. B.; Girardin, Stephen E.; Philpott, Dana J.] Univ Toronto, Dept Immunol, Toronto, ON, Canada; [Mukherjee, Tapas; Cabral-Fernandes, Liliane; Girardin, Stephen E.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada		Philpott, DJ (corresponding author), Univ Toronto, Dept Immunol, Toronto, ON, Canada.	dana.philpott@utoronto.ca		Foerster, Elisabeth/0000-0002-3271-0782	Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [FDN-14333]; Natural Sciences and Engineering CouncilNatural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-201]	This work was supported by the Canadian Institutes of Health Research [MOP-12353]; Canadian Institutes of Health Research [FDN-14333]; Natural Sciences and Engineering Council [RGPIN-201].	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J	Liu, XH; Xu, YJ; Li, Y; Pan, YC; Sun, ZH; Zhao, SL; Hou, YY				Liu, Xinghan; Xu, Yujun; Li, Yi; Pan, Yuchen; Sun, Zhiheng; Zhao, Shuli; Hou, Yayi			Ganoderma lucidum fruiting body extracts inhibit colorectal cancer by inducing apoptosis, autophagy, and G0/G1 phase cell cycle arrest in vitro and in vivo	AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH			English	Article						Ganoderma lucidum fruiting body extracts; colorectal cancer; apoptosis; autophagy	POLYSACCHARIDES	Although previous studies have found that Ganoderma lucidum extracts have the ability to directly resist tumor proliferation and reduce metastasis and invasion, the effect of the extracts of Ganoderma lucidum fruiting body (GLE) on cancer is not clarified. This study intends to investigate the anticancer role of GLE on HCT116 colorectal cancer cells in vitro and in vivo. The effects of GLE on the proliferation, apoptosis, autophagy and cell cycle arrest of HCT116 cells were detected by cell counting kit-8 (CCK-8), flow cytometry, electron microscope, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. Xenografted mouse models were used to evaluate the tumor growth inhibition effect of GLE in vivo. GLE could significantly inhibit the viability of four tumor cell lines (A549, SW1990, SKOV3 and HCT116) and HCT116 cells were more sensitive to GLE treatment with a half inhibitory concentration of 106 mu g/mL. GLE treatment induced apoptosis of HCT116 cells by downregulating of the ratio of Bcl-2 to Bax and increasing cleaved caspase-3 and poly ADP-ribose polymerase (PARP) protein expression. Autophagy of HCT116 cells also increased after GLE treatment, as shown by observation of autophagosomes formation and altered protein expressions in the mTOR pathway. In addition, GLE treatment led to G0/G1 cell cycle arrest as evidenced by flow cytometry analysis and changes in cell-cycle-related gene expressions at the mRNA levels. Of note, in vivo evaluation indicated that GLE significantly inhibited tumor weight and tumor volume and decreased Ki67 expression. In summary, GLE has potential to be developed as an anticancer agent against colorectal cancer, and further evaluation is needed.	[Liu, Xinghan; Xu, Yujun; Li, Yi; Pan, Yuchen; Sun, Zhiheng; Hou, Yayi] Nanjing Univ, Med Sch, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China; [Zhao, Shuli] Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing 210006, Peoples R China; [Hou, Yayi] Nanjing Univ, Jiangsu Key Lab Mol Med, Nanjing 210093, Peoples R China		Hou, YY (corresponding author), Nanjing Univ, Med Sch, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China.; Zhao, SL (corresponding author), Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing 210006, Peoples R China.	shulizhao79@163.com; yayihou@nju.edu.cn			special fund for Provincial Key Research and Development of Jiangsu Province [BE2019617]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572557, 81872114]	This work was supported by a special fund for Provincial Key Research and Development of Jiangsu Province (grant number: BE2019617) and the National Natural Science Foundation of China (grant number: 81572557, 81872114).	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J. Transl. Res.		2020	12	6					2675	2684					10	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	MJ7DE	WOS:000548246400006	32655799				2022-04-25	
J	Zheng, HC; Zhao, S; Xue, H; Zhao, EH; Jiang, HM; Hao, CL				Zheng, Hua-chuan; Zhao, Shuang; Xue, Hang; Zhao, En-hong; Jiang, Hua-mao; Hao, Chang-lai			The Roles of Beclin 1 Expression in Gastric Cancer: A Marker for Carcinogenesis, Aggressive Behaviors and Favorable Prognosis, and a Target of Gene Therapy	FRONTIERS IN ONCOLOGY			English	Article						Beclin 1; gastric cancer; gene therapy; carcinogenesis; aggressive behaviors; prognosis	EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL-CANCER; INDUCED APOPTOSIS; POOR-PROGNOSIS; AUTOPHAGY; PROMOTES; INVASION; BECN1; TUMORIGENESIS; SENSITIVITY	Beclin 1 is encoded by Becn1, and plays a role in tumorigenesis, neurodegeneration, apoptosis and autophagy. Here, the aggressive phenotypes and relevant proteins were examined after Beclin 1 expression was altered in gastric cancer cells. We also observed the effects of Beclin 1 on gastric carcinogenesis using Becn1 knockout mice. Finally, clinicopathological significances of Beclin 1 expression were analyzed using meta- and bioinformatics analyses. Becn1 overexpression was found to inhibit proliferation, glucose metabolism, migration and invasion of gastric cancer cells, whereas its knockdown caused the opposite effects. Beclin 1 suppressed the tumor growth by decreasing proliferation and increasing apoptosis. The heterozygous abrogation of Becn1 in gastric pit, parietal and chief cells could not cause any epithelial lesion. Beclin 1-mediated chemoresistance was closely linked to the autophagy, Bax underexpression, and the overexpression of Bcl-2, LRP1, MDR1, and ING5. Bioinformatics analysis showed higher Becn1 mRNA expression in intestinal- than diffuse-type carcinomas (P<0.05), and in male than female gastric cancer patients (P<0.05). Becn1 hyperexpression was positively associated with both overall and progression-free survival rates of the cancer patients (P<0.05). Meta-analysis showed that down-regulated Beclin 1 expression in gastric cancer was positively with lymph node metastasis, TNM staging, dedifferentiation and poor prognosis (P<0.05). Becn1-related signal pathways in gastric cancer included prostate, lung, renal, colorectal, endometrial and thyroid cancers, glioma, and leukemia, the metabolism of amino acid, lipid and sugar, and some signal pathways of insulin, MAPK, TRL, VEGF, JAK-STAT, chemokine, p53, lysosome, peroxidome and ubiquitin-mediated protein degradation (P<0.05). These suggested that Beclin 1 might be considered as a potential marker of gastric carcinogenesis, aggressiveness and prognostic prediction, and as a target of gene therapy in gastric cancer.	[Zheng, Hua-chuan; Zhao, Shuang; Xue, Hang] Chengde Med Univ, Affiliated Hosp, Dept Oncol, Chengde, Peoples R China; [Zheng, Hua-chuan; Zhao, Shuang; Xue, Hang] Chengde Med Univ, Affiliated Hosp, Expt Ctr, Chengde, Peoples R China; [Zhao, En-hong] Chengde Med Univ, Affiliated Hosp, Dept Surg, Chengde, Peoples R China; [Jiang, Hua-mao] Jinzhou Med Univ, Affiliated Hosp 1, Dept Urol, Jinzhou, Peoples R China; [Hao, Chang-lai] Chengde Med Univ, Affiliated Hosp, Dept Hematol, Chengde, Peoples R China		Hao, CL (corresponding author), Chengde Med Univ, Affiliated Hosp, Dept Hematol, Chengde, Peoples R China.	haochanglai882@163.com			Award for Liaoning Distinguished Professor; National Natural Scientific Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672700]	This study was supported by Award for Liaoning Distinguished Professor, and National Natural Scientific Foundation of China (81672700).	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Oncol.	DEC 23	2020	10								613679	10.3389/fonc.2020.613679			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	PP6HX	WOS:000605962600001	33425768	Green Published, gold			2022-04-25	
J	Xie, B; Nie, SL; Hu, G; Xiong, L; Hu, F; Li, M; Peng, TS; Nie, J; He, YH				Xie, Biao; Nie, Shaolin; Hu, Gui; Xiong, Li; Hu, Fan; Li, Mei; Peng, Tianshu; Nie, Jing; He, Yongheng			The Involvement of NF-kappa B/Klotho Signaling in Colorectal Cancer Cell Survival and Invasion	PATHOLOGY & ONCOLOGY RESEARCH			English	Article						LPS; NF-kappa B; Colorectal cancer; Klotho	EXPRESSION INDUCES APOPTOSIS; TUMOR-SUPPRESSOR; KLOTHO; INFLAMMATION; RESTORATION; AUTOPHAGY	Lipopolysaccharide significantly increased invasion, cell proliferation, and phospho-NF-kappa B p65 and phospho-IGF-1R protein, but decreased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 cells in SW480 and HT29 colorectal cancer cells. In contrast, NF-kappa B inhibitor exhibited a counteract effect of lipopolysaccharide. Transfection of Toll-like receptor 4 shRNA significantly decreased phospho-NF-kappa B p65 and phospho-IGF-1R protein levels, invasion, but significantly increased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 in SW480 and HT29 cells. In conclusion, inflammation inhibits klotho gene expression in colorectal cancer cells through activation of Toll-like receptor 4 /NF-kappa B signal pathway.	[Xie, Biao; Hu, Fan; Li, Mei; He, Yongheng] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Anorectal Surg 1, 139 Renmin Rd, Changsha 410005, Hunan, Peoples R China; [Nie, Shaolin] Hunan Prov Tumor Hosp, Dept Colorectal Surg, Changsha 410013, Hunan, Peoples R China; [Hu, Gui] Cent S Univ, Xiangya Hosp 3, Dept Gastrointestinal Surg, Changsha 410013, Hunan, Peoples R China; [Xiong, Li] Cent S Univ, Xiangya Hosp 2, Dept Hepatobiliary Surg, Changsha 410008, Hunan, Peoples R China; [Peng, Tianshu] Hunan Slack King Lab Anim Co Ltd, Changsha 4100125, Hunan, Peoples R China; [Nie, Jing] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Anorectal Surg 4, Changsha 410005, Hunan, Peoples R China		He, YH (corresponding author), Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Anorectal Surg 1, 139 Renmin Rd, Changsha 410005, Hunan, Peoples R China.	heyongheng1964@163.com			Postdoctoral Science Foundation of ChinaChina Postdoctoral Science Foundation [2016 M602416]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81704089]; Postdoctoral Science Fund Special Grant of China [2017 T100603]; 2016 Postdoctoral Researcher Daily Funding of Hunan Province [49]; Department of Education Key Project of Hunan Province [15A024]; Changsha City's Outstanding Innovation Youth Training Program [kq 1707012]	This study was supported by the Postdoctoral Science Foundation of China (2016 M602416), National Natural Science Foundation of China (81704089), Postdoctoral Science Fund Special Grant of China (2017 T100603), 2016 Postdoctoral Researcher Daily Funding of Hunan Province (49), the Department of Education Key Project of Hunan Province (15A024), and Changsha City's Outstanding Innovation Youth Training Program (kq 1707012).	American Cancer Society (ACS), 2014, COL CANC FACTS FIG 2; [Anonymous], 2017, CA-CANCER J CLIN, DOI DOI 10.3322/CAAC.21395; Liu BD, 2015, CANCER CELL, V27, P370, DOI 10.1016/j.ccell.2015.02.004; Roy A, 2016, INT IMMUNOPHARMACOL, V40, P79, DOI 10.1016/j.intimp.2016.08.026; Shu GS, 2013, CELL ONCOL, V36, P121, DOI 10.1007/s13402-012-0118-0; Sims GP, 2010, ANNU REV IMMUNOL, V28, P367, DOI 10.1146/annurev.immunol.021908.132603; Tang XW, 2016, LAB INVEST, V96, P197, DOI 10.1038/labinvest.2015.86; Terzic J, 2010, GASTROENTEROLOGY, V138, P2101, DOI 10.1053/j.gastro.2010.01.058; Viennois Emilie, 2013, Transl Gastrointest Cancer, V2, P21; Wang LJ, 2011, AM J CANCER RES, V1, P111; Wu C, 2015, MOL CELL ENDOCRINOL, V417, P84, DOI 10.1016/j.mce.2015.09.024; Xie B, 2013, PATHOL ONCOL RES, V19, P611, DOI 10.1007/s12253-013-9663-8; Xie BA, 2013, HUM PATHOL, V44, P795, DOI 10.1016/j.humpath.2012.07.023; Xie B, 2013, CANCER CELL INT, V13, DOI 10.1186/1475-2867-13-18; Zhang GL, 2000, J ENDOTOXIN RES, V6, P453, DOI 10.1179/096805100101532414; Zhou XX, 2015, J CANCER RES CLIN, V141, P961, DOI 10.1007/s00432-014-1788-y; Zhu QC, 2013, ASIAN PAC J CANCER P, V14, P2689, DOI 10.7314/APJCP.2013.14.5.2689	17	5	5	2	4	SPRINGER	DORDRECHT	VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS	1219-4956	1532-2807		PATHOL ONCOL RES	Pathol. Oncol. Res.	OCT	2019	25	4					1553	1565		10.1007/s12253-018-0493-6			13	Oncology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pathology	JH3JE	WOS:000492663100032	30612312				2022-04-25	
J	Fujii, S; Mitsunaga, S; Yamazaki, M; Hasebe, T; Ishii, G; Kojima, M; Kinoshita, T; Ueno, T; Esumi, H; Ochiai, A				Fujii, Satoshi; Mitsunaga, Shuichi; Yamazaki, Manabu; Hasebe, Takahiro; Ishii, Genichiro; Kojima, Motohiro; Kinoshita, Taira; Ueno, Takashi; Esumi, Hiroyasu; Ochiai, Atsushi			Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome	CANCER SCIENCE			English	Article							PROGNOSTIC-FACTORS; DUCTAL CARCINOMA; ADENOCARCINOMA; HYPOXIA; RESECTION; TOLERANCE; SURVIVAL; GROWTH; TUMORS	Because autonomous proliferating cancer cells are often exposed to hypoxic conditions, there must be an alternative metabolic pathway, such as autophagy, that allows them to obtain energy when both oxygen and glucose are depleted. We previously reported finding that autophagy actually contributes to cancer cell survival in colorectal cancers both in vitro and in vivo. Pancreatic cancer remains a devastating and poorly understood malignancy, and hypoxia in pancreatic cancers is known to increase their malignant potential. In the present study archival pancreatic cancer tissue was retrieved from 71 cases treated by curative pancreaticoduodenectomy. Autophagy was evaluated by immunohistochemical staining with anti-LC3 antibody, as LC3 is a key component of autophagy and has been used as a marker of autophagy. The results showed that strong LC3 expression in the peripheral area of pancreatic cancer tissue was correlated with a poor outcome (P = 0.0170) and short disease-free period (P = 0.0118). Two of the most significant correlations among the clinicopathological factors tested were found between the peripheral intensity level of LC3 expression and tumor size (P = 0.0098) or tumor necrosis (P = 0.0127). Activated autophagy is associated with pancreatic cancer cells, and autophagy is thought to be a response to factors in the cancer microenvironment, such as hypoxia and poor nutrient supply. This is the first study to report the clinicopathological significance of autophagy in pancreatic cancer.	[Fujii, Satoshi; Yamazaki, Manabu; Ishii, Genichiro; Kojima, Motohiro; Ochiai, Atsushi] Natl Canc Ctr Hosp E, Res Ctr Innovat Oncol, Div Pathol, Chiba 2778577, Japan; [Mitsunaga, Shuichi] Natl Canc Ctr Hosp E, Div Hepatobiliary & Pancreat Oncol, Chiba 2778577, Japan; [Hasebe, Takahiro] Natl Canc Ctr, Ctr Canc Control & Informat Serv, Clin Trials & Practice Support Div, Off Pathol Consultat & Serv,Chuo Ku, Tokyo 1040045, Japan; [Kinoshita, Taira] Natl Canc Ctr Hosp E, Dept Hepatobiliary Pancreat Surg, Chiba 2778577, Japan; [Ueno, Takashi] Juntendo Univ, Dept Biochem, Sch Med, Bunkyo Ku, Tokyo 1138421, Japan; [Esumi, Hiroyasu] Natl Canc Ctr Hosp E, Res Ctr Innovat Oncol, Canc Physiol Project, Chiba 2778577, Japan		Ochiai, A (corresponding author), Natl Canc Ctr Hosp E, Res Ctr Innovat Oncol, Div Pathol, 6-5-1 Kashiwanoha, Chiba 2778577, Japan.	aochiai@east.ncc.go.jp	Yamazaki, Manabu/AAV-1263-2020; Ishii, Genichiro/E-2913-2012	Yamazaki, Manabu/0000-0002-7156-1820; 	Ministry of Health, Labour, and WelfareMinistry of Health, Labour and Welfare, Japan	This work was supported by a grant from the Ministry of Health, Labour, and Welfare for the Third-Term Comprehensive 10-year Strategy for Cancer Control. We wish to thank Miss Mai Okumoto for her excellent technical assistance.	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J	Zhang, W; Yeo, MC; Tang, FY; Popovich, DG				Zhang, Wei; Yeo, Mei Ching; Tang, Fang Yin; Popovich, David G.			Bioactive responses of Hep-G2 cells to soyasaponin extracts differs with respect to extraction conditions	FOOD AND CHEMICAL TOXICOLOGY			English	Article						Oleanane triterpenoids; Soyasaponins; Differentiation; Hep-G2	COLON-CANCER CELLS; LIQUID-CHROMATOGRAPHY; TRITERPENOID SAPONINS; SIALIC ACIDS; HELA-CELLS; PROLIFERATION; APOPTOSIS; SURFACE; MACROAUTOPHAGY; EXPRESSION	Soyasaponins are bioactive oleanane triterpenoids found in soy and other legumes. The effect of two methanolic extractions of soy flour, room temperature (RT) and reflux (RE) extractions on composition and bioactive properties in hepatocarcinoma cells (Hep-G2) were investigated. A greater amount of 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP) conjugated soyasaponins beta g was measured in RT and a greater amount of the structurally related non-DDMP soyasaponins I and III were detected in RE. MTT cell viability yielded an LC50 of 0.926 +/- 0.08 mg/mL for RT and 0.546 +/- 0.06 mg/mL for RE. Via-Count viability assay showed similar results for RE as the MTT assay however, RT treatment produced no difference compared with the control. Analysis using TUNEL and cell cycle analysis revealed that RE treatment induced apoptosis and flow cytometry forward side scatter and morphological assessment of RT showed evidence of Hep-G2 differentiation after 72 h. Differences in the bioactivities may be attributed to the different concentration of DDMP conjugated soyasaponin beta g recovered in RT and RE extracts. (C) 2009 Elsevier Ltd. All rights reserved.	[Zhang, Wei; Yeo, Mei Ching; Tang, Fang Yin; Popovich, David G.] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore		Popovich, DG (corresponding author), Natl Univ Singapore, Dept Chem, Sci Dr 4, Singapore 117543, Singapore.	chmpdg@nus.edu.sg	Zhang, Wei/G-8229-2016	Zhang, Wei/0000-0003-2691-2721; Popovich, David/0000-0002-8630-320X	National University of Singapore (NUS)National University of Singapore; Singapore Ministry of EducationMinistry of Education, Singapore [R-143-050-287-133/101]	The authors acknowledge the National University of Singapore (NUS) and the Singapore Ministry of Education (Grants R-143-050-287-133/101) for financial support and graduate scholarship (WZ).	Bernas T, 2002, CYTOMETRY, V47, P236, DOI 10.1002/cyto.10080; Chang WW, 2006, BIOCHEM BIOPH RES CO, V341, P614, DOI 10.1016/j.bbrc.2005.12.216; DAVEBY YD, 1998, J SCI FOOD AGR, V14, P1; Ellington AA, 2006, CARCINOGENESIS, V27, P298, DOI 10.1093/carcin/bgi214; Ellington AA, 2005, CARCINOGENESIS, V26, P159, DOI 10.1093/carcin/bgh297; Fournier DB, 1998, CANCER EPIDEM BIOMAR, V7, P1055; Gurfinkel DM, 2005, INT J FOOD SCI NUTR, V56, P501, DOI 10.1080/09637480500460601; Gurfinkel DM, 2003, NUTR CANCER, V47, P24, DOI 10.1207/s15327914nc4701_3; Hsu CC, 2005, GYNECOL ONCOL, V96, P415, DOI 10.1016/j.ygyno.2004.10.010; Hu J, 2002, J AGR FOOD CHEM, V50, P2587, DOI 10.1021/jf0114740; KUDOU S, 1993, BIOSCI BIOTECH BIOCH, V57, P546, DOI 10.1271/bbb.57.546; Leu YL, 2008, J MED CHEM, V51, P1740, DOI 10.1021/jm701151c; MOSMANN T, 1983, J IMMUNOL METHODS, V65, P55, DOI 10.1016/0022-1759(83)90303-4; OAKENFULL D, 1990, EUR J CLIN NUTR, V44, P79; PILATTE Y, 1993, GLYCOBIOLOGY, V3, P201, DOI 10.1093/glycob/3.3.201; Popovich DG, 2004, PHYTOCHEMISTRY, V65, P337, DOI 10.1016/j.phytochem.2003.11.020; SHIRAIWA M, 1991, AGR BIOL CHEM TOKYO, V55, P911, DOI 10.1080/00021369.1991.10870686; WARREN L, 1972, P NATL ACAD SCI USA, V69, P1838, DOI 10.1073/pnas.69.7.1838; Xiao JX, 2007, EXP TOXICOL PATHOL, V59, P35, DOI 10.1016/j.etp.2007.02.004; Xiao JX, 2007, TOXICOL IN VITRO, V21, P820, DOI 10.1016/j.tiv.2007.01.025; Yamamoto H, 2008, ANN HEMATOL, V87, P87, DOI 10.1007/s00277-007-0381-8; Yoshiki Y, 1998, BIOSCI BIOTECH BIOCH, V62, P2291, DOI 10.1271/bbb.62.2291; Zhang W, 2008, J AGR FOOD CHEM, V56, P2603, DOI 10.1021/jf0731550; Zhang XW, 2000, ACTA PHARMACOL SIN, V21, P364; [No title captured]	25	15	17	0	12	PERGAMON-ELSEVIER SCIENCE LTD	OXFORD	THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND	0278-6915	1873-6351		FOOD CHEM TOXICOL	Food Chem. Toxicol.	SEP	2009	47	9					2202	2208		10.1016/j.fct.2009.06.006			7	Food Science & Technology; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Food Science & Technology; Toxicology	489PF	WOS:000269432000007	19520140				2022-04-25	
J	Pin, F; Minero, VG; Penna, F; Muscaritoli, M; De Tullio, R; Baccino, FM; Costelli, P				Pin, Fabrizio; Minero, Valerio G.; Penna, Fabio; Muscaritoli, Maurizio; De Tullio, Roberta; Baccino, Francesco M.; Costelli, Paola			Interference with Ca2+-Dependent Proteolysis Does Not Alter the Course of Muscle Wasting in Experimental Cancer Cachexia	FRONTIERS IN PHYSIOLOGY			English	Article						muscle protein turnover; calpains; calpastatin; muscle atrophy; proteostasis	TUMOR-BEARING RATS; ENDOPLASMIC-RETICULUM STRESS; SKELETAL-MUSCLE; CALPAIN ACTIVATION; CALPASTATIN; DEGRADATION; PATHWAY; ATROPHY; SYSTEM; MICE	Protein hypercatabolism significantly contributes to the onset and progression of muscle wasting in cancer cachexia. In this regard, a major role is played by the ATP-ubiquitin-proteasome-dependent pathway and by autophagy. However, little is known about the relevance of the Ca2+-dependent proteolytic system. Since previous results suggested that this pathway is activated in the skeletal muscle of tumor hosts, the present study was aimed to investigate whether inhibition of Ca2+-dependent proteases (calpains) may improve cancer-induced muscle wasting. Two experimental models of cancer cachexia were used, namely the AH-130 Yoshida hepatoma and the C26 colon carcinoma. The Ca2+-dependent proteolytic system was inhibited by treating the animals with dantrolene or by overexpressing in the muscle calpastatin, the physiologic inhibitor of Ca2+-dependent proteases. The results confirm that calpain-1 is overexpressed and calpastatin is reduced in the muscle of rats implanted with the AH-130 hepatoma, and show for the first time that the Ca2+-dependent proteolytic system is overactivated also in the C26-bearing mice. Yet, administration of dantrolene, an inhibitor of the Ca2+-dependent proteases, did not modify tumor-induced body weight loss and muscle wasting in the AH-130 hosts. Dantrolene was also unable to reduce the enhancement of protein degradation rates occurring in rats bearing the AH-130 hepatoma. Similarly, overexpression of calpastatin in the tibialis muscle of the C26 hosts did not improve muscle wasting at all. These observations suggest that inhibiting a single proteolytic system is not a good strategy to contrast cancer-induced muscle wasting. In this regard, a more general and integrated approach aimed at targeting the catabolic stimuli rather than the proteolytic activity of a single pathway would likely be the most appropriate therapeutic intervention.	[Pin, Fabrizio; Minero, Valerio G.; Penna, Fabio; Baccino, Francesco M.; Costelli, Paola] Univ Turin, Dept Clin & Biol Sci, Turin, Italy; [Muscaritoli, Maurizio] Sapienza Univ, Dept Clin Med, Rome, Italy; [De Tullio, Roberta] Univ Genoa, Dept Expt Med, Genoa, Italy		Costelli, P (corresponding author), Univ Turin, Dept Clin & Biol Sci, Turin, Italy.	paola.costelli@unito.it	Penna, Fabio/K-5090-2016	Penna, Fabio/0000-0002-2774-6027	Associazione Italiana per la Ricerca sul Cancro, Milano (PRIN) [AIRC-IG9153]; Ministero per I'Universita e la Ricerca, Roma (PRIN); University of Torino; Regione PiemonteRegione Piemonte	The work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC-IG9153), Milano, Ministero per I'Universita e la Ricerca, Roma (PRIN projects), University of Torino (ex-60% funds), and Regione Piemonte.	Argiles JM, 2014, NAT REV CANCER, V14, P754, DOI 10.1038/nrc3829; Assi M, 2016, FREE RADICAL BIO MED, V91, P204, DOI 10.1016/j.freeradbiomed.2015.12.019; BARACOS VE, 1995, AM J PHYSIOL-ENDOC M, V268, pE996, DOI 10.1152/ajpendo.1995.268.5.E996; Bohnert KR, 2016, FASEB J, V30, P3053, DOI 10.1096/fj.201600250RR; Bonetto A, 2009, CURR CANCER DRUG TAR, V9, P608, DOI 10.2174/156800909789057015; Borges F H, 2014, Pathophysiology, V21, P257, DOI 10.1016/j.pathophys.2014.05.003; Busquets S, 2000, BBA-GEN SUBJECTS, V1475, P5, DOI 10.1016/S0304-4165(00)00050-7; Chacon-Cabrera A, 2014, J CELL PHYSIOL, V229, P1660, DOI 10.1002/jcp.24611; COSTELLI P, 1993, J CLIN INVEST, V92, P2783, DOI 10.1172/JCI116897; Costelli P, 2002, CYTOKINE, V19, P1, DOI 10.1006/cyto.2002.1036; Costelli P, 2001, BRIT J CANCER, V84, P946, DOI 10.1054/bjoc.2001.1696; Dargelos E, 2010, EXP CELL RES, V316, P115, DOI 10.1016/j.yexcr.2009.07.025; De Tullio R, 1999, BIOCHEM J, V343, P467; De Tullio R, 2000, FEBS LETT, V475, P17, DOI 10.1016/S0014-5793(00)01613-6; De Tullio R, 2014, BBA-MOL CELL RES, V1843, P2583, DOI 10.1016/j.bbamcr.2014.07.002; De Tullio R, 2009, BBA-GEN SUBJECTS, V1790, P182, DOI 10.1016/j.bbagen.2008.11.002; Fermoselle C, 2013, EXP PHYSIOL, V98, P1349, DOI 10.1113/expphysiol.2013.072496; Goll DE, 2003, PHYSIOL REV, V83, P731, DOI 10.1152/physrev.00029.2002; Huang JR, 2016, PHYSIOL RES, V65, P547, DOI 10.33549/physiolres.933087; Isaac ST, 2016, CURR DRUG TARGETS, V17, P1140, DOI 10.2174/1389450116666150416115721; Langou K, 2010, J NEUROCHEM, V114, P795, DOI 10.1111/j.1471-4159.2010.06806.x; Lee J. 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Physiol.	APR 19	2017	8								213	10.3389/fphys.2017.00213			9	Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Physiology	EW9TZ	WOS:000402863600001	28469577	Green Published, gold			2022-04-25	
J	Wang, L; Zhang, HP; Sun, M; Yin, ZH; Qian, JH				Wang, Li; Zhang, Huiping; Sun, Min; Yin, Zhanghua; Qian, Jihong			High mobility group box 1-mediated autophagy promotes neuroblastoma cell chemoresistance	ONCOLOGY REPORTS			English	Article						HMGB1; autophagy; Beclin-1; proliferation; invasion; chemoresistance	IN-VITRO; REGULATES AUTOPHAGY; COLORECTAL-CANCER; INDUCED APOPTOSIS; DRUG-RESISTANCE; 1 HMGB1; EXPRESSION; OSTEOSARCOMA; CARCINOMA; PROTEIN	Neuroblastoma (NB) is one of the most common tumors in childhood. Unfortunately, the survival outcomes remain unsatisfactory since NB commonly develops multidrug resistance. Recent studies have demonstrated that the high mobility group box 1 (HMGB1)-mediated autophagy promotes chemoresistance in osteosarcoma, lung adenocarcinoma and ovarian cancer, but the exact molecular mechanism underlying HMGB1-mediated autophagy in NB has not been clearly defined. In the present study, we investigated the role of HMGB1 in the development of resistance to anticancer agents in NB. Anticancer agents including doxorubicin, cisplatin and etoposide each induced HMGB1 upregulation, promoted cytosolic HMGB1 translocation and the elevation of autophagic activity in human NB cells. RNA interference-mediated knockdown of HMGB1 restored the chemosensitivity of NB cells. Furthermore, mechanistic investigation revealed that HMGB1 promoted the proliferative activity and invasive potential of NB cells. HMGB1 enhanced drug resistance by inducing Beclin-l-mediated autophagy, an intracellular self-defense mechanism known to confer drug resistance. In addition, we found that HMGB1 facilitated autophagic progression and reduced oxidative stress induced by doxorubicin. Therefore, through its role as a regulator of autophagy, HMGB1 is a critical factor in the development of chemoresistance and tumorigenesis, and it may be a novel target for improving the efficacy of NB therapy.	[Wang, Li; Zhang, Huiping; Sun, Min; Yin, Zhanghua; Qian, Jihong] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Neonatol, Shanghai 200092, Peoples R China		Qian, JH (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Neonatol, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China.	qianjh668@163.com					BIEDLER JL, 1994, CANCER RES, V54, P666; Brezniceanu ML, 2003, FASEB J, V17, P1295, DOI 10.1096/fj.02-0621fje; Chen J, 2012, J CELL PHYSIOL, V227, P3629, DOI 10.1002/jcp.24069; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Faraco G, 2007, J NEUROCHEM, V103, P590, DOI 10.1111/j.1471-4159.2007.04788.x; Fu LL, 2013, INT J BIOCHEM CELL B, V45, P921, DOI 10.1016/j.biocel.2013.02.007; Furfaro AL, 2014, BBA-MOL BASIS DIS, V1842, P613, DOI 10.1016/j.bbadis.2013.12.008; Guazzi S, 2003, GENE EXPR PATTERNS, V3, P29, DOI 10.1016/S1567-133X(02)00093-5; Huang J, 2012, CANCER RES, V72, P230, DOI 10.1158/0008-5472.CAN-11-2001; Lanvers-Kaminsky C, 2005, ONCOL REP, V14, P751; Lockshin RA, 2004, INT J BIOCHEM CELL B, V36, P2405, DOI 10.1016/j.biocel.2004.04.011; Meyer A, 2008, LEUKEMIA LYMPHOMA, V49, P1184, DOI 10.1080/10428190802064909; Michaelis M, 2009, MOL CANCER, V8, DOI 10.1186/1476-4598-8-80; Mohan N, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0078958; Moreira AC, 2014, BBA-MOL BASIS DIS, V1842, P2468, DOI 10.1016/j.bbadis.2014.09.015; Murai T, 2001, J BIOL CHEM, V276, P6797, DOI 10.1074/jbc.M009355200; Pan BZ, 2014, MOL CANCER, V13, DOI 10.1186/1476-4598-13-165; Pedrazzi M, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0044518; Petiot A, 2000, J BIOL CHEM, V275, P992, DOI 10.1074/jbc.275.2.992; Reismann M, 2009, EUR J PEDIATR SURG, V19, P224, DOI 10.1055/s-0029-1202778; Shokoohinia Y, 2014, BIOMED RES INT, V2014, DOI 10.1155/2014/156848; Singla Shivani, 2014, Toxicol Int, V21, P191, DOI 10.4103/0971-6580.139808; Suren D, 2014, MED SCI MONITOR, V20, P530, DOI 10.12659/MSM.890531; Tang D, 2010, ONCOGENE, V29, P5299, DOI 10.1038/onc.2010.261; Tang DL, 2011, CELL METAB, V13, P701, DOI 10.1016/j.cmet.2011.04.008; Tang DL, 2010, J CELL BIOL, V190, P881, DOI 10.1083/jcb.200911078; Tonini GP, 2006, CURR PHARM DESIGN, V12, P2303, DOI 10.2174/138161206777585193; Ueda M, 2014, ANTICANCER RES, V34, P5357; Wang L, 2014, BIOCHEM BIOPH RES CO, V448, P448, DOI 10.1016/j.bbrc.2014.04.120; Wittig JC, 2002, AM FAM PHYSICIAN, V65, P1123; Wu D, 2008, J PATHOL, V216, P167, DOI 10.1002/path.2391; Yang S, 2014, J LEUKOCYTE BIOL, V95, P563, DOI 10.1189/jlb.0713412; Yang YH, 2014, FREE RADICAL BIO MED, V77, P10, DOI 10.1016/j.freeradbiomed.2014.08.028; Yang YH, 2013, APOPTOSIS, V18, P1363, DOI 10.1007/s10495-013-0867-x; Zhang L, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0110626; Zhang Y, 2012, ONCOGENE, V31, P1055, DOI 10.1038/onc.2011.290; Zhao ZF, 2014, INT J MOL MED, V33, P271, DOI 10.3892/ijmm.2013.1578; Zhou Y, 2014, SCI REP-UK, V4, DOI 10.1038/srep05382	38	26	28	0	9	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1021-335X	1791-2431		ONCOL REP	Oncol. Rep.	DEC	2015	34	6					2969	2976		10.3892/or.2015.4278			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CV9OR	WOS:000364617000019	26397184	Bronze			2022-04-25	
J	Gao, H; Shi, XF; Chen, QQ; Che, BC; Yin, HJ; Li, YX				Gao, Hao; Shi, Xiafei; Chen, Qianqian; Che, Bochen; Yin, Huijuan; Li, Yingxin			Deep proteome profiling of SW837 cells treated by photodynamic therapy (PDT) reveals the underlying mechanisms of metronomic and acute PDTs	PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY			English	Article						Metronomic photodynamic therapy; Acute photodynamic therapy; Colorectal cancer; Proteome; SWATH-MS; Differentially expressed protein	COLORECTAL-CANCER TREATMENT; OF-THE-ART; A431 CELLS; DEATH; CARCINOMA; APOPTOSIS; PATHWAYS; DESFERRIOXAMINE; PHOTOFRIN; AUTOPHAGY	Aim: Metronomic photodynamic therapy (mPDT) with a longer irradiation time and lower energy compared with acute (or classic) photodynamic therapy (aPDT) is a more effective treatment than aPDT for tumor cells, especially colorectal cancer. However, the underlying mechanisms of the superior effects of mPDT are unknown. Methods: we used SWATH-MS (sequential window acquisition of all theoretical mass spectra) to identify differentially expressed proteins (DEPs) specific to aPDT (conventional fluence rate, 20 mW/cm(2), 4 min 10 s), mPDT (metronomic fluence rate, 0.4 mW/cm(2), 3.5 h), and control groups of SW837 cells. The photosensitizer used in both PDT methods was aminolevulinic acid which were incubated with the cells before irradiation. Results: A total of 6805 proteins were identified in the three groups of SW837 cells. aPDT induced 333 DEPs and mPDT induced 1716 DEPs compared with the control. We identified 185 common DEPs in the two PDT groups, 148 different DEPs in the aPDT group, and 1531 different DEPs in the mPDT group. Most of the 185 common DEPs were involved in the extracellular component, participated in the processes of vesicle transport and secretion, binding, and hydrolase/catalytic activity. They were also involved in PI3K-Akt, cGMP-PKG, RAS, and aAMP signaling pathways. In addition, the 1531 different DEPs in the mPDT group participated in similar processes and molecular functions, but in a more complex manner than those in the aPDT group. Conclusion: our proteome data suggest that mPDT has a complex tumor destruction mechanism with more involved proteins compared with aPDT, which may explain the better tumor killing effect of mPDT.	[Gao, Hao] Tianjin Peoples Hosp, Dept Colorectal Surg, Tianjin Union Med Ctr, 190 Jieyuan Rd, Tianjin 300121, Peoples R China; [Shi, Xiafei; Chen, Qianqian; Che, Bochen; Yin, Huijuan; Li, Yingxin] Chinese Acad Med Sci & Peking Union Med Coll, Lab Laser Med, Inst Biomed Engn, 236 Baidi Rd, Tianjin 300192, Peoples R China		Yin, HJ (corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, Lab Laser Med, Inst Biomed Engn, 236 Baidi Rd, Tianjin 300192, Peoples R China.	yinzi490@163.com			Fund Program "CAMS Initiative for Innovative Medicine" [2018-I2M-AI-011]	We thank the Fund Program "CAMS Initiative for Innovative Medicine to H.Y. (2018-I2M-AI-011)" for support.	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Ther.	SEP	2020	31								101809	10.1016/j.pdpdt.2020.101809			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NZ2QQ	WOS:000576941600004	32437970				2022-04-25	
J	Levy, J; Cacheux, W; Bara, MA; L'Hermitte, A; Lepage, P; Fraudeau, M; Trentesaux, C; Lemarchand, J; Durand, A; Crain, AM; Marchiol, C; Renault, G; Dumont, F; Letourneur, F; Delacres, M; Schmitt, A; Terris, B; Perret, C; Chamaillard, M; Couty, JP; Romagnolo, B				Levy, Jonathan; Cacheux, Walfran; Bara, Medhi Ait; L'Hermitte, Antoine; Lepage, Patricia; Fraudeau, Marie; Trentesaux, Coralie; Lemarchand, Julie; Durand, Aurelie; Crain, Anne-Marie; Marchiol, Carmen; Renault, Gilles; Dumont, Florent; Letourneur, Franck; Delacres, Myriam; Schmitt, Alain; Terris, Benoit; Perret, Christine; Chamaillard, Mathias; Couty, Jean-Pierre; Romagnolo, Beatrice			Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth	NATURE CELL BIOLOGY			English	Article							AUTOPHAGY GENE ATG16L1; REGULATORY T-CELLS; TUMORIGENESIS; CANCER; MICE; INFLAMMATION; MOUSE; PROGRESSION; ACTIVATION; EXPRESSION	Here, we show that autophagy is activated in the intestinal epithelium in murine and human colorectal cancer and that the conditional inactivation of Atg7 in intestinal epithelial cells inhibits the formation of pre-cancerous lesions in Apc(+/-) mice by enhancing anti-tumour responses. The antibody-mediated depletion of CD8(+) T cells showed that these cells are essential for the anti-tumoral responses mediated by the inhibition of autophagy. We show that Atg7 deficiency leads to intestinal dysbiosis and that the microbiota is required for anticancer responses. In addition, Atg7 deficiency resulted in a stress response accompanied by metabolic defects, AMPK activation and p53-mediated cell-cycle arrest in tumour cells but not in normal tissue. This study reveals that the inhibition of autophagy within the epithelium may prevent the development and progression of colorectal cancer in genetically predisposed patients.	[Levy, Jonathan; Cacheux, Walfran; Bara, Medhi Ait; L'Hermitte, Antoine; Fraudeau, Marie; Trentesaux, Coralie; Lemarchand, Julie; Durand, Aurelie; Crain, Anne-Marie; Marchiol, Carmen; Renault, Gilles; Dumont, Florent; Letourneur, Franck; Schmitt, Alain; Terris, Benoit; Perret, Christine; Couty, Jean-Pierre; Romagnolo, Beatrice] Univ Paris 05, CNRS, Inst Cochin, UMR8104, F-75014 Paris, France; [Levy, Jonathan; Cacheux, Walfran; Bara, Medhi Ait; L'Hermitte, Antoine; Fraudeau, Marie; Trentesaux, Coralie; Lemarchand, Julie; Durand, Aurelie; Crain, Anne-Marie; Marchiol, Carmen; Renault, Gilles; Dumont, Florent; Letourneur, Franck; Schmitt, Alain; Terris, Benoit; Perret, Christine; Couty, Jean-Pierre; Romagnolo, Beatrice] Inst Natl Sante & Rech Med INSFRM, U1016, F-75014 Paris, France; [Cacheux, Walfran] Inst Curie, Dept Med Oncol, F-75248 Paris 05, France; [Cacheux, Walfran] Inst Curie, Dept Genet, Pharmacogen Unit, F-75248 Paris 05, France; [Lepage, Patricia] INRA, Micalis UMR1319, F-78352 Jouy En Josas, France; [Lepage, Patricia] AgroParis Tech, Micalis UMR1319, F-78350 Jouy En Josas, France; [Crain, Anne-Marie; Couty, Jean-Pierre] Univ Paris Diderot, Sorbonne Paris Cite, UFR Sci Vivant, F-75013 Paris, France; [Delacres, Myriam; Chamaillard, Mathias] Univ Lille Nord France, F-59000 Lille, France; [Delacres, Myriam; Chamaillard, Mathias] Ctr Infect & Immun Lille, Inst Pasteur Lille, F-59800 Lille, France; [Delacres, Myriam; Chamaillard, Mathias] CNRS, Unite Mixle Rech, F-59046 Lille, France; [Delacres, Myriam; Chamaillard, Mathias] Inst Nat Sante & Rech Med, F-59045 Lille, France; [Terris, Benoit] Univ Paris 05, Hop Cochin, AP HP, Serv Anat & Cytol Pathol, F-75014 Paris, France		Romagnolo, B (corresponding author), Univ Paris 05, CNRS, Inst Cochin, UMR8104, F-75014 Paris, France.	beatrice.romagnolo@inserm.fr	Romagnolo, Béatrice/D-5017-2017; Lepage, Patricia/D-4362-2014; Chamaillard, Mathias/L-6542-2013; Couty, Jean-Pierre/P-5268-2017; Terris, Benoit/P-1497-2017; Perret-Mayeux, Christine/L-3297-2017	Romagnolo, Béatrice/0000-0001-8772-3604; Lepage, Patricia/0000-0002-9501-6771; Chamaillard, Mathias/0000-0002-0243-9717; Marchiol, Carmen/0000-0002-9666-7939; Renault, Gilles/0000-0003-2273-1229; COUTY, Jean-Pierre/0000-0003-3492-9136; Trentesaux, Coralie/0000-0003-3387-4890; perret, christine/0000-0003-4710-7051	Institut National du CancerInstitut National du Cancer (INCA) France; Comite de Paris de la Ligue Contre le Cancer; Cancer Research Personalized Medicine (CARPEM); Poste d'acceuil INSERM; Ministere de la Recherche et de la Technologie; la Fondation Arc; InsermInstitut National de la Sante et de la Recherche Medicale (Inserm)European Commission; Fondation pour la Recherche Medicale ('Equipe FRM')Fondation pour la Recherche Medicale	We thank M. Komatsu (Niigata University, Japan) and S. Robine (Institut Curie, France) for a generous supply of mutant mice, S. Pham, P. Mariani, Y. Bieche, S. Vacher, B. Violet, M. Foretz, B. Radenen-Bussiere and V. Maillet for technical help and for helpful discussions. We are grateful to the staff of Cochin's animal housing facility and in particular to F. Lager and I. Lagoutte. This work was supported by Institut National du Cancer, the Comite de Paris de la Ligue Contre le Cancer, la Fondation Arc, and by the Cancer Research Personalized Medicine (CARPEM). W.C. was supported by Poste d'acceuil INSERM, M.F. and F.D. by CARPEM, and J.L. held a fellowship from the Ministere de la Recherche et de la Technologie and was also financially supported by la Fondation Arc. This work was also supported by funds from Inserm and by grants from the Fondation pour la Recherche Medicale ('Equipe FRM 2013' to M.C.).	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Cell Biol.	AUG	2015	17	8					1062	U440		10.1038/ncb3206			24	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	CO0NE	WOS:000358847700013	26214133				2022-04-25	
J	Kim, D; Choi, BH; Ryoo, IG; Kwak, MK				Kim, Donghyeok; Choi, Bo-hyun; Ryoo, In-geun; Kwak, Mi-Kyoung			High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling	CELL DEATH & DISEASE			English	Article							TRANSCRIPTION FACTOR NRF2; INITIATING CELLS; RESISTANCE; AUTOPHAGY; ACTIVATION; THERAPY; IDENTIFICATION; CHEMOTHERAPY; EXPRESSION; PATHWAY	Aldehyde dehydrogenase 1A1 (ALDH1A1) is one of cancer stem cell (CSC) markers, and high ALDH1 expression has been related to drug resistance and facilitated tumor growth. In this study, we investigated the potential involvement of nuclear factor erythroid 2-like 2 (NFE2L2/NRF2) in CSC-like properties of ALDH-high ovarian CSCs. Our experimental system, ALDH1A1-high (ALDH-H) subpopulation, was isolated and stabilized using doxorubicin-resistant ovarian cancer A2780 cells. ALDH-H exerted CSC-like properties such as drug resistance, colony/sphere formation, and enhanced tumor growth along with high levels of CSCs markers compared to ALDH1A1-low (ALDH-L). Levels of NRF2 and subsequent target genes substantially increased in ALDH-H cells, and the increase in ALDH1A1 and p62 was associated with NRF2 upregulation. ALDH1A1-silencing blocked increases in NRF2, drug efflux transporters, and p62, along with CSC markers in ALDH-H cells. The inhibition of p62, which was elevated in ALDH-H, suppressed NRF2 activation. High NRF2 level was confirmed in the ALDH1-high subpopulation from colon cancer HCT116 cells. The functional implication of NRF2 activation in ovarian CSCs was verified by two experimental approaches. First, CSC-like properties such as high CSC markers, chemoresistance, colony/sphere formation, and tumor growth were significantly inhibited by NRF2-silencing in ALDH-H cells. Second, all-trans retinoic acid (ATRA) suppressed ALDH1 expression, inhibiting NRF2 activation, which led to the attenuation of CSC-like properties in ALDH-H cells but not in ALDH-L cells. These results provide insight into the molecular basis of the ALDH1A1-mediated development of CSC-like properties such as stress/treatment resistance, and further suggest the therapeutic potential of ATRA in ALDH-high ovarian CSCs.	[Kim, Donghyeok; Choi, Bo-hyun; Kwak, Mi-Kyoung] Catholic Univ Korea, Grad Sch, Dept Pharm, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea; [Ryoo, In-geun; Kwak, Mi-Kyoung] Catholic Univ Korea, Integrated Res Inst Pharmaceut Sci, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea; [Kwak, Mi-Kyoung] Catholic Univ Korea, Coll Pharm, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea		Kwak, MK (corresponding author), Catholic Univ Korea, Grad Sch, Dept Pharm, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea.; Kwak, MK (corresponding author), Catholic Univ Korea, Integrated Res Inst Pharmaceut Sci, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea.	mkwak@catholic.ac.kr			National Research Foundation of Korea (NRF) - Korea government (MSIP) [NRF-2015R1A2A1A10054384, NRF-2013M3A9B5075839]; BK21Plus grant of NRF - Korean government [22A20130012250]	This study was financially supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korea government (MSIP; NRF-2015R1A2A1A10054384, NRF-2013M3A9B5075839). This study was also supported by the BK21Plus grant of NRF funded by Korean government (22A20130012250).	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AUG 30	2018	9								896	10.1038/s41419-018-0903-4			17	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	GT8YO	WOS:000444826200011	30166520	Green Published, gold			2022-04-25	
J	Kim, HS; Quon, MJ; Kim, JA				Kim, Hae-Suk; Quon, Michael J.; Kim, Jeong-a			New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate	REDOX BIOLOGY			English	Review						Polyphenol; EGCG; Anti-oxidant; Pro-oxidant	COLON-CANCER CELLS; 67-KDA LAMININ RECEPTOR; NITRIC-OXIDE SYNTHASE; ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; FACTOR-BETA-RECEPTOR; SMOOTH-MUSCLE-CELLS; HIGH-FAT DIET; (-)-EPIGALLOCATECHIN GALLATE; INSULIN-RESISTANCE	Green tea is rich in polyphenol flavonoids including catechins. Epigallocatechin 3-gallate (EGCG) is the most abundant and potent green tea catechin. EGCG has been extensively studied for its beneficial health effects as a nutriceutical agent. Based upon its chemical structure, EGCG is often classified as an antioxidant However, treatment of cells with EGCG results in production of hydrogen peroxide and hydroxyl radicals in the presence of Fe (III). Thus, EGCG functions as a pro-oxidant in some cellular contexts. Recent investigations have revealed many other direct actions of EGCG that are independent from anti-oxidative mechanisms. In this review, we discuss these novel molecular mechanisms of action for EGCG. In particular, EGCG directly interacts with proteins and phospholipids in the plasma membrane and regulates signal transduction pathways, transcription factors, DNA methylation, mitochonclrial function, and autophagy to exert many of its beneficial biological actions. (C) 2014 The Authors. Published by Elsevier B.V. All rights reserved.	[Kim, Hae-Suk; Kim, Jeong-a] Univ Alabama Birmingham, Div Endocrinol Diabet & Metab, Dept Med, UAB Comprehens Diabet Ctr, Birmingham, AL 35294 USA; [Kim, Jeong-a] Univ Alabama Birmingham, UAB Comprehens Diabet Ctr, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA; [Quon, Michael J.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA		Kim, JA (corresponding author), Univ Alabama Birmingham, Div Endocrinol Diabet & Metab, Dept Med, UAB Comprehens Diabet Ctr, Birmingham, AL 35294 USA.	jakim@uab.edu		QUON, MICHAEL/0000-0002-5289-3707; Quon, Michael/0000-0002-9601-9915	American Diabetes AssociationAmerican Diabetes Association [1-09-JF-33, 1-12-BS-99, 1-13-BS-150]; American Heart AssociationAmerican Heart Association [13GRNT17220057]; UAB diabetes research center - National Institutes of Health [P60 DK-079626]; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [P30DK079637, P30DK072488, P60DK079626, P30DK079626] Funding Source: NIH RePORTER	This study was supported by the American Diabetes Association (1-09-JF-33; 1-12-BS-99 to J.K; 1-13-BS-150 to M.J.Q), American Heart Association (13GRNT17220057 to J.K), and UAB diabetes research center sponsored pilot and feasibility program supported by the National Institutes of Health (P60 DK-079626).	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J	Han, J; Zhang, J; Zhang, CL				Han, Jun; Zhang, Jing; Zhang, Chengliang			Irinotecan-Induced Steatohepatitis: Current Insights	FRONTIERS IN ONCOLOGY			English	Review						irinotecan; chemotherapy; hepatotoxicity; hepatic steatosis; steatohepatitis	CHEMOTHERAPY-ASSOCIATED HEPATOTOXICITY; METASTATIC COLORECTAL-CANCER; PREOPERATIVE CHEMOTHERAPY; MITOCHONDRIAL DYSFUNCTION; PREDICTS STEATOHEPATITIS; LIVER METASTASES; ADIPOSE-TISSUE; PHASE-II; MECHANISMS; AUTOPHAGY	The hepatotoxicity of irinotecan is drawing wide concern nowadays due to the widespread use of this chemotherapeutic against various solid tumors, particularly metastatic colorectal cancer. Irinotecan-induced hepatotoxicity mainly manifests as transaminase increase and steatosis with or without transaminase increase, and is accompanied by vacuolization, and lobular inflammation. Irinotecan-induced steatohepatitis (IIS) increases the risk of morbidity and mortality in patients with colorectal cancer liver metastasis (CRCLM). The major risks and predisposing factors for IIS include high body mass index (BMI) or obesity, diabetes, and high-fat diet. Mitochondrial dysfunction and autophagy impairment may be involved in the pathogenesis of IIS. However, there is currently no effective preventive or therapeutic treatment for this condition. Thus, the precise mechanisms underlying the pathogenesis of IIS should be deciphered for the development of therapeutic drugs. This review summarizes the current knowledge and research progress on IIS.	[Han, Jun; Zhang, Chengliang] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan, Peoples R China; [Han, Jun] Jianghan Univ, Dept Pharm, Affiliated Hosp, Wuhan, Peoples R China; [Zhang, Jing] Wuhan Red Cross Hosp, Wuhan, Peoples R China		Zhang, CL (corresponding author), Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan, Peoples R China.	cfzhang@tjh.tjmu.edu.cn			scientific research project of Wuhan NO.6 hospital [LX19013]	This work was supported by grants from the scientific research project of Wuhan NO.6 hospital (No. LX19013 to JH).	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Oncol.	OCT 11	2021	11								754891	10.3389/fonc.2021.754891			6	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	WU7EA	WOS:000716703200001	34707997	gold, Green Published			2022-04-25	
J	Zhou, JM; Wang, M; Mao, AR; Zhao, YM; Wang, LR; Xu, Y; Jia, H; Wang, L				Zhou, Jiamin; Wang, Miao; Mao, Anrong; Zhao, Yiming; Wang, Longrong; Xu, Ye; Jia, Hao; Wang, Lu			Long noncoding RNA MALAT1 sponging miR-26a-5p to modulate Smad1 contributes to colorectal cancer progression by regulating autophagy	CARCINOGENESIS			English	Article							EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR SUPPRESSION; PROMOTES; MIGRATION; INVASION; NETWORK; CELLS	Accumulating evidences have suggested that bone morphogenetic protein (BMP)-Smad have a functional role in regulating autophagy in the development of human colorectal cancer (CRC). However, the regulatory mechanisms controlling this process remain unclear. Here, we showed that Smad1, the key effector of BMP2-Smad signaling, induces autophagy by upregulating autophagy-related gene 5 (ATG5) expression, and Smad1 binds to the proximal promoter to induce its expression. Moreover, BMP2 induces autophagy in CRC. Overexpression of Smad1 promotes tumorigenesis and migration of CRC cells, and knockdown of ATG5 is able to rescue the Smad1-induced promotion of CRC proliferation and migration partially. Mechanistically, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) may act as a competing endogenous RNA by binding with miR-26a-5p competitively and thus modulating the de-repression of downstream target Smad1. Furthermore, clinical analysis results show that Smad1 is positively correlated with MALAT1 and negatively correlated with miR-26a-5p in CRC samples. In conclusion, our results demonstrated that Smad1 may serve as an oncogene in CRC through autophagy. [GRAPHICS] .	[Zhou, Jiamin; Wang, Miao; Mao, Anrong; Zhao, Yiming; Wang, Longrong; Wang, Lu] Fudan Univ, Shanghai Canc Ctr, Dept Hepat Surg, Shanghai 200032, Peoples R China; [Zhou, Jiamin; Wang, Miao; Mao, Anrong; Zhao, Yiming; Wang, Longrong; Xu, Ye; Wang, Lu] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China; [Xu, Ye] Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai 200032, Peoples R China; [Jia, Hao] Shanghai Jiao Tong Univ, Sch Med, Fac Basic Med, Shanghai 200025, Peoples R China		Wang, L (corresponding author), Fudan Univ, Shanghai Canc Ctr, Dept Hepat Surg, Shanghai 200032, Peoples R China.; Xu, Y; Wang, L (corresponding author), Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China.; Xu, Y (corresponding author), Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai 200032, Peoples R China.; Jia, H (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Fac Basic Med, Shanghai 200025, Peoples R China.	fonney@sjtu.edu.cn; wang.lu99@hotmail.com		Jia, Hao/0000-0003-1856-6013	National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31970679, 81902438]; Shanghai Rising-Star Program [19QA1405000]	This work was supported by the National Science Foundation of China (31970679, 81902438), Shanghai Rising-Star Program (19QA1405000).	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J	Edeler, D; Kaluderovic, MR; Dojcinovic, B; Schmidt, H; Kaluderovic, GN				Edeler, David; Kaluderovic, Milena R.; Dojcinovic, Biljana; Schmidt, Harry; Kaluderovic, Goran N.			SBA-15 mesoporous silica particles loaded with cisplatin induce senescence in B16F10 cells	RSC ADVANCES			English	Article							DRUG-DELIVERY SYSTEMS; ANTICANCER ACTIVITY; CANCER-CELLS; CO-DELIVERY; NANOPARTICLES; COMPLEXES; AUTOPHAGY; STRATEGY; CYTOTOXICITY; CHEMOTHERAPY	The anticancer drug cisplatin (CP) is loaded into SBA-15 mesoporous silica (SBA-15 vertical bar CP) and its release from the nanomaterial is studied. The CP-loaded SBA-15 is tested against four tumor cell lines: mouse malignant melanoma B16F10, human adenocarcinoma HeLa, colon HT-29 and prostate PC3. Most importantly, the superiority of this novel material in comparison to CP arises from the fact that the CP-grafted nanomaterial SBA-15 (-> SBA-15 vertical bar CP) is enhancing cessation of proliferation along with induction of senescence in B16F10 in approximately 3.5 times lower concentration. The control material loaded with therapeutically inactive K-2[PtCl4] (-> SBA-15 vertical bar TC) showed no antitumor activity. To a large extent, SBA15| CP-induced senescence might present a safe approach in tumor treatment. Such cells can be cleared by immune cells resulting in efficient tumor regression. So far only apoptotic agents are being exploited in clinics, thus an understanding of the chemotherapeutic-induced senescence will allow oncologists to explore this essential tumor suppressor mechanism.	[Edeler, David; Kaluderovic, Goran N.] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany; [Edeler, David; Schmidt, Harry] Martin Luther Univ Halle Wittenberg, Inst Chem, Kurt Mothes Str 2, D-06120 Halle, Germany; [Kaluderovic, Milena R.] Univ Hosp Leipzig, Dept Oral Maxillary Facial & Reconstruct Plast Su, Liebigstr 12, D-04103 Leipzig, Germany; [Dojcinovic, Biljana] Univ Belgrade, Inst Chem Technol & Met, Dept Chem, Studentski Trg 12-14, Belgrade 11000, Serbia		Kaluderovic, GN (corresponding author), Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany.	goran.kaluderovic@ipb-halle.de	Kaluderovic, Goran/AAR-7347-2021	Kaluderovic, Goran/0000-0001-5168-1000; Dojcinovic, Biljana/0000-0003-1479-8060			Ahn B, 2013, J MATER CHEM B, V1, P2829, DOI 10.1039/c3tb20319k; Arnesano F, 2009, COORDIN CHEM REV, V253, P2070, DOI 10.1016/j.ccr.2009.01.028; Azimov F., 2012, J U CHEM TECHNOL MET, V47, P333; Braun K, 2016, J COLLOID INTERF SCI, V475, P161, DOI 10.1016/j.jcis.2016.05.002; 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Taratula O, 2011, J DRUG TARGET, V19, P900, DOI 10.3109/1061186X.2011.622404; van Rijt SH, 2015, ACS NANO, V9, P2377, DOI 10.1021/nn5070343; Vicencio JM, 2008, GERONTOLOGY, V54, P92, DOI 10.1159/000129697; Vivero-Escoto JL, 2015, NANOMATERIALS-BASEL, V5, P2302, DOI 10.3390/nano5042302; Wan XJ, 2011, MACROMOL RAPID COMM, V32, P1082, DOI 10.1002/marc.201100198; White E, 2009, GENE DEV, V23, P784, DOI 10.1101/gad.1795309; Wu W, 2016, INT J PHARMACEUT, V511, P65, DOI 10.1016/j.ijpharm.2016.06.133; Xie WL, 2015, IND ENG CHEM RES, V54, P1505, DOI 10.1021/ie5045007; Xie WL, 2014, CHEM ENG J, V239, P60, DOI 10.1016/j.cej.2013.11.009; Yingchoncharoen P, 2016, PHARMACOL REV, V68, P701, DOI 10.1124/pr.115.012070; Yuan ZM, 2016, NANOTECHNOLOGY, V27, DOI 10.1088/0957-4484/27/24/245101; Zhao DY, 1998, J AM CHEM SOC, V120, P6024, DOI 10.1021/ja974025i	74	17	17	0	13	ROYAL SOC CHEMISTRY	CAMBRIDGE	THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND		2046-2069		RSC ADV	RSC Adv.		2016	6	112					111031	111040		10.1039/c6ra22596a			10	Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	EE3CD	WOS:000389463600062		Green Published			2022-04-25	
J	Deng, YC; Wu, L; Ding, QS; Yu, HG				Deng, Yunchao; Wu, Lu; Ding, Qianshan; Yu, Honggang			AGXT2L1 is downregulated in carcinomas of the digestive system	ONCOLOGY LETTERS			English	Article						alanine-glyoxylate aminotransferase 2-like 1; digestive cancer; pathology; autophagy	AUTOPHAGY; EXPRESSION; CANCER; PHOSPHATIDYLCHOLINE; IDENTIFICATION; METABOLISM; HEALTH	Alanine-glyoxylate aminotransferase 2-like 1 (AGXT2L1) is a modulator of phospholipid metabolism, and its role in tumor biology is obscure. Previously, significant downregulation of AGXT2L1 has been observed in hepatocellular carcinoma. The aim of the present study was to investigate AGXT2L1 expression and its association with the clinical characteristics of common carcinomas of the digestive system. In the present study, the expression levels of AGXT2L1 were detected by immunohistochemical staining in colorectal cancer (CRC), gastric cancer and pancreatic cancer tissues. The associations between AGXT2L1 expression and clinicopathological features were analyzed using public gene expression datasets. Small interfering RNA was transfected into SW480 and HCT116 cells to explore the role of AGXT2L1 in CRC cells. AGXT2L1 expression was significantly decreased in cancerous tissues compared with in normal tissues, and low AGXT2L1 expression was associated with an unfavorable prognosis in patients. Furthermore, it was revealed that AGXT2L1 may regulate phosphatidylinositol and phosphatidylserine metabolism in cancerous tissues, and that decreased AGXT2L1 expression could induce autophagy in CRC cells. Overall, the present study provides a basis for further understanding of the role of AGXT2L1 and its association with autophagy in cancer.	[Deng, Yunchao; Wu, Lu; Ding, Qianshan; Yu, Honggang] Wuhan Univ, Dept Gastroenterol, Renmin Hosp, 238 Jiefang Rd, Wuhan 430060, Hubei, Peoples R China; [Deng, Yunchao; Wu, Lu; Ding, Qianshan; Yu, Honggang] Wuhan Univ, Hubei Key Lab Digest Syst, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China		Ding, QS; Yu, HG (corresponding author), Wuhan Univ, Dept Gastroenterol, Renmin Hosp, 238 Jiefang Rd, Wuhan 430060, Hubei, Peoples R China.	iamdqs@163.com; yuhonggang1968@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672387, 81703030]	The present study was supported by National Natural Science Foundation of China (grant nos. 81672387 and 81703030).	Cui JA, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0017819; Cui JA, 2011, NUCLEIC ACIDS RES, V39, P1197, DOI 10.1093/nar/gkq960; Ding QS, 2016, J CLIN PATHOL, V69, P215, DOI 10.1136/jclinpath-2015-203042; Fotheringham J, 2000, BBA-MOL CELL BIOL L, V1485, P1, DOI 10.1016/S1388-1981(00)00025-1; Garcia H, 2011, ONCOTARGET, V2, P783; Giatromanolaki A, 2010, J CLIN PATHOL, V63, P867, DOI 10.1136/jcp.2010.079525; Gual P, 2017, AM J PHYSIOL-CELL PH, V312, pC263, DOI 10.1152/ajpcell.00295.2016; Hurley JH, 2017, ANNU REV BIOCHEM, V86, P225, DOI 10.1146/annurev-biochem-061516-044820; Keckesova Z, 2017, NATURE, V543, P681, DOI 10.1038/nature21408; Kowalik MA, 2016, ONCOTARGET, V7, P5788, DOI 10.18632/oncotarget.6810; Lai K, 2014, J CLIN PATHOL, V67, P854, DOI 10.1136/jclinpath-2014-202529; Lamb CA, 2013, NAT REV MOL CELL BIO, V14, P759, DOI 10.1038/nrm3696; Li ZY, 2006, CELL METAB, V3, P321, DOI 10.1016/j.cmet.2006.03.007; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Pavlovic Z, 2013, INT J MOL SCI, V14, P2529, DOI 10.3390/ijms14022529; Qiu Y, 2017, PROTEIN SCI, V26, P1674, DOI 10.1002/pro.3186; Ravikumar B, 2010, PHYSIOL REV, V90, P1383, DOI 10.1152/physrev.00030.2009; Rockenfeller P, 2015, CELL DEATH DIFFER, V22, P499, DOI 10.1038/cdd.2014.219; Saha S, 2018, BIOMED PHARMACOTHER, V104, P485, DOI 10.1016/j.biopha.2018.05.007; Schiroli D, 2013, IUBMB LIFE, V65, P645, DOI 10.1002/iub.1178; Shao L, 2008, BIOL PSYCHIAT, V64, P89, DOI 10.1016/j.biopsych.2007.11.010; Smith JJ, 2010, GASTROENTEROLOGY, V138, P958, DOI 10.1053/j.gastro.2009.11.005; Sui XB, 2011, AUTOPHAGY, V7, P565, DOI 10.4161/auto.7.6.14073; Tooze SA, 2013, ESSAYS BIOCHEM, V55, P29, DOI [10.1042/BSE0550029, 10.1042/bse0550029]; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; van der Veen JN, 2017, BBA-BIOMEMBRANES, V1859, P1558, DOI 10.1016/j.bbamem.2017.04.006; Veiga-da-Cunha M, 2012, J BIOL CHEM, V287, P7246, DOI 10.1074/jbc.M111.323485; Wu Y, 2019, SCI ADV, V5, DOI 10.1126/sciadv.aax7525; Zaffagnini G, 2016, J MOL BIOL, V428, P1714, DOI 10.1016/j.jmb.2016.02.004; Zhang XX, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0138820	30	0	0	1	2	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	AUG	2020	20	2					1318	1326		10.3892/ol.2020.11645			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NG2RJ	WOS:000563832100037	32724374	gold, Green Published			2022-04-25	
J	Liu, BW; Yan, XF; Hou, ZJ; Zhang, L; Zhang, DW				Liu, Bingwu; Yan, Xinfeng; Hou, Zuojia; Zhang, Lei; Zhang, Duwen			Impact of Bupivacaine on malignant proliferation, apoptosis and autophagy o f human colorectal cancer SW480 cells through regulating NF-kappa B signaling path	BIOENGINEERED			English	Article						Bupivacaine; colorectal cancer; nf-kappa B; apoptosis; autophagy	LOCAL-ANESTHETIC BUPIVACAINE; EFFICACY; SURGERY; DEATH	To probe into the impact of Bupivacaine on colorectal cancer (CRC) proliferation, apoptosis, and autophagy through regulating the NE-KB signaling pathway. Our work treated CRC cells with Bupivacaine, detected cell vitality through MTT assay, apoptosis through flow cytometry, cell migration through wound healing assay, NF-KB activity through immunofluorescence, inflammatory factor level, including TNF-alpha, IL-1 beta as well as IL-6 through ESLIA, apoptosis factor mRNA expression, including Bcl-2, Bax and caspase-3q through qRT-PCR, and protein expression linking with NF-KB signaling pathway as well as autophagy-related proteins via western blot. In in vivo experiments, we explored the impact of Bupivacaine on tumor volume, tumor and NF-kappa B expression. The results showed that 1 mM Bupivacaine was available to signally inhibit CRC cell vitality, promoted apoptosis rate and apoptosis gene expression, like Bax, and caspase-3, inhibited Bcl-2 expression, inhibited cancer cell migration, promoted autophagy-related protein LC3B II/LC3B I ratio and beclin-1 expression, and inhibited p62 expression. Additionally, it could elevate inflammatory factor level and induce IKK and I kappa B phosphorylation as well as NE-kappa B proteins. In in vivo experiments, Bupivacaine inhibited tumor volume and tumor, as well as NF-kappa B expression. In short, bupivacaine is available to inhibit CRC proliferation through regulating NE-kappa B signaling pathway, promote apoptosis and autophagy, and can be used as a potential drug to treat CRC in the future. [GRAPHICS] .	[Liu, Bingwu; Yan, Xinfeng] Second Children & Womens Healthcare Jinan City, Dept Anesthesiol, Jinan, Shandong, Peoples R China; [Hou, Zuojia] Laiwu Peoples Hosp Jinan City, Dept Anesthesiol, Jinan, Shandong, Peoples R China; [Zhang, Lei] Laiwu Iron & Steel Grp Laiwu Min Co Ltd, Dept Anesthesiol, Staff Hosp, Jinan, Shandong, Peoples R China; [Zhang, Duwen] Guizhou Prov Peoples Hosp, Dept Anesthesiol, 83 East Zhongshan Rd, Guiyang 550002, Guizhou, Peoples R China		Zhang, DW (corresponding author), Guizhou Prov Peoples Hosp, Dept Anesthesiol, 83 East Zhongshan Rd, Guiyang 550002, Guizhou, Peoples R China.	zhangdw_3@hotmail.com					Cheng L, 2021, J BIOENERG BIOMEMBR, V53, P415, DOI 10.1007/s10863-021-09901-8; Dan JP, 2018, BIOMED PHARMACOTHER, V103, P823, DOI 10.1016/j.biopha.2018.04.106; de Ridder I, 2021, BBA-MOL CELL RES, V1868, DOI 10.1016/j.bbamcr.2021.118983; Eden C, 2018, SURG ONCOL, V27, P266, DOI 10.1016/j.suronc.2018.05.001; Exadaktylos AK, 2006, ANESTHESIOLOGY, V105, P660, DOI 10.1097/00000542-200610000-00008; Fan LH, 2019, EUR J PHARMACOL, V850, P43, DOI 10.1016/j.ejphar.2019.01.025; Fares KM, 2015, PAIN MED, V16, P1186, DOI 10.1111/pme.12687; Guo D, 2016, FUND CLIN PHARMACOL, V30, P307, DOI 10.1111/fcp.12197; Hauseman ZJ, 2020, MOL CELL, V79, P68, DOI 10.1016/j.molcel.2020.05.029; Kanemitsu Y, 2021, J CLIN ONCOL, V39, P1098, DOI 10.1200/JCO.20.02447; Kim B, 2015, SURG ENDOSC, V29, P714, DOI 10.1007/s00464-014-3730-4; Li R, 2018, BMC CANCER, V18, DOI 10.1186/s12885-018-4576-2; Li TC, 2019, J ANESTH, V33, P17, DOI 10.1007/s00540-018-2577-6; Li Y., 2021, ARCH BIOCHEM BIOPHYS; Marshall RS, 2019, FRONT MOL BIOSCI, V6, DOI 10.3389/fmolb.2019.00040; Onorati AV, 2018, CANCER-AM CANCER SOC, V124, P3307, DOI 10.1002/cncr.31335; Patel M, 2018, TRANSL RES, V197, P43, DOI 10.1016/j.trsl.2018.02.002; Piawah S, 2019, CANCER-AM CANCER SOC, V125, P4139, DOI 10.1002/cncr.32163; Provenzale D, 2018, J NATL COMPR CANC NE, V16, P939, DOI 10.6004/jnccn.2018.0067; Rawla P, 2019, GASTROENTEROL REV, V14, P89, DOI 10.5114/pg.2018.81072; Vega-Rubin-de-Celis S, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21239210; Wang T, 2021, CELL CYCLE, V20, P1181, DOI 10.1080/15384101.2021.1930357; Wang X, 2021, BIOENGINEERED, V12, P44, DOI 10.1080/21655979.2020.1857120; Wong RSY, 2011, J EXP CLIN CANC RES, V30, DOI 10.1186/1756-9966-30-87; Xia F, 2021, MED RES REV, V41, P1644, DOI 10.1002/med.21772; Xuan W, 2016, SCI REP-UK, V6, DOI 10.1038/srep26277; Ye F, 2017, MED GAS RES, V7, P204, DOI 10.4103/2045-9912.215751; Yu L, 2017, BLOOD REV, V31, P77, DOI 10.1016/j.blre.2016.10.001; Zhang JL, 2017, EXP THER MED, V13, P1074, DOI 10.3892/etm.2017.4058	29	3	3	3	7	TAYLOR & FRANCIS INC	PHILADELPHIA	530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA	2165-5979	2165-5987		BIOENGINEERED	Bioengineered	JAN 1	2021	12	1					2723	2733		10.1080/21655979.2021.1937911			11	Biotechnology & Applied Microbiology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology	SV7PA	WOS:000664010000001	34151717	gold, Green Published			2022-04-25	
J	Li, B; Wang, Z; Xie, JM; Wang, G; Qian, LQ; Guan, XM; Shen, XP; Qin, ZH; Shen, GH; Li, XQ; Gao, QG				Li, Bin; Wang, Zhong; Xie, Jia-ming; Wang, Gang; Qian, Li-qiang; Guan, Xue-mei; Shen, Xue-ping; Qin, Zheng-hong; Shen, Gen-hai; Li, Xiao-qiang; Gao, Quan-gen			TIGAR knockdown enhanced the anticancer effect of aescin via regulating autophagy and apoptosis in colorectal cancer cells	ACTA PHARMACOLOGICA SINICA			English	Article						TIGAR; aescin; apoptosis; autophagy; colorectal cancer	FACTOR-KAPPA-B; BETA-ESCIN; TP53-INDUCED GLYCOLYSIS; HEPATOCELLULAR-CARCINOMA; GLIOMA-CELLS; IDENTIFICATION; INHIBITION; STATISTICS; RESISTANCE; PATHWAY	Our previous study showed that TP53-induced glycolysis and apoptosis regulator (TIGAR) regulated ROS, autophagy, and apoptosis in response to hypoxia and chemotherapeutic drugs. Aescin, a triterpene saponin, exerts anticancer effects and increases ROS levels. The ROS is a key upstream signaling to activate autophagy. Whether there is a crosstalk between TIGAR and aescin in regulating ROS, autophagy, and apoptosis is unknown. In this study, we found that aescin inhibited cell viability and colony formation, and induced DNA damage, cell cycle arrest, and apoptosis in cancer cell lines HCT-116 and HCT-8 cells. Concurrently, aescin increased the expression of TIGAR, ROS levels, and autophagy activation. Knockdown of TIGAR enhanced the anticancer effects of aescin in vitro and in vivo, whereas overexpression of TIGAR or replenishing TIGAR downstream products, NADPH and ribose, attenuated aescin-induced apoptosis. Furthermore, aescin-induced ROS elevation and autophagy activation were further strengthened by TIGAR knockdown in HCT-116 cells. However, autophagy inhibition by knockdown of autophagy-related gene ATGS or 3-methyladenine (3-MA) exaggerated aescin-induced apoptosis when TIGAR was knocked down. In conclusion, TIGAR plays a dual role in determining cancer cell fate via inhibiting both apoptosis and autophagy in response to aescin, which indicated that inhibition of TIGAR and/or autophagy may be a junctional therapeutic target in treatment of cancers with aescin.	[Li, Bin; Li, Xiao-qiang] Soochow Univ, Affiliated Hosp 2, Dept Vasc Surg, Suzhou 215007, Peoples R China; [Li, Bin; Wang, Gang; Qian, Li-qiang; Guan, Xue-mei; Shen, Xue-ping; Shen, Gen-hai; Gao, Quan-gen] First Peoples Hosp Wu Jiang, Dept Gen Surg, Suzhou 215200, Peoples R China; [Li, Bin; Qin, Zheng-hong] Soochow Univ, Jiangsu Key Lab Prevent & Translat Med Geriatr Di, Jiangsu Key Lab Translat Res & Therapy Neuropsyco, Coll Pharmaceut Sci,Dept Pharmacol, Suzhou 215123, Peoples R China; [Li, Bin; Qin, Zheng-hong] Soochow Univ, Jiangsu Key Lab Prevent & Translat Med Geriatr Di, Jiangsu Key Lab Translat Res & Therapy Neuropsyco, Coll Pharmaceut Sci,Lab Aging & Nervous Dis, Suzhou 215123, Peoples R China; [Wang, Zhong; Xie, Jia-ming] Soochow Univ, Affiliated Hosp 2, Dept Gen Surg, Suzhou 215007, Peoples R China		Li, XQ (corresponding author), Soochow Univ, Affiliated Hosp 2, Dept Vasc Surg, Suzhou 215007, Peoples R China.; Shen, GH; Gao, QG (corresponding author), First Peoples Hosp Wu Jiang, Dept Gen Surg, Suzhou 215200, Peoples R China.	wjsgh3026@sina.com; flytsg@126.com; wjyygqg@sohu.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770483, 81602613]; Jiangsu Provincial Commission of Health and Family Planning [YG201402, YG201503]; Jiangsu Provincial Medical Youth Talent [QNRC2016249]; Jiangsu Provincial Science and Technology office [BL2014043]; Suzhou Science and Technology Bureau [SYSD2013041, SYSD2016044, SYSD2017041, SYS201788]; Suzhou Health and Family Planning Commission Program [LCZX201504]; Wujiang District Science and Technology Bureau [WS201301]; Wujiang District Commission of Health and Family Planning [WWK201607, WWK201609]	This work was supported by grants from National Natural Science Foundation of China (No. 81770483 and 81602613), Jiangsu Provincial Commission of Health and Family Planning (No. YG201402 and YG201503), Jiangsu Provincial Medical Youth Talent (No. QNRC2016249), Jiangsu Provincial Science and Technology office (No. BL2014043), Suzhou Science and Technology Bureau (No. SYSD2013041, SYSD2016044, SYSD2017041, and SYS201788), Suzhou Health and Family Planning Commission Program (No. LCZX201504), Wujiang District Science and Technology Bureau (No. WS201301), and Wujiang District Commission of Health and Family Planning (No. WWK201607 and WWK201609).	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Sin.	JAN	2019	40	1					111	121		10.1038/s41401-018-0001-2			11	Chemistry, Multidisciplinary; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	HG2EA	WOS:000454774700012	29769743	Green Published, Bronze			2022-04-25	
J	Wang, YX; Lin, C; Cui, LJ; Yang, WH; Li, QM; Liu, ZJ; Miao, XP				Wang, Yu-Xuan; Lin, Cheng; Cui, Lu-Jia; Yang, Wan-He; Li, Qiu-Min; Liu, Zhan-Ju; Miao, Xin-Pu			Rauwolfia vomitoria Extract Represses Colorectal Cancer Cell Autophagy and Promotes Apoptosis	PHARMACOLOGY			English	Article						Colorectal cancer; Rauwolfia vomitoria extract; Autophagy; Apoptosis; Digestive tract tumors	ANTITUMOR ACTIVITIES; POTENTIATION; METASTASIS; THERAPY; DRUGS; DEATH	Background: Colorectal cancer (CRC) is one of the most frequent digestive tract tumors in the world with an increasing incidence. Currently, surgical resection and chemotherapy are the main therapeutic options; however, their effects are limited by various adverse reactions. Rauwolfia vomitoria extract (Rau) has been shown to repress the progression of multiple human cancers; however, whether Rau plays a role in CRC remains undetermined. Methods: Influences of Rau treatment on HCT-116 and LoVo cells were estimated via MTT and colony formation experiments. Flow cytometry analysis was adopted to evaluate the apoptosis rate of HCT-116 and LoVo cells. Apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and autophagy-related proteins (LC3 and P62) were assessed by Western blotting. Effects of Rau on autophagy of HCT-116 and LoVo cell were evaluated through GFP-LC3 analysis. In vivo xenograft tumor assay was conducted to further examine the role of Rau in CRC tumor growth. Results: Rau remarkably repressed HCT-116 and LoVo cell viability and promoted HCT-116 and LoVo cell apoptosis in vitro in a dose-dependent manner. Rau increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2 in HCT-116 and LoVo cells. Moreover, Rau was demonstrated to decrease the LC3||/LC3| ratio and increase the level of P62 in HCT-116 and LoVo cells. In addition, we found that Rau repressed xenograft tumor growth and also repressed autophagy in vivo. Conclusion: Our findings revealed that Rau repressed CRC cell viability and autophagy in vitro and in vivo, suggesting that Rau might be a potent therapeutic agent of CRC.	[Wang, Yu-Xuan; Lin, Cheng; Cui, Lu-Jia; Yang, Wan-He; Li, Qiu-Min; Miao, Xin-Pu] Hainan Gen Hosp, Dept Gastroenterol, Haikou, Hainan, Peoples R China; [Liu, Zhan-Ju] Tongji Univ, Dept Gastroenterol, Shanghai Peoples Hosp 10, Shanghai, Peoples R China		Miao, XP (corresponding author), Hainan Gen Hosp, Dept Gastroenterol, Haikou, Hainan, Peoples R China.	maoxinpu@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81360603]; Natural Science Foundation of Hainan Province [813215]	This work was supported by the National Natural Science Foundation of China (Grant No. 81360603) and Natural Science Foundation of Hainan Province (Grant No. 813215).	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J	Kwon, Y; Kim, M; Jung, HS; Kim, Y; Jeoung, D				Kwon, Yoojung; Kim, Misun; Jung, Hyun Suk; Kim, Youngmi; Jeoung, Dooil			Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments	CANCERS			English	Review						anti-EGFR treatments; autophagy; EGFR signaling; co-targeting	GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; EXTRACELLULAR VESICLES; TUMOR PROGRESSION; COLORECTAL-CANCER; CARCINOMA-CELLS; DRUG-RESISTANCE; MTOR-INHIBITOR	Epidermal growth factor receptor (EGFR) plays critical roles in cell proliferation, tumorigenesis, and anti-cancer drug resistance. Overexpression and somatic mutations of EGFR result in enhanced cancer cell survival. Therefore, EGFR can be a target for the development of anti-cancer therapy. Patients with cancers, including non-small cell lung cancers (NSCLC), have been shown to response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR antibodies. However, resistance to these anti-EGFR treatments has developed. Autophagy has emerged as a potential mechanism involved in the acquired resistance to anti-EGFR treatments. Anti-EGFR treatments can induce autophagy and result in resistance to anti-EGFR treatments. Autophagy is a programmed catabolic process stimulated by various stimuli. It promotes cellular survival under these stress conditions. Under normal conditions, EGFR-activated phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling inhibits autophagy while EGFR/rat sarcoma viral oncogene homolog (RAS)/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) signaling promotes autophagy. Thus, targeting autophagy may overcome resistance to anti-EGFR treatments. Inhibitors targeting autophagy and EGFR signaling have been under development. In this review, we discuss crosstalk between EGFR signaling and autophagy. We also assess whether autophagy inhibition, along with anti-EGFR treatments, might represent a promising approach to overcome resistance to anti-EGFR treatments in various cancers. In addition, we discuss new developments concerning anti-autophagy therapeutics for overcoming resistance to anti-EGFR treatments in various cancers.	[Kwon, Yoojung; Kim, Misun; Jung, Hyun Suk; Jeoung, Dooil] Kangwon Natl Univ, Coll Nat Sci, Dept Biochem, Chunchon 24341, South Korea; [Kim, Youngmi] Hallym Univ, Coll Med, Inst New Frontier Res, Chunchon 24251, South Korea		Jeoung, D (corresponding author), Kangwon Natl Univ, Coll Nat Sci, Dept Biochem, Chunchon 24341, South Korea.	kkwon89@kangwon.ac.kr; misunjtl@naver.com; hsjung@kangwon.ac.kr; kym8389@hanmail.net; jeoungd@kangwon.ac.kr			National Research Foundation [2017R1A2A2A05001029, 2017M3A9G7072417, 2018R1D1A1B07043498]; BK21 plus Program	This work was supported by National Research Foundation Grants (2017R1A2A2A05001029, 2017M3A9G7072417, 2018R1D1A1B07043498), a grant from the BK21 plus Program.	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J	Hinze, L; Labrosse, R; Degar, J; Han, T; Schatoff, EM; Schreek, S; Karim, S; McGuckin, C; Sacher, JR; Wagner, F; Stanulla, M; Yuan, C; Sicinska, E; Giannakis, M; Ng, K; Dow, LE; Gutierrez, A				Hinze, Laura; Labrosse, Roxane; Degar, James; Han, Teng; Schatoff, Emma M.; Schreek, Sabine; Karim, Salmaan; McGuckin, Connor; Sacher, Joshua R.; Wagner, Florence; Stanulla, Martin; Yuan, Chen; Sicinska, Ewa; Giannakis, Marios; Ng, Kimmie; Dow, Lukas E.; Gutierrez, Alejandro			Exploiting the Therapeutic Interaction of WNT Pathway Activation and Asparaginase for Colorectal Cancer Therapy	CANCER DISCOVERY			English	Article							GENETIC ALTERATIONS; PROTEIN; MUTATIONS; RNF43; DIFFERENTIATION; GSK-3-ALPHA; HOMEOSTASIS; AUTOPHAGY; SURVIVAL; HOMOLOG	Colorectal cancer is driven by mutations that activate canonical WNT/beta-catenin signaling, but inhibiting WNT has significant on-target toxicity, and there are no approved therapies targeting dominant oncogenic drivers. We recently found that activating a beta-catenin-independent branch of WNT signaling that inhibits GSK3-dependent protein degradation induces asparaginase sensitivity in drug-resistant leukemias. To test predictions from our model, we turned to colorectal cancer because these cancers can have WNT-activating mutations that function either upstream (i.e., R-spondin fusions) or downstream (APC or beta-catenin mutations) of GSK3, thus allowing WNT/beta-catenin and WNT-induced asparaginase sensitivity to be unlinked genetically. We found that asparaginase had little efficacy in APC or beta-catenin-mutant colorectal cancer, but was profoundly toxic in the setting of R-spondin fusions. Pharmacologic GSK3 alpha inhibition was sufficient for asparaginase sensitization in APC or beta-catenin-mutant colorectal cancer, but not in normal intestinal progenitors. Our findings demonstrate that WNT-induced therapeutic vulnerabilities can be exploited for colorectal cancer therapy. SIGNIFICANCE Solid tumors are thought to be asparaginase-resistant via de novo asparagine synthesis. In leukemia, GSK3 alpha-dependent protein degradation, a catabolic amino acid source, mediates asparaginase resistance. We found that asparaginase is profoundly toxic to colorectal cancers with WNT-activating mutations that inhibit GSK3. Aberrant WNT activation can provide a therapeutic vulnerability in colorectal cancer.	[Hinze, Laura; Labrosse, Roxane; Degar, James; Karim, Salmaan; McGuckin, Connor; Gutierrez, Alejandro] Harvard Med Sch, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA; [Hinze, Laura; Schreek, Sabine; Stanulla, Martin] Hannover Med Sch, Dept Pediat Hematol & Oncol, Hannover, Germany; [Han, Teng; Schatoff, Emma M.] Weill Cornell Med, Sandra & Edward Meyer Canc Ctr, New York, NY USA; [Han, Teng; Schatoff, Emma M.; Dow, Lukas E.] Weill Cornell Med, Veil Cornell Grad Sch Med Sci, New York, NY USA; [Schatoff, Emma M.] Weill Cornell Rockefeller Sloan Kettering Triins, New York, NY USA; [Sacher, Joshua R.; Wagner, Florence] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA; [Yuan, Chen; Giannakis, Marios; Ng, Kimmie] Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA; [Sicinska, Ewa] Dana Farber Canc Inst, Dept Oncol Pathol, Boston, MA 02115 USA; [Giannakis, Marios] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA; [Dow, Lukas E.] Weill Cornell Med, Dept Med, New York, NY USA; [Dow, Lukas E.] Weill Cornell Med, Dept Biochem, New York, NY USA; [Gutierrez, Alejandro] Harvard Med Sch, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA		Gutierrez, A (corresponding author), Boston Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA.	alejandro.gutierrez@childrens.harvard.edu	; Sacher, Joshua/M-7463-2016	Degar, James/0000-0002-5387-9069; Sacher, Joshua/0000-0003-4381-3979; McGuckin, Connor/0000-0001-8860-9926	NIH/NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA193651]; Boston Children's Hospital Translational Investigator Service; Dana-Farber Cancer Institute Medical Oncology Translational Grant Award; ERA-NET Transcan/European Commission under the 7th Framework Programme (FP7); German National Academic Foundation; Biomedical Education Program; Conquer Cancer Foundation of ASCO Career Development Award; Project P-Fund; Cancer Research UKCancer Research UK [C10674/A27140]; Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant [SU2C-AACRDT22-17]; American Association for Cancer Research; Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the NIH [T32GM07739]; NCI/NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [1 F31 CA224800-01]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 CA205406]; DODUnited States Department of Defense [CA160344]; CHPA Investigatorship at Boston Children's Hospital	We thank Kimberly Stegmaier, Daniel Bauer, Alex Kentsis, Scott Armstrong, Gabriela Zurek, Nikolaus Kuehn-Velten, Mark Kellogg, Timothy Hagan, Otari Chipashvili, and Sung-Yun Pai for advice and discussion, and Meaghan McGuinness and Casey O'Brien for experimental assistance. This work was supported by NIH/NCI R01 CA193651, the Boston Children's Hospital Translational Investigator Service, a Dana-Farber Cancer Institute Medical Oncology Translational Grant Award, and the ERA-NET Transcan/European Commission under the 7th Framework Programme (FP7). L. Hinze was supported by the German National Academic Foundation and the Biomedical Education Program. M. Giannakis was supported by a Conquer Cancer Foundation of ASCO Career Development Award, the Project P-Fund, the Cancer Research UK C10674/A27140 Grand Challenge Award, and a Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (grant number: SU2C-AACRDT22-17). Stand Up To Cancer (SU2C) is a division of the Entertainment Industry Foundation, and research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. E.M. Schatoff was supported by a Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the NIH under award number T32GM07739 to the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD/PhD Program, and an F31 Award from the NCI/NIH under grant number 1 F31 CA224800-01. K. Ng was supported by NIH R01 CA205406 and DOD CA160344. A. Gutierrez was supported by a CHPA Investigatorship at Boston Children's Hospital.	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NOV	2020	10	11					1690	1705		10.1158/2159-8290.CD-19-1472			16	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	OJ1OE	WOS:000583736200024	32703769	Bronze, Green Accepted			2022-04-25	
J	Jing, XM; Yang, FM; Shao, CC; Wei, K; Xie, MY; Shen, H; Shu, YQ				Jing, Xinming; Yang, Fengming; Shao, Chuchu; Wei, Ke; Xie, Mengyan; Shen, Hua; Shu, Yongqian			Role of hypoxia in cancer therapy by regulating the tumor microenvironment	MOLECULAR CANCER			English	Review						Cancer therapy; Chemotherapy; Drug resistance; Hypoxia; Tumor microenvironment	INDUCIBLE FACTORS; DNA-DAMAGE; COLORECTAL-CANCER; INDUCED RESISTANCE; ESOPHAGEAL CANCER; INDUCED APOPTOSIS; DRUG-RESISTANCE; CARCINOMA-CELLS; GLYOXALASE I; AUTOPHAGY	Aim Clinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy resistance. The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and to highlight the potential of hypoxia-targeted therapy. Methods Relevant published studies were retrieved from PubMed, Web of Science, and Embase using keywords such as hypoxia, cancer therapy, resistance, TME, cancer, apoptosis, DNA damage, autophagy, p53, and other similar terms. Results Recent studies have shown that hypoxia is associated with poor prognosis in patients by regulating the TME. It confers resistance to conventional therapies through a number of signaling pathways in apoptosis, autophagy, DNA damage, mitochondrial activity, p53, and drug efflux. Conclusion Hypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment.	[Jing, Xinming; Yang, Fengming; Shao, Chuchu; Xie, Mengyan; Shen, Hua; Shu, Yongqian] Nanjing Med Univ, Affiliated Sir Run Run Hosp, Dept Oncol, Nanjing, Jiangsu, Peoples R China; [Jing, Xinming; Yang, Fengming; Shao, Chuchu; Xie, Mengyan; Shen, Hua; Shu, Yongqian] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing, Jiangsu, Peoples R China; [Wei, Ke] Nanjing Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Nanjing, Jiangsu, Peoples R China		Shen, H; Shu, YQ (corresponding author), Nanjing Med Univ, Affiliated Sir Run Run Hosp, Dept Oncol, Nanjing, Jiangsu, Peoples R China.	medshenhua@126.com; shuyongqian1998@163.com	Shu, Yongqian/ABD-5698-2021		Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20171484]; Project of Invigorating Health Care through Science, Technology, and Education (Jiangsu Provincial Medical Youth Talent) [QNRC2016856]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672896]; Summit of the Six Top Talents Program of Jiangsu Province [2017-WSN-179]; Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX18_1483, KYCX18_1482]; Priority Academic Program Development of Jiangsu Higher Education Institutions [JX10231801]; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81874230]; Jiangsu Social Development Project [BE2018726]	This study was supported by grants from the Natural Science Foundation of Jiangsu Province (Grants No BK20171484), the Project of Invigorating Health Care through Science, Technology, and Education (Jiangsu Provincial Medical Youth Talent QNRC2016856), the National Natural Science Foundation of China (No. 81672896), the Summit of the Six Top Talents Program of Jiangsu Province (2017-WSN-179), the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_1483), the Priority Academic Program Development of Jiangsu Higher Education Institutions (JX10231801), Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. KYCX18_1482), The Natural Science Foundation of China (81874230) and the Jiangsu Social Development Project (BE2018726).	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Cancer	NOV 11	2019	18	1							157	10.1186/s12943-019-1089-9			15	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	JM8BE	WOS:000496432800001	31711497	Green Published, gold	Y	N	2022-04-25	
J	Zeng, XF; Liu, Q; Yang, YH; Jia, WK; Li, SP; He, DS; Ma, RD				Zeng, Xiaofei; Liu, Qing; Yang, Yanhui; Jia, Weikun; Li, Shuping; He, Dongsheng; Ma, Ruidong			Placenta-specific protein 8 promotes the proliferation of lung adenocarcinoma PC-9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway	ONCOLOGY LETTERS			English	Article						lung adenocarcinoma; placenta-specific protein 8; proliferation; Erk1/2; epidermal growth factor receptor tyrosine kinase inhibitor	CANCER; PLAC8; RESISTANCE; REACTIVATION; CONTRIBUTES; METASTASIS; EXPRESSION; SYNERGIZES; MUTATIONS; REGULATOR	Placenta-specific protein 8 (PLAC8) is a conserved protein with a molecular weight of 12.5 kDa. The specific function of this protein has not been fully elucidated, however, PLAC8 has been found to play an important tumor regulatory role in certain types of cancer, including colon, pancreatic and liver cancer. PLAC8 also participates in the regulation of the cell cycle, autophagy, epithelial-mesenchymal transition and other cellular functions, indicating its potential as a molecular target worth further investigation. The present study investigated the effect of PLAC8 on the proliferation of lung adenocarcinoma PC-9 cells and their sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It was found that the inhibition of PLAC8 expression in PC-9 cells resulted in significantly decreased proliferation, whereas overexpression of PLAC8 significantly increased the proliferation (P<0.05) of PC-9 cells. Furthermore, inhibition of PLAC8 expression resulted in decreased activity of the ERK signaling pathway, while PLAC8 overexpression increased activity of this pathway. Inhibition of the ERK signaling pathway with U0126 reversed the effects induced by inhibiting or overexpressing PLAC8 on cell proliferation. In addition, overexpression of PLAC8 significantly decreased the sensitivity of PC-9 cells to gefitinib, and this effect was reversed by U0126. Overall, these results suggest that PLAC8 is involved in the regulation of proliferation of lung adenocarcinoma PC-9 cells and impacts their sensitivity to an EGFR-TKI. Thus, PLAC8 is a potential novel target in lung adenocarcinoma for future studies.	[Zeng, Xiaofei; Jia, Weikun; Li, Shuping; He, Dongsheng; Ma, Ruidong] Chengdu Med Coll, Affiliated Hosp 1, Dept Cardiothorac Surg, 278 Middle Sect Baoguang Ave, Chengdu 610500, Sichuan, Peoples R China; [Liu, Qing] Chengdu Fifth Peoples Hosp, Dept Cardiothorac Surg, Chengdu 611130, Sichuan, Peoples R China; [Yang, Yanhui] First Peoples Hosp Neijiang, Dept Cardiothorac Surg, Neijiang 641000, Sichuan, Peoples R China		Ma, RD (corresponding author), Chengdu Med Coll, Affiliated Hosp 1, Dept Cardiothorac Surg, 278 Middle Sect Baoguang Ave, Chengdu 610500, Sichuan, Peoples R China.	ma-ruidong@163.com			Scientific Research Topics of Sichuan Education Department [18ZA0165]	This study was supported by the Scientific Research Topics of Sichuan Education Department (grant no. 18ZA0165).	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Lett.	NOV	2019	18	5					5621	5627		10.3892/ol.2019.10911			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	JW7HS	WOS:000503219600132	31620204	Green Published, gold			2022-04-25	
J	Marcucci, F; Rumio, C				Marcucci, Fabrizio; Rumio, Cristiano			Glycolysis-induced drug resistance in tumors-A response to danger signals?	NEOPLASIA			English	Review						Glycolysis; Tumors; Drug resistance; EMT; Danger; Apoptosis	PYRUVATE-KINASE M2; COLON-CANCER CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; OVERCOMES SORAFENIB RESISTANCE; CYTOCHROME-C RELEASE; BREAST-CANCER; GLUCOSE-METABOLISM; CARCINOMA-CELLS; GASTRIC-CANCER; LACTATE-DEHYDROGENASE	Tumor cells often switch from mitochondrial oxidative metabolism to glycolytic metabolism even under aerobic conditions. Tumor cell glycolysis is accompanied by several nonenzymatic activities among which induction of drug resistance has important therapeutic implications. In this article, we review the main aspects of glycolysis-induced drug resistance. We discuss the classes of antitumor drugs that are affected and the components of the glycolytic pathway (transporters, enzymes, metabolites) that are involved in the induction of drug resistance. Glycolysis-associated drug resistance occurs in response to stimuli, either cell-autonomous (e.g., oncoproteins) or deriving from the tumor microenvironment (e.g., hypoxia or pseudohypoxia, mechanical cues, etc.). Several mechanisms mediate the induction of drug resistance in response to glycolytic metabolism: inhibition of apoptosis, induction of epithelial-mesenchymal transition, induction of autophagy, inhibition of drug influx and increase of drug efflux. We suggest that drug resistance in response to glycolysis comes into play in presence of qualitative (e.g., expression of embryonic enzyme isoforms, post-translational enzyme modifications) or quantitative (e.g., overexpression of enzymes or overproduction of metabolites) alterations of glycolytic metabolism. We also discern similarities between changes occurring in tumor cells in response to stimuli inducing glycolysis-associated drug resistance and those occurring in cells of the innate immune system in response to danger signals and that have been referred to as danger-associated metabolic modifications. Eventually, we briefly address that also mitochondrial oxidative metabolism may induce drug resistance and discuss the therapeutic implications deriving from the fact that the main energy-generating metabolic pathways may be both at the origin of antitumor drug resistance.	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J	Zhao, Y; Wu, HN; Xing, XY; Ma, YQ; Ji, SP; Xu, XY; Zhao, X; Wang, SS; Jiang, WY; Fang, CY; Zhang, L; Yan, F; Wang, XJ				Zhao, Yan; Wu, Huina; Xing, Xiaoyan; Ma, Yuqian; Ji, Shengping; Xu, Xinyue; Zhao, Xin; Wang, Sensen; Jiang, Wenyan; Fang, Chunyan; Zhang, Lei; Yan, Fang; Wang, Xuejian			CD13 Induces Autophagy to Promote Hepatocellular Carcinoma Cell Chemoresistance Through the P38/Hsp27/CREB/ATG7 Pathway	JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS			English	Article							LIVER-CANCER; AMINOPEPTIDASE-N; TRANSCRIPTIONAL REGULATION; COLORECTAL-CANCER; DRUG-RESISTANCE; DOWN-REGULATION; P38 MAPK; PROTEIN; APOPTOSIS; CREB	The chemoresistance of hepatocellular carcinoma (HCC) is a serious problem that directly hinders the effect of chemotherapeutic agents. We previously reported that Aminopeptidase N (CD13) inhibition can enhance the cytotoxic efficacy of chemotherapy agents. In the present study, we use liver cancer cells to explore the molecular mechanism accounting for the relationship between CD13 and chemoresistance. We demonstrate that CD13 overexpression activates the P38/heat shock protein 27/cAMP response element-binding protein (CREB) signaling pathway to limit the efficacy of cytotoxic agents. Moreover, blockade of P38 or CREB sensitizes HCC cells to 5-fluorouracil. Then we reveal that CREB binds to the autophagy related 7 (ATG7) promoter to induce autophagy and promote HCC cell chemoresistance. CD13 inhibition also downregulates the expression of ATG7, autophagy, and tumor cell growth in vivo. Overall, the combination a CD13 inhibitor and chemotherapeutic agents may be a potential strategy for overcoming drug resistance in HCC. SIGNIFICANCE STATEMENT Our study demonstrates that Aminopeptidase N (CD13) promotes hepatocellular carcinoma (HCC) cell chemoresistance via the P38/heat shock protein 27/cAMP response element-binding protein (CREB) pathway. CREB regulates autophagy related 7 transcription and expression to induce autophagy. Our results collectively suggest that CD13 may serve as a potential target for overcoming HCC resistance.	[Zhao, Yan; Wu, Huina; Xing, Xiaoyan; Ma, Yuqian; Ji, Shengping; Xu, Xinyue; Zhao, Xin; Wang, Sensen; Jiang, Wenyan; Fang, Chunyan; Zhang, Lei; Yan, Fang; Wang, Xuejian] Weifang Med Univ, Sch Pharm, 7166 Baotong West Rd, Weifang 261053, Shandong, Peoples R China; [Wu, Huina] Southwestern Lu Hosp, Dept Pharm, Liaocheng, Shandong, Peoples R China		Yan, F; Wang, XJ (corresponding author), Weifang Med Univ, Sch Pharm, 7166 Baotong West Rd, Weifang 261053, Shandong, Peoples R China.	yanfang303@wfmc.edu.cn; wxj2901@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81503108]; Qing Chuang science and technology plan of colleges and universities in Shandong Province [2019KJM001]; Project of Shandong Province Higher Educational Science and Technology Program [J17KA255]; University Students Science and Technology Innovation Fund Project [201910438027X, KX2019025]	This work was supported by the National Natural Science Foundation of China [Grant 81503108]; Qing Chuang science and technology plan of colleges and universities in Shandong Province [Grant 2019KJM001]; Project of Shandong Province Higher Educational Science and Technology Program [Grant J17KA255]; and University Students Science and Technology Innovation Fund Project [Grants 201910438027X and KX2019025].	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Pharmacol. Exp. Ther.	SEP 1	2020	374	3					512	520		10.1124/jpet.120.265637			9	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	NR9XB	WOS:000571914300016	32571958	Bronze			2022-04-25	
J	Heuvel, JPV; Thompson, JT; Albrecht, P; Mandetta, D; Kamerow, H; Ford, JP				Heuvel, John P. Vanden; Thompson, Jerry T.; Albrecht, Prajakta; Mandetta, Donald; Kamerow, Harry; Ford, John P.			Differential nucleobase protection against 5-fluorouracil toxicity for squamous and columnar cells: implication for tissue function and oncogenesis	INVESTIGATIONAL NEW DRUGS			English	Article						5-fluorouracil; Cancer chemotherapy; Pyrimidine salvage; Toxicity prevention; Preclinical studies; Oncogenesis	SUBSTRATE-SPECIFICITY; GENE-EXPRESSION; AUTOPHAGY; METABOLISM; MECHANISMS; DISEASE; S-1; PHOSPHORIBOSYLTRANSFERASE; PATHWAY; PROTEIN	Purpose The goal of these studies was to test if local excess of a normal nucleobase substrate prevents the toxicity of protracted 5FU exposure used in human cancer treatment. Methods Messenger RNA expression studies were performed of 5FU activating enzymes in human colon cancer cells lines (CaCo-2, HT-29), primary human gingival cells (HEGP), and normal esophageal and gastric clinical tissue samples. Excess nucleobase was then used in vitro to protect cells from 5FU toxicity. Results Pyrimidine salvage pathways predominate in squamous cells of the gingiva (HEGP) and esophageal tissue. Excess salvage nucleobase uracil but not adenine prevented 5FU toxicity in HEGP cells. Pyrimidine de novo synthesis predominates in columnar Caco-2, HT-29 and gastric tissue. Excess nucleobase adenine but not uracil prevented 5FU toxicity to Caco-2 and HT-29 cells. Conclusion The directed application of the normal nucleobase uracil to the squamous cells of the oral mucosa and palms and soles together with the delivery of the normal nucleobase adenine to the columnar cells of the GI tract may enable the safe delivery of higher 5FU dose intensity. These results also suggest a feature of tissue function where squamous cells grow largely by recycling overlying tissue cell components. Columnar cells use absorbed surface nutrients for de novo growth. A disruption of this tissue function can result in growth derived from an underlying nutrient source. That change would also cause the loss of the region of cell turnover at the tissue surface. Subsequent cell proliferation with limiting nutrient availability could promote oncogenesis in such initiated tissue.	[Heuvel, John P. Vanden; Thompson, Jerry T.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA; [Heuvel, John P. Vanden; Thompson, Jerry T.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA; [Heuvel, John P. 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New Drugs	OCT	2015	33	5					1003	1011		10.1007/s10637-015-0259-x			9	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	CW4PD	WOS:000364972700001	26123924	hybrid, Green Published			2022-04-25	
J	Focaccetti, C; Bruno, A; Magnani, E; Bartolini, D; Principi, E; Dallaglio, K; Bucci, EO; Finzi, G; Sessa, F; Noonan, DM; Albini, A				Focaccetti, Chiara; Bruno, Antonino; Magnani, Elena; Bartolini, Desiree; Principi, Elisa; Dallaglio, Katiuscia; Bucci, Eraldo O.; Finzi, Giovanna; Sessa, Fausto; Noonan, Douglas M.; Albini, Adriana			Effects of 5-Fluorouracil on Morphology, Cell Cycle, Proliferation, Apoptosis, Autophagy and ROS Production in Endothelial Cells and Cardiomyocytes	PLOS ONE			English	Article							CANCER-PATIENTS; BREAST-CANCER; IN-VITRO; MOLECULAR-MECHANISMS; GROWTH-FACTOR; ANTICANCER DRUGS; CARDIO-ONCOLOGY; FOLINIC ACID; HUMAN LIVER; CARDIOTOXICITY	Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical processes. 5-Fluorouracil (5-FU) and its prodrug Capecitabine are widely used in the treatment of several solid tumors (gastro-intestinal, gynecological, head and neck, breast carcinomas). Therapy with fluoropyrimidines is associated with a wide range of adverse effects, including diarrhea, dehydration, abdominal pain, nausea, stomatitis, and hand-foot syndrome. Among the 5-FU side effects, increasing attention is given to cardiovascular toxicities induced at different levels and intensities. Since the mechanisms related to 5-FU-induced cardiotoxicity are still unclear, we examined the effects of 5-FU on primary cell cultures of human cardiomyocytes and endothelial cells, which represent two key components of the cardiovascular system. We analyzed at the cellular and molecular level 5-FU effects on cell proliferation, cell cycle, survival and induction of apoptosis, in an experimental cardioncology approach. We observed autophagic features at the ultrastructural and molecular levels, in particular in 5-FU exposed cardiomyocytes. Reactive oxygen species (ROS) elevation characterized the endothelial response. These responses were prevented by a ROS scavenger. We found induction of a senescent phenotype on both cell types treated with 5-FU. In vivo, in a xenograft model of colon cancer, we showed that 5-FU treatment induced ultrastructural changes in the endothelium of various organs. Taken together, our data suggest that 5-FU can affect, both at the cellular and molecular levels, two key cell types of the cardiovascular system, potentially explaining some manifestations of 5-FU-induced cardiovascular toxicity.	[Focaccetti, Chiara; Bruno, Antonino; Bartolini, Desiree; Principi, Elisa; Noonan, Douglas M.] IRCCS MultiMed, Ctr Sci & Technol, Milan, Italy; [Magnani, Elena; Dallaglio, Katiuscia; Albini, Adriana] IRCCS Arcispedale Santa Maria Nuova, Dept Res & Stat, Reggio Emilia, Italy; [Bucci, Eraldo O.] IRCCS MultiMed, Oncol Unit, Castellanza, VA, Italy; [Finzi, Giovanna; Sessa, Fausto] Osped Circolo Varese, Dept Pathol, Varese, Italy; [Sessa, Fausto] Univ Insubria, Dept Surg & Morphol Sci, Varese, Italy; [Noonan, Douglas M.] Univ Insubria, Dept Biotechnol & Life Sci, Varese, Italy		Albini, A (corresponding author), IRCCS Arcispedale Santa Maria Nuova, Dept Res & Stat, Reggio Emilia, Italy.	albini.adriana@gmail.com	Principi, Elisa/O-2424-2015; Noonan, Douglas M/A-8620-2010; Focaccetti, Chiara/AAD-9378-2019; Bartolini, Desirée/K-5319-2016; Bruno, Antonino/J-7066-2016	Noonan, Douglas M/0000-0001-8058-0719; Focaccetti, Chiara/0000-0002-7334-3966; Bartolini, Desirée/0000-0003-3849-757X; Bruno, Antonino/0000-0002-4790-0861; Principi, Elisa/0000-0003-3747-1167; Albini, Adriana/0000-0002-9624-5103	Ministero Italiano della Salute, Grande Progetto Strategico (GPS); Ministero dell'Istruzione dell'Universita e della Ricerca, PRIN (Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale) [2010NECHBX 003]; AIRC (Associazione Italiana per la Ricerca sul Cancro)Fondazione AIRC per la ricerca sul cancro [IG10228]	These studies were supported by the Ministero Italiano della Salute, Grande Progetto Strategico (GPS), by the Ministero dell'Istruzione dell'Universita e della Ricerca, PRIN (Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale) 2010NECHBX 003, AIRC (Associazione Italiana per la Ricerca sul Cancro) (IG10228). AB is a FIRC (Fondazione Italiana per la Ricerca sul Cancro) fellow. KD is a Fondazione Veronesi fellow. The authors thank Paola Corradino for assistance and bibliography and Alessandra Panvini Rosati for secretarial help. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Cui, XM; Shen, WB; Wang, GH; Huang, ZY; Wen, DP; Yang, YL; Liu, Y; Cui, L				Cui, Ximao; Shen, Wenbin; Wang, Guanghui; Huang, Zhenyu; Wen, Dongpeng; Yang, Yili; Liu, Yun; Cui, Long			Ring finger protein 152 inhibits colorectal cancer cell growth and is a novel prognostic biomarker	AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH			English	Article						Colorectal cancer; RNF152; prognosis; proliferation; E3 ligase	TOTAL MESORECTAL EXCISION; UBIQUITIN LIGASE; RNF152; DOMAIN	Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. RING finger-related E3 ubiquitin ligases play a role in tumorigenesis and can function either as oncogenes or tumor suppressors based on their target proteins. Here, we show that the expression of RNF152, a ring finger protein, in CRC tissues was significantly reduced compared with adjacent non-cancerous tissues. High expression levels of RNF152 correlated with better prognosis in patients with colorectal cancer. Low expression of RNF152 correlated with lymphatic metastasis. Overexpression of RNF152 inhibited CRC cell proliferation both in vitro and in vivo by inactivating the mechanistic target of rapamycin complex 1 (mTORC1) and inducing autophagy and apoptotic cell death. This strong inhibition was dependent on the E3 ligase activity of RNF152. Ectopic expression of the RNF152-CS-mutant, which lacks E3 ligase activity, significantly restored the proliferation ability of CRC cells. Our findings showed that RNF152 inhibits colorectal cancer growth and may be a novel prognostic biomarker for the treatment of CRC.	[Cui, Ximao; Shen, Wenbin; Wang, Guanghui; Huang, Zhenyu; Wen, Dongpeng; Liu, Yun; Cui, Long] Shanghai Jiao Tong Univ, Dept Colorectal & Anal Surg, Xinhua Hosp, Sch Med, 1665 Kongjiang Rd, Shanghai, Peoples R China; [Wang, Guanghui] Guizhou Prov Peoples Hosp, Guiyang, Guizhou, Peoples R China; [Yang, Yili] Chinese Acad Med Sci, Suzhou Inst Syst Med, Ctr Syst Med, Suzhou, Jiangsu, Peoples R China		Liu, Y; Cui, L (corresponding author), Shanghai Jiao Tong Univ, Dept Colorectal & Anal Surg, Xinhua Hosp, Sch Med, 1665 Kongjiang Rd, Shanghai, Peoples R China.	yunliudr@126.com; cuilong@xinhua-med.com.cn			National High Technology Research and Development Program of China (863 Program)National High Technology Research and Development Program of China [SQ2014SFOZD00314]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81372636, 81572378, 81302089]; Natural Science Foundation of Shanghai Municipal Commission of Health and Family Planning [201740122, 2015-4Y0203]	This study was funded by the National High Technology Research and Development Pro-gram of China (863 Program; Grant No. SQ2014SFOZD00314), the National Natural Science Foundation of China (Grant Nos. 81372636, 81572378, and 81302089) and the Natural Science Foundation of Shanghai Municipal Commission of Health and Family Planning (Grant Nos. 201740122 and 2015-4Y0203). We are very grateful to Dr. Lu Deng and Prof. Ping Wang for their help.SS	Borden KLB, 1996, CURR OPIN STRUC BIOL, V6, P395, DOI 10.1016/S0959-440X(96)80060-1; Cui XM, 2017, BIOCHEM BIOPH RES CO, V483, P609, DOI 10.1016/j.bbrc.2016.12.095; Cui XM, 2016, ONCOL LETT, V12, P1529, DOI 10.3892/ol.2016.4789; Deng L, 2015, MOL CELL, V58, P804, DOI 10.1016/j.molcel.2015.03.033; Deshaies RJ, 2009, ANNU REV BIOCHEM, V78, P399, DOI 10.1146/annurev.biochem.78.101807.093809; Fang SY, 2000, J BIOL CHEM, V275, P8945, DOI 10.1074/jbc.275.12.8945; Fu JH, 2012, BMC SYST BIOL, V6, DOI 10.1186/1752-0509-6-68; Geng R, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.400; HEALD RJ, 1986, LANCET, V1, P1479; Joazeiro CAP, 2000, CELL, V102, P549, DOI 10.1016/S0092-8674(00)00077-5; Kim J, 2011, NAT CELL BIOL, V13, P132, DOI 10.1038/ncb2152; Lee JP, 2010, MOL CANCER RES, V8, P93, DOI 10.1158/1541-7786.MCR-08-0491; Lipkowitz S, 2011, NAT REV CANCER, V11, P629, DOI 10.1038/nrc3120; Lorick KL, 1999, P NATL ACAD SCI USA, V96, P11364, DOI 10.1073/pnas.96.20.11364; Marine JC, 2010, CELL DEATH DIFFER, V17, P93, DOI 10.1038/cdd.2009.68; Planas-Paz L, 2016, NAT CELL BIOL, V18, P467, DOI 10.1038/ncb3337; Sankaranarayanan R, 2010, LANCET ONCOL, V11, P165, DOI 10.1016/S1470-2045(09)70335-3; Siegel R, 2012, CA-CANCER J CLIN, V62, P10, DOI 10.3322/caac.20138; van Gijn W, 2011, LANCET ONCOL, V12, P575, DOI 10.1016/S1470-2045(11)70097-3; Wang GH, 2017, J CANCER RES CLIN, V143, P971, DOI 10.1007/s00432-017-2362-1; Weissman AM, 2001, NAT REV MOL CELL BIO, V2, P169, DOI 10.1038/35056563; Welcsh PL, 2001, HUM MOL GENET, V10, P705, DOI 10.1093/hmg/10.7.705; Wiederschain D, 2009, CELL CYCLE, V8, P498, DOI 10.4161/cc.8.3.7701; Yamamoto F, 2007, ELECTROPHORESIS, V28, P1882, DOI 10.1002/elps.200700093; Zhang SL, 2010, PROTEIN CELL, V1, P656, DOI 10.1007/s13238-010-0083-1	25	4	6	2	6	E-CENTURY PUBLISHING CORP	MADISON	40 WHITE OAKS LN, MADISON, WI 53711 USA	1943-8141			AM J TRANSL RES	Am. 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J	Wang, SS; Li, MY; Liu, Y; Vlantis, AC; Chan, JYK; Xue, LB; Hu, BG; Yang, SC; Chen, MX; Zhou, SM; Guo, W; Zeng, XH; Qiu, SQ; van Hasselt, CA; Tong, MCF; Chen, GG				Wang, Shanshan; Li, Ming-Yue; Liu, Yi; Vlantis, Alexander C.; Chan, Jason Y. K.; Xue, Lingbin; Hu, Bao-Guang; Yang, Shucai; Chen, Mo-Xian; Zhou, Shaoming; Guo, Wei; Zeng, Xianhai; Qiu, Shuqi; van Hasselt, C. Andrew; Tong, Michael C. F.; Chen, George G.			The role of microRNA in cisplatin resistance or sensitivity	EXPERT OPINION ON THERAPEUTIC TARGETS			English	Review						Cisplatin; miRNA; resistance; sensitivity; cancer	CELL LUNG-CANCER; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN NASOPHARYNGEAL CARCINOMA; OVARIAN-CANCER; STEM-CELLS; GASTRIC-CANCER; OSTEOSARCOMA CELLS; COLORECTAL-CANCER; MITOCHONDRIAL FISSION; MULTIDRUG-RESISTANCE	Introduction Cisplatin is a chemotherapy drug that has been used to treat a number of cancers for decades, and is still one of the most commonly used anti-cancer agents. However, some patients do not respond to cisplatin while other patients who were originally sensitive to cisplatin eventually develop chemoresistance, leading to treatment failure or/and tumor recurrence. Areas Covered Different mechanisms contribute to cisplatin resistance or sensitivity, involving multiple pathways or/and processes such as DNA repair, DNA damage response, drug transport, and apoptosis. Among the various mechanisms, it appears that microRNAs play an important role in determining the resistance or sensitivity. In this article, we analyzed and summarized recent findings in this area, with the aim that these data can aid further research and understanding, leading to the eventual reduction of cisplatin resistance. Expert Commentary microRNAs can positively or negatively regulate cisplatin resistance by acting on molecules or/and pathways related to apoptosis, autophagy, hypoxia, cancer stem cells, NF-kappa B, and Notch1. It appears that the modulation of relevant microRNAs can effectively re-sensitize cancer cells to cisplatin regimen in certain types of cancers including breast, colorectal, gastric, liver, lung, ovarian, prostate, testicular, and thyroid cancers.	[Wang, Shanshan] Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Guangzhou, Guangdong, Peoples R China; [Wang, Shanshan; Vlantis, Alexander C.; Chan, Jason Y. K.; Xue, Lingbin; van Hasselt, C. Andrew; Tong, Michael C. F.; Chen, George G.] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Otorhinolaryngol Head & Neck Surg, Shatin, Hong Kong, Peoples R China; [Li, Ming-Yue; Liu, Yi] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Surg, Hong Kong, Peoples R China; [Zeng, Xianhai; Qiu, Shuqi] Inst ENT, DShenzhen Key Lab ENT, Shenzhen, Shandong, Peoples R China; [Zeng, Xianhai; Qiu, Shuqi] Longgang ENT Hosp, Shenzhen, Shandong, Peoples R China; [Vlantis, Alexander C.; Chan, Jason Y. K.; Zeng, Xianhai; Qiu, Shuqi; van Hasselt, C. Andrew; Tong, Michael C. F.; Chen, George G.] Chinese Univ Hong Kong, Longgang ENT Hosp, Shenzhen Ear Nose & Throat Joint Res Ctr, Shenzhen, Peoples R China; [Hu, Bao-Guang] Binzhou Med Univ, Affiliated Hosp, Dept Gastrointestinal Surg, Shenzhen, Peoples R China; [Yang, Shucai] Pingshan Dist Peoples Hosp Shenzhen, Dept Clin Lab, Shenzhen, Guangdong, Peoples R China; [Chen, Mo-Xian; Zhou, Shaoming] Shenzhen Childrens Hosp, Div Gastroenterol, Shenzhen, Peoples R China; [Guo, Wei] Shenzhen Ritzcon Biol Technol Co LTD, Shenzhen, Guangdong, Peoples R China		Tong, MCF; Chen, GG (corresponding author), Chinese Univ Hong Kong, Prince Wales Hosp, Dept Otorhinolaryngol Head & Neck Surg, Shatin, Hong Kong, Peoples R China.	mtong@ent.cuhk.edu.hk; gchen@cuhk.edu.hk	yang, shucai/AAZ-4319-2021; Chan, Jason/H-4049-2017	Chan, Jason/0000-0002-9480-4637; shucai, YANG/0000-0002-9694-828X; Zeng, Xianhai/0000-0002-9519-0112; Tong, Michael CF/0000-0002-9418-5223	Research Grants Council of the Hong Kong Special Administrative RegionHong Kong Research Grants Council [14109716]	This study was supported by grants from the Research Grants Council of the Hong Kong Special Administrative Region (No. 14109716).	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Ther. Targets	SEP 1	2020	24	9					885	897		10.1080/14728222.2020.1785431		JUL 2020	13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	OC5BH	WOS:000547434000001	32559147				2022-04-25	
J	Songyang, YY; Song, TB; Shi, Z; Li, W; Yang, SYS; Li, DJ				Songyang, Yiyan; Song, Tianbao; Shi, Zhan; Li, Wen; Yang, Songyisha; Li, Dejia			Effect of vitamin D on malignant behavior of non-small cell lung cancer cells	GENE			English	Article						Vitamin D; Lung cancer; PI3K/AKT/mTOR	NF-KAPPA-B; 1,25-DIHYDROXYVITAMIN D-3; SIDE-POPULATION; COLON-CANCER; CISPLATIN; GEMCITABINE; INHIBITION; AUTOPHAGY; PROTEINS; GROWTH	Objective: To investigate the effects of vitamin D on the malignant behavior of A549 and NCI-H1975 tumor cells (proliferation, apoptosis, invasion, metastasis and drug resistance-related proteins) and the activation of the PI3K/AKT/mTOR signaling pathway, in order to evaluate the effect of vitamin D on the therapeutic action of cisplatin. Method: In vitro cell experiments, CCK-8, flow cytometry, transwell, scratches, MTT and Western blot were used to reveal the effect of vitamin D on non-small cell lung cancer (NSCLC), and the expression of PI3K/AKT/mTOR signaling pathway was also detected. In vivo animal experiments, the nude mice were divided into four groups: control group, vitamin D treatment group, cisplatin treatment group and vitamin D + cisplatin combined treatment group. After tumor formation in vitro, tumor volume changes were calculated and tumor growth curves were drawn, collected tumor tissues for pathological sections. Western blot was used to detect the expression changes of drug-resistance related proteins in tumor tissues. Meanwhile, protein expression changes of PI3K/AKT/mTOR signaling pathway in tumor tissues were detected. Result: In vitro experiments confirm Vitamin D can inhibit the proliferation, invasion and metastasis of non-small cell lung cancer cells A549 and NCI-H1975, promoting cell apoptosis, up-regulate the sensitivity of chemotherapy drugs. These effects of vitamin D may be correlated with the PI3K/AKT/mTOR signaling pathway. In vivo animal experiments, the changes in tumor volume, tumor inflammatory infiltration range, expression of drug-resistant related proteins and signaling pathway related proteins in mice were as follows: The vitamin D and cisplatin combined treatment group was significantly smaller than the control group. Conclusion: Vitamin D can inhibit the proliferation, invasion and metastasis of non-small cell lung cancer (NSCLC) cells A549 and NCI-H1975 and promote apoptosis, up-regulate the sensitivity of chemotherapy drugs. The effect of vitamin D on NSCLC cells A549 and NCI-H1975 was correlated with the PI3K/AKT/mTOR signaling pathway. Vitamin D also promotes the therapeutic effect of CDDP.	[Songyang, Yiyan] Wuhan Univ, Dept Pharm, Renmin Hosp, Wuhan, Peoples R China; [Li, Dejia] Wuhan Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Wuhan, Peoples R China; [Song, Tianbao] Wuhan Univ, Sch Basic Med Sci, Dept Immunol, Wuhan, Peoples R China; [Shi, Zhan] Univ Toronto, Human Biol Program, Toronto, ON M5S 3J6, Canada; [Li, Wen] Wuhan Univ, Dept Emergency, Renmin Hosp, Wuhan, Peoples R China; [Yang, Songyisha] Hubei Univ Chinese Med, Coll Pharm, Wuhan, Peoples R China		Li, DJ (corresponding author), Wuhan Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Wuhan, Peoples R China.	lidj123123@126.com					Aranda F, 2015, ONCOGENE, V34, P3053, DOI 10.1038/onc.2014.234; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Chaudhry M, 2001, CANCER CHEMOTH PHARM, V47, P429, DOI 10.1007/s002800000251; D'Orsi B, 2017, NEUROCHEM INT, V109, P162, DOI 10.1016/j.neuint.2017.03.010; Ding Guo-Fang, 2011, Chinese Journal of Natural Medicines, V9, P151, DOI 10.3724/SP.J.1009.2011.00151; Galanski M, 2006, RECENT PAT ANTI-CANC, V1, P285, DOI 10.2174/157489206777442287; Galluzzi L, 2012, ONCOGENE, V31, P1869, DOI 10.1038/onc.2011.384; Getzenberg RH, 1997, UROLOGY, V50, P999, DOI 10.1016/S0090-4295(97)00408-1; Ghosh J, 2016, J CLIN INVEST, V126, P2621, DOI 10.1172/JCI84565; Giovannucci E, 2005, CANCER CAUSE CONTROL, V16, P83, DOI 10.1007/s10552-004-1661-4; Hershberger PA, 2002, MOL CANCER THER, V1, P821; Huang CF, 2017, EXP THER MED, V14, P4174, DOI 10.3892/etm.2017.5097; Jongbloet PH, 2006, INT J EPIDEMIOL, V35, P1359, DOI 10.1093/ije/dyl206; Joyce H, 2015, EXPERT OPIN DRUG MET, V11, P795, DOI 10.1517/17425255.2015.1028356; Keysar SB, 2017, JNCI-J NATL CANCER I, V109, DOI 10.1093/jnci/djw189; Koshizuka K, 1999, BREAST CANCER RES TR, V53, P113, DOI 10.1023/A:1006123819675; Liu GM, 2010, INT J CANCER, V126, P631, DOI 10.1002/ijc.24762; LOINTIER P, 1987, ANTICANCER RES, V7, P817; Ma YY, 2010, CANCER-AM CANCER SOC, V116, P3294, DOI 10.1002/cncr.25059; Mu GG, 2015, DIGEST DIS SCI, V60, P1067, DOI 10.1007/s10620-014-3394-x; PRESTAYKO AW, 1979, CANCER TREAT REV, V6, P17, DOI 10.1016/S0305-7372(79)80057-2; Rai V, 2017, ANTICANCER RES, V37, P3991, DOI 10.21873/anticanres.11784; Ravid A, 1999, CANCER RES, V59, P862; Reck M, 2013, LANCET, V382, P709, DOI 10.1016/S0140-6736(13)61502-0; Ren LQ, 2020, BIOMED RES INT, V2020, DOI 10.1155/2020/9396512; Saracci R, 2008, LANCET, V372, P291, DOI 10.1016/S0140-6736(08)61109-5; Sharma K, 2014, AUTOPHAGY, V10, P2346, DOI 10.4161/15548627.2014.993283; Shi RX, 2007, MOL CANCER THER, V6, P1338, DOI 10.1158/1535-7163.MCT-06-0638; Shin MH, 2002, JNCI-J NATL CANCER I, V94, P1301, DOI 10.1093/jnci/94.17.1301; Singh S, 2012, MOL CANCER, V11, DOI 10.1186/1476-4598-11-73; Singletary K, 2008, CANCER EPIDEM BIOMAR, V17, P1596, DOI 10.1158/1055-9965.EPI-07-2917; SKOWRONSKI RJ, 1993, ENDOCRINOLOGY, V132, P1952, DOI 10.1210/en.132.5.1952; Su C, 2010, J BIOL REG HOMEOS AG, V24, P19; Sun CC, 2015, J BIOL CHEM, V290, P17784, DOI 10.1074/jbc.M115.655019; Tavera-Mendoza L, 2006, EMBO REP, V7, P180, DOI 10.1038/sj.embor.7400594; VINKVANWIJNGAARDEN T, 1994, CANCER RES, V54, P5711; Wang Q, 2000, CANCER RES, V60, P2040; Xu M, 2013, CANCER LETT, V333, P152, DOI 10.1016/j.canlet.2013.01.002; Ylikomi T, 2002, VITAM HORM, V64, P357, DOI 10.1016/S0083-6729(02)64010-5; Zhao JM, 2020, J ETHNOPHARMACOL, V250, DOI 10.1016/j.jep.2019.112492; Zhou S, 2001, NAT MED, V7, P1028, DOI 10.1038/nm0901-1028	41	2	2	4	20	ELSEVIER	AMSTERDAM	RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS	0378-1119	1879-0038		GENE	Gene	FEB 5	2021	768								145309	10.1016/j.gene.2020.145309		JAN 2021	10	Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Genetics & Heredity	PS9JT	WOS:000608238700008	33197518				2022-04-25	
J	Dastghaib, S; Mokarram, P; Erfani, M; Ghavami, S; Hosseini, SV; Zamani, M				Dastghaib, Sanaz; Mokarram, Pooneh; Erfani, Mehran; Ghavami, Saeid; Hosseini, Seyed Vahid; Zamani, Mozhdeh			Endoplasmic reticulum Metallo protease 1, a triggering factor for unfolded protein response and promising target in colorectal cancer	BIOLOGIA			English	Article						ERMP1; Unfolded protein response; Endoplasmic reticulum stress; Colorectal cancer	CELL-DEATH; ER STRESS; PATHWAY; ACTIVATION; UPR; OVEREXPRESSION; MECHANISM; AUTOPHAGY	Unfolded protein response (UPR) pathway is a promising target for cancer treatment because of its over-activation in different cancers and its role in tumorigenesis and chemotherapeutic drug resistance. Endoplasmic Reticulum Metallo Protease 1 (ERMP1) is overexpressed in cancers such as colorectal cancer. The ERMP1 role in UPR activation was previously reported in breast cancer. We aimed to investigate the ERMP1 role in the UPR activation in colorectal cancer. In this regard, ERMP1 gene was silenced in colorectal cancer HCT116 cell line using specific small hairpin RNA (shRNA). Then, UPR associated protein markers including inositol requiring enzyme 1 (IRE1 alpha), activating transcription factor 6 (ATF-6), eukaryotic initiation factor 2 alpha (eIF2 alpha) and phosphorylated eIF2 alpha (P- eIF2 alpha) were evaluated using western blot. We found that ERMP1 gene expression and all of the above UPR associated protein markers were significantly decreased after ERMP1 gene silencing. Therefore, it seems that ERMP1 plays an important role in UPR activation. Since the overexpression of ERMP1 as a potential oncogene can highly activate the UPR pathway in colorectal cancer, it can be considered as a promising target for colorectal cancer treatment. However, further investigations are required to confirm these findings.	[Dastghaib, Sanaz] Shiraz Univ Med Sci, Endocrinol & Metab Res Ctr, Shiraz, Iran; [Mokarram, Pooneh; Zamani, Mozhdeh] Shiraz Univ Med Sci, Autophagy Res Ctr, Shiraz, Iran; [Mokarram, Pooneh; Erfani, Mehran] Shiraz Univ Med Sci, Fac Med, Dept Biochem, Shiraz, Iran; [Erfani, Mehran] Islamic Azad Univ, Arak Branch, Dept Med Lab Sci, Fac Med Sci, Arak, Iran; [Ghavami, Saeid] Univ Manitoba, Max Rady Fac Hlth Sci, Dept Human Anat & Cell Sci, Rady Coll Med, Winnipeg, MB, Canada; [Hosseini, Seyed Vahid; Zamani, Mozhdeh] Shiraz Univ Med Sci, Colorectal Res Ctr, Shiraz 71936355899, Iran		Zamani, M (corresponding author), Shiraz Univ Med Sci, Autophagy Res Ctr, Shiraz, Iran.; Zamani, M (corresponding author), Shiraz Univ Med Sci, Colorectal Res Ctr, Shiraz 71936355899, Iran.	mozhdeh.zamani63@gmail.com	Erfani, Mehran/AAR-9705-2021; Dastghaib, Sanaz/ABD-5899-2021; Zamani, Mozhdeh/N-9607-2016	Erfani, Mehran/0000-0001-9593-5383; Dastghaib, Sanaz/0000-0001-8553-9221; Zamani, Mozhdeh/0000-0001-7856-6029	Shiraz University of Medical Sciences [16117]	This work was financially supported by Shiraz University of Medical Sciences (Grant No.16117).	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J	Das, K; Datta, A; Frontera, A; Wen, YS; Roma-Rodrigues, C; Raposo, LR; Fernandes, AR; Hung, CH				Das, Kuheli; Datta, Amitabha; Frontera, Antonio; Wen, Yuh-Sheng; Roma-Rodrigues, Catarina; Raposo, Luis R.; Fernandes, Alexandra R.; Hung, Chen-Hsiung			Zn(II) and Co(II) derivatives anchored with scorpionate precursor: Antiproliferative evaluation in human cancer cell lines	JOURNAL OF INORGANIC BIOCHEMISTRY			English	Article						Zn(II); Co(II); Antiproliferative; Cancer cell lines; Autophagy, ROS	SPIN-RESONANCE-SPECTRA; COORDINATION CHEMISTRY; PLATINUM COMPLEXES; METAL-COMPLEXES; LIGANDS; SPECTROSCOPY; COBALT(II); IRON(III); COPPER; BLOOD	A 'scorpionate' type precursor [bdtbpza = bis(3,5-di-t-butylpyrazol-1-yl)acetate] has been employed to synthesize two mononuclear Zn-II and Co-II derivatives, namely [Zn(bdtbpza)(2) (H2O)(2)]center dot 2.5CH(3)OH center dot 2[(CH3)(3)C-C3H2N2-(CH3)(3)] (1) and lCo(bdtbpza)(2)(CH3OH)(4)] (2) in good yield. Single crystal X-ray diffraction analysis reveals that in 1, the Zn-II atom is tetrahedrally surrounded by a pair of O-acetate atoms of two bis(pyrazol-1-yl)acetate units and two water molecules; while in 2, the Co-II atom shows an octahedral environment coordinating a pair of O-acetate atoms of two bis(pyrazol-1-yl)acetate units along with four methanol molecules. The EPR spectra of 2 recorded at 77 and 298 K confirmed the tetragonal symmetry of the high spin Co(II). The DFT (Density functional theory) computation is in good agreement with the geometry proposed for compounds 1 and 2. Both the compounds display a high antiproliferative activity against HCT116 (colorectal carcinoma) and A2780 (ovarian carcinoma) cell lines compared to human normal dermal fibroblasts. In the case of A2780 cells, compounds 1 and 2 exhibit IC50 values that are similar to those described for cisplatin, a widely used chemotherapeutic drug. Exposure of A2780 cells to the IC50 concentration of each compound led to an increase of the number of apoptotic and autophagic cells. In the case of compound 1, the accumulation of intracellular ROS (Reactive oxygen species) is responsible for triggering A2780 cell death.	[Das, Kuheli; Datta, Amitabha; Wen, Yuh-Sheng; Hung, Chen-Hsiung] Acad Sinica, Inst Chem, Taipei 115, Taiwan; [Frontera, Antonio] Univ Illes Balears, Dept Quim, Crta Valldemossa Km 7-5, Palma De Mallorca 07122, Baleares, Spain; [Roma-Rodrigues, Catarina; Raposo, Luis R.; Fernandes, Alexandra R.] Univ Nova Lisboa, Fac Ciencias & Tecnol, DCV, UCIBIO, Campus Caparica, P-2829516 Caparica, Portugal		Datta, A; Hung, CH (corresponding author), Acad Sinica, Inst Chem, Taipei 115, Taiwan.; Fernandes, AR (corresponding author), Univ Nova Lisboa, Fac Ciencias & Tecnol, DCV, UCIBIO, Campus Caparica, P-2829516 Caparica, Portugal.	amitd_ju@yahoo.co.in; ma.fernandes@fct.unl.pt; chhung@gate.sinica.edu.tw	Hung, Chen-Hsiung/B-6638-2013; Roma-Rodrigues, Catarina/S-6144-2016; Frontera, Antonio/G-4517-2010; Fernandes, Alexandra R/C-7465-2011; Raposo, Luís/AAX-1610-2021; Roma-Rodrigues, Catarina/AAT-5658-2021; Raposo, Luís R/T-3754-2017	Hung, Chen-Hsiung/0000-0002-8060-348X; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Frontera, Antonio/0000-0001-7840-2139; Fernandes, Alexandra R/0000-0003-2054-4438; Raposo, Luís/0000-0002-8637-346X; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Raposo, Luís R/0000-0002-8637-346X	Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan; Applied Molecular Biosciences Unit-UCIBIO from FCT/MCTES, Portugal [UID/Multi/04378/2019]	AD and CHH would like to express their appreciation to the Ministry of Science and Technology, Taiwan for financial assistance. This work is also supported by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019), Portugal. The authors acknowledge A. Silva for preliminary biological assays. Our sincere thanks to Prof. Chiara Massera for her valuable suggestion in crystallographic description.	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Inorg. Biochem.	JAN	2020	202								110881	10.1016/j.jinorgbio.2019.110881			11	Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	JV9NK	WOS:000502686300012	31698185				2022-04-25	
J	Wei, L; Chen, ZH; Cheng, N; Li, X; Chen, J; Wu, DH; Dong, M; Wu, XY				Wei, Li; Chen, Zhanhong; Cheng, Na; Li, Xing; Chen, Jie; Wu, Donghao; Dong, Min; Wu, Xiangyuan			MicroRNA-126 Inhibit Viability of Colorectal Cancer Cell by Repressing mTOR Induced Apoptosis and Autophagy	ONCOTARGETS AND THERAPY			English	Article						CRC; miR-126; mTOR; apoptosis; autophagy	TUMOR-SUPPRESSOR; MIR-126; EXPRESSION; PATHWAY; GROWTH; PROLIFERATION; INFLAMMATION; INVASION	Objective: Colorectal cancer (CRC) is a fatal disease, and tumor development is a complex cellular event involving a multistep cascade process involving proliferation, invasion, and migration. In recent years, it has been shown that microRNA-126 (miR-126) plays a key role in the tumorigenesis of CRC, but further studies are required to investigate the regulatory mechanisms through which this miRNA affects cell viability, autophagy, and apoptosis in CRC. We aimed to study the effect of miR-126 in gene regulation in CRC HCT116 cells. Methods: CRC biopsy samples and normal colorectal tissue samples were used for miRNA profiling. Real-time quantitative PCR and WB were utilized to detect RNA and protein levels. MTT and colony formation assays were performed to examine cell viability. Furthermore, an immunofluorescence assay and Annexin V/PI flow cytometry were performed to detect autophagy and apoptosis, respectively. Results: The expression of miR-126 was downregulated in CRC biopsies and cell lines compared with that in normal cells and tissues. The upregulation of miR-126 resulted in impaired viability and growth of CRC cells. Furthermore, with the overexpression of miR-126, cell autophagy was increased, as evidenced by LC3-I/II transformation and p62 degradation. Meanwhile, apoptosis induction was also observed because of the increased miR-126 levels. The autophagy inhibitor Bafilomycin A1 (BafA1) repressed both autophagy and apoptosis, indicating that miR-126 induced autophagy was responsible for the induction of apoptosis. A dual-luciferase reporter assay (DLRA) and bioinformatics prediction revealed that miR-126 silenced the mTOR gene by targeting the 3'-UTR. mTOR mRNA levels in CRC biopsy tissues and cell lines were upregulated to a greater extent than that in normal cells and tissues. Furthermore, HCT116 cells transfected with an miR-126 mimic showed a decreased expression of mTOR. In addition, the overexpression of mTOR counteracted miR-126 on autophagy and apoptosis. Conclusion: Our study demonstrated that miR-126-induced can regulate the activity of CRC cells via autophagy and apoptosis and suggested a new mechanism of miR-126-mTOR interaction in CRC pathogenesis.	[Wei, Li; Chen, Zhanhong; Li, Xing; Chen, Jie; Wu, Donghao; Dong, Min; Wu, Xiangyuan] Sun Yat Sen Univ, Affiliated Hosp 3, Med Oncol, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China; [Cheng, Na] Sun Yat Sen Univ, Affiliated Hosp 3, Pathol, Guangzhou 510630, Guangdong, Peoples R China		Dong, M; Wu, XY (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 3, Med Oncol, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China.	dongmin@mail.sysu.edu.cn; xiangyunwu100@163.com					Banerjee N, 2013, CARCINOGENESIS, V34, P2814, DOI 10.1093/carcin/bgt295; Bartel DP, 2009, CELL, V136, P215, DOI 10.1016/j.cell.2009.01.002; Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; Chen HX, 2014, ONCOTARGET, V5, P11873, DOI 10.18632/oncotarget.2662; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Din FVN, 2012, GASTROENTEROLOGY, V142, P1504, DOI 10.1053/j.gastro.2012.02.050; Feng RH, 2010, CANCER LETT, V298, P50, DOI 10.1016/j.canlet.2010.06.004; Francipane MG, 2014, ONCOTARGET, V5, P49, DOI 10.18632/oncotarget.1548; Guo CG, 2008, GENE CHROMOSOME CANC, V47, P939, DOI 10.1002/gcc.20596; Heras-Sandoval D, 2014, CELL SIGNAL, V26, P2694, DOI 10.1016/j.cellsig.2014.08.019; Kim H, 2017, MOL CARCINOGEN, V56, P197, DOI 10.1002/mc.22484; Li N, 2013, MOL CELL BIOCHEM, V380, P107, DOI 10.1007/s11010-013-1664-0; Li XF, 2009, ONCOGENE, V28, P3937, DOI 10.1038/onc.2009.245; Li Z, 2013, MOL CELL BIOCHEM, V381, P233, DOI 10.1007/s11010-013-1707-6; Liu B, 2009, LUNG CANCER, V66, P169, DOI 10.1016/j.lungcan.2009.01.010; Liu YL, 2014, GENE CHROMOSOME CANC, V53, P358, DOI 10.1002/gcc.22146; Liu YL, 2014, INT J ONCOL, V44, P203, DOI 10.3892/ijo.2013.2168; Long GW, 2012, INT J BIOL SCI, V8, P811, DOI 10.7150/ijbs.4439; Manfredi S, 2006, ANN SURG, V244, P254, DOI 10.1097/01.sla.0000217629.94941.cf; Meister J, 2010, THESCIENTIFICWORLDJO, V10, P2090, DOI 10.1100/tsw.2010.198; Saito Y, 2009, BIOCHEM BIOPH RES CO, V379, P726, DOI 10.1016/j.bbrc.2008.12.098; Wang F, 2015, INT J IMMUNOPATH PH, V28, P362, DOI 10.1177/0394632015598849; Wang SS, 2008, DEV CELL, V15, P261, DOI 10.1016/j.devcel.2008.07.002; Wu XD, 2017, MOL MED REP, V16, P7112, DOI 10.3892/mmr.2017.7459; Wu XL, 2018, J CELL BIOCHEM, V119, P2356, DOI 10.1002/jcb.26399; Yin J, 2014, CHINESE J CANCER RES, V26, P95, DOI 10.3978/j.issn.1000-9604.2014.02.07; Zhang J, 2008, BIOCHEM BIOPH RES CO, V377, P136, DOI 10.1016/j.bbrc.2008.09.089; Zhang Q, 2015, BIOCHEM BIOPH RES CO, V465, P64, DOI 10.1016/j.bbrc.2015.07.130; Zhang T, 2013, BIOMED RES INT, V2013, DOI 10.1155/2013/761617; Zou WJ, 2018, BIOCHEM BIOPH RES CO, V503, P3212, DOI 10.1016/j.bbrc.2018.08.127	30	14	15	0	5	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2020	13						2459	2468		10.2147/OTT.S238348			10	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	KX0ZS	WOS:000521613100001	32273718	gold, Green Published			2022-04-25	
J	Shen, T; Cai, LD; Liu, YH; Li, S; Gan, WJ; Li, XM; Wang, JR; Guo, PD; Zhou, Q; Lu, XX; Sun, LN; Li, JM				Shen, Tong; Cai, Ling-Dong; Liu, Yu-Hong; Li, Shi; Gan, Wen-Juan; Li, Xiu-Ming; Wang, Jing-Ru; Guo, Peng-Da; Zhou, Qun; Lu, Xing-Xing; Sun, Li-Na; Li, Jian-Ming			Ube2v1-mediated ubiquitination and degradation of Sirt1 promotes metastasis of colorectal cancer by epigenetically suppressing autophagy	JOURNAL OF HEMATOLOGY & ONCOLOGY			English	Article						Ubiquitin-conjugating E2 enzyme; Autophagy; Epithelial mesenchymal transition; Metastasis; Colorectal cancer	EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN BREAST-CANCER; SELECTIVE AUTOPHAGY; CONJUGATING ENZYME; ACTIVATION; PROTEIN; TUMORIGENESIS; CELLS; KINASE; INHIBITION	Background: Ubiquitination is a basic post-translational modification for cellular homeostasis, and members of the conjugating enzyme (E2) family are the key components of the ubiquitin-proteasome system. However, the role of E2 family in colorectal cancer (CRC) is largely unknown. Our study aimed to investigate the role of Ube2v1, one of the ubiquitin-conjugating E2 enzyme variant proteins (Ube2v) but without the conserved cysteine residue required for the catalytic activity of E2s, in CRC. Methods: Immunohistochemistry and real-time RT-PCR were used to study the expressions of Ube2v1 at protein and mRNA levels in CRC, respectively. Western blotting and immunofluorescence, transmission electron microscopy, and in vivo rescue experiments were used to study the functional effects of Ube2v1 on autophagy and EMT program. Quantitative mass spectrometry, immunoprecipitation, ubiquitination assay, western blotting, and real-time RT-PCR were used to analyze the effects of Ube2v1 on histone H4 lysine 16 acetylation, interaction with Sirt1, ubiquitination of Sirt1, and autophagy-related gene expression. Results: Ube2v1 was elevated in CRC samples, and its increased expression was correlated with poorer survival of CRC patients. Ube2v1 promoted migration and invasion of CRC cells in vitro and tumor growth and metastasis of CRC cells in vivo. Interestingly, Ube2v1suppressed autophagy program and promoted epithelial mesenchymal transition (EMT) and metastasis of CRC cells in an autophagy-dependent pattern in vitro and in vivo. Moreover, both rapamycin and trehalose attenuated the enhanced Ube2v1-mediated lung metastasis by inducing the autophagy pathway in an orthotropic mouse xenograft model of lung metastasis. Mechanistically, Ube2v1 promoted Ubc13-mediated ubiquitination and degradation of Sirt1 and inhibited histone H4 lysine 16 acetylation, and finally epigenetically suppressed autophagy gene expression in CRC. Conclusions: Our study functionally links Ube2v1, an E2 member in the ubiquitin-proteasome system, to autophagy program, thereby shedding light on developing Ube2v1 targeted therapy for CRC patients.	[Shen, Tong; Cai, Ling-Dong; Li, Shi; Gan, Wen-Juan; Li, Xiu-Ming; Wang, Jing-Ru; Guo, Peng-Da; Zhou, Qun; Lu, Xing-Xing; Sun, Li-Na; Li, Jian-Ming] Soochow Univ, Med Sch, Dept Pathol, Suzhou 215123, Peoples R China; [Liu, Yu-Hong] Southern Med Univ, Baoan Hosp, Dept Pathol, Shenzhen 518101, Peoples R China		Li, JM (corresponding author), Soochow Univ, Med Sch, Dept Pathol, Suzhou 215123, Peoples R China.	jianmingli@suda.edu.cn			National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81525020, 81502033, 81272300, 31570753]; Postdoctoral Science Foundation of Jiangsu ProvinceChina Postdoctoral Science Foundation [1302029B]; Science and Technology Foundation of Suzhou [SYS201412]	This work was supported by the National Nature Science Foundation of China (Grants81525020, 81502033, 81272300, and 31570753), the Postdoctoral Science Foundation (1302029B) of Jiangsu Province, and Science and Technology Foundation of Suzhou (SYS201412).	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Hematol. Oncol.	JUL 17	2018	11								95	10.1186/s13045-018-0638-9			16	Oncology; Hematology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Hematology	GN6YE	WOS:000439249700001	30016968	Green Published, gold			2022-04-25	
J	Kritikou, I; Giannopoulou, E; Koutras, AK; Labropoulou, VT; Kalofonos, HP				Kritikou, Ismini; Giannopoulou, Efstathia; Koutras, Angelos K.; Labropoulou, Vassiliki T.; Kalofonos, Haralabos P.			The combination of antitumor drugs, exemestane and erlotinib, induced resistance mechanism in H358 and A549 non-small cell lung cancer (NSCLC) cell lines	PHARMACEUTICAL BIOLOGY			English	Article						Beclin-1; EGFR; migration; mitochondria	GROWTH-FACTOR RECEPTOR; COLON-CANCER; ESTROGEN-RECEPTOR; EGF RECEPTOR; INHIBITORS; THERAPY; GEFITINIB; REPLACEMENT; CARCINOMA; AROMATASE	Context: Estrogens in non-small-cell lung cancer (NSCLC) are important, and their interaction with epidermal growth factor receptor (EGFR) might be crucial. Objective: This study investigates the effect of exemestane, an aromatase inhibitor, and erlotinib, an EGFR inhibitor, on human NSCLC cell lines; H23, H358 and A549. Materials and methods: A cell proliferation assay was used for measuring cell number, apoptosis assay for detecting apoptosis and necrosis and immunoblotting for beclin-1 and Bcl-2 proteins detection. An immunofluorescence assay was used for EGFR localization. A migration assay and zymography were used for cell motility and metalloproteinases (MMPs) expression, respectively. Results: Exemestane, erlotinib or their combination decreased cell proliferation and increased apoptosis. Exemestane's half maximal inhibitory concentration (IC50) was 50 mu M for H23 and H358 cells and 20 mu M for A549. The IC50 of erlotinib was 25 mM for all cell lines. Apoptosis increase induced by exemestane was 58.0 (H23), 186.3 (H358) and 34.7% (A549) and by erlotinib was 16.7 (H23), 65.3 (H358) and 66.3% (A549). A synergy effect was observed only in H23 cells. Noteworthy, the combination of exemestane and erlotinib decreased beclin-1 protein levels (32.3 +/- 19.2%), an indicator of autophagy, in H23 cells. The combination of exemestane and erlotinib partially reversed the EGFR translocation to mitochondria and decreased MMP levels and migration. Discussion and conclusions: The benefit from a dual targeting of aromatase and EGFR seems to be regulated by NSCLC cell content. The diverse responses of cells to agents might be influenced by the dominance of certain molecular pathways.	[Kritikou, Ismini; Giannopoulou, Efstathia; Koutras, Angelos K.; Labropoulou, Vassiliki T.; Kalofonos, Haralabos P.] Univ Hosp Patras, Patras Med Sch, Clin Oncol Lab, Rion 26504, Greece; [Koutras, Angelos K.; Labropoulou, Vassiliki T.; Kalofonos, Haralabos P.] Univ Hosp Patras, Dept Med, Div Oncol, Rion 26504, Greece		Kalofonos, HP (corresponding author), Univ Hosp Patras, Patras Med Sch, Dept Med, Div Oncol, Rion 26504, Greece.	kalofonos@upatras.gr		Kalofonos, Haralabos/0000-0002-3286-778X	EOGE Oncological Research Fund	We would like to thank the Medical School, University of Patras, Greece, for providing us the Advanced Light Microscopy facility, EOGE Oncological Research Fund for financial support and Gregoris Iconomou, PhD, Quality of life Unit, Division of Oncology, University Hospital of Patras, Greece for linguistic editing.	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Biol.	APR	2014	52	4					444	452		10.3109/13880209.2013.841718			9	Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy	AF2BX	WOS:000334518700006					2022-04-25	
J	Lenis-Rojas, OA; Carvalho, B; Cabral, R; Silva, M; Friaes, S; Roma-Rodrigues, C; Meireles, MSH; Gomes, CSB; Fernandez, JAA; Vila, SF; Rubiolo, JA; Sanchez, L; Baptista, PV; Fernandes, AR; Royo, B				Lenis-Rojas, Oscar A.; Carvalho, Beatriz; Cabral, Rui; Silva, Margarida; Friaes, Sofia; Roma-Rodrigues, Catarina; Meireles, Marta S. H.; Gomes, Clara S. B.; Fernandez, Jhonathan A. A.; Vila, Sabela F.; Rubiolo, Juan A.; Sanchez, Laura; Baptista, Pedro, V; Fernandes, Alexandra R.; Royo, Beatriz			Manganese(I) tricarbonyl complexes as potential anticancer agents	JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY			English	Article						Mn(I) complexes; Antiproliferative activity; Cancer; In vivo models; A2780 tumor cells	CO-RELEASING PROPERTIES; CARBON-MONOXIDE; DINUCLEAR METALLACYCLES; GOLD NANOPARTICLES; CANCER-THERAPY; IN-VITRO; CYTOTOXICITY; DELIVERY; CELLS; MODULATION	The antiproliferative activity of [Mn(CO)(3)((NN)-N-boolean AND)Br] ((NN)-N-boolean AND = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)(3)(acridine)(phendione)]OTf (2) and [Mn(CO)(3)(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).	[Lenis-Rojas, Oscar A.; Friaes, Sofia; Meireles, Marta S. H.; Royo, Beatriz] Inst Tecnol Quim & Biol Antonio Xavier, ITQB NOVA, Av Republ, P-2780157 Oeiras, Portugal; [Carvalho, Beatriz; Cabral, Rui; Silva, Margarida; Roma-Rodrigues, Catarina; Baptista, Pedro, V; Fernandes, Alexandra R.] NOVA Univ Lisbon, NOVA Sch Sci & Technol, Dept Life Sci, UCIBIO Appl Mol Biosci Unit, P-2819516 Caparica, Portugal; [Carvalho, Beatriz; Cabral, Rui; Silva, Margarida; Roma-Rodrigues, Catarina; Gomes, Clara S. B.; Baptista, Pedro, V; Fernandes, Alexandra R.] NOVA Univ Lisbon, NOVA Sch Sci & Technol, Associate Lab I4HB Inst Hlth & Bioecon, P-2819516 Caparica, Portugal; [Silva, Margarida] Univ Lisbon, Fac Farm, Imed, Av Prof Gama Pinto, P-1649003 Lisbon, Portugal; [Gomes, Clara S. B.] NOVA Sch Sci & Technol, Dept Quim, LAQV REQUIMTE, P-2829516 Caparica, Portugal; [Gomes, Clara S. B.] NOVA Sch Sci & Technol, Dept Quim, UCIBIO, P-2829516 Caparica, Portugal; [Fernandez, Jhonathan A. A.] Univ Campinas UNICAMP, Lab Zebrafish, Dept Med Genet & Genom Med, Sch Med Sci, Campinas, SP, Brazil; [Vila, Sabela F.; Rubiolo, Juan A.; Sanchez, Laura] Univ Santiago de Compostela, Fac Vet, Dept Zool Genet & Antropol Fis, Lugo 27002, Spain; [Sanchez, Laura] Hlth Res Inst Santiago Compostela IDIS, Preclin Anim Models Grp, Santiago De Compostela 15706, Spain		Lenis-Rojas, OA; Royo, B (corresponding author), Inst Tecnol Quim & Biol Antonio Xavier, ITQB NOVA, Av Republ, P-2780157 Oeiras, Portugal.; Fernandes, AR (corresponding author), NOVA Univ Lisbon, NOVA Sch Sci & Technol, Dept Life Sci, UCIBIO Appl Mol Biosci Unit, P-2819516 Caparica, Portugal.; Fernandes, AR (corresponding author), NOVA Univ Lisbon, NOVA Sch Sci & Technol, Associate Lab I4HB Inst Hlth & Bioecon, P-2819516 Caparica, Portugal.	oscar.rojas@itqb.unl.pt; ma.fernandes@fct.unl.pt; broyo@itqb.unl.pt	Roma-Rodrigues, Catarina/S-6144-2016; Baptista, Pedro/A-1237-2009; Rojas, Oscar/ABE-2206-2021; Gomes, Clara S. B./H-7759-2012; Sanchez Pinon, Laura/L-2411-2014; Ferreira-Silva, Margarida/T-5012-2017	Roma-Rodrigues, Catarina/0000-0002-8676-6562; Rojas, Oscar/0000-0002-5914-5787; Gomes, Clara S. B./0000-0003-3672-0045; Sanchez Pinon, Laura/0000-0001-7927-5303; Ferreira-Silva, Margarida/0000-0002-5724-2823	FCT-FundacAo para a Ciencia e a Tecnologia, I.P., Project MOSTMICRO-ITQBPortuguese Foundation for Science and Technology [UIDB/04612/2020, UIDP/04612/2020]; FEDER through COMPETE; POCIEuropean Commission; PORL; FCT through PIDDACPortuguese Foundation for Science and Technology; FCT-FundacAo para a Ciencia e a Tecnologia, I.P. of the Research Unit on Applied Molecular Biosciences-UCIBIOPortuguese Foundation for Science and Technology [UIDP/04378/2020, UIDB/04378/2020]; Associate Laboratory Institute for Health and Bioeconomy-i4HB [LA/P/0140/2020]; FEDER funds through COMPETE2020-Programa Operacional Competitividade e InternacionalizacAo (POCI) [LISBOA-01-0145-FEDER-007660]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission; POPH-Programa Operacional Potencial Humano; FSE (European Social Fund)European Social Fund (ESF); CoordenacAo de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); program CAPES/PRINT [88887.470075/2019-00]; ACUIGEN from the Universidad de Santiago de Compostela [GI-1251]; Xunta de GaliciaXunta de GaliciaEuropean Commission [ED431C 2018/28]; FundacAo para a Ciencia e a TecnologiaPortuguese Foundation for Science and TechnologyEuropean Commission [UIDB/50006/2020, UIDP/50006/2020]; FCT-MCTESPortuguese Foundation for Science and TechnologyEuropean Commission [RECI/BBB-BEP/0124/2012];  [022161]	This work was funded by national funds through FCT-FundacAo para a Ciencia e a Tecnologia, I.P., Project MOSTMICRO-ITQB with refs UIDB/04612/2020 and UIDP/04612/2020. The NMR spectrometers at CERMAX are integrated in the National NMR, Network (PTNMR) and are partially supported by Infrastructure Project No. 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). This work is financed by national funds from FCT-FundacAo para a Ciencia e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences-UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB. Oscar A. Lenis-Rojas acknowledges Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e InternacionalizacAo (POCI) and by national funds through FCT, POPH-Programa Operacional Potencial Humano, and FSE (European Social Fund) for the CEEC 2017 Initiative. Jhonathan A.A Fernandez acknowledges CoordenacAo de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) and the program CAPES/PRINT Proc. 88887.470075/2019-00 for the financial support. Sabela F Vila, Juan A. Rubiolo, and Laura Sanchez acknowledge ACUIGEN (GI-1251) from the Universidad de Santiago de Compostela and Xunta de Galicia proyect ED431C 2018/28 for the financial support. Clara S. B. Gomes acknowledges the Associate Laboratory for Green Chemistry-LAQV and the Applied Molecular Biosciences Unit-UCIBIO. LAQV is financed by national funds from FundacAo para a Ciencia e a Tecnologia (UIDB/50006/2020, UIDP/50006/2020). X-ray infrastructure financed by FCT-MCTES through project RECI/BBB-BEP/0124/2012. The authors acknowledge M. Baleia and I. Goncalves for pDNA, gDNA, and preliminary BAX/BCL-2 data, respectively.	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Biol. Inorg. Chem.	FEB	2022	27	1					49	64		10.1007/s00775-021-01910-7		OCT 2021	16	Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	YX8VK	WOS:000712210400001	34713347				2022-04-25	
J	Bach, DH; Kim, SH; Hong, JY; Park, HJ; Oh, DC; Lee, SK				Bach, Duc-Hiep; Kim, Seong-Hwan; Hong, Ji-Young; Park, Hyen Joo; Oh, Dong-Chan; Lee, Sang Kook			Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1 alpha and Induces Apoptosis in Human Colorectal Cancer Cells	MARINE DRUGS			English	Article						salternamide A (SA); HIF-1; PI3K; Akt; mTOR; p42; p44 MAPK; STAT3; cell death	INDUCIBLE FACTOR 1-ALPHA; GENE-EXPRESSION; PROTEIN-KINASES; BINDING; STAT3; CARCINOMA; AUTOPHAGY; GROWTH; HIF-1; FACTOR-1-ALPHA	Hypoxia inducible factor-1 (HIF-1) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. HIF-1 is overexpressed in various cancers and therefore represents a considerable chemotherapeutic target. Salternamide A (SA), a novel small molecule that is isolated from a halophilic Streptomyces sp., is a potent cytotoxic agent against a variety of human cancer cell lines. However, the mechanisms by which SA inhibits tumor growth remain to be elucidated. In the present study, we demonstrate that SA efficiently inhibits the hypoxia-induced accumulation of HIF-1 in a time- and concentration-dependent manner in various human cancer cells. In addition, SA suppresses the upstream signaling of HIF-1, such as PI3K/Akt/mTOR, p42/p44 MAPK, and STAT3 signaling under hypoxic conditions. Furthermore, we found that SA induces cell death by stimulating G2/M cell cycle arrest and apoptosis in human colorectal cancer cells. Taken together, SA was identified as a novel small molecule HIF-1 inhibitor from marine natural products and is potentially a leading candidate in the development of anticancer agents.	[Bach, Duc-Hiep; Kim, Seong-Hwan; Hong, Ji-Young; Park, Hyen Joo; Oh, Dong-Chan; Lee, Sang Kook] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea		Lee, SK (corresponding author), Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea.	bdhiep90@snu.ac.kr; yanberk@snu.ac.kr; jyhong7876@daum.net; phj00@snu.ac.kr; dongchanoh@snu.ac.kr; sklee61@snu.ac.kr	Bach, Duc-Hiep/V-5276-2017	Bach, Duc-Hiep/0000-0002-9826-3137	National Research Foundation (NRF) - Korean government (MEST) (NRF) [2009-0083533]; MarineBio Research Program of the NRF (NRF) [2012-0006712]	This work was supported by a National Research Foundation (NRF) grant funded by the Korean government (MEST) (NRF No. 2009-0083533) and a grant from the MarineBio Research Program of the NRF (NRF No. 2012-0006712).	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Drugs	NOV	2015	13	11					6962	6976		10.3390/md13116962			15	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	CX4CI	WOS:000365645400021	26610526	Green Published, gold, Green Submitted			2022-04-25	
J	Klose, J; Kattner, S; Borgstrom, B; Volz, C; Schmidt, T; Schneider, M; Oredsson, S; Strand, D; Ulrich, A				Klose, Johannes; Kattner, Sarah; Borgstrom, Bjorn; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Oredsson, Stina; Strand, Daniel; Ulrich, Alexis			Semi-synthetic salinomycin analogs exert cytotoxic activity against human colorectal cancer stem cells	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Salinomycin; Salinomycin analogs; Colorectal cancer; Apoptosis; Cancer stem cells	SELECTIVITY; AUTOPHAGY; GROWTH	Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin. The impact of salinomycin and its analogs on tumor cell number, migration, cell death, and cancer stem cell specifity was analyzed. Exposure of human colorectal cancer cells to the C20-O-acylated analogs of salinomycin resulted in reduced tumor cell number and impaired tumor cell migration at lower concentrations than salinomycin. When used at higher (micromolar) concentrations, these effects were accompanied by induction of apoptotic cell death. Salinomycin analogs further expose improved activity against cancer stem cells compared to salinomycin. (C) 2017 Elsevier Inc. All rights reserved.	[Klose, Johannes; Kattner, Sarah; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Ulrich, Alexis] Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Neuenheimer Feld 110, D-69120 Heidelberg, Germany; [Borgstrom, Bjorn; Strand, Daniel] Lund Univ, Ctr Anal & Synth, Dept Chem, Lund, Sweden; [Oredsson, Stina] Lund Univ, Dept Biol, Lund, Sweden		Klose, J (corresponding author), Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Neuenheimer Feld 110, D-69120 Heidelberg, Germany.	Johannes.Klose@med.uni-heidelberg.de; sarahkatt@web.de; bjom.borgstrom@chem.lu.se; Claudia.Volz@med.uni-heidelberg.de; Thomas1.Schmidt@med.uni.heidelberg.de; m.schneider@uni-heidelberg.de; stina.oredsson@biol.lu.se; daniel.strand@chem.lu.se; Alexis.Ulrich@med.uni-heidelberg.de	Schmidt, Thomas/Y-8431-2019	Schmidt, Thomas/0000-0002-7166-3675; Strand, Daniel/0000-0002-6113-4657	Heidelberger Stiftung Chirurgie; Swedish Cancer foundation	This study was supported by Heidelberger Stiftung Chirurgie to JK and the Swedish Cancer foundation.	Borgstrom B, 2016, ACS MED CHEM LETT, V7, P635, DOI 10.1021/acsmedchemlett.6b00079; Borgstrom B, 2013, CHEM COMMUN, V49, P9944, DOI 10.1039/c3cc45983g; Melo FDE, 2017, NATURE, V543, P676, DOI 10.1038/nature21713; Dewangan J, 2017, TUMOR BIOL, V39, DOI 10.1177/1010428317695035; Dong TT, 2011, ANN SURG ONCOL, V18, P1797, DOI 10.1245/s10434-011-1561-2; Grubor-Bauk B, 2016, GENE THER, V23, P26, DOI 10.1038/gt.2015.86; Gupta PB, 2009, CELL, V138, P645, DOI 10.1016/j.cell.2009.06.034; Huang EH, 2009, CANCER RES, V69, P3382, DOI 10.1158/0008-5472.CAN-08-4418; Huang XL, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2142-3; Huang XL, 2014, ACS CHEM BIOL, V9, P1587, DOI 10.1021/cb5002153; Ketola K, 2012, BRIT J CANCER, V106, P99, DOI 10.1038/bjc.2011.530; Klose J, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2879-8; Klose J, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0095970; Lieke T, 2012, BMC CANCER, V12, DOI 10.1186/1471-2407-12-466; Lobo NA, 2007, ANNU REV CELL DEV BI, V23, P675, DOI 10.1146/annurev.cellbio.22.010305.104154; Mao J, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2013.515; Mizushima N, 2010, CELL, V140, P313, DOI 10.1016/j.cell.2010.01.028; PLUMLEE KH, 1995, J VET DIAGN INVEST, V7, P419, DOI 10.1177/104063879500700327; Schneider CA, 2012, NAT METHODS, V9, P671, DOI 10.1038/nmeth.2089; Story Phillipa, 2004, N Z Med J, V117, pU799; Verdoodt B, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0044132; Xipell E, 2016, ONCOTARGET, V7, P30626, DOI [10.16632/oncotarget.8905, 10.18632/oncotarget.8905]; Zhang GN, 2011, CANCER LETT, V313, P137, DOI 10.1016/j.canlet.2011.05.030; Zhou J, 2013, TOXICOL LETT, V222, P139, DOI 10.1016/j.toxlet.2013.07.022	24	7	7	1	8	ACADEMIC PRESS INC ELSEVIER SCIENCE	SAN DIEGO	525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA	0006-291X	1090-2104		BIOCHEM BIOPH RES CO	Biochem. Biophys. Res. Commun.	JAN 1	2018	495	1					53	59		10.1016/j.bbrc.2017.10.147			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	FU5MM	WOS:000423897600009	29107689				2022-04-25	
J	Singh, A; Patel, P; Jageshwar; Patel, VK; Jain, DK; Kamal, M; Rajak, H				Singh, Avineesh; Patel, Preeti; Jageshwar; Patel, Vijay Kumar; Jain, Deepak Kumar; Kamal, M.; Rajak, Harish			The Safety, Efficacy and Therapeutic Potential of Histone Deacetylase Inhibitors with Special Reference to Panobinostat in Gastrointestinal Tumors: A Review of Preclinical and Clinical Studies	CURRENT CANCER DRUG TARGETS			English	Review						HDAC; HDACi; panobinostat; combination therapy; GI tumors; preclinical and clinical studies	GROWTH-FACTOR-BETA; PANCREATIC-CANCER CELLS; VIRUS-X PROTEIN; SUBEROYLANILIDE HYDROXAMIC ACID; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA CELLS; HUMAN COLORECTAL-CANCER; NF-KAPPA-B; GASTRIC-CANCER; HEPATOMA-CELLS	Histone deacetylase inhibitors (HDACi) have been demonstrated as an emerging class of anticancer drugs involved in regulation of gene expression and chromatin remodeling thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac (R), LBH589) is developed by Novartis Pharmaceuticals and a newly US FDA approved drug for the multiple myeloma. It is under clinical investigation for a range of hematological and solid tumors worldwide in both oral and intravenous formulations. Panobinostat inhibits tumor cell growth by interacting with acetylation of histones and nonhistone proteins as well as various apoptotic, autophagy-mediated targets and various tumorigenesis pathways involved in the development of cancer. The current article summarizes the status of panobinostat in gastrointestinal cancers. Preclinical and clinical data suggest that panobinostat has potential inhibitory activity in hepatocellular, pancreatic, colorectal, gastric and gastrointestinal stromal tumors. Clinical evaluations of panobinostat are currently underway. Herein, we have also reviewed the rationale behind the combination therapy under the trials and possible future prospective for the treatment of GI tumors.	[Singh, Avineesh; Patel, Preeti; Jageshwar; Patel, Vijay Kumar; Jain, Deepak Kumar; Rajak, Harish] Guru Ghasidas Univ, Inst Pharmaceut Sci, Med Chem Res Lab, Bilaspur 495009, CG, India; [Kamal, M.] Prince Sattam Bin Abdulaziz Univ, Coll Pharm, Dept Pharmaceut Chem, Al Kharj 11942, Saudi Arabia		Rajak, H (corresponding author), Guru Ghasidas Univ, Inst Pharmaceut Sci, Bilaspur, India.	harishdops@yahoo.co.in	Patel, Preeti/AAD-2040-2021; Kamal, Mehnaz/AAE-7681-2019; Rajak, Harish/AAP-5981-2021	Patel, Preeti/0000-0003-1606-2241; Kamal, Mehnaz/0000-0002-3585-0828; PATEL, VIJAY KUMAR/0000-0002-0392-3308; Rajak, Harish/0000-0003-2008-2827	Council of Scientific & Industrial Research (CSIR), New DelhiCouncil of Scientific & Industrial Research (CSIR) - India; Science & Engineering Research Board - Department of Science & Technology (SERB-DST), New DelhiDepartment of Science & Technology (India)Science Engineering Research Board (SERB), India; All India Council for Technical Education (AICTE), New DelhiAll India Council for Technical Education (AICTE)	One of the authors, Avineesh Singh is thankful to the Council of Scientific & Industrial Research (CSIR), New Delhi for awarding Senior Research Fellowship and financial assistance. One of the authors, Harish Rajak is grateful to Science & Engineering Research Board - Department of Science & Technology (SERB-DST), New Delhi, and All India Council for Technical Education (AICTE), New Delhi for providing financial assistance in the form of a Research Project and CAYT scheme, respectively.	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Cancer Drug Targets		2018	18	8					720	736		10.2174/1568009617666170630124643			17	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GU9NG	WOS:000445673000001	28669336				2022-04-25	
J	Zhang, LZ; Qi, WH; Zhao, G; Liu, LX; Xue, H; Hu, WX; Wang, QQ; Li, CS				Zhang, Li-ze; Qi, Wen-hai; Zhao, Gang; Liu, Lin-xun; Xue, Hui; Hu, Wen-xiu; Wang, Qian-qian; Li, Chun-sheng			Correlation between PTEN and P62 gene expression in rat colorectal cancer cell	SAUDI JOURNAL OF BIOLOGICAL SCIENCES			English	Article						Autophagy; PTEN gene; p62; Colorectal cancer; pEGFP-N1-PTEN plasmid; Regulation	SIGNALING PATHWAY; LARYNGEAL-CANCER; UBIQUITINATION; GROWTH	Objective: Autophagy is a cellular pathway that regulates the transportation and degradation of cytoplasmic macromolecules and organelles towards lysosome, which is often related to the tumorigenesis and tumor suppression. Here, we investigate the regulating effect of PTEN gene on autophagy-related protein P62 in rat colorectal cancer (CRC) cells and explore the application value of PTEN gene in clinic. Methods: Rat colorectal cancer was induced by intraperitoneal injection of 1,2-dimethyl hydrazine in male ACI rats. A total of 20 rats were randomly selected from those successfully induced with CRC as the experimental group, while 10 healthy rats as control. The rat CRC cells were isolated and cultured. After transfecting the rat CRC cells with pEGFP-N1-PTEN plasmid, RT-PCR was adopted to examine that gene expression of p62 and PTEN, while Western blotting was used to detect the protein expression of p62 and PTEN. Also, the proliferation of CRC cells was measured by MTT assay. Results: The expression of PTEN gene in the experimental group was significantly inhibited as compared with the control group, while the expression of P62 gene was significantly increased (p < 0.05). Western blotting demonstrated that the PTEN protein in the experimental group was lower, while the expression of P62 protein was higher. When the CRC cells were transfected with pEGFP-N1-PTEN plasmid, the PTEN expressions were elevated, while p62 was down-regulated. Also, the proliferation of CRC cells was inhibited. Conclusion: The expression of PTEN gene is negatively correlated with the expression of P62 gene in rat CRC cells. And the expression of PTEN gene can inhibit the occurrence and development of colorectal cancer, thus providing theoretical basis for future clinical treatment. (C) 2019 Production and hosting by Elsevier B.V. on behalf of King Saud University.	[Zhang, Li-ze; Zhao, Gang] Qingdao Univ, Dept Anorectal, Affiliated Hosp, Qingdao 266555, Shandong, Peoples R China; [Qi, Wen-hai] Yanan Univ, Dept Anorectal Surg, Affiliated Hosp, Yanan 716000, Peoples R China; [Liu, Lin-xun] Qinghai Prov Peoples Hosp, Dept Gen Surg, Xining 410035, Qinghai, Peoples R China; [Xue, Hui] Qingdao Hiser Hosp, Dept Gynecol, Qingdao 266000, Shandong, Peoples R China; [Hu, Wen-xiu] Inner Mongolia Med Univ, Dept Gen Surg, Affiliated Hosp, Hohhot 010050, Peoples R China; [Wang, Qian-qian] Qingdao Univ, Dept Anorectal, Songshan Hosp, Qingdao 266042, Shandong, Peoples R China; [Li, Chun-sheng] Jilin Univ, Gastrointestinal Colorectal & Anal Surg, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China		Li, CS (corresponding author), Jilin Univ, Gastrointestinal Colorectal & Anal Surg, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China.	orf046@163.com	Zong, Guangdeng/AAA-3896-2020	Lize, Zhang/0000-0002-7241-2683			Chatenoud L, 2016, INT J CANCER, V138, P833, DOI 10.1002/ijc.29833; Cheng MR, 2013, MOL CANCER, V12, DOI 10.1186/1476-4598-12-166; Falchetti A, 2005, ARTHRITIS RES THER, V7, pR1289, DOI 10.1186/ar1828; Forastiere AA, 2018, J CLIN ONCOL, V36, P1143, DOI 10.1200/JCO.2017.75.7385; Haapaniemi A, 2016, HEAD NECK-J SCI SPEC, V38, P36, DOI 10.1002/hed.23834; Korn T, 2007, NATURE, V448, P484, DOI 10.1038/nature05970; Lague MN, 2008, CARCINOGENESIS, V29, P2062, DOI 10.1093/carcin/bgn186; Lipkowitz S, 2003, BREAST CANCER RES, V5, P8, DOI 10.1186/bcr541; McCabe Nuala, 2016, Oncoscience, V3, P54; Ortega-Molina A, 2013, TRENDS ENDOCRIN MET, V24, P184, DOI 10.1016/j.tem.2012.11.002; Slattery ML, 2010, CARCINOGENESIS, V31, P1604, DOI 10.1093/carcin/bgq142; Steuer CE, 2017, CA-CANCER J CLIN, V67, P32, DOI 10.3322/caac.21386; Xiao J, 2015, GENE DEV, V29, P184, DOI 10.1101/gad.252528.114; Zhang YX, 2018, ONCOTARGETS THER, V11, P2037, DOI 10.2147/OTT.S147855; Zhao D, 2017, NATURE, V542, P484, DOI 10.1038/nature21357; Zhu JJ, 2012, ONCOL REP, V28, P2290, DOI 10.3892/or.2012.2065	16	3	3	0	1	ELSEVIER	AMSTERDAM	RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS	1319-562X			SAUDI J BIOL SCI	Saudi J. Biol. Sci.	DEC	2019	26	8					1986	1990		10.1016/j.sjbs.2019.08.006			5	Biology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics	JV3YY	WOS:000502303000013	31885487	Green Published, gold			2022-04-25	
J	Anwar, MA; Abou Kheir, W; Eid, S; Fares, J; Liu, XQ; Eid, AH; Eid, AA				Anwar, M. Akhtar; Abou Kheir, Wassim; Eid, Stephanie; Fares, Joanna; Liu, Xiaoqi; Eid, Ali H.; Eid, Assaad A.			Colorectal and Prostate Cancer Risk in Diabetes: Metformin, an Actor behind the Scene	JOURNAL OF CANCER			English	Review						Diabetes; Colorectal Cancer; Prostate Cancer; Metformin; AMPK; mTOR	ACTIVATED PROTEIN-KINASE; COENZYME-A REDUCTASE; ABERRANT CRYPT FOCI; IN-VITRO; AMPK; INHIBITION; PHOSPHORYLATION; MELLITUS; EPIGENETICS; APOPTOSIS	Both diabetes and cancer are prevalent diseases whose incidence rates are increasing worldwide, especially in countries that are undergoing rapid industrialization changes. Apparently, lifestyle risk factors including diet, physical inactivity and obesity play pivotal, yet preventable, roles in the etiology of both diseases. Epidemiological studies provide strong evidence that subjects with diabetes are at significantly higher risk of developing many forms of cancer and especially solid tumors. In addition to pancreatic and breast cancer, the incidence of colorectal cancer and prostate cancer is increased in type 2 diabetes. While diabetes (type 2) and cancer share many risk factors, the biological links between the two diseases are poorly characterized. In this review, we highlight the mechanistic pathways that link diabetes to colorectal and prostate cancer and the use of Metformin, a diabetes drug, to prevent and/or treat colorectal and prostate cancer. We review the role of AMPK activation in autophagy, oxidative stress, inflammation, apoptosis, and cell cycle progression.	[Anwar, M. Akhtar; Eid, Ali H.] Qatar Univ, Dept Biol & Environm Sci, Coll Arts & Sci, Doha, Qatar; [Abou Kheir, Wassim; Eid, Stephanie; Fares, Joanna; Eid, Assaad A.] Amer Univ Beirut, Dept Anat Cell Biol & Physiol, Fac Med, Beirut 11072020, Lebanon; [Liu, Xiaoqi] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA		Eid, AA (corresponding author), Amer Univ Beirut, Dept Anat Cell Biol & Physiol, Fac Med, Bliss St 11-0236, Beirut 11072020, Lebanon.	ali.eid@qu.edu.qa; ae49@aub.edu.lb	Eid, Ali Hussein/ABD-6291-2021; Abou-Kheir, Wassim/AAP-2587-2020	Eid, Ali Hussein/0000-0003-3004-5675; Abou-Kheir, Wassim/0000-0001-9719-9324; Eid, Stephanie/0000-0003-3775-7544	Qatar National Research Fund (a member of Qatar Foundation) [NPRP 5-409-3-112]	This publication was made possible by grant # NPRP 5-409-3-112 from the Qatar National Research Fund (a member of Qatar Foundation). The Statements made herein are solely the responsibility of the authors.	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Cancer		2014	5	9					736	744		10.7150/jca.9726			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AY4OF	WOS:000347557400003	25368673	Green Published, Green Submitted, gold			2022-04-25	
J	Liu, SP; Fei, WQ; Shi, QL; Li, Q; Kuang, YY; Wang, C; He, C; Hu, XT				Liu, Shuiping; Fei, Weiqiang; Shi, Qinglan; Li, Qiang; Kuang, Yeye; Wang, Chan; He, Chao; Hu, Xiaotong			CHAC2, downregulated in gastric and colorectal cancers, acted as a tumor suppressor inducing apoptosis and autophagy through unfolded protein response	CELL DEATH & DISEASE			English	Article							MESSENGER-RNA; CELL-DEATH; ER STRESS; TRANSCRIPTION; ATF6; GENE; XBP1; MITOCHONDRIA; GLUTATHIONE; EXPRESSION	Tumor suppressor genes play a key role in cancer pathogenesis. Through massive expression profiling we identified CHAC2 as a frequently downregulated gene in gastric and colorectal cancers. Immunohistochemistry and western blot revealed that CHAC2 was downregulated in most tumor tissues, and 3-year survival rate of patients with high CHAC2 expression was significantly higher than that of patients with low CHAC2 expression (P<0.001 and P=0.001, respectively). The data of univariate analysis and multivariate analysis suggested that CHAC2 could serve as an independent prognostic marker. Our results showed for the first time that CHAC2 was degraded by the ubiquitin-proteasome pathway and CHAC2 expression inhibited tumor cell growth, proliferation, migration in vitro and in vivo. Mechanistic study showed that CHAC2 induced mitochondrial apoptosis and autophagy through unfolded protein response. So in gastric and colorectal cancer CHAC2 acted as a tumor suppressor and might have therapeutic implication for patients.	[Liu, Shuiping; Fei, Weiqiang; Shi, Qinglan; Li, Qiang; Kuang, Yeye; Wang, Chan; He, Chao; Hu, Xiaotong] Zhejiang Univ, Sir Run Run Shaw Hosp, Biomed Res Ctr, Hangzhou 310016, Zhejiang, Peoples R China; [Liu, Shuiping; Fei, Weiqiang; Shi, Qinglan; Li, Qiang; Kuang, Yeye; Wang, Chan; He, Chao; Hu, Xiaotong] Zhejiang Univ, Sir Run Run Shaw Hosp, Key Lab Biotherapy Zhejiang Prov, Hangzhou 310016, Zhejiang, Peoples R China		Hu, XT (corresponding author), Zhejiang Univ, Sir Run Run Shaw Hosp, Biomed Res Ctr, Hangzhou 310016, Zhejiang, Peoples R China.; Hu, XT (corresponding author), Zhejiang Univ, Sir Run Run Shaw Hosp, Key Lab Biotherapy Zhejiang Prov, Hangzhou 310016, Zhejiang, Peoples R China.	huxt@srrsh.com	Hu, Xiao-tong/K-5820-2019		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81071651, 81372622, 81672362]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ17H160009]	This study was supported by National Natural Science Foundation of China (81071651, 81372622 and 81672362) and Natural Science Foundation of Zhejiang Province (LQ17H160009).	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AUG	2017	8								e3009	10.1038/cddis.2017.405			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	FG1JB	WOS:000409550500047	28837156	Green Published, gold			2022-04-25	
J	Ghavami, S; Asoodeh, A; Klonisch, T; Halayko, AJ; Kadkhoda, K; Kroczak, TJ; Gibson, SB; Booy, EP; Naderi-Manesh, H; Los, M				Ghavami, Saeid; Asoodeh, Ahmad; Klonisch, Thomas; Halayko, Andrew J.; Kadkhoda, Kamran; Kroczak, Tadeusz J.; Gibson, Spencer B.; Booy, Evan P.; Naderi-Manesh, Hossein; Los, Marek			Brevinin-2R(1) semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						antibacterial peptide; defensin; Brevinin-2R; cell death; caspase activation; lysosomotrophic agent; late and early endosome; ROS; mitochondrial pathway; targetted cancer therapy	KAPPA-B ACTIVATION; ANTIMICROBIAL PEPTIDES; RANA-ESCULENTA; INDUCED APOPTOSIS; OXIDATIVE STRESS; CYTOCHROME-C; SOLID TUMORS; CATHEPSIN-D; BH3 DOMAIN; EXPRESSION	Brevinin-2R is a novel non-hemolytic defensin that was isolated from the skin of the frog Rana ridibunda. It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T-cell leukemia), BJAB (B-cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF-7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells including peripheral blood mononuclear cells (PBMC), T cells and human lung fibroblasts. Jurkat and MCF-7 cells overexpressing Bcl2, and L929 and MCF-7 over-expressing a dominant-negative mutant of a pro-apoptotic BNIP3 (Delta TM-BNIP3) were largely resistant towards Brevinin-2R treatment. The decrease in mitochondrial membrane potential (Delta Psi m), or total cellular ATP levels, and increased reactive oxygen species (ROS) production, but not caspase activation or the release of apoptosis-inducing factor (AIF) or endonuclease G (Endo G), were early indicators of Brevinin-2R-triggered death. Brevinin-2R interacts with both early and late endosomes. Lysosomal membrane permeabilization inhibitors and inhibitors of cathepsin-B and cathepsin-L prevented Brevinin-2R-induced cell death. Autophagosomes have been detected upon Brevinin-2R treatment. Our results show that Brevinin-2R activates the lysosomalmitochondrial death pathway, and involves autophagy-like cell death.	[Los, Marek] BioApplicat Enterprises, Winnipeg, MB R2V 2N6, Canada; [Ghavami, Saeid; Kadkhoda, Kamran; Kroczak, Tadeusz J.; Gibson, Spencer B.; Booy, Evan P.] Manitoba Inst Cell Biol, Dept Biochem & Med Genet, Winnipeg, MB R3E 0V9, Canada; [Asoodeh, Ahmad; Naderi-Manesh, Hossein] Tarbiat Modares Univ, Fac Basic Sci, Dept Biophys & Biochem, Tehran, Iran; [Asoodeh, Ahmad] Ferdowsi Univ Mashhad, Fac Sci, Dept Chem, Mashhad, Iran; [Klonisch, Thomas] Univ Manitoba, Fac Med, Dept Human Anat & Cell Sci, Winnipeg, MB, Canada; [Halayko, Andrew J.] Univ Manitoba, Dept Physiol, Winnipeg, MB, Canada		Los, M (corresponding author), BioApplicat Enterprises, 34 Vanier Dr, Winnipeg, MB R2V 2N6, Canada.	bioappl@gmail.com	Asoodeh, Ahmad/H-1484-2011; Ghavami, Saeid/Q-8918-2016; Klonisch, Thomas/W-9923-2019	Asoodeh, Ahmad/0000-0002-1406-0595; Naderi-Manesh, Hossein/0000-0002-4227-171X; Los, Marek/0000-0001-9518-1411; Ghavami, Saeid/0000-0001-5948-508X; Gibson, Spencer/0000-0003-0119-732X			BAKER MA, 1993, CANCER RES, V53, P3052; 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Cell. Mol. Med.	JUN	2008	12	3					1005	1022		10.1111/j.1582-4934.2008.00129.x			18	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	304JG	WOS:000256105200020	18494941	Green Published			2022-04-25	
J	Yan, JH; Dou, XY; Zhou, J; Xiong, YF; Mo, L; Li, LH; Lei, YL				Yan, Jianghong; Dou, Xiaoyun; Zhou, Jing; Xiong, Yuanfeng; Mo, Ling; Li, Longhao; Lei, Yunlong			Tubeimoside-I sensitizes colorectal cancer cells to chemotherapy by inducing ROS-mediated impaired autophagolysosomes accumulation	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH			English	Article						Tubeimoside-I; Autophagy; ROS; AMPK; Chemosensitivity	MITOCHONDRIAL DYSFUNCTION; CYTOCHROME-C; PHASE ARREST; AUTOPHAGY; APOPTOSIS; CYTOTOXICITY; STATISTICS; GROWTH; AMPK	Background Tubeimoside-I (TBM), a plant-derived bioactive compound, shows antitumor activity in different tumors and can enhance the efficacy of chemotherapeutic agents. However, the detail mechanism underlying remains to be elucidated. Methods The cytotoxic potential of TBM towards CRC cells was examined by CCK8 assay, colony formation, LDH release assay, flow cytometry method and Western blots. The ROS levels, autophagy, apoptosis, chemosensitivity to 5-FU or DOX, etc. were determined between control and TBM-treated CRC cells. Results In this study, we found that TBM could inhibit proliferation and induce apoptosis in colorectal cancer (CRC) cells. Intriguingly, TBM treatment could either promote autophagy initiation by ROS-induced AMPK activation, or block autophagy flux through inhibiting lysosomal hydrolytic enzymes, which leaded to massive impaired autophagylysosomes accumulation. Administration of autophagy initiation inhibitor (3-MA or selective ablation of autophagy related proteins) relieves TBM-induced CRC suppression, while combination use of autophagy flux inhibitor chloroquine (CQ) slightly augments TBM-induced cell death, suggesting that impaired autophagylysosomes accumulation contributes to TBM-induced growth inhibition in CRC cells. Notably, as an autophagy flux inhibitor, TBM works synergistically with 5-fluorouracil (5-FU) or doxorubicin (DOX) in CRC suppression. Conclusion Together, our study provides new insights regarding the anti-tumor activity of TBM against CRC, and established potential applications of TBM for CRC combination therapies in clinic.	[Yan, Jianghong; Dou, Xiaoyun] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Yan, Jianghong; Xiong, Yuanfeng; Mo, Ling] Chongqing Med Univ, Dept Med Lab Technol, Chongqing 400016, Peoples R China; [Li, Longhao] Chongqing Med Univ, Dept Oncol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Zhou, Jing; Lei, Yunlong] Chongqing Med Univ, Dept Biochem & Mol Biol & Mol Med, Chongqing 400016, Peoples R China; [Zhou, Jing; Lei, Yunlong] Chongqing Med Univ, Canc Res Ctr, Chongqing 400016, Peoples R China		Li, LH (corresponding author), Chongqing Med Univ, Dept Oncol, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Lei, YL (corresponding author), Chongqing Med Univ, Dept Biochem & Mol Biol & Mol Med, Chongqing 400016, Peoples R China.; Lei, YL (corresponding author), Chongqing Med Univ, Canc Res Ctr, Chongqing 400016, Peoples R China.	llh@hospital.cqmu.edu.cn; leiyunglong@cqmu.edu.cn		Lei, Yunlong/0000-0002-7918-0221	Chinese NSFCNational Natural Science Foundation of China (NSFC) [31400999, 81872014]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN201800417, KJQN201800429]	This work was supported by grants from the Chinese NSFC (31400999, 81872014), and Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJQN201800417, KJQN201800429).	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Exp. Clin. Cancer Res.	AUG 14	2019	38	1							353	10.1186/s13046-019-1355-0			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IQ4WY	WOS:000480753500002	31412953	gold, Green Published			2022-04-25	
J	Ahn, JH; Jang, GH; Lee, M				Ahn, Jun-Ho; Jang, Gun-Hee; Lee, Michael			Defective autophagy in multidrug resistant cells may lead to growth inhibition by BH3-mimetic gossypol	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article							BREAST-CANCER CELLS; COLON-CARCINOMA; GENE-EXPRESSION; MITOTIC ARREST; TUNEL ASSAY; APOPTOSIS; DEATH; (-)-GOSSYPOL; MECHANISM; INSIGHTS	The clinical efficacy of many chemotherapeutic agents has been reduced due to the development of drug resistance. In this article, we aimed to validate gossypol, a natural BH3 mimetic found in cottonseeds, as a potential therapeutic to overcome multidrug resistance (MDR). Gossypol was found to retain its efficacy in v-Ha-ras-transformed NIH 3T3 cells that overexpressed P-glycoprotein (Ras-NIH 3T3/Mdr), which was similar to the efficacy observed in their parental counterparts (Ras-NIH 3T3). A rhodamine assay revealed that the alteration of MDR activity did not contribute to the cytotoxic effect of gossypol. Gossypol caused a G2/M arrest by the induction of p21Cip1 and the down-regulation of p27Kip1 expression in Ras-NIH 3T3 cells, whereas no significant G2/M arrest was exhibited in Ras-NIH 3T3/Mdr cells. Surprisingly, a 48-h treatment with gossypol induced apoptotic cell death in Ras-NIH 3T3 cells; however, gossypol induced both apoptosis and necrosis in Ras-NIH 3T3/Mdr cells, as determined with flow cytometry analysis. More notably, gossypol preferentially induced autophagy in Ras-NIH 3T3 cells but not in Ras-NIH 3T3/Mdr cells. Coimmunoprecipitation and flow cytometric analysis revealed that gossypol-induced autophagy is independent of the dissociation of Beclin 1 from Bcl-2 in Ras-NIH 3T3 cells. Taken together, these results suggest that the antiproliferative activity of gossypol appears to be due to cell-cycle arrest at the G2/M phase, with the induction of apoptosis in Ras-NIH 3T3 cells. In addition, defective autophagy might contribute to apoptotic and necrotic cell death in response to gossypol in Ras-NIH 3T3/Mdr cells. J. Cell. Physiol. 228: 14961505, 2013. (c) 2012 Wiley Periodicals, Inc.	[Ahn, Jun-Ho; Jang, Gun-Hee; Lee, Michael] Univ Incheon, Div Life Sci, Coll Life Sci & Bioengn, Inchon 406772, South Korea		Lee, M (corresponding author), Univ Incheon, Div Life Sci, Coll Life Sci & Bioengn, 12-1 Songdo Dong, Inchon 406772, South Korea.	mikelee@incheon.ac.kr			Basic Science Research Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and TechnologyMinistry of Education, Science and Technology, Republic of Korea [2010-0022172]	This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0022172).	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Cell. Physiol.	JUL	2013	228	7					1496	1505		10.1002/jcp.24305			10	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	113PX	WOS:000316681100016	23254564				2022-04-25	
J	Tuli, HS; Mittal, S; Aggarwal, D; Parashar, G; Parashar, NC; Upadhyay, SK; Barwal, TS; Jain, A; Kaur, G; Savla, R; Sak, K; Kumar, M; Varol, M; Iqubal, A; Sharma, AK				Tuli, Hardeep Singh; Mittal, Sonam; Aggarwal, Diwakar; Parashar, Gaurav; Parashar, Nidarshana Chaturvedi; Upadhyay, Sushil Kumar; Barwal, Tushar Singh; Jain, Aklank; Kaur, Ginpreet; Savla, Raj; Sak, Katrin; Kumar, Manoj; Varol, Mehmet; Iqubal, Ashif; Sharma, Anil Kumar			Path of Silibinin from diet to medicine: A dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance	SEMINARS IN CANCER BIOLOGY			English	Article						Silibinin; Flavonolignans; Apoptosis; Cell cycle arrest; Anti-angiogenesis; Anti-metastasis; Clinical studies	CELL-CYCLE ARREST; INDUCED GROWTH-INHIBITION; SILYBUM-MARIANUM L.; LONG NONCODING RNAS; INDUCED AUTOPHAGIC DEATH; COLORECTAL-CANCER CELLS; PROSTATE TUMOR-GROWTH; CARCINOMA DU145 CELLS; NF-KAPPA-B; BREAST-CANCER	In the last few decades, targeting cancer by the use of dietary phytochemicals has gained enormous attention. The plausible reason and believe or mind set behind this fact is attributed to either lesser or no side effects of natural compounds as compared to the modern chemotherapeutics, or due to their conventional use as dietary components by mankind for thousands of years. Silibinin is a naturally derived polyphenol (a flavonolignans), possess following biochemical features; molecular formula C25H22O10, Molar mass: 482.44 g/mol, Boiling point 793 degrees C, with strikingly high antioxidant and anti-tumorigenic properties. The anti-cancer properties of Silibinin are determined by a variety of cellular pathways which include induction of apoptosis, cell cycle arrest, inhibition of angiogenesis and metastasis. In addition, Silibinin controls modulation of the expression of aberrant miRNAs, inflammatory response, and synergism with existing anti-cancer drugs. Therefore, modulation of a vast array of cellular responses and homeostatic aspects makes Silibinin an attractive chemotherapeutic agent. However, like other polyphenols, the major hurdle to declare Silibinin a translational chemotherapeutic agent, is its lesser bioavailability. After summarizing the chemistry and metabolic aspects of Silibinin, this extensive review focuses on functional aspects governed by Silibinin in chemoprevention with an ultimate goal of summarizing the evidence supporting the chemopreventive potential of Silibinin and clinical trials that are currently ongoing, at a single platform.	[Tuli, Hardeep Singh; Aggarwal, Diwakar; Parashar, Gaurav; Parashar, Nidarshana Chaturvedi; Upadhyay, Sushil Kumar; Sharma, Anil Kumar] Maharishi Markandeshwar Deemed be Univ, Dept Biotechnol, Mullana Ambala 133207, Haryana, India; [Mittal, Sonam] Jawaharlal Nehru Univ, Sch Biotechnol, New Delhi, India; [Barwal, Tushar Singh; Jain, Aklank] Cent Univ Punjab, Dept Zool, Bathinda 151001, Punjab, India; [Kaur, Ginpreet; Savla, Raj] Shobhaben Pratapbhai Patel Sch Pharm & Technol Ma, Dept Pharmacol, SVKMs, NMIMS, Mumbai 400056, Maharashtra, India; [Sak, Katrin] NGO Praeventio, EE-50407 Tartu, Estonia; [Kumar, Manoj] Maharishi Markandeshwar Univ, Dept Chem, Sadopur, India; [Varol, Mehmet] Mugla Sitki Kocman Univ, Dept Mol Biol & Genet, Fac Sci, TR-48000 Mugla, Turkey; [Iqubal, Ashif] Jamia Hamdard Deemed be Univ, Sch Pharmaceut Educ & Res, Dept Pharmacol, Delhi, India		Sharma, AK (corresponding author), Maharishi Markandeshwar Deemed be Univ, Dept Biotechnol, Mullana Ambala 133207, Haryana, India.	anibiotech18@gmail.com	VAROL, Mehmet/AES-2638-2022; 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J	Li, YY; Zhang, L; Zhou, J; Luo, SH; Huang, R; Zhao, CC; Diao, AP				Li, Yuyin; Zhang, Li; Zhou, Jie; Luo, Shenheng; Huang, Rui; Zhao, Changcai; Diao, Aipo			Nedd4 E3 ubiquitin ligase promotes cell proliferation and autophagy	CELL PROLIFERATION			English	Article							MEMBRANE PERMEABILIZATION; CYTOCHROME-C; PATHWAY; GROWTH; CANCER; ASSOCIATION; DEGRADATION; RELOCATION; STABILITY; RELEASE	ObjectivesNedd4 (neural precursor cell expressed developmentally down-regulated protein 4) is a member of the HECT E3 ubiquitin ligases, and is elevated in prostate, bladder and colorectal cancers, and promotes colonic cell population expansion. Up to now, molecular mechanisms of how Nedd4 functions, have not been well understood. Materials and methodsIn this study, shRNA was used to reduce expression of Nedd4 in the human prostate carcinoma cell line DU145. To analyse effects of Nedd4 on cell proliferation, MTT and colony formation assays were performed. DAPI staining and FACS analysis were used to investigate outcomes of Nedd4 activity, on apoptosis. Results of Nedd4 expression on lysosomal membrane permeabilization and autophagy were further investigated using acridine orange (AO) staining, immunofluorescence and western blot analysis. ResultsWe found that in HeLa cells, expression of Nedd4 promoted cell proliferation, whereas its knockdown inhibited colony formation and induced apoptosis in DU145 cells. Furthermore, down-regulation of Nedd4 in DU145 cells promoted lysosomal membrane permeabilization. We also found that down-regulation of Nedd4 inhibited autophagy in both DU145 and A549 cells. Investigation into mechanisms involved revealed that knockdown of endogenous Nedd4 expression notably increased activated mTOR (p-mTOR) levels, which suggests that mTOR signalling was involved in the Nedd4-mediated autophagy. ConclusionsOur results indicate that expression of Nedd4 promoted cell proliferation and colony formation but prevented apoptosis. Moreover, Nedd4 promoted autophagy and was associated with the mTOR signalling pathway.	[Li, Yuyin; Zhang, Li; Zhou, Jie; Luo, Shenheng; Huang, Rui; Zhao, Changcai; Diao, Aipo] Tianjin Univ Sci & Technol, Sch Biotechnol, Key Lab Ind Fermentat Microbiol, Minist Educ, Tianjin 300457, Peoples R China		Diao, AP (corresponding author), Tianjin Univ Sci & Technol, Sch Biotechnol, Tianjin Econ & Technol Dev Area TEDA, 29,13th Ave, Tianjin 300457, Peoples R China.	diaoaipo@tust.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402952]; program for Changjiang University Scholars and Innovative Research Team [IRT1166]; Tianjin Natural Science Foundation grant [10JCZDJC16800]	We are grateful to Dr. Edward McKenzie (University of Manchester, UK) for critical reading of the manuscript. This research is supported by the National Natural Science Foundation of China (81402952), program for Changjiang University Scholars and Innovative Research Team (IRT1166) and a Tianjin Natural Science Foundation grant (10JCZDJC16800).	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JUN	2015	48	3					338	347		10.1111/cpr.12184			10	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	CH7JL	WOS:000354212100009	25809873	Green Published			2022-04-25	
J	Thongnuanjan, P; Soodvilai, S; Fongsupa, S; Thipboonchoo, N; Chabang, N; Munyoo, B; Tuchinda, P; Soodvilai, S				Thongnuanjan, Penjai; Soodvilai, Sirima; Fongsupa, Somsak; Thipboonchoo, Natechanok; Chabang, Napason; Munyoo, Bamroong; Tuchinda, Patoomratana; Soodvilai, Sunhapas			Panduratin A Derivative Protects against Cisplatin-Induced Apoptosis of Renal Proximal Tubular Cells and Kidney Injury in Mice	MOLECULES			English	Article						apoptosis; chemotherapy; cyclohexanyl chalcone; kidney; oxidative stress	MITOCHONDRIAL DYSFUNCTION; INDUCED NEPHROTOXICITY; KAEMPFERIA-PANDURATA; MECHANISMS; TOXICITIES; AMIFOSTINE; AUTOPHAGY; TRANSPORT; KINASE; ALPHA	Background: Panduratin A is a bioactive cyclohexanyl chalcone exhibiting several pharmacological activities, such as anti-inflammatory, anti-oxidative, and anti-cancer activities. Recently, the nephroprotective effect of panduratin A in cisplatin (CDDP) treatment was revealed. The present study examined the potential of certain compounds derived from panduratin A to protect against CDDP-induced nephrotoxicity. Methods: Three derivatives of panduratin A (DD-217, DD-218, and DD-219) were semi-synthesized from panduratin A. We investigated the effects and corresponding mechanisms of the derivatives of panduratin A for preventing nephrotoxicity of CDDP in both immortalized human renal proximal tubular cells (RPTEC/TERT1 cells) and mice. Results: Treating the cell with 10 mu M panduratin A significantly reduced the viability of RPTEC/TERT1 cells compared to control (panduratin A: 72% & PLUSMN; 4.85%). Interestingly, DD-217, DD-218, and DD-219 at the same concentration did not significantly affect cell viability (92% & PLUSMN; 8.44%, 90% & PLUSMN; 7.50%, and 87 & PLUSMN; 5.2%, respectively). Among those derivatives, DD-218 exhibited the most protective effect against CDDP-induced renal proximal tubular cell apoptosis (control: 57% & PLUSMN; 1.23%; DD-218: 19% & PLUSMN; 10.14%; DD-219: 33% & PLUSMN; 14.06%). The cytoprotective effect of DD-218 was mediated via decreases in CDDP-induced mitochondria dysfunction, intracellular reactive oxygen species (ROS) generation, activation of ERK1/2, and cleaved-caspase 3 and 7. In addition, DD-218 attenuated CDDP-induced nephrotoxicity by a decrease in renal injury and improved in renal dysfunction in C57BL/6 mice. Importantly, DD-218 did not attenuate the anti-cancer efficacy of CDDP in non-small-cell lung cancer cells or colon cancer cells. Conclusions: This finding suggests that DD-218, a derivative of panduratin A, holds promise as an adjuvant therapy in patients receiving CDDP.	[Thongnuanjan, Penjai; Soodvilai, Sunhapas] Mahidol Univ, Fac Sci, Multidisciplinary Unit, Toxicol Grad Program, Rama VI Rd, Bangkok 10400, Thailand; [Thongnuanjan, Penjai; Thipboonchoo, Natechanok; Soodvilai, Sunhapas] Mahidol Univ, Fac Sci, Res Ctr Transport Prot Med Innovat, Dept Physiol, Rama VI Rd, Bangkok 10400, Thailand; [Soodvilai, Sirima] Rangsit Univ, Coll Pharm, Dept Pharmaceut Technol, Pathum Thani 12000, Thailand; [Fongsupa, Somsak] Thammasat Univ, Fac Allied Hlth Sci, Dept Med Technol, Pathum Thani 12121, Thailand; [Chabang, Napason] Mahidol Univ, Fac Sci, Sch Bioinnovat & Biobased Prod Intelligence, Rama VI Rd, Bangkok 10400, Thailand; [Munyoo, Bamroong; Tuchinda, Patoomratana; Soodvilai, Sunhapas] Mahidol Univ, Excellent Ctr Drug Discovery, Rama VI Rd, Bangkok 10400, Thailand		Soodvilai, S (corresponding author), Mahidol Univ, Fac Sci, Multidisciplinary Unit, Toxicol Grad Program, Rama VI Rd, Bangkok 10400, Thailand.; Soodvilai, S (corresponding author), Mahidol Univ, Fac Sci, Res Ctr Transport Prot Med Innovat, Dept Physiol, Rama VI Rd, Bangkok 10400, Thailand.; Soodvilai, S (corresponding author), Mahidol Univ, Excellent Ctr Drug Discovery, Rama VI Rd, Bangkok 10400, Thailand.	penjai.tho@gmail.com; sirima.s@rsu.ac.th; fongsupa.mu@gmail.com; Joy_nate@hotmail.com; Napason.cha@mahidol.ac.th; Br_411@hotmail.com; scptcster@gmail.com; sunhapas.soo@mahidol.ac.th			Thailand Science Research and Innovation [RSA6280082]; Mahidol University; International Research Network (IRN), Thailand Research Funds [IRN5804PHDW02]	This work was supported by the Thailand Science Research and Innovation (Grant No. RSA6280082 to Sunhapas Soodvilai) and Mahidol University. Pe.T. was supported by the International Research Network (IRN), Thailand Research Funds (Grant No. IRN5804PHDW02).	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J	Chen, JD; Sun, SX; Zha, DS; Wu, JG; Mao, LM; Deng, H; Chu, XW; Luo, HJ; Zha, LY				Chen, Jiading; Sun, Suxia; Zha, Dingsheng; Wu, Jiguo; Mao, Limei; Deng, Hong; Chu, Xinwei; Luo, Haiji; Zha, Longying			Soyasaponins Prevent H2O2-Induced Inhibition of Gap Junctional Intercellular Communication by Scavenging Reactive Oxygen Species in Rat Liver Cells	NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL			English	Article							SOYBEAN SAPONINS; HELA-CELLS; COLON; CANCER; PROLIFERATION; PHYTOCHEMICALS; MACROAUTOPHAGY; ACTIVATION; INDUCTION; PRESSURE	It appears to be more practical and effective to prevent carcinogenesis by targeting the tumor promotion stage. Gap junctional intercellular communication (GJIC) is strongly involved in carcinogenesis, especially the tumor promotion stage. Considerable interest has been focused on the chemoprevention activities of soyasaponin (SS), which are major phytochemicals found in soybeans and soy products. However, less is known about the preventive effects of SS (especially SS with different chemical structures) against tumor promoter-induced inhibition of GJIC. We investigated the protective effects of SS-A(1), SS-A(2), and SS-I against hydrogen peroxide (H2O2)-induced GJIC inhibition and reactive oxygen species (ROS) production in Buffalo rat liver (BRL) cells. The present results clearly show for the first time that SS-A(1), SS-A(2), and SS-I prevent the H2O2-induced GJIC inhibition by scavenging ROS in BRL cells in a dose-dependent manner at the concentration range of from 25 to 100 mu g/mL. Soyasaponins attenuated the H2O2-induced ROS through potentiating the activities of superoxide dismutase and glutathione peroxidase. This may be an important mechanism by which SS protects against tumor promotion. In addition, various chemical structures of SS appear to exhibit different protective abilities against GJIC inhibition. This may partly attribute to their differences in ROS-scavenging activities.	[Chen, Jiading; Sun, Suxia; Mao, Limei; Deng, Hong; Chu, Xinwei; Luo, Haiji; Zha, Longying] Southern Med Univ, Sch Publ Hlth & Trop Med, Dept Nutr & Food Hyg, Guangzhou 510515, Guangdong, Peoples R China; [Zha, Dingsheng] Jinan Univ, Affiliated Hosp 1, Dept Orthoped Surg, Guangzhou, Guangdong, Peoples R China; [Wu, Jiguo] Southern Med Univ, Sch Publ Hlth & Trop Med, Dept Environm Hlth Sci, Guangzhou 510515, Guangdong, Peoples R China		Zha, LY (corresponding author), Southern Med Univ, Sch Publ Hlth & Trop Med, Dept Nutr & Food Hyg, 1838 Guangzhou Ave North, Guangzhou 510515, Guangdong, Peoples R China.	lyzhasmu@126.com		Sun, Suxia/0000-0002-1159-6191	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81102130, 81202204]; Medical Scientific Research Foundation of Guangdong Province [A2011357]; Fundamental Research Funds for the Central Universities, ChinaFundamental Research Funds for the Central Universities [21612303]; Medical Scientific Research Foundation of Guangdong Province, China [WSTJJ20111125340822197903142037]; Scientific Research Training Foundation of the First Affiliated Hospital of Jinan University, China [2012-1]	This work was financially supported by National Natural Science Foundation of China (No. 81102130), Medical Scientific Research Foundation of Guangdong Province (A2011357) and partly by the Fundamental Research Funds for the Central Universities, China (No. 21612303), Medical Scientific Research Foundation of Guangdong Province, China (No. WSTJJ20111125340822197903142037), the Youth Project of Scientific Research Training Foundation of the First Affiliated Hospital of Jinan University, China (No. 2012-1) and National Natural Science Foundation of China (No. 81202204). Jiading Chen and Suxia Sun contributed equally to this work.	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Cancer	NOV 17	2014	66	8					1342	1351		10.1080/01635581.2014.956245			10	Oncology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Nutrition & Dietetics	AT3WI	WOS:000344863600009	25268883				2022-04-25	
J	Takada, Y; Sayama, T; Kikuchi, A; Kato, S; Tatsuzaki, N; Nakamoto, Y; Suzuki, A; Tsukamoto, C; Ishimoto, M				Takada, Yoshitake; Sayama, Takashi; Kikuchi, Akio; Kato, Shin; Tatsuzaki, Nana; Nakamoto, Yumi; Suzuki, Ayako; Tsukamoto, Chigen; Ishimoto, Masao			Genetic analysis of variation in sugar chain composition at the C-22 position of group A saponins in soybean, Glycine max (L.) Merrill	BREEDING SCIENCE			English	Article						genetic analysis; Glycine max (L.) Merrill; Glycine soja Sieb. et Zucc.; group A saponin; sugar chain composition; mapping	COLON-CANCER CELLS; LINKAGE MAP; SOYASAPOGENOL-A; STRUCTURAL ELUCIDATION; SEEDS; SOYASAPONINS; MARKERS; MACROAUTOPHAGY; BISDESMOSIDES; INHERITANCE	Saponins are a diverse group of secondary metabolites widely distributed in plants. Some saponins in soybean seeds have medicinal properties, but the terminal acetylated sugar at the C-22 position of group A saponins in seed hypocotyls causes a bitter and astringent taste. We used cultivated and wild soybean accessions classified into four different group A saponin phenotypes, including non-acetylated A0-alpha g and deacetyl-Af, as parents to obtain four F-2 populations and a population of recombinant inbred lines to test their genetic relationship. The gene controlling the phenotype of the group A saponins in each line was mapped near the simple sequence repeat marker Satt336 on soybean chromosome 7 (linkage group M). An allelism test of the A0-alpha g and deacetyl-Af variants revealed no segregation of Aa and Ab phenotypes in the progeny, although the genes controlling the two phenotypes have been assigned to two different loci, Sg-1 and Sg-2. These results suggest that the four group A saponin phenotypes are controlled by multiple alleles at the single locus Sg-1.	[Takada, Yoshitake] Natl Agr Res Ctr Western Reg, Kagawa 7658508, Japan; [Sayama, Takashi; Nakamoto, Yumi; Suzuki, Ayako; Ishimoto, Masao] Natl Agr Res Ctr Hokkaido Reg, Sapporo, Hokkaido 0628555, Japan; [Kikuchi, Akio; Kato, Shin] Natl Agr Res Ctr Tohoku Reg, Akita 0192112, Japan; [Tatsuzaki, Nana; Tsukamoto, Chigen] Iwate Univ, Grad Sch Agr, Morioka, Iwate 0208550, Japan		Takada, Y (corresponding author), Natl Agr Res Ctr Western Reg, 1-3-1 Senyuu, Kagawa 7658508, Japan.	yottake@affrc.go.jp			Ministry of Agriculture, Forestry and Fisheries of JapanMinistry of Agriculture Forestry & Fisheries - Japan [18063]	This work was supported by the Ministry of Agriculture, Forestry and Fisheries of Japan (Research Project for Utilizing Advanced Technologies in Agriculture, Forestry and Fisheries, 18063).	BURROWS JC, 1987, PHYTOCHEMISTRY, V26, P1214, DOI 10.1016/S0031-9422(00)82387-0; Cregan PB, 1999, CROP SCI, V39, P1464, DOI 10.2135/cropsci1999.3951464x; Ellington AA, 2006, CARCINOGENESIS, V27, P298, DOI 10.1093/carcin/bgi214; Ellington AA, 2005, CARCINOGENESIS, V26, P159, DOI 10.1093/carcin/bgh297; Hisano H, 2007, DNA RES, V14, P271, DOI 10.1093/dnares/dsm025; Hwang TY, 2009, DNA RES, V16, P213, DOI 10.1093/dnares/dsp010; Ishii Y, 2006, BIOL PHARM BULL, V29, P1759, DOI 10.1248/bpb.29.1759; Kato S., 2007, Bulletin of the National Agricultural Research Center for Tohoku Region, P29; Kikuchi A, 1999, BREEDING SCI, V49, P167, DOI 10.1270/jsbbs.49.167; KITAGAWA I, 1988, CHEM PHARM BULL, V36, P2819; KITAGAWA I, 1982, CHEM PHARM BULL, V30, P2294; Kosambi DD, 1943, ANN EUGENIC, V12, P172, DOI 10.1111/j.1469-1809.1943.tb02321.x; KUDOU S, 1992, BIOSCI BIOTECH BIOCH, V56, P142, DOI 10.1271/bbb.56.142; KUDOU S, 1993, BIOSCI BIOTECH BIOCH, V57, P546, DOI 10.1271/bbb.57.546; OKUBO K, 1992, BIOSCI BIOTECH BIOCH, V56, P99, DOI 10.1271/bbb.56.99; SHIMOYAMADA M, 1990, AGR BIOL CHEM TOKYO, V54, P77, DOI 10.1080/00021369.1990.10869887; SHIRAIWA M, 1990, AGR BIOL CHEM TOKYO, V54, P1347, DOI 10.1080/00021369.1990.10870134; SHIRAIWA M, 1991, AGR BIOL CHEM TOKYO, V55, P911, DOI 10.1080/00021369.1991.10870686; SHIRAIWA M, 1991, AGR BIOL CHEM TOKYO, V55, P315, DOI 10.1080/00021369.1991.10870574; Song QJ, 2004, THEOR APPL GENET, V109, P122, DOI 10.1007/s00122-004-1602-3; TANIYAMA T, 1988, CHEM PHARM BULL, V36, P2829; TOPPING DL, 1980, AM J CLIN NUTR, V33, P783, DOI 10.1093/ajcn/33.4.783; TSUKAMOTO C, 1992, PHYTOCHEMISTRY, V31, P4139, DOI 10.1016/0031-9422(92)80429-I; TSUKAMOTO C, 1993, PHYTOCHEMISTRY, V34, P1351, DOI 10.1016/0031-9422(91)80028-Y; Voorrips RE, 2002, J HERED, V93, P77, DOI 10.1093/jhered/93.1.77; Xia Z, 2007, DNA RES, V14, P257, DOI 10.1093/dnares/dsm027	26	25	28	1	13	JAPANESE SOC BREEDING	TOKYO	UNIV TOKYO, GRADUATE SCHOOL AGRICULTURAL LIFE SCIENCES, BUNKYO-KU, TOKYO, 113-8657, JAPAN	1344-7610	1347-3735		BREEDING SCI	Breed. Sci.	MAR	2010	60	1					3	8		10.1270/jsbbs.60.3			6	Agronomy; Plant Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Agriculture; Plant Sciences	590IS	WOS:000277219600002		Bronze			2022-04-25	
J	Wu, SH; Sun, CB; Tian, D; Li, YY; Gao, XQ; He, S; Li, TY				Wu, Shuhua; Sun, Chenbo; Tian, Dong; Li, Yangyang; Gao, Xiangqian; He, Shuang; Li, Tangyue			Expression and clinical significances of Beclin1, LC3 and mTOR in colorectal cancer	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY			English	Article						Colorectal cancer; Beclin1; LC3; mTOR; prognosis	DECREASED EXPRESSION; AUTOPHAGY; TUMORIGENESIS; PROGRESSION; PATTERNS; GABARAP; MARKER	Autophagy is related to cancer and other diseases, and compromised autophagy could promote chromosome instability associated with carcinogenesis and tumor progression. The role of autophagy in the growth and metastasis of colorectal cancer (CRC) remains poorly understood. Beclin1 mediates autophagic initiation, and LC3 is a specific marker for autophagy. Inactivation of mTOR caused by cellular hypoxia or energy deficiency induces autophagic activity. This study aims to examine the expression and clinical significance of these proteins in CRC. Immunohistochemistry results showed that the positive expression rates of Beclin1, LC3, and mTOR in cancer tissues were 90.50%, 87.19%, and 46.28%, respectively, which were higher than those in adjacent tissues (P < 0.05). Differentiation degree and lymph node metastasis were associated with LC3 overexpression (P < 0.05) but not with Beclin1 (P > 0.05). Lymph node metastasis was also related to mTOR. Spearman analysis results showed that LC3 expression was positively correlated with Beclin1 but negatively correlated with mTOR (r = 0.593 and -0.165, respectively; P < 0.01). Beclin1 expression was also not associated with mTOR (P > 0.05). Survival analysis further indicated that LC3, mTOR, and lymph node metastasis were independent prognostic factors in CRC. Real-time PCR results and Western blot indicated that Beclin1, LC3, and mTOR expression in CRC was significantly higher than that in adjacent tissues (P < 0.01). The aberrant protein expression may be associated with the development and progression of CRC. The LC3 and mTOR genes must be simultaneously detected to evaluate progression and prognosis of CRC.	[Wu, Shuhua; Sun, Chenbo] Binzhou Med Univ Hosp, Dept Pathol, Binzhou 256603, Shandong, Peoples R China; [Tian, Dong; Li, Yangyang; Gao, Xiangqian; He, Shuang; Li, Tangyue] Binzhou Med Univ, Dept Pathol, Binzhou, Shandong, Peoples R China		Wu, SH (corresponding author), Binzhou Med Univ Hosp, Dept Pathol, Binzhou 256603, Shandong, Peoples R China.	wsh6108@126.com; dongtianbz@163.com			Technology Development Project of Shandong Province [2010GSF10259]	This work was supported by Technology Development Project of Shandong Province (2010GSF10259). The authors thank Yuhong Zhu for technical assistance.	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J. Clin. Exp. Pathol.		2015	8	4					3882	3891					10	Oncology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pathology	CM5OP	WOS:000357737900046	26097572				2022-04-25	
J	Scott, AJ; Arcaroli, JJ; Bagby, SM; Yahn, R; Huber, KM; Serkova, NJ; Nguyen, A; Kim, J; Thorburn, A; Vogel, J; Quackenbush, KS; Capasso, A; Schreiber, A; Blatchford, P; Klauck, PJ; Pitts, TM; Eckhardt, SG; Messersmith, WA				Scott, Aaron J.; Arcaroli, John J.; Bagby, Stacey M.; Yahn, Rachel; Huber, Kendra M.; Serkova, Natalie J.; Nguyen, Anna; Kim, Jihye; Thorburn, Andrew; Vogel, Jon; Quackenbush, Kevin S.; Capasso, Anna; Schreiber, Anna; Blatchford, Patrick; Klauck, Peter J.; Pitts, Todd M.; Eckhardt, S. Gail; Messersmith, Wells A.			Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms	MOLECULAR CANCER THERAPEUTICS			English	Article							HEPATOCYTE GROWTH-FACTOR; CONTRAST-ENHANCED MRI; C-MET; INHIBITION; METASTASIS; PATHWAYS; INVASION; THERAPY; KINASE; TARGET	Antiangiogenic therapy used in treatment of metastatic colorectal cancer (mCRC) inevitably succumbs to treatment resistance. Upregulation of MET may play an essential role to acquired anti-VEGF resistance. We previously reported that cabozantinib (XL184), an inhibitor of receptor tyrosine kinases (RTK) including MET, AXL, and VEGFR2, had potent antitumor effects in mCRC patient-derived tumor explant models. In this study, we examined the mechanisms of cabozantinib sensitivity, using regorafenib as a control. The tumor growth inhibition index (TGII) was used to compare treatment effects of cabozantinib 30 mg/kg daily versus regorafenib 10 mg/kg daily for a maximum of 28 days in 10 PDX mouse models. In vivo angiogenesis and glucose uptake were assessed using dynamic contrast-enhanced (DCE)-MRI and [F-18]-FDG-PET imaging, respectively. RNA-Seq, RTK assay, and immunoblotting analysis were used to evaluate gene pathway regulation in vivo and in vitro. Analysis of TGII demonstrated significant antitumor effects with cabozantinib compared with regorafenib (average TGII 3.202 vs. 48.48, respectively; P = 0.007). Cabozantinib significantly reduced vascularity and glucose uptake compared with baseline. Gene pathway analysis showed that cabozantinib significantly decreased protein activity involved in glycolysis and upregulated proteins involved in autophagy compared with control, whereas regorafenib did not. The combination of two separate anti-autophagy agents, SBI-0206965 and chloroquine, plus cabozantinib increased apoptosis in vitro. Cabozantinib demonstrated significant antitumor activity, reduction in tumor vascularity, increased autophagy, and altered cell metabolism compared with regorafenib. Our findings support further evaluation of cabozantinib and combinational approaches targeting autophagy in colorectal cancer. (C) 2018 AACR.	[Scott, Aaron J.] Banner Univ Arizona, Canc Ctr, Div Hematol & Oncol, Tucson, AZ USA; [Arcaroli, John J.; Bagby, Stacey M.; Yahn, Rachel; Nguyen, Anna; Kim, Jihye; Quackenbush, Kevin S.; Capasso, Anna; Schreiber, Anna; Blatchford, Patrick; Klauck, Peter J.; Pitts, Todd M.; Messersmith, Wells A.] Univ Colorado, Div Med Oncol, Anschutz Med Campus, Aurora, CO USA; [Arcaroli, John J.; Bagby, Stacey M.; Yahn, Rachel; Huber, Kendra M.; Serkova, Natalie J.; Nguyen, Anna; Kim, Jihye; Thorburn, Andrew; Vogel, Jon; Quackenbush, Kevin S.; Capasso, Anna; Schreiber, Anna; Blatchford, Patrick; Klauck, Peter J.; Pitts, Todd M.; Messersmith, Wells A.] Univ Colorado, Canc Ctr, Aurora, CO USA; [Huber, Kendra M.; Serkova, Natalie J.] Univ Colorado, Dept Anesthesia, Anschutz Med Campus, Aurora, CO USA; [Thorburn, Andrew] Univ Colorado, Dept Pharmacol, Anschutz Med Campus, Aurora, CO USA; [Vogel, Jon] Univ Colorado, Dept Surg, Anschutz Med Campus, Aurora, CO USA; [Eckhardt, S. Gail] Univ Texas Austin, Div Med Oncol, Austin, TX 78712 USA; [Eckhardt, S. Gail] Univ Texas Austin, Dell Med Sch, Dept Oncol, Austin, TX 78712 USA; [Eckhardt, S. Gail] Univ Texas Austin, Dell Med Sch, Canc Programs, Austin, TX 78712 USA		Scott, AJ (corresponding author), Banner Univ Arizona, Ctr Canc, 1501 N Campbell Ave,Rm 1916, Tucson, AZ 85724 USA.	ajscott@email.arizona.edu		Yahn, Rachel/0000-0001-8848-3593	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01CA152303-01]; University of Colorado Cancer Center Shared Resource [P30CA046934]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA152303, P30CA046934] Funding Source: NIH RePORTER	This work was supported by the NIH (1R01CA152303-01; to W.A. Messersmith) and the University of Colorado Cancer Center Shared Resource (P30CA046934; to W.A. Messersmith). Support was also received by Exelixis (to T.M. Pitts). We also thank the patients who consented to allow their tumor tissue to be used in these experiments.	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Cancer Ther.	OCT	2018	17	10					2112	2122		10.1158/1535-7163.MCT-17-0131			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HI0QA	WOS:000456145700004	30026382	Green Accepted			2022-04-25	
J	Chen, PJ; Luo, XY; Nie, PP; Wu, BY; Xu, W; Shi, XP; Chang, HC; Li, B; Yu, XR; Zou, ZZ				Chen, Pinjia; Luo, Xiaoyong; Nie, Peipei; Wu, Baoyan; Xu, Wei; Shi, Xinpeng; Chang, Haocai; Li, Bing; Yu, Xiurong; Zou, Zhengzhi			CQ synergistically sensitizes human colorectal cancer cells to SN-38/CPT-11 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk	FREE RADICAL BIOLOGY AND MEDICINE			English	Article						Chloroquine; SN-38; P53; ROS; Apoptosis; Colorectal cancer	ROS-MEDIATED MECHANISMS; PHASE-II TRIAL; OXIDATIVE STRESS; MEMBRANE PERMEABILIZATION; ANTIOXIDANT FUNCTION; P53 MUTATIONS; INHIBITION; AUTOPHAGY; IRINOTECAN; CHLOROQUINE	Autophagy plays a key role in supporting cell survival against chemotherapy-induced apoptosis. In this study, we found the chemotherapy agent SN-38 induced autophagy in colorectal cancer (CRC) cells. However, inhibition of autophagy using a small molecular inhibitor 3-methyladenine (3-MA) and ATG5 siRNA did not increase SN-38induced cytotoxicity in CRC cells. Notably, another autophagy inhibitor chloroquine (CQ) synergistically enhanced the anti-tumor activity of SN-38 in CRC cells with wild type (WT) p53. Subsequently, we identified a potential mechanism of this cooperative interaction by showing that CQ and SN-38 acted together to trigger reactive oxygen species (ROS) burst, upregulate p53 expression, elicit the loss of lysosomal membrane potential (LMP) and mitochondrial membrane potential (Aym). In addition, ROS induced by CQ plus SN-38 upregulated p53 levels by activating p38, conversely, p53 stimulated ROS. These results suggested that ROS and p53 reciprocally promoted each other's production and cooperated to induce CRC cell death. Moreover, we showed induction of ROS and p53 by the two agents provoked the loss of LMP and AWm. Altogether, all results suggested that CQ synergistically sensitized human CRC cells with WT p53 to SN-38 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk. Lastly, we showed that CQ could enhance CRC cells response to CPT 11 (a prodrug of SN-38) in xenograft models. Thus the combined treatment might represent an attractive therapeutic strategy for the treatment of CRC.	[Chen, Pinjia; Luo, Xiaoyong; Shi, Xinpeng; Li, Bing; Yu, Xiurong] Zhengzhou Univ, Dept Oncol, Affiliated Luoyang Cent Hosp, Luoyang, Peoples R China; [Nie, Peipei; Xu, Wei] Guangzhou Med Univ, KingMed Diagnost & KingMed Sch Lab Med, Guangzhou, Guangdong, Peoples R China; [Wu, Baoyan; Chang, Haocai; Zou, Zhengzhi] South China Normal Univ, MOE Key Lab Laser Life Sci, Joint Lab Laser Oncol, Canc Ctr,Sun Yat Sen Univ,Coll Biophoton, 55 Zhongshan Rd West, Guangzhou, Guangdong, Peoples R China; [Wu, Baoyan; Chang, Haocai; Zou, Zhengzhi] South China Normal Univ, Inst Laser Life Sci, Joint Lab Laser Oncol, Canc Ctr,Sun Yat Sen Univ,Coll Biophoton, 55 Zhongshan Rd West, Guangzhou, Guangdong, Peoples R China		Zou, ZZ (corresponding author), South China Normal Univ, MOE Key Lab Laser Life Sci, Joint Lab Laser Oncol, Canc Ctr,Sun Yat Sen Univ,Coll Biophoton, 55 Zhongshan Rd West, Guangzhou, Guangdong, Peoples R China.; Zou, ZZ (corresponding author), South China Normal Univ, Inst Laser Life Sci, Joint Lab Laser Oncol, Canc Ctr,Sun Yat Sen Univ,Coll Biophoton, 55 Zhongshan Rd West, Guangzhou, Guangdong, Peoples R China.	zouzhengzhi@m.scnu.edu.cn	bin, li/AAK-6880-2020		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402187, 81371646]; Ph.D Start-up Fund of Natural Science Foundation of Guangdong Province [2014A030310505]; Foundation for Distinguished Young Talents in Higher Education of Guangdong [C1085229]	This study was supported by grants from the National Natural Science Foundation of China (Nos. 81402187 and 81371646), the Ph.D Start-up Fund of Natural Science Foundation of Guangdong Province (No. 2014A030310505 to Z. Zou), the Foundation for Distinguished Young Talents in Higher Education of Guangdong (No. C1085229 to Z. Zou).	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Biol. Med.	MAR	2017	104						280	297		10.1016/j.freeradbiomed.2017.01.033			18	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	EN4HJ	WOS:000395968300023	28131902				2022-04-25	
J	Shyu, RY; Wang, CH; Wu, CC; Chen, ML; Lee, MC; Wang, LK; Jiang, SY; Tsai, FM				Shyu, Rong-Yaun; Wang, Chun-Hua; Wu, Chang-Chieh; Chen, Mao-Liang; Lee, Ming-Cheng; Wang, Lu-Kai; Jiang, Shun-Yuan; Tsai, Fu-Ming			Tazarotene-Induced Gene 1 Enhanced Cervical Cell Autophagy through Transmembrane Protein 192	MOLECULES AND CELLS			English	Article						all-trans retinoic acid; autophagy; Beclin-1; LC3B; tazarotene-induced gene 1; transmembrane protein 192	RETINOID RESPONSE GENE; ACID RECEPTOR-BETA; NASOPHARYNGEAL CARCINOMA; TUMOR-SUPPRESSOR; PROMOTER HYPERMETHYLATION; LYSOSOMAL MEMBRANE; DNA METHYLATION; TIG1; DIFFERENTIATION; BECLIN-1	Tazarotene-induced gene 1 (TIG1) is a retinoic acid-inducible protein that is considered a putative tumor suppressor. The expression of TIG1 is decreased in malignant prostate carcinoma or poorly differentiated colorectal adenocarcinoma, but TIG1 is present in benign or well-differentiated tumors. Ectopic TIG1 expression led to suppression of growth in cancer cells. However, the function of TIG1 in cell differentiation is still unknown. Using a yeast two-hybrid system, we found that transmembrane protein 192 (TMEM192) interacted with TIG1. We also found that both TIG1A and TIG1B isoforms interacted and co-localized with TMEM192 in HtTA cervical cancer cells. The expression of TIG1 induced the expression of autophagy-related proteins, including Beclin-1 and LC-3B. The silencing of TMEM192 reduced the TIG1-mediated upregulation of autophagic activity. Furthermore, silencing of either TIG1 or TMEM192 led to alleviation of the upregulation of autophagy induced by all-trans retinoic acid. Our results demonstrate that the expression of TIG1 leads to cell autophagy through TMEM192. Our study also suggests that TIG1 and TMEM192 play an important role in the all-trans retinoic acid-mediated upregulation of autophagic activity.	[Shyu, Rong-Yaun] Buddhist Tzuchi Med Fdn, Taipei Tzuchi Hosp, Dept Internal Med, New Taipei 231, Taiwan; [Wang, Chun-Hua] Buddhist Tzuchi Med Fdn, Taipei Tzuchi Hosp, Dept Dermatol, New Taipei 231, Taiwan; [Wu, Chang-Chieh] Natl Def Med Ctr, Triserv Gen Hosp, Dept Surg, Taipei 114, Taiwan; [Chen, Mao-Liang; Lee, Ming-Cheng; Jiang, Shun-Yuan; Tsai, Fu-Ming] Buddhist Tzuchi Med Fdn, Taipei Tzuchi Hosp, Dept Res, New Taipei 231, Taiwan; [Wang, Lu-Kai] Chang Gung Univ, Chang Gung Mem Hosp, Inst Radiol Res, Radiat Biol Core Lab, Taoyuan 333, Taiwan		Jiang, SY; Tsai, FM (corresponding author), Buddhist Tzuchi Med Fdn, Taipei Tzuchi Hosp, Dept Res, New Taipei 231, Taiwan.	jiang.shunyuan@gmail.com; afu2215@gmail.com	Chen, Mao-Liang/AAH-1283-2019	Tsai, Fu-Ming/0000-0002-4563-0458	Taipei Tzuchi Hospital through Buddhist Tzuchi Medical Foundation, Taipei, Taiwan [TCRD-TPE-105-17]; Core Laboratory of the Buddhist Tzuchi General Hospital	This work was supported by a grant (TCRD-TPE-105-17) from the Taipei Tzuchi Hospital through the Buddhist Tzuchi Medical Foundation, Taipei, Taiwan. The authors thank the Core Laboratory of the Buddhist Tzuchi General Hospital for support.	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Cells	DEC 31	2016	39	12					877	887		10.14348/molcells.2016.0161			11	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	EJ4IE	WOS:000393179300006	27989102	Green Published, Green Submitted, hybrid			2022-04-25	
J	Abdel-Aziz, AK; Azab, SSE; Youssef, SS; El-Sayed, AM; El-Demerdash, E; Shouman, S				Abdel-Aziz, Amal Kamal; Azab, Samar Saad Eldeen; Youssef, Samar Samir; El-Sayed, Abeer Mostafa; El-Demerdash, Ebtehal; Shouman, Samia			Modulation of Imatinib Cytotoxicity by Selenite in HCT116 Colorectal Cancer Cells	BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY			English	Article							GASTROINTESTINAL STROMAL TUMOR; KINASE INHIBITOR STI571; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; SODIUM SELENITE; AUTOPHAGY INHIBITION; GROWTH-INHIBITION; APOPTOSIS; ACTIVATION; MECHANISMS	Imatinib is a principal therapeutic agent for targeting colorectal tumours. However, mono-targeting by imatinib does not always achieve complete cancer eradication. Selenite, a well-known chemopreventive agent, is commonly used in cancer patients. In this study, we aimed to explore whether selenite can modulate imatinib cytotoxicity in colorectal cancer cells. HCT116 cells were treated with different concentrations of imatinib and/or selenite for 24, 48 and 72hr. Imatinib-selenite interaction was analysed using isobologram equation. As indicators of apoptosis, DNA fragmentation, caspase-3 activity, Bcl-2 expression were explored. Autophagic machinery was also checked by visualizing acidic vesicular organelles and measuring Beclin-1 expression. Furthermore, reactive oxygen and nitrogen species were also examined. This study demonstrated that selenite synergistically augmented imatinib cytotoxicity in HCT116 cells as demonstrated by combination and dose reduction indices. Supranutritional dose of selenite when combined with imatinib induced apoptotic machinery by decreasing Bcl-2 expression, increasing caspase-3 activity and subsequently fragmenting DNA and blunted cytoprotective autophagy by decreasing Beclin-1 expression and autophagosomes formation. Moreover, their combination induced cell cycle S-phase block, increased total thiol content and reduced nitric oxide levels. In conclusion, selenite synergizes imatinib cytotoxicity through multi-barrelled molecular targeting, providing a novel therapeutic approach for colorectal cancer.	[Abdel-Aziz, Amal Kamal; Azab, Samar Saad Eldeen; El-Demerdash, Ebtehal] Ain Shams Univ, Pharmacol & Toxicol Dept, Fac Pharm, Cairo, Egypt; [Youssef, Samar Samir] Natl Res Ctr, Microbial Biotechnol Dept, Cairo, Egypt; [El-Sayed, Abeer Mostafa] Cairo Univ, Natl Canc Inst, Dept Pathol, Tissue Culture & Cytogenet Unit, Cairo 11796, Egypt; [Shouman, Samia] Cairo Univ, Natl Canc Inst, Dept Canc Biol, Cairo 11796, Egypt		Shouman, S (corresponding author), Cairo Univ, Natl Canc Inst, Dept Canc Biol, Kasr Alani St, Cairo 11796, Egypt.	samiasshouman@yahoo.com	Abdel-Aziz, Amal Kamal/AAA-1360-2021; El-Demerdash, Ebtehal/ABE-6729-2020; Abdel-Aziz, Amal Kamal/AAB-9050-2019; Elsayed, Abeer Mostafa/I-5973-2019; shouman, samia/F-5395-2018	Abdel-Aziz, Amal Kamal/0000-0003-1709-1183; Elsayed, Abeer Mostafa/0000-0002-8135-8025; shouman, samia/0000-0002-2883-8775; Youssef, Samar/0000-0001-7114-4325; Azab, Samar/0000-0002-0253-8280			Arthur CR, 2007, BIOCHEM PHARMACOL, V74, P981, DOI 10.1016/j.bcp.2007.07.003; Attoub S, 2002, CANCER RES, V62, P4879; Blagosklonny MV, 2005, CELL CYCLE, V4, P269, DOI 10.4161/cc.4.2.1493; Brozmanova J, 2010, ARCH TOXICOL, V84, P919, DOI 10.1007/s00204-010-0595-8; Cao TM, 2006, ANN HEMATOL, V85, P434, DOI 10.1007/s00277-005-0046-4; Chou TC, 2006, PHARMACOL REV, V58, P621, DOI 10.1124/pr.58.3.10; Cianchi F, 2004, CLIN CANCER RES, V10, P2694, DOI 10.1158/1078-0432.CCR-03-0192; Connelly-Frost A, 2009, NUTR CANCER, V61, P165, DOI 10.1080/01635580802404188; Crowley LC, 2013, ONCOL REP, V29, P2261, DOI 10.3892/or.2013.2377; ELLMAN GL, 1959, ARCH BIOCHEM BIOPHYS, V82, P70, DOI 10.1016/0003-9861(59)90090-6; Ertmer A, 2007, LEUKEMIA, V21, P936, DOI 10.1038/sj.leu.2404606; Fang WF, 2010, INT J CANCER, V127, P32, DOI 10.1002/ijc.25029; Gajiwala KS, 2009, P NATL ACAD SCI USA, V106, P1542, DOI 10.1073/pnas.0812413106; Gallegos A, 1997, CANCER RES, V57, P4965; Gottesman MM, 2002, ANNU REV MED, V53, P615, DOI 10.1146/annurev.med.53.082901.103929; Gupta A, 2010, P NATL ACAD SCI USA, V107, P14333, DOI 10.1073/pnas.1000248107; Guruswamy S, 2008, GENE REGUL SYST BIO, V2, P163; Hamai A, 2006, ONCOGENE, V25, P7618, DOI 10.1038/sj.onc.1209738; Huang F, 2009, FREE RADICAL BIO MED, V46, P1186, DOI 10.1016/j.freeradbiomed.2009.01.026; Huguet F, 2008, MOL CANCER THER, V7, P398, DOI 10.1158/1535-7163.MCT-07-2023; Hwang YY, 2009, AM J HEMATOL, V84, P302, DOI 10.1002/ajh.21383; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Jiang Q, 2012, BMB REP, V45, P194, DOI 10.5483/BMBRep.2012.45.3.194; Joensuu H, 2001, NEW ENGL J MED, V344, P1052, DOI 10.1056/NEJM200104053441404; Karsa LV, 2010, BEST PRACT RES CL GA, V24, P381, DOI 10.1016/j.bpg.2010.06.004; KiremidjianSchumacher L, 1996, BIOL TRACE ELEM RES, V52, P227, DOI 10.1007/BF02789164; Koukourakis MI, 2010, BRIT J CANCER, V103, P1209, DOI 10.1038/sj.bjc.6605904; Kralova V, 2012, TOXICOL IN VITRO, V26, P258, DOI 10.1016/j.tiv.2011.12.010; Kralova V, 2009, TOXICOL IN VITRO, V23, P1497, DOI 10.1016/j.tiv.2009.07.012; Kwee JK, 2008, ANTI-CANCER DRUG, V19, P975, DOI 10.1097/CAD.0b013e3283140c6f; Luo HY, 2012, COLLOID SURFACE B, V94, P304, DOI 10.1016/j.colsurfb.2012.02.006; Luo H, 2012, CANCER LETT, V315, P78, DOI 10.1016/j.canlet.2011.10.014; Mahon FX, 2000, BLOOD, V96, P1070, DOI 10.1182/blood.V96.3.1070.015k17_1070_1079; Maiuri MC, 2007, NAT REV MOL CELL BIO, V8, P741, DOI 10.1038/nrm2239; Miranda KM, 2001, NITRIC OXIDE-BIOL CH, V5, P62, DOI 10.1006/niox.2000.0319; NICHOLSON DW, 1995, NATURE, V376, P37, DOI 10.1038/376037a0; Okano M, 2014, J PEDIAT HEMATOL ONC, V36, P200, DOI 10.1097/MPH.0000000000000038; Pagmantidis V, 2008, AM J CLIN NUTR, V87, P181, DOI 10.1093/ajcn/87.1.181; Park J, 2005, BIOCHEM BIOPH RES CO, V336, P942, DOI 10.1016/j.bbrc.2005.08.201; Park SH, 2012, TOXICOL LETT, V212, P252, DOI 10.1016/j.toxlet.2012.06.007; Ren Y, 2009, BMB REP, V42, P599, DOI 10.5483/BMBRep.2009.42.9.599; Rikiishi H, 2007, J BIOENERG BIOMEMBR, V39, P91, DOI 10.1007/s10863-006-9065-7; Rubin BP, 2010, AUTOPHAGY, V6, P1190, DOI 10.4161/auto.6.8.13430; Rumjanek VM, 2013, BIOSCIENCE REP, V33, P875, DOI 10.1042/BSR20130067; Schroeder CP, 2004, BIOL TRACE ELEM RES, V99, P17, DOI 10.1385/BTER:99:1-3:017; Sharma PS, 2009, CURR PHARM DESIGN, V15, P758, DOI 10.2174/138161209787582219; SKEHAN P, 1990, J NATL CANCER I, V82, P1107, DOI 10.1093/jnci/82.13.1107; Tsuchihara K, 2009, CANCER LETT, V278, P130, DOI 10.1016/j.canlet.2008.09.040; Tsujimoto Y, 2005, CELL DEATH DIFFER, V12, P1528, DOI 10.1038/sj.cdd.4401777; Wang WL, 2000, ONCOGENE, V19, P3521, DOI 10.1038/sj.onc.1203698	50	13	13	0	4	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1742-7835	1742-7843		BASIC CLIN PHARMACOL	Basic Clin. Pharmacol. Toxicol.	JAN	2015	116	1					37	46		10.1111/bcpt.12281			10	Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy; Toxicology	AX4OH	WOS:000346911100007	24930392				2022-04-25	
J	Zhu, RZ; Yang, G; Cao, Z; Shen, KX; Zheng, LF; Xiao, JC; You, L; Zhang, TP				Zhu, Ruizhe; Yang, Gang; Cao, Zhe; Shen, Kexin; Zheng, Lianfang; Xiao, Jianchun; You, Lei; Zhang, Taiping			The prospect of serum and glucocorticoid-inducible kinase 1 (SGK1) in cancer therapy: a rising star	THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY			English	Review						autophagy; calcium signaling; chemoresistance; immunoregulation; PI3K signaling; SGK1; therapeutic target	REGULATORY T-CELLS; PROTEIN-KINASE; BREAST-CANCER; PRECLINICAL MODEL; DOWN-REGULATION; POOR-PROGNOSIS; OVARIAN-CANCER; LUNG-CANCER; ER STRESS; INHIBITOR	Serum and glucocorticoid-inducible kinase 1 (SGK1) is an AGC kinase that has been reported to be involved in a variety of physiological and pathological processes. Recent evidence has accumulated that SGK1 acts as an essential Akt-independent mediator of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway in cancer. SGK1 is overexpressed in several tumors, including prostate cancer, colorectal carcinoma, glioblastoma, breast cancer, and endometrial cancer. The functions of SGK1 include regulating tumor growth, survival, metastasis, autophagy, immunoregulation, calcium (Ca2+) signaling, cancer stem cells, cell cycle, and therapeutic resistance. In this review, we introduce the pleiotropic role of SGK1 in the development and progression of tumors, summarize its downstream targets, and integrate the knowledge provided by preclinical studies that the prospect of SGK1 inhibition as a potential therapeutic approach.	[Zhu, Ruizhe; Yang, Gang; Cao, Zhe; Shen, Kexin; Xiao, Jianchun; You, Lei; Zhang, Taiping] Chinese Acad Med Sci & Peking Union Med Coll, Dept Gen Surg, Peking Union Med Coll Hosp, 1 Shuaifuyuan, Beijing 100730, Peoples R China; [Zheng, Lianfang] Chinese Acad Med Sci & Peking Union Med Coll, Dept Nucl Med, Peking Union Med Coll Hosp, Beijing, Peoples R China		Zhang, TP (corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, Dept Gen Surg, Peking Union Med Coll Hosp, 1 Shuaifuyuan, Beijing 100730, Peoples R China.	tpingzhang@yahoo.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772639, 81802475, 81972258, 81974376]; Natural Science Foundation of BeijingBeijing Natural Science Foundation [7192157]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [198831]; National Key R&D Program of China [2018YFE0118600]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019XK320001]	The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by grants from the National Natural Science Foundation of China (No. 81772639; 81802475; 81972258; 81974376); Natural Science Foundation of Beijing (No. 7192157); CAMS Innovation Fund for Medical Sciences (CIFMS) (No.2016-I2M-1-001); China Postdoctoral Science Foundation (No.198831); National Key R&D Program of China (2018YFE0118600); Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019XK320001).	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Adv. Med. Oncol.	JUL	2020	12								1758835920940946	10.1177/1758835920940946			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	MR7XR	WOS:000553805200001	32728395	Green Published, gold			2022-04-25	
J	Wang, H; Maurer, BJ; Liu, YY; Wang, E; Allegood, JC; Kelly, S; Symolon, H; Liu, Y; Merrill, AH; Gouaze-Andersson, V; Yu, JY; Giuliano, AE; Cabot, MC				Wang, Hongtao; Maurer, Barry J.; Liu, Yong-Yu; Wang, Elaine; Allegood, Jeremy C.; Kelly, Samuel; Symolon, Holly; Liu, Ying; Merrill, Alfred H., Jr.; Gouaze-Andersson, Valerie; Yu, Jing Yuan; Giuliano, Armando E.; Cabot, Myles C.			N-(4-hydroxyphenyl)retinamide increases dihydroceramide and synergizes with dimethylsphingosine to enhance cancer cell	MOLECULAR CANCER THERAPEUTICS			English	Article							FENRETINIDE-INDUCED APOPTOSIS; PHASE-I TRIAL; MULTIDRUG-RESISTANCE; SPHINGOID BASES; FUMONISIN B-1; CERAMIDE; LINES; AUTOPHAGY; NEUROBLASTOMA; CYTOTOXICITY	Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is cytotoxic in many cancer cell types. Studies have shown that elevation of ceramide species plays a role in 4-HPR cytotoxicity. To determine 4-HPR activity in a multidrug-resistant cancer cell line as well as to study ceramide metabolism, MCF-7/AdrR cells (redesignated NCI/ADR-RES) were treated with 4-HPR and sphingolipids were analyzed. TLC analysis of cells radiolabeled with [(3) H]palmitic acid showed that 4-HPR elicited a dose-responsive increase in radioactivity migrating in the ceramide region of the chromatogram and a decrease in cell viability. Results from liquid chromatography/electrospray tandem mass spectrometry revealed large elevations in dihydroceramides (N-acylsphinganines), but not desaturated ceramides, and large increases in complex dihydrosphingolipids (dihydrosphingomyelins, monohexosyldihydroceramides), sphinganine, and sphinganine 1-phosphate. To test the hypothesis that elevation of sphinganine participates in the cytotoxicity of 4-HPR, cells were treated with the sphingosine kinase inhibitor D-erythro-N,N-dimethylsphingosine (DMS), with and without 4-HPR. After 24 h, the 4-HPR/DMS combination caused a 9-fold increase in sphinganine that was sustained through + 48 hours, decreased sphinganine 1-phosphate, and increased cytotoxicity. Increased dihydrosphingolipids and sphinganine were also found in HL-60 leukemia cells and HT-29 colon cancer cells treated with 4-HPR. The 4-HPR/DMS combination elicited increased apoptosis in all three cell lines. We propose that a mechanism of 4-HPR-induced cytotoxicity involves increases in dihydrosphingolipids, and that the synergy between 4-HPR and DMS is associated with large increases in cellular sphinganine. These studies suggest that enhanced clinical efficacy of 4-HPR may be realized through regimens containing agents that modulate sphingoid base metabolism.	[Wang, Hongtao; Maurer, Barry J.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA USA; [Liu, Yong-Yu] Univ Louisiana Monroe, Coll Pharm, Monroe, LA USA; [Wang, Elaine; Allegood, Jeremy C.; Kelly, Samuel; Symolon, Holly; Liu, Ying; Merrill, Alfred H., Jr.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA; [Wang, Elaine; Allegood, Jeremy C.; Kelly, Samuel; Symolon, Holly; Liu, Ying; Merrill, Alfred H., Jr.] Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA; [Gouaze-Andersson, Valerie; Yu, Jing Yuan; Giuliano, Armando E.; Cabot, Myles C.] St Johns Hlth Ctr, John Wayne Canc Inst, Gonda Goldschmied Res Labs, Santa Monica, CA USA		Merrill, AH (corresponding author), Georgia Tech Res Inst, Sch Biol, Atlanta, GA 30332 USA.	al.merrill@biology.gatech.edu; cabot@jwci.org	Liu, Yong-Yu/H-8593-2014; Gouaze-Andersson, Valerie/O-9180-2014	Gouaze-Andersson, Valerie/0000-0002-1797-515X; Merrill, Alfred/0000-0002-6673-968X; Liu, Yong-Yu/0000-0002-7968-0162	USPHSUnited States Department of Health & Human ServicesUnited States Public Health Service [GM77391, CA95339, CA87525, GM69338]; Department of the Army DAMD [17-99-1-9228, 04-1-0491]; Susan G. Komen Breast Cancer FoundationSusan G. Komen Breast Cancer Foundation [BCTR0402450]; Ben B. and Joyce E. Eisenberg Foundation (Los Angeles, CA); Fashion Footwear Association of New York Charitable Foundation (New York, NY); Avon Foundation (New York, NY); Association for Breast and Prostate Cancer Studies (Santa Monica, CA); Sandra Krause and William Fitzgerald (Los Angeles, CA); NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R21CA095339, U19CA087525] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM077391, U54GM069338] Funding Source: NIH RePORTER	USPHS Grants GM77391, CA95339, CA87525 and GM69338 (LIPID MAPS); Department of the Army DAMD 17-99-1-9228 (Postdoctoral Traineeship in Breast Cancer Research, to H.W.); Department of the Army DAMD 04-1-0491 (Postdoctoral Traineeship in Breast Cancer Research, to VG-A); The Susan G. Komen Breast Cancer Foundation, grant number BCTR0402450, and by funding from the Ben B. and Joyce E. Eisenberg Foundation (Los Angeles, CA), the Fashion Footwear Association of New York Charitable Foundation (New York, NY), Avon Foundation (New York, NY), the Association for Breast and Prostate Cancer Studies (Santa Monica, CA), Sandra Krause and William Fitzgerald (Los Angeles, CA).	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Cancer Ther.	SEP	2008	7	9					2967	2976		10.1158/1535-7163.MCT-08-0549			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	350XP	WOS:000259387300038	18790777				2022-04-25	
J	Nishio, T; Kurabe, N; Goto-Inoue, N; Nakamura, T; Sugimura, H; Setou, M; Maekawa, M				Nishio, Tomohisa; Kurabe, Nobuya; Goto-Inoue, Naoko; Nakamura, Toshio; Sugimura, Haruhiko; Setou, Mitsutoshi; Maekawa, Masato			Immunohistochemical expression analysis of leucine-rich PPR-motif-containing protein (LRPPRC), a candidate colorectal cancer biomarker identified by shotgun proteomics using iTRAQ	CLINICA CHIMICA ACTA			English	Article						Colorectal cancer; iTRAQ; LRPPRC; Immunohistochemistry; Differentiation	BREAST-CANCER; APOPTOSIS; AUTOPHAGY; CELLS; TAGS	Background: Colorectal cancer (CRC) is the fourth most frequent cause of cancer deaths in the world. Novel biomarkers for the diagnosis, prognosis, and treatment of CRC are required to improve the clinical strategy. Methods: We applied shotgun proteomics using isobaric tags for relative and absolute quantitation (iTRAQ) to identify novel biomarkers of CRC, and then we detected leucine-rich PPR-motif-containing protein (LRPPRC) expression in 83 normal colorectal tissues and 133 CRC tissues by immunohistochemistry. Results: A total of 570 proteins were identified using iTRAQ. We validated the expression of LRPPRC protein by immunohistochemical analysis of the 77 proteins that showed expression changes in the cancer tissues > 1.5 fold the levels in the normal tissues. The expression levels of LRPPRC were significantly higher in CRC tissues than those in normal colorectal tissues, and the expression levels were related with tumor differentiation and especially high in moderately differentiated CRC tissues. Conclusion: We identified a novel, differentially expressed protein, LRPPRC, which has the potential to serve as a molecular target for diagnosis and/or prognosis of CRC.	[Nishio, Tomohisa; Maekawa, Masato] Hamamatsu Univ Sch Med, Dept Lab Med, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan; [Nishio, Tomohisa; Goto-Inoue, Naoko; Setou, Mitsutoshi] Hamamatsu Univ Sch Med, Dept Cell Biol & Anat, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan; [Nishio, Tomohisa] Sekisui Med Co Ltd, Tsukuba Res Inst, 3-3-1 Kouyoudai, Ryugasaki 3010852, Japan; [Kurabe, Nobuya; Sugimura, Haruhiko] Hamamatsu Univ Sch Med, Dept Tumor Pathol, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan; [Nakamura, Toshio] Hamamatsu Univ Sch Med, Dept Surg 2, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan; [Nakamura, Toshio] Fujieda Municipal Gen Hosp, Dept Surg, 4-1-11 Surugadai, Fujieda, Shizuoka 4268677, Japan		Maekawa, M (corresponding author), Hamamatsu Univ Sch Med, Dept Lab Med, Hamamatsu, Shizuoka 4313192, Japan.	mmaekawa@hama-med.ac.jp		Maekawa, Masato/0000-0001-9710-5324	Ministry of Education, Science, Sports, Culture and Technology (MEXT) of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [23659295]; Ministry of Health, Labour and Welfare, JapanMinistry of Health, Labour and Welfare, Japan [19-19,10103838]; MEXTMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [S-001]; MEXT/JSPS KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [JP15H05898B1]; National Cancer Center Research and Development FundNational Cancer Center - Japan [28A-1]; Center of Innovation Program of JST; MEXTMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Smoking Research Foundation; Grants-in-Aid for Scientific ResearchMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [15H05898, 15H05897] Funding Source: KAKEN	This work was supported in part by a Grant-in-Aid for Challenging Exploratory Research (No. 23659295) from the Ministry of Education, Science, Sports, Culture and Technology (MEXT) of Japan and grants from the Ministry of Health, Labour and Welfare, Japan (19-19,10103838), MEXT (S-001), MEXT/JSPS KAKENHI (JP15H05898B1), the National Cancer Center Research and Development Fund (28A-1), the Center of Innovation Program of JST, MEXT, and the Smoking Research Foundation.	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Chim. Acta	AUG	2017	471						276	282		10.1016/j.cca.2017.06.011			7	Medical Laboratory Technology	Science Citation Index Expanded (SCI-EXPANDED)	Medical Laboratory Technology	FD2ZK	WOS:000407403100045	28622966	Green Submitted			2022-04-25	
J	Wang, LP; Yun, L; Wang, XJ; Sha, LY; Wang, LN; Sui, YY; Zhang, H				Wang, Luping; Yun, Lu; Wang, Xiaojun; Sha, Liying; Wang, Luning; Sui, Yingying; Zhang, Hui			RETRACTED: Endoplasmic reticulum stress triggered by Soyasapogenol B promotes apoptosis and autophagy in colorectal cancer (Retracted article. See vol. 254, 2020)	LIFE SCIENCES			English	Article; Retracted Publication						Soy B; Colorectal cancer; Endoplasmic reticulum stress; Apoptosis; Autophagy	SOYASAPONINS; CELLS; PREVENTION; IV	Aim: Colorectal cancer (CRC) is a common human malignancy which accounts for 600,000 deaths annually at the global level. Soyasapogenol B (Soy B), an ingredient of soybean, has been found to exert anti-proliferative activities in vitro in human breast cancer cells. The current study aimed to evaluate the efficacy of Soy B in suppressing CRC. Methods and materials: The effect of Soy B on cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. The effect of Soy B on cell proliferation was determined using colony formation assay. The percentage of apoptotic cells was determined by the TUNEL assay and flow cytometry following Annexin V-FITC/Propidium Iodide (PI) double staining. JC-1 staining was performed to examine the change in mitochondrial membrane potential. Autophagy was examined by acridine orange staining and mRFP-GFP-LC3 adenovirus transfection. Caspase-12 activities were determined by ELISA kit. Western blotting was used to determine the expression of relevant proteins. To investigate the role of autophagy in the pro-death and pro-apoptotic activities of Soy B, autophagy inhibitors Bafilomycin A1 (Baf-A1) and Atg5 siRNA were utilized. TUDCA and CHOP shRNA were utilized to block ER stress. Moreover, a CRC xenograft murine model was used to analyze the therapeutic efficacy of Soy B in vivo. Key findings: Soy B treatment decreased the number of viable cells and colonies formed in CRC cell lines. Moreover, Soy B treatment promoted the apoptotic cell death via the intrinsic pathway and autophagy which positively contributed to cell death and apoptosis. In addition, our results showed that ER stress, triggered by Soy B, mediated apoptosis and autophagy. In vivo results revealed that Soy B could suppress tumor growth, which was associated with increased ER stress, accompanied with apoptosis and autophagy induction. Significance: Soy B was able to promote cell death in vitro and in vivo. Our findings highlight the possibility of utilizing Soy B as a chemotherapeutic agent to prevent and treat CRC.	[Wang, Luping; Wang, Xiaojun; Sha, Liying; Wang, Luning; Sui, Yingying; Zhang, Hui] Qingdao Univ, Affiliated Hosp, Qingdao, Shandong, Peoples R China; [Yun, Lu] Qingdao Cent Hosp, Qingdao, Shandong, Peoples R China		Zhang, H (corresponding author), 16 Jiangsu Rd, Qingdao 266003, Peoples R China.	huizhangqyfu@163.com					Amin Hala A., 2018, Biotechnology Reports, V17, P55, DOI 10.1016/j.btre.2017.12.007; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Cheng SY, 2018, APOPTOSIS, V23, P314, DOI 10.1007/s10495-018-1456-9; Gao H, 2017, ACTA PHARMACOL SIN, V38, P1618, DOI 10.1038/aps.2017.154; Han M., 2018, ACTA PHARM SIN; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Healy SJM, 2009, EUR J PHARMACOL, V625, P234, DOI 10.1016/j.ejphar.2009.06.064; Iwamoto K, 2018, BIOCHEM BIOPHYS REP, V16, P44, DOI 10.1016/j.bbrep.2018.09.006; Janji B, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.00887; Kamo S, 2014, NUTRITION, V30, P596, DOI 10.1016/j.nut.2013.10.017; Kerwin S. 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FEB 1	2019	218						16	24		10.1016/j.lfs.2018.12.023			9	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	HH4WO	WOS:000455727100003	30553871				2022-04-25	
J	Ouyang, HC; Li, Q; Zhong, JK; Xia, FF; Zheng, SL; Lu, JH; Deng, YY; Hu, YZ				Ouyang, Haichun; Li, Qian; Zhong, Jiankai; Xia, Fengfan; Zheng, Sulin; Lu, Jianhua; Deng, Yuanyan; Hu, Yunzhao			Combination of melatonin and irisin ameliorates lipopolysaccharide-induced cardiac dysfunction through suppressing the Mst1-JNK pathways	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						ATP; cardiomyocyte; irisin; LPS; melatonin; mitochondria	COLON-CANCER CELLS; CARDIOMYOCYTE APOPTOSIS; HEART-FAILURE; AUTOPHAGY; STRESS; INJURY; INHIBITION; INFLAMMATION; HYPERTROPHY; NECROPTOSIS	Despite significant advances in therapies in past decades, the mortality rate of septic cardiomyopathy remains high. The aim of this study is to explore the therapeutic effects of combined treatment using melatonin and irisin in a mouse model of lipopolysaccharide (LPS)-mediated septic cardiomyopathy. Our data found that melatonin and irisin could further attenuate LPS-induced myocardial depression. Molecular investigation illustrated that melatonin and irisin cotreatment sustained cardiomyocyte viability and improved mitochondrial function under LPS stress. Pathway analysis demonstrated that macrophage-stimulating 1 (Mst1), which was significantly activated by LPS, was drastically inhibited by melatonin/irisin cotreatment. Mechanically, Mst1 activated c-Jun N-terminal kinase (JNK) pathway and the latter induced oxidative stress, adenosine triphosphate metabolism disorder, mitochondrial membrane potential reduction, and cardiomyocyte death activation. Melatonin and irisin cotreatment effectively inhibited the Mst1-JNK pathway and, thus, promoted cardiomyocyte survival and mitochondrial homeostasis. Interestingly, Mst1 overexpression abolished the beneficial effects of melatonin and irisin in vivo and in vitro. Altogether, our results confirmed that melatonin and irisin combination treatment could protect heart against sepsis-induced myocardial depression via modulating the Mst1-JNK pathways.	[Ouyang, Haichun; Zhong, Jiankai; Xia, Fengfan; Zheng, Sulin; Lu, Jianhua; Hu, Yunzhao] Southern Med Univ, Shunde Hosp, Dept Cardiol, Peoples Hosp Shunde Foshan 1, Foshan 528300, Guangdong, Peoples R China; [Li, Qian] Southern Med Univ, Nanfang Hosp, Dept Emergency Med, Guangzhou, Peoples R China; [Deng, Yuanyan] Southern Med Univ, Integrated Hosp Tradit Chinese Med, Dept Cardiol, Guangzhou 510315, Peoples R China		Hu, YZ (corresponding author), Southern Med Univ, Shunde Hosp, Dept Cardiol, Peoples Hosp Shunde Foshan 1, Foshan 528300, Guangdong, Peoples R China.; Deng, YY (corresponding author), Southern Med Univ, Integrated Hosp Tradit Chinese Med, Dept Cardiol, Guangzhou 510315, Peoples R China.	dengyuanyan@126.com; sdhuyz@163.com			Natural Science Foundation of Guangdong Province of ChinaNational Natural Science Foundation of Guangdong Province [2018A030313067]; Science and Technology Innovation Project from Foshan, Guangdong [FS0AA-KJ218-1301-0006, FS0AA-KJ218-1301-0010]; Key Specialist Department Training Project of Foshan City, Guangdong Province of China [Fspy 3-2015034]	Natural Science Foundation of Guangdong Province of China, Grant/Award Number: 2018A030313067; Science and Technology Innovation Project from Foshan, Guangdong, Grant/Award Numbers: FS0AA-KJ218-1301-0006, FS0AA-KJ218-1301-0010; Key Specialist Department Training Project of Foshan City, Guangdong Province of China, Grant/Award Number: Fspy 3-2015034	Abeysuriya RG, 2018, J PINEAL RES, V64, DOI 10.1111/jpi.12474; Abukar Y, 2018, BASIC RES CARDIOL, V113, DOI 10.1007/s00395-018-0695-9; Afonso CB, 2019, REDOX BIOL, V23, DOI 10.1016/j.redox.2018.101066; Afonso MB, 2018, CELL DEATH DIFFER, V25, P857, DOI 10.1038/s41418-017-0019-x; Alvarez-Fernandez M, 2018, CELL DEATH DIFFER, V25, P828, DOI 10.1038/s41418-017-0024-0; Angelova PR, 2018, REDOX BIOL, V14, P474, DOI 10.1016/j.redox.2017.10.016; Armartmuntree N, 2018, REDOX BIOL, V14, P637, DOI 10.1016/j.redox.2017.11.011; Ba XQ, 2018, REDOX BIOL, V14, P669, DOI 10.1016/j.redox.2017.11.008; Baines CP, 2005, J MOL CELL CARDIOL, V38, P47, DOI 10.1016/j.yjmcc.2004.11.004; Battelli MG, 2019, REDOX BIOL, V21, DOI 10.1016/j.redox.2018.101070; Bellomo C, 2018, CELL DEATH DIFFER, V25, P885, DOI 10.1038/s41418-017-0021-3; Bellot GL, 2019, REDOX BIOL, V20, P307, DOI 10.1016/j.redox.2018.10.014; Biernacki M, 2018, REDOX BIOL, V15, P41, DOI 10.1016/j.redox.2017.11.022; Botker HE, 2018, BASIC RES CARDIOL, V113, DOI 10.1007/s00395-018-0696-8; Bramasole L, 2019, REDOX BIOL, V20, P533, DOI 10.1016/j.redox.2018.11.010; Cameron AR, 2018, REDOX BIOL, V14, P187, DOI 10.1016/j.redox.2017.08.018; Care A, 2018, CELL DEATH DIFFER, V25, P477, DOI 10.1038/s41418-017-0051-x; Chandrasekharan A, 2019, REDOX BIOL, V20, P379, DOI 10.1016/j.redox.2018.10.013; Chen HB, 2018, CELL DEATH DIFFER, V25, P646, DOI 10.1038/s41418-018-0060-4; Chen L, 2016, APOPTOSIS, V21, P1291, DOI 10.1007/s10495-016-1287-5; Cheng Z, 2019, J CELL MOL MED, V23, P543, DOI 10.1111/jcmm.13958; Cheng Z, 2018, J MOL CELL CARDIOL, V125, P117, DOI 10.1016/j.yjmcc.2018.08.028; Chiong M, 2011, CELL DEATH DIS, V2, DOI 10.1038/cddis.2011.130; Corbalan JJ, 2016, BASIC RES CARDIOL, V111, DOI 10.1007/s00395-016-0549-2; Davidson SM, 2018, BASIC RES CARDIOL, V113, DOI 10.1007/s00395-018-0704-z; Dehdashtian E, 2018, LIFE SCI, V193, P20, DOI 10.1016/j.lfs.2017.12.001; DeLeon-Pennell KY, 2018, BASIC RES CARDIOL, V113, DOI 10.1007/s00395-018-0699-5; Deussen A, 2018, BASIC RES CARDIOL, V113, DOI 10.1007/s00395-018-0693-y; Ding MG, 2018, J PINEAL RES, V64, DOI 10.1111/jpi.12447; Edwards KS, 2018, BASIC RES CARDIOL, V113, DOI 10.1007/s00395-018-0707-9; Feng H, 2016, INT J CARDIOL, V203, P145, DOI 10.1016/j.ijcard.2015.10.109; Gandarillas A, 2018, CELL DEATH DIFFER, V25, P471, DOI 10.1038/s41418-017-0040-0; Gao GY, 2018, BIOMED PHARMACOTHER, V108, P1208, DOI 10.1016/j.biopha.2018.06.172; Goiran T, 2018, CELL DEATH DIFFER, V25, P873, DOI 10.1038/s41418-017-0016-0; Gong HJ, 2018, CELL DEATH DIFFER, V25, P1063, DOI 10.1038/s41418-018-0085-8; Gonzalez A, 2003, CARDIOVASC RES, V59, P549, DOI 10.1016/S0008-6363(03)00498-X; Hasna J, 2018, CELL DEATH DIFFER, V25, P691, DOI 10.1038/s41418-017-0007-1; Hay J. 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Cell. Physiol.	OCT	2020	235	10					6647	6659		10.1002/jcp.29561		JAN 2020	13	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	MZ8KE	WOS:000508956600001	31976559				2022-04-25	
J	Koustas, E; Sarantis, P; Theoharis, S; Saetta, AA; Chatziandreou, I; Kyriakopoulou, G; Giannopoulou, I; Michelli, M; Schizas, D; Papavassiliou, AG; Karamouzis, MV				Koustas, Evangelos; Sarantis, Panagiotis; Theoharis, Stamatios; Saetta, Angelica A.; Chatziandreou, Ilenia; Kyriakopoulou, Georgia; Giannopoulou, Ioanna; Michelli, Maria; Schizas, Dimitrios; Papavassiliou, Athanasios G.; Karamouzis, Michalis V.			Autophagy-related Proteins as a Prognostic Factor of Patients With Colorectal Cancer	AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS			English	Article						autophagy; Beclin-1; chemotherapy; colorectal cancer	BECLIN 1; PROGRESSION; EXPRESSION; MATURATION; INTERPLAY; TUMORS; CELLS; P53	Objectives: Autophagy plays a dual role in tumorigenesis. In the initial stages, it promotes cell survival and suppresses carcinogenesis, whereas in cancer development, it induces cancer cell survival. In this study, we investigate the role of autophagy as a protective or tumor suppressor mechanism in colorectal cancer (CRC) cell lines and evaluate its role as a potential biomarker in human tumor samples. Materials and Methods: The data of 68 patients with CRC treated at our Department from January 1 to December 31, 2016 were analyzed. Immunohistochemistry evaluation of p62, LC3B, Beclin-1, and Rab-7 in formalin-fixed paraffin-embedded tissue samples was performed and their expression was correlated with clinicopathologic characteristics, mutation status, and therapeutic approach. The chi(2) was used to test an association among categorical variables. Survival curves were estimated using the Kaplan-Meier method and differences were assessed using the log-rank test. Colo-205, HT29, SW-480, and Caco-2 cell lines were also used so as to test the autophagy markers with oxaliplatin, irinotecan, hydroxychloroquine, and 3-methyladenine. Results: Overexpression of Beclin-1 is associated with poor survival (P=0.001) in patients with CRC treated with chemotherapy, irrespective of the stage and mutational status. Rab-7 is also correlated with progression-free survival (PFS) (P=0.088). Oxaliplatin (10 and 20 mu M) and irinotecan (10 and 20 mu M) inhibit autophagy in microsatellite stable (MSS) CRC cell lines. The inhibition of autophagy in MSS CRC cell lines after treatment with oxaliplatin and irinotecan is further identified through monodancylcadaverine staining. Moreover, inhibition of autophagy with molecules such as hydroxychloroquine (20 mu M) and 3-methyladenine (5 mM) was identified by the accumulation of p62 and LC3B. Conclusions: Beclin-1 is an independent prognostic factor of overall survival and PFS. Also, Rab-7 is identified as an independent prognostic factor of PFS. Besides, several chemotherapeutic drugs such as oxaliplatin and irinotecan inhibit autophagy in MSS CRC cell lines in a similar way like hydroxychloroquine and 3-methyladenine. Thus, in MSS patients who develop chemoresistance, a combination of other therapies that include an autophagy inhibitor could be more beneficial. Further clinical trials are needed to investigate these therapeutic strategies.	[Koustas, Evangelos; Sarantis, Panagiotis; Kyriakopoulou, Georgia; Papavassiliou, Athanasios G.] Univ Athens, Sch Med, Laiko Hosp, Mol Oncol Unit,Dept Biol Chem, Athens, Greece; [Theoharis, Stamatios; Saetta, Angelica A.; Chatziandreou, Ilenia; Giannopoulou, Ioanna; Michelli, Maria] Univ Athens, Sch Med, Laiko Hosp, Dept Pathol, Athens, Greece; [Schizas, Dimitrios] Univ Athens, Sch Med, Laiko Hosp, Dept Surg 1, Athens, Greece; [Karamouzis, Michalis V.] Univ Athens, Sch Med, Laiko Hosp, Dept Internal Med 1, Athens, Greece		Karamouzis, MV (corresponding author), Univ Athens, Dept Biol Chem, Sch Med, 75 M Asias St, Athens 11527, Greece.	mkaramouz@med.uoa.gr	Koustas, Evangelos/ABE-9336-2020; Sarantis, Panagiotis/AAF-4774-2021; Karamouzis, Michalis/AAD-2860-2020	Sarantis, Panagiotis/0000-0001-5848-7905; Saetta, Angelica A./0000-0002-4862-3413; CHATZIANDREOU, ILENIA/0000-0002-4940-5581			Aredia Francesca, 2012, Cells, V1, P520, DOI 10.3390/cells1030520; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Burada F, 2015, WORLD J GASTRO ONCOL, V7, P271, DOI 10.4251/wjgo.v7.i11.271; Chude CI, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18061279; Cianfanelli V, 2015, CELL CYCLE, V14, P959, DOI 10.1080/15384101.2015.1021526; Colella B, 2019, CANCERS, V11, DOI 10.3390/cancers11030312; Goulielmaki M, 2016, ONCOTARGET, V7, P9188, DOI 10.18632/oncotarget.6942; Guerra F, 2016, CELLS-BASEL, V5, DOI 10.3390/cells5030034; Huijbers A, 2012, ENDOCR-RELAT CANCER, V19, pL15, DOI 10.1530/ERC-11-0302; Hyttinen JMT, 2013, BBA-MOL CELL RES, V1833, P503, DOI 10.1016/j.bbamcr.2012.11.018; Jin SK, 2007, AUTOPHAGY, V3, P28, DOI 10.4161/auto.3269; Kihara A, 2001, J CELL BIOL, V152, P519, DOI 10.1083/jcb.152.3.519; Kim EK, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0171280; Koustas E, 2019, CANCERS, V11, DOI 10.3390/cancers11040533; Koustas E, 2018, WORLD J GASTRO ONCOL, V10, P367, DOI 10.4251/wjgo.v10.i11.367; Koustas E, 2018, PLOS ONE, V13, DOI 10.1371/journal.pone.0207227; Lamb CA, 2013, BIOESSAYS, V35, P34, DOI 10.1002/bies.201200130; Lee JW, 2006, PATHOLOGY, V38, P312, DOI 10.1080/00313020600820880; Liu JC, 2014, EMBO MOL MED, V6, P1542, DOI 10.15252/emmm.201404402; Liu WJ, 2016, CELL MOL BIOL LETT, V21, DOI 10.1186/s11658-016-0031-z; Ma KG, 2013, OSTEOARTHR CARTILAGE, V21, P2030, DOI 10.1016/j.joca.2013.10.002; Manic G, 2014, MOL CELL ONCOL, V1, DOI 10.4161/mco.29911; Marinkovic M, 2018, OXID MED CELL LONGEV, V2018, DOI 10.1155/2018/8023821; Marino G, 2007, J BIOL CHEM, V282, P18573, DOI 10.1074/jbc.M701194200; Mellor HR, 2007, CANCER METAST REV, V26, P553, DOI 10.1007/s10555-007-9080-0; Mizushima N, 2002, CELL STRUCT FUNCT, V27, P421, DOI 10.1247/csf.27.421; Mizushima N, 2011, ANNU REV CELL DEV BI, V27, P107, DOI 10.1146/annurev-cellbio-092910-154005; Park JM, 2013, CANCER BIOL THER, V14, P100, DOI 10.4161/cbt.22954; Pasquier B, 2016, CELL MOL LIFE SCI, V73, P985, DOI 10.1007/s00018-015-2104-y; Perera R, 2015, NATURE, V524, P361, DOI 10.1038/nature14587; Qian HR, 2017, ONCOTARGET, V8, P62759, DOI 10.18632/oncotarget.18663; Qiu MZ, 2015, ONCOTARGET, V6, P38658, DOI 10.18632/oncotarget.6130; Rangwala R, 2014, AUTOPHAGY, V10, P1369, DOI 10.4161/auto.29118; Reggiori F, 2017, J MOL BIOL, V429, P486, DOI 10.1016/j.jmb.2017.01.002; Riihimaki M, 2016, SCI REP-UK, V6, DOI 10.1038/srep29765; Sakellariou S, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2213-5; Schaaf MB, 2019, CELL DEATH DIFFER, V26, P665, DOI 10.1038/s41418-019-0287-8; Schmitz KJ, 2016, WORLD J SURG ONCOL, V14, DOI 10.1186/s12957-016-0946-x; Shpilka T, 2011, GENOME BIOL, V12, DOI 10.1186/gb-2011-12-7-226; Takahashi Y, 2008, BIF BECN1, V9, P1; Thunnissen E, 2018, ARCH PATHOL LAB MED, V142, P408, DOI 10.5858/arpa.2017-0106-SA; Tsikalakis S, 2018, PATHOL RES PRACT, V214, P826, DOI 10.1016/j.prp.2018.04.019; Xu YH, 2018, FRONT PHARMACOL, V9, DOI 10.3389/fphar.2018.00234; Yang A, 2014, CANCER DISCOV, V4, P905, DOI 10.1158/2159-8290.CD-14-0362; Yang X, 2015, CELL BIOSCI, V5, DOI 10.1186/s13578-015-0005-2; Yue ZY, 2003, P NATL ACAD SCI USA, V100, P15077, DOI 10.1073/pnas.2436255100; Yun CW, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19113466; Zhou Y, 2015, INT J CLIN EXP PATHO, V8, P9428	48	10	10	1	5	LIPPINCOTT WILLIAMS & WILKINS	PHILADELPHIA	TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA	0277-3732	1537-453X		AM J CLIN ONCOL-CANC	Am. J. Clin. Oncol.-Cancer Clin. Trials	OCT	2019	42	10					767	776		10.1097/COC.0000000000000592			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	JC9PI	WOS:000489607600006	31517637	Green Published, hybrid			2022-04-25	
J	Stoll, G; Enot, D; Mlecnik, B; Galon, J; Zitvogel, L; Kroemer, G				Stoll, Gautier; Enot, David; Mlecnik, Bernhard; Galon, Jerome; Zitvogel, Laurence; Kroemer, Guido			Immune-related gene signatures predict the outcome of neoadjuvant chemotherapy	ONCOIMMUNOLOGY			English	Article						autophagy; breast cancer; colorectal cancer; endoplasmic stress; immunogenic cell death; tumor-infiltrating lymphocytes	TUMOR-INFILTRATING LYMPHOCYTES; CALRETICULIN EXPOSURE; CELLULAR CLEARANCE; CANCER; AUTOPHAGY; STRESS; CELLS; EXPRESSION; DOXORUBICIN; METASTASIS	There is ample evidence that neoadjuvant chemotherapy of breast carcinoma is particularly efficient if the tumor presents signs of either a pre-existent or therapy-induced anticancer immune response. Antineoplastic chemotherapies are particularly beneficial if they succeed in inducing immunogenic cell death, hence converting the tumor into its own therapeutic vaccine. Immunogenic cell death is characterized by a pre-mortem stress response including endoplasmic reticulum stress and autophagy. Based on these premises, we attempted to identify metagenes that reflect an intratumoral immune response or local stress responses in the transcriptomes of breast cancer patients. No consistent correlations between immune-and stress-related metagenes could be identified across several cohorts of patients, representing a total of 1045 mammary carcinomas. Moreover, few if any, of the stress-relevant metagenes influenced the probability of pathological complete response to chemotherapy. In contrast, several immune-relevant metagenes had a significant positive impact on response rates. This applies in particular to a CXCL 13-centered, highly reproducible metagene signature reflecting the intratumoral presence of interferon-gamma-producing T cells.	[Stoll, Gautier; Mlecnik, Bernhard; Galon, Jerome; Kroemer, Guido] Univ Paris 05, Paris, France; [Stoll, Gautier; Kroemer, Guido] INSERM, U1138, Cordeliers Res Ctr, Equipe Labellisee Ligue Natl Canc 11, Paris, France; [Enot, David; Kroemer, Guido] Metabol Platform, Villejuif, France; [Enot, David; Kroemer, Guido] Cell Biol Platform, Villejuif, France; INSERM, U1138, Lab Integrat Canc Immunol, Paris, France; [Mlecnik, Bernhard; Galon, Jerome] Univ Paris 06, Cordeliers Res Ctr, Paris, France; [Mlecnik, Bernhard; Galon, Jerome] INSERM, U1015, Villejuif, France; [Zitvogel, Laurence] Univ Paris 11, Fac Med, Le Kremlin Bicetre, France; [Zitvogel, Laurence] Ctr Clin Invest Biotherapies Canc CICBT 507, Villejuif, France; [Zitvogel, Laurence; Kroemer, Guido] INSERM, U848, Villejuif, France; [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France		Kroemer, G (corresponding author), Univ Paris 05, Paris, France.	kroemer@orange.fr	Kroemer, Guido/AAY-9859-2020; mlecnik, bernhard/AAT-7467-2021; KROEMER, Guido/B-4263-2013; Galon, Jerome/G-9838-2019	KROEMER, Guido/0000-0002-9334-4405; Galon, Jerome/0000-0001-9635-1339; Stoll, Gautier/0000-0002-0862-4139	Ligue contre le Cancer (equipe labelisee)Ligue nationale contre le cancer; Agence National de la Recherche (ANR)French National Research Agency (ANR); Association pour la recherche sur le cancer (ARC)Fondation ARC pour la Recherche sur le Cancer; Canceropole Ile-de-FranceRegion Ile-de-France; Institut National du Cancer (INCa)Institut National du Cancer (INCA) France; Fondation Bettencourt-Schueller; Fondation de FranceFondation de France; Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale; European Commission (ArtForce)European CommissionEuropean Commission Joint Research Centre; European Research Council (ERC)European Research Council (ERC)European Commission; LabEx Immuno-Oncology; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); Paris Alliance of Cancer Research Institutes (PACRI)	G.K. is supported by the Ligue contre le Cancer (equipe labelisee); Agence National de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI). We thank also TCGA Research Network for generating TCGA data sets.	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J	Zhang, NY; Zhang, XX; Xu, WB; Zhang, XX; Mu, ZP				Zhang, Nanyang; Zhang, Xianxiang; Xu, Wenbing; Zhang, Xiaoxiao; Mu, Zepeng			CircRNA_103948 inhibits autophagy in colorectal cancer in a ceRNA manner	ANNALS OF THE NEW YORK ACADEMY OF SCIENCES			English	Article						circRNA_103948; miR-1236-3p; TPT1; autophagy; CRC	TUMOR PROTEIN; CIRCULAR RNA; MIR-1236-3P; STATISTICS; TCTP	Circular RNA (circRNA) is implicated in many types of cancer; however, the expression and role of circRNAs in colorectal cancer (CRC) remains poorly understood. In this study, a circRNA microarray assay was performed to detect abnormally expressed circRNAs in CRC, and tissue arrays were used to determine the prognosis for CRC patients. Cell counting kit-8, clone formation, wound healing, and transwell assays were used to evaluate cell functions in vitro, and a mouse subcutaneous tumor model was designed for in vivo analysis. Autophagy was observed using confocal laser scanning and transmission electron microscopy. The expression of circRNA, miRNA, and mRNA was detected using qPCR; western blot, RNA pull-down assay, RNA immunoprecipitation, and dual luciferase assessment were applied for mechanistic studies. We found that circRNA_103948 expression is upregulated in CRC tissues, compared with adjacent normal tissues, and associated with poor prognosis. Knockdown of circRNA_103948 suppressed CRC both in vitro and in vivo. Mechanistically, circRNA_103948 could directly bind to miR-1236-3p and relieve suppression of the target TPT1. Furthermore, circRNA_103948 inhibited autophagy of CRC cells. Taken together, circRNA_103948 knockdown inhibited CRC cell growth by targeting miR-1236-3p/TPT1 axis-mediated autophagy. Thus, the circRNA_103948/miR-1236-3p/TPT1 axis affects CRC progression via modulation of autophagy.	[Zhang, Nanyang; Xu, Wenbing; Zhang, Xiaoxiao; Mu, Zepeng] Qingdao Univ, Med Res Ctr, Affiliated Hosp, 1677 Wutaishan Rd, Qingdao 266500, Shandong, Peoples R China; [Zhang, Xianxiang] Qingdao Univ, Dept Gastrointestinal Surg, Affiliated Hosp, Qingdao, Shandong, Peoples R China; [Xu, Wenbing] Qingdao Univ, Dept Reprod Med, Affiliated Hosp, Qingdao, Shandong, Peoples R China		Zhang, NY (corresponding author), Qingdao Univ, Med Res Ctr, Affiliated Hosp, 1677 Wutaishan Rd, Qingdao 266500, Shandong, Peoples R China.	nanyang.zhang@outlook.com	Zhang, Nanyang/AAU-7575-2021	Zhang, Nanyang/0000-0001-5765-6770	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81802473]; Qingdao Science and Technology Plan on Application and Basic Research, Youth Special Program [19-91-78-jch]; 2018 QingdaoWest Coast New Area Distinct Special Program on Science [SPST-1832041]; Youth Program of Research Foundation of The Affiliated Hospital of Qingdao University	This study was funded by the National Natural Science Foundation of China (81802473), 2019 Qingdao Science and Technology Plan on Application and Basic Research, Youth Special Program 19-91-78-jch, 2018 QingdaoWest Coast New Area Distinct Special Program on Science (SPST-1832041),and the Youth Program of Research Foundation of The Affiliated Hospital of Qingdao University. We thank Dr. Meng Zhang for writing and revising the manuscript.	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NOV	2021	1503	1			SI		88	101		10.1111/nyas.14679		SEP 2021	14	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	XA5JQ	WOS:000692735800001	34480353				2022-04-25	
J	Shen, LD; Qi, WH; Bai, JJ; Zuo, CY; Bai, DL; Gao, WD; Zong, XL; Hao, TT; Ma, Y; Cao, GC				Shen, Lian-Dong; Qi, Wen-Hai; Bai, Jiang-Jiang; Zuo, Chun-Yi; Bai, Dong-Lin; Gao, Wei-Dong; Zong, Xin-Ling; Hao, Ting-Ting; Ma, Yan; Cao, Guang-Cai			Resibufogenin inhibited colorectal cancer cell growth and tumorigenesis through triggering ferroptosis and ROS production mediated by GPX4 inactivation	ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY			English	Article						colorectal cancer; ferroptosis; GPX4; oxidative stress; resibufogenin	GLUTATHIONE-PEROXIDASE 4; DEATH	Resibufogenin (RB) has been used for cancer treatment, but the underlying mechanisms are still unclear. This study aimed to investigate the effects of RB treatment on colorectal cancer (CRC) cells, and to determine the underlying mechanisms. The cell counting kit-8 assay was used to determine cell viability. Cell morphology was observed under light microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was employed to detect cell apoptosis. Intracellular ferrous iron (Fe2+), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species levels were detected by using commercial iron assay kit, MDA assay kit, GSH assay kit, and 2,7-dichlorodihydrofluorescein diacetate probes, respectively. The protein expressions were determined by Western blot and immunohistochemistry. RB inhibited cell viability in the CRC cell lines (HT29 and SW480) in a dose- and time-dependent manner, and caused cytotoxicity to the normal colonic epithelial cell line (NCM460) at high dose. Similarly, RB induced morphological changes in CRC cells from normal to round shape, and promoted cell death. Of note, RB triggered oxidative stress and ferroptotic cell death in CRC cells, and only ferroptosis inhibitors (deferoxamine and ferrostatin-1), instead of inhibitors for other types of cell death (apoptosis, autophagy, and necroptosis), reversed the inhibitory effects of RB on CRC cell proliferation. Furthermore, glutathione peroxidase 4 (GPX4) was inactivated by RB treatment, and overexpression of GPX4 alleviated RB-induced oxidative cell death in CRC cells. Consistently, the in vivo experiments validated that RB also triggered oxidative stress, and inhibited CRC cells growth and tumorigenicity in mice models. RB can inhibit CRC cells growth and tumorigenesis by triggering ferroptotic cell death in a GPX4 inactivation-dependent manner.	[Shen, Lian-Dong; Qi, Wen-Hai; Bai, Jiang-Jiang; Zuo, Chun-Yi; Bai, Dong-Lin; Gao, Wei-Dong; Zong, Xin-Ling; Hao, Ting-Ting; Cao, Guang-Cai] Yanan Univ, Dept Anorectal Surg, Affiliated Hosp, 43 North St, Yanan 716000, Shaanxi, Peoples R China; [Ma, Yan] Yanan Peoples Hosp, Dept Med Cardiovasc, Yanan, Shaanxi, Peoples R China		Cao, GC (corresponding author), Yanan Univ, Dept Anorectal Surg, Affiliated Hosp, 43 North St, Yanan 716000, Shaanxi, Peoples R China.	38741819@qq.com					Ali SM, 2018, ANN SURG ONCOL, V25, P32, DOI 10.1245/s10434-016-5745-7; An PJ, 2019, ACS APPL MATER INTER, V11, P42988, DOI 10.1021/acsami.9b16124; Angius A, 2019, INT J MED SCI, V16, P1480, DOI 10.7150/ijms.35269; Belavgeni A, 2019, P NATL ACAD SCI USA, V116, P22269, DOI 10.1073/pnas.1912700116; Carbone M, 2019, CANCER RES, V79, P5149, DOI 10.1158/0008-5472.CAN-19-2453; Chen XH, 2019, ACS CHEM NEUROSCI, V10, P4824, DOI 10.1021/acschemneuro.9b00539; Hambright WS, 2017, REDOX BIOL, V12, P8, DOI 10.1016/j.redox.2017.01.021; Han QR, 2018, J TRANSL MED, V16, DOI 10.1186/s12967-018-1580-x; Hasakova K, 2019, PLOS ONE, V14, DOI 10.1371/journal.pone.0224396; Imai H, 2017, CURR TOP MICROBIOL, V403, P143, DOI 10.1007/82_2016_508; Khoshinani HM, 2017, JPN J RADIOL, V35, P664, DOI 10.1007/s11604-017-0679-y; Kim JH, 2015, WORLD J GASTROENTERO, V21, P5158, DOI 10.3748/wjg.v21.i17.5158; Kinowaki Y, 2018, LAB INVEST, V98, P609, DOI 10.1038/s41374-017-0008-1; Li Q, 2019, N-S ARCH PHARMACOL, V392, P1477, DOI 10.1007/s00210-019-01687-2; Li S, 2019, FRONT ONCOL, V9, DOI 10.3389/fonc.2019.01080; Lu Z, 2018, ONCOL LETT, V16, P3297, DOI 10.3892/ol.2018.8979; Ma B, 2017, FUTURE ONCOL, V13, P2489, DOI 10.2217/fon-2017-0310; Ning J, 2015, DRUG METAB DISPOS, V43, P299, DOI 10.1124/dmd.114.060996; Park S, 2018, ANIM CELLS SYST, V22, P334, DOI 10.1080/19768354.2018.1512521; Peng GQ, 2019, ONCOL REP, V41, P1264, DOI 10.3892/or.2018.6905; Sui XB, 2018, FRONT PHARMACOL, V9, DOI 10.3389/fphar.2018.01371; Tang HX, 2019, INT J PHARMACEUT, V572, DOI 10.1016/j.ijpharm.2019.118782; Uddin MN, 2012, HYPERTENS PREGNANCY, V31, P70, DOI 10.3109/10641955.2010.525275; Wang GX, 2017, CELL REP, V21, P2926, DOI 10.1016/j.celrep.2017.11.030; Wang Y, 2019, MOL MED REP, V20, P4081, DOI 10.3892/mmr.2019.10660; Wu CH, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-017-18935-1; Yin Y, 2017, CLIN CANCER RES, V23, P7375, DOI 10.1158/1078-0432.CCR-17-1283; Zhang X., 2019, J CELLULAR PHYSL, V235, P3425; Zou Y, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-09277-9	29	17	17	4	31	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1932-8486	1932-8494		ANAT REC	Anat. Rec.	FEB	2021	304	2					313	322		10.1002/ar.24378		FEB 2020	10	Anatomy & Morphology	Science Citation Index Expanded (SCI-EXPANDED)	Anatomy & Morphology	PT4TA	WOS:000511455800001	31961485				2022-04-25	
J	Janssen, K; Horn, S; Niemann, MT; Daniel, PT; Schulze-Osthoff, K; Fischer, U				Janssen, Katja; Horn, Sibylle; Niemann, Mathis T.; Daniel, Peter T.; Schulze-Osthoff, Klaus; Fischer, Ute			Inhibition of the ER Ca2+ pump forces multidrug-resistant cells deficient in Bak and Bax into necrosis	JOURNAL OF CELL SCIENCE			English	Article						ER stress; PARP; SERCA; Bak; Bax; Necrosis; Multidrug resistance; UPR; Autophagy; Ire1	ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; MITOCHONDRIAL PERMEABILITY TRANSITION; INDUCED APOPTOSIS; POLY(ADP-RIBOSE) POLYMERASE; HEMATOPOIETIC MALIGNANCIES; MEMBRANE PERMEABILIZATION; MUTATIONAL INACTIVATION; PROAPOPTOTIC BAX; PROSTATE-CANCER	Tumor cells deficient in the proapoptotic proteins Bak and Bax are resistant to chemotherapeutic drugs. Here, we demonstrate that murine embryonic fibroblasts deficient for both Bak and Bax are, however, efficiently killed by thapsigargin, a specific inhibitor of ER Ca2+ pumps that induces ER stress by depleting ER Ca2+ stores. In the presence of Bak and Bax, thapsigargin eliminates cells by release of mitochondrial cytochrome c and subsequent caspase activation, which leads to the proteolytic inactivation of the molecular necrosis switch PARP-1 and results in apoptosis. By contrast, in the absence of Bak and Bax, a failure to activate caspases results in PARP-1-mediated ATP depletion. The subsequent necrosis is not prevented by autophagy as an alternative energy source. Moreover, in cells deficient for both Bak and Bax, thapsigargin induces permanent mitochondrial damage by Ca2+ overload, permeability transition and membrane rupture. Thus, even though deficiency in Bak and Bax protects these cells against apoptosis, it does not compromise necrosis induced by SERCA inhibitors. Importantly, thapsigargin induces caspase-independent cell death also in colon and prostate carcinoma cells deficient in Bak and Bax expression. Therefore, targeted application of ER stressors such as thapsigargin might be a promising approach for the treatment of Bak- and Bax-deficient, drug-resistant tumors.	[Janssen, Katja; Horn, Sibylle; Niemann, Mathis T.; Schulze-Osthoff, Klaus; Fischer, Ute] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany; [Janssen, Katja; Horn, Sibylle; Niemann, Mathis T.; Schulze-Osthoff, Klaus; Fischer, Ute] Univ Dusseldorf, Inst Mol Med, D-40225 Dusseldorf, Germany; [Daniel, Peter T.] Univ Med Ctr Charite, Dept Hematol Oncol & Tumor Immunol, D-13125 Berlin, Germany		Fischer, U (corresponding author), Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany.	ute.fischer@uni-tuebingen.de	Schulze-Osthoff, Klaus/N-9025-2013	Schulze-Osthoff, Klaus/0000-0003-1443-2720	Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [SFB773, GRK 1302]; Deutsche Krebshilfe, the Comprehensive Cancer Centre TubingenDeutsche Krebshilfe; Medical Faculty of the University Dusseldorf	The authors wish to thank Marion Nissen for electron microscopy, Reza Ahmadian, Hidenori Ichijo, Randal J. Kaufman, Stanley J. Korsmeyer, Heinz Mehlhorn, Roland Piekorz, Ingo Schmitz, Hans- Uwe Simon, Andreas Strasser, Andreas Villunger, Bert Vogelstein and Erwin F. Wagner for valuable materials and helpful discussion. This work was supported by the Deutsche Forschungsgemeinschaft (SFB773, GRK 1302), the Deutsche Krebshilfe, the Comprehensive Cancer Centre Tubingen, and a grant of the Medical Faculty of the University Dusseldorf.	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J	Fu, SJ; Wang, YH; Li, H; Chen, LL; Liu, QZ				Fu, Shijian; Wang, Yanhong; Li, Hang; Chen, Leilei; Liu, Quanzhong			Regulatory Networks of LncRNA MALAT-1 in Cancer	CANCER MANAGEMENT AND RESEARCH			English	Review						long noncoding RNA; tumorigenesis; metastasis-associated lung adenocarcinoma transcript 1; regulatory cascade; oncogene; tumor suppressor	LONG NONCODING RNA; SQUAMOUS-CELL CARCINOMA; ADENOCARCINOMA TRANSCRIPT 1; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA; LUNG ADENOCARCINOMA; GASTRIC-CANCER; PROMOTES PROLIFERATION; COLORECTAL-CANCER; DOWN-REGULATION	Long noncoding (lnc)RNAs are a group of RNAs with a length greater than 200 nt that do not encode a protein but play an essential role in regulating the expression of target genes in normal biological contexts as well as pathologic processes including tumorigenesis. The lncRNA metastasis-associated lung adenocarcinoma transcript (MALAT)-1 has been widely studied in cancer. In this review, we describe the known functions of MALAT-1; its mechanisms of action; and associated signaling pathways and their clinical significance in different cancers. In most malignancies, including lung, colorectal, thyroid, and other cancers, MALAT-1 functions as an oncogene and is upregulated in tumors and tumor cell lines. MALAT-1 has a distinct mechanism of action in each cancer type and is thus at the center of large gene regulatory networks. Dysregulation of MALAT-1 affects cellular processes such as alternative splicing, epithelial mesenchymal transition, apoptosis, and autophagy, which ultimately results in the abnormal cell proliferation, invasion, and migration that characterize cancers. In other malignancies, such as glioma and endometrial carcinoma, MALAT-1 functions as a tumor suppressor and thus forms additional regulatory networks. The current evidence indicates that MALAT-1 and its associated signaling pathways can serve as diagnostic or prognostic biomarker or therapeutic target in the treatment of many cancers.	[Fu, Shijian; Li, Hang] Harbin Med Univ, Affiliated Hosp 1, Harbin 150081, Peoples R China; [Wang, Yanhong] Shantou Univ, Affiliated Hosp, Yuebei Peoples Hosp Shaoguan, Dept Lab Med, Shaoguan 512025, Peoples R China; [Chen, Leilei] Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Dept Cardiol, Beijing 100029, Peoples R China; [Liu, Quanzhong] Harbin Med Univ, Dept Med Genet, Harbin 150081, Peoples R China		Liu, QZ (corresponding author), Harbin Med Univ, Dept Med Genet, Harbin 150081, Peoples R China.	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J	Pantelic, ND; Zmejkovski, BB; Bozic, B; Dojcinovic, B; Banjac, NR; Wessjohann, LA; Kaluderovic, GN				Pantelic, Nebojsa D.; Zmejkovski, Bojana B.; Bozic, Bojan; Dojcinovic, Biljana; Banjac, Nebojsa R.; Wessjohann, Ludger A.; Kaluderovic, Goran N.			Synthesis, characterization and in vitro biological evaluation of novel organotin(IV) compounds with derivatives of 2-(5-arylidene-2,4-dioxothiazolidin-3-yl)propanoic acid	JOURNAL OF INORGANIC BIOCHEMISTRY			English	Article						Tin(IV); In vitro; Prostate cancer; Apoptosis; Autophagy; NO	ANTITUMOR-ACTIVITY; METAL-COMPLEXES; CARBOXYLATE COMPLEXES; CYTOTOXIC ACTIVITY; ANTICANCER; TITANOCENE; PLATINUM; INHIBITION; REACTIVITY; DICHLORIDE	Two novel triphenyltin(IV) compounds, [Ph(3)SnL1] (L1 = 2-(5-(4- fluorobenzylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (1)) and [Ph(3)SnL2] (L2 = 2-(5-(5-methyl-2-furfurylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (2)) were synthesized and characterized by FT-IR, (H-1 and C-13) NMR spectroscopy, mass spectrometry, and elemental microanalysis. The in vitro anticancer activity of the synthesized organotin(IV) compounds was determined against four tumor cell lines: PC-3 (prostate), HT-29 (colon), MCF-7 (breast), and HepG2 (hepatic) using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. The IC50 values are found to be in the range from 0.11 to 0.50 mu M. Compound 1 exhibits the highest activity toward PC-3 cells (IC50 = 0.115 +/- 0.009 mu M; CV assay). The tin and platinum uptake in PC-3 cells showed a threefold lower uptake of tin in comparison to platinum (as cisplatin). Together with its higher activity this indicates a much higher cell inhibition potential of the tin compounds (calculated to ca. 50 to 100 times). Morphological analysis suggested that the compounds induce apoptosis in PC-3 cells, and flow cytometry analysis revealed that 1 and 2 induce autophagy as well as NO (nitric oxide) production.	[Pantelic, Nebojsa D.; Kaluderovic, Goran N.] Univ Appl Sci Merseburg, Dept Engn & Nat Sci, Eberhard Leibnitz Str 2, D-06217 Merseburg, Germany; [Pantelic, Nebojsa D.; Banjac, Nebojsa R.] Univ Belgrade, Fac Agr, Dept Chem & Biochem, Nemanjina 6, Belgrade, Serbia; [Pantelic, Nebojsa D.; Wessjohann, Ludger A.; Kaluderovic, Goran N.] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany; [Zmejkovski, Bojana B.; Dojcinovic, Biljana] Univ Belgrade, Inst Chem Technol & Met, Dept Chem, Studentski Trg 14, Belgrade 11000, Serbia; [Bozic, Bojan] Univ Belgrade, Fac Biol, Inst Physiol & Biochem, Studentski Trg 14, Belgrade 11000, Serbia		Kaluderovic, GN (corresponding author), Univ Appl Sci Merseburg, Dept Engn & Nat Sci, Eberhard Leibnitz Str 2, D-06217 Merseburg, Germany.	goran.kaluderovic@hs-merseburg.de	Wessjohann, Ludger/AAZ-3838-2021; Bozic, Bojan/ABA-3278-2020; Kaluderovic, Goran/AAR-7347-2021	Kaluderovic, Goran/0000-0001-5168-1000; Wessjohann, Ludger A./0000-0003-2060-8235; Pantelic, Nebojsa D./0000-0003-1843-9890; Bozic, Bojan/0000-0001-9910-2741	Ministry of Education, Science and Technological Development of the Republic of Serbia [172035, 175033]; National Scholarship for Postdoctoral Studies of the Republic of Serbia; German Academic Exchange Service (DAAD)Deutscher Akademischer Austausch Dienst (DAAD) [57448219]	This research was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, [grant numbers: 172035 and 175033] and National Scholarship for Postdoctoral Studies of the Republic of Serbia (N. D. Pantelic). The authors acknowledge financial support from the German Academic Exchange Service (DAAD) [grant number: 57448219].	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Inorg. Biochem.	OCT	2020	211								111207	10.1016/j.jinorgbio.2020.111207			8	Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	NJ9DO	WOS:000566344500012	32801055				2022-04-25	
J	Ngaffo, CMN; Tchangna, RSV; Mbaveng, AT; Kamga, J; Harvey, FM; Ngadjui, BT; Bochet, CG; Kuete, V				Ngaffo, Carine M. N.; Tchangna, Rodrigue S., V; Mbaveng, Armelle T.; Kamga, Justin; Harvey, Freya M.; Ngadjui, Bonaventure T.; Bochet, Christian G.; Kuete, Victor			Botanicals from the leaves of Acacia sieberiana had better cytotoxic effects than isolated phytochemicals towards MDR cancer cells lines	HELIYON			English	Article						Acacia sieberiana; Apoptosis; Cytotoxicity; Fabaceae; Multi-drug resistance; Phytochemicals; Metabolite; Pharmaceutical science; Cancer research; Toxicology; Pharmacology	CAMEROONIAN MEDICINAL-PLANTS; MULTIDRUG-RESISTANCE; BREAST-CANCER; MODES; INHIBITION; FLAVONOIDS; AUTOPHAGY; TRANSPORTER; CARCINOMA; APOPTOSIS	The efficiency of cancer chemotherapy is seriously hampered by the development of resistance of neoplastic cells cytotoxic agents. In the present investigation, the cytotoxicity of the dichloromethane-methanol (1:1) extract of Acacia sieberiana (ASL), fractions (ASLa-c) from the leaves and isolated compounds: chrysoeriol-7-O-rutinoside (1), luteolin-7-O-rutinoside (2), chrysoeriol-7-O-beta-D-glucopyranoside (3), Apigenin-7-O-beta-D-glucopyranoside (4), luteolin-30,40-dimethoxylether-7-O-beta-D-glucoside (5) and luteolin (6) was investigated. The study was extended to assessment of the mode of induction of apoptosis by ASL. The resazurin reduction assay (RRA) was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed by flow cytometry. A caspase-Glo assay was used to evaluate caspase activities. Botanicals ASL, ASLb and ASLc as well as doxorubicin displayed observable IC50 values towards the nine tested cancer cell lines while ASLa and compounds 1-7 had selective activities. The IC50 values ranged from 13.45 mu g/mL (in CCRF-CEM leukemia cells) to 33.20 mu g/mL (against MDA-MB-231-BCRP breast adenocarcinoma cells) for ASL, from 16.42 mu g/mL (in CCRF-CEM cells) to 29.64 mu g/mL (against MDA-MB-231-pcDNA cells) for ASLc, and from 22.94 mu g/mL MDA-MB-231-BCRP cells) to 40.19 mu g/mL (against HCT116 (p53-/-) colon adenocarcinoma cells) for ASLb (Table 1), and from 0.02 mu M (against CCRF-CEM cells) to 122.96 mu M (against CEM/ADR5000 cells) for doxorubicin. ASL induced apoptosis in CCRF-CEM cells, mediated by ROS production. Acacia sieberiana is a good cytotoxic plant and should be further explored to develop an anticancer phytomedicine to combat both sensitive and drug resistant phenotypes.	[Ngaffo, Carine M. N.; Mbaveng, Armelle T.; Kuete, Victor] Univ Dschang, Fac Sci, Dept Biochem, Dschang, Cameroon; [Tchangna, Rodrigue S., V; Kamga, Justin; Ngadjui, Bonaventure T.] Univ Yaounde I, Fac Sci, Dept Chem, Yaounde, Cameroon; [Kamga, Justin; Harvey, Freya M.; Bochet, Christian G.] Univ Fribourg, Fac Sci & Med, Dept Chem, Chemin Musee 9, CH-1700 Fribourg, Switzerland		Kuete, V (corresponding author), Univ Dschang, Fac Sci, Dept Biochem, Dschang, Cameroon.	kuetevictor@yahoo.fr		KAMGA, Justin/0000-0003-4822-8293; Kuete, Victor/0000-0002-1070-1236; Harvey, Freya/0000-0002-9877-4041; Bochet, Christian/0000-0003-4267-0523	Alexander von Humboldt (AvH) foundationAlexander von Humboldt Foundation [CMR 1163890]; Swiss Government Excellence Scholarship [2017.1063]	This work was supported by the Alexander von Humboldt (AvH) foundation (Grant no.: CMR 1163890 GF-E to ATM) and the Swiss Government Excellence Scholarship (Grant no.: 2017.1063 to JK).	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J	Mazewski, C; Kim, MS; de Mejia, EG				Mazewski, Candice; Kim, Morgan Sanha; de Mejia, Elvira Gonzalez			Anthocyanins, delphinidin-3-O-glucoside and cyanidin-3-O-glucoside, inhibit immune checkpoints in human colorectal cancer cells in vitro and in silico	SCIENTIFIC REPORTS			English	Article							COLON-CANCER; PROLIFERATION; EXTRACTS; BIOAVAILABILITY; ACTIVATION; STABILITY; AUTOPHAGY; PURPLE; GRAPE	The objective was to assess anti-progression and stimulatory immune response effects among anthocyanins (ANC) and their metabolites on human colorectal cancer cells in vitro and in silico. Pure phenolics including delphinidin-3-O-glucoside (D3G) and its metabolites, delphinidin (DC) and gallic acid (GA), were tested alone or in combination, on HCT-116 and HT-29 human colorectal cancer cells (100-600 mu g/mL). HCT-116 and HT-29 50% inhibition concentrations (mu g/mL) were 396 +/- 23 and 329 +/- 17 for D3G; 242 +/- 16 and > 600 for DC; and 154 +/- 5 and 81 +/- 5 for GA, respectively. Using molecular docking, cyanidin-3-O-glucoside (C3G) showed the highest potential to inhibit immune checkpoints: programmed cell death protein-1 (PD-1) (-6.8 kcal/mol) and programmed death-ligand-1 (PD-L1) (-9.6 kcal/mol). C3G, D3G, DC, GA, and D3G-rich extracts decreased PD-L1 protein expression in HCT-116 cells. C3G decreased PD-L1 fluorescence intensity by 39%. ANC decreased PD-1 expression in peripheral blood mononuclear cells in monoculture by 41% and 55%, and co-culture with HCT-116 and HT-29 cells by 39% and 26% (C3G) and 50% and 51% (D3G), respectively. D3G and C3G, abundant in plant foods, showed potential for binding with and inhibiting immune checkpoints, PD-1 and PD-L1, which can activate immune response in the tumor microenvironment and induce cancer cell death.	[Mazewski, Candice; de Mejia, Elvira Gonzalez] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA; [Kim, Morgan Sanha] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA		de Mejia, EG (corresponding author), Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA.	edemejia@illinois.edu		DE MEJIA, ELVIRA/0000-0001-7426-9035	USDA National Institute of Food and Agriculture Hatch project [1014457]	This work was partially supported by USDA National Institute of Food and Agriculture Hatch project 1014457.	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J	Zou, YF; Chen, ZX; He, XW; He, XS; Wu, XR; Chen, YF; Wu, XJ; Wang, JP; Lan, P				Zou, Yifeng; Chen, Zexian; He, Xiaowen; He, Xiaosheng; Wu, Xianrui; Chen, Yufeng; Wu, Xiaojian; Wang, Jianping; Lan, Ping			High expression levels of unc-51-like kinase 1 as a predictor of poor prognosis in colorectal cancer	ONCOLOGY LETTERS			English	Article						ULK1; prognosis; colorectal cancer	AMERICAN JOINT COMMITTEE; ADJUVANT CHEMOTHERAPY; AUTOPHAGY; BIOMARKER; PHOSPHORYLATION; THERAPY; EDITION; AMPK	Colorectal cancer (CRC) is one of the most common and lethal cancers worldwide. Unc-51-like kinase 1 (ULK1) plays an important role in autophagy, which is widely involved in human CRC. The aim of the present study was to investigate the clinical and prognostic significance of the expression of ULK1 in human CRC. Expression of ULK1 in 339 CRC specimens (tumor-node-metastasis stages I-IV) was assessed by immunohistochemistry. The optimal cutpoint of the expression of ULK1 was assessed by the X-tile program, and the patients were divided into 2 groups of high or low expression levels of ULK1, accordingly. Correlation analysis between the expression of ULK1 and the clinicopathological variables in CRC demonstrated that the expression of ULK1 was significantly associated with gender and tumor differentiation. Univariate Cox regression analysis indicated that high expression levels of ULK1 were a risk factor for overall and disease-free survival. Therefore, the high expression levels of ULK1 may be a useful independent biomarker for predicting a poor prognosis in patients with CRC.	[Zou, Yifeng; Chen, Zexian; He, Xiaowen; He, Xiaosheng; Wu, Xianrui; Chen, Yufeng; Wu, Xiaojian; Wang, Jianping; Lan, Ping] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal & Anal Surg, Guangzhou 510655, Guangdong, Peoples R China		Lan, P (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal & Anal Surg, 26 Yuancun Erheng Rd, Guangzhou 510655, Guangdong, Peoples R China.	sumslp@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81300367]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [S2013010014186]	The current work was supported by the National Natural Science Foundation of China (No. 81300367) and the Natural Science Foundation of Guangdong Province (No. S2013010014186).	Brezden-Masley C, 2014, SURG ONCOL CLIN N AM, V23, P49, DOI 10.1016/j.soc.2013.09.009; Cai MY, 2011, MOL MED, V17, P12, DOI 10.2119/molmed.2010.00103; CAMP RL, 2004, CLIN CANCER RES, V10, P7252, DOI DOI 10.1158/1078-0432.CCR-04-0713; Edge SB, 2010, ANN SURG ONCOL, V17, P1471, DOI 10.1245/s10434-010-0985-4; Graziano F, 2003, ANN ONCOL, V14, P1026, DOI 10.1093/annonc/mdg284; Honscheid P, 2014, INT J RADIAT BIOL, V90, P628, DOI 10.3109/09553002.2014.907932; Hosokawa N, 2009, MOL BIOL CELL, V20, P1981, DOI 10.1091/mbc.E08-12-1248; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Jiang S, 2011, CANCER SCI, V102, P1568, DOI 10.1111/j.1349-7006.2011.01964.x; Jung CH, 2009, MOL BIOL CELL, V20, P1992, DOI 10.1091/mbc.E08-12-1249; Kim J, 2011, NAT CELL BIOL, V13, P132, DOI 10.1038/ncb2152; Kim KH, 2011, COLORECTAL DIS, V13, pE220, DOI 10.1111/j.1463-1318.2011.02625.x; Lee JW, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0015394; Mathonnet M, 2014, WORLD J GASTROENTERO, V20, P4189, DOI 10.3748/wjg.v20.i15.4189; Mizushima N, 2008, NATURE, V451, P1069, DOI 10.1038/nature06639; Mizushima N, 2010, CURR OPIN CELL BIOL, V22, P132, DOI 10.1016/j.ceb.2009.12.004; Nagtegaal ID, 2010, J CLIN ONCOL, V28, pE397, DOI 10.1200/JCO.2010.28.5726; O'Connell JB, 2004, JNCI-J NATL CANCER I, V96, P1420, DOI 10.1093/jnci/djh275; Oh Ho-Suk, 2007, Cancer Res Treat, V39, P61, DOI 10.4143/crt.2007.39.2.61; RAESIDE DE, 1976, PHYS MED BIOL, V21, P181, DOI 10.1088/0031-9155/21/2/001; Rizzo S, 2010, CANCER TREAT REV, V36, pS56, DOI 10.1016/S0305-7372(10)70021-9; Ross JS, 2011, BIOMARK MED, V5, P319, DOI [10.2217/bmm.11.38, 10.2217/BMM.11.38]; Schmukler E, 2014, ONCOTARGET, V5, P577, DOI 10.18632/oncotarget.1775; Siegel R, 2011, CA-CANCER J CLIN, V61, P212, DOI 10.3322/caac.20121; Tang J, 2012, BREAST CANCER RES TR, V134, P549, DOI 10.1007/s10549-012-2080-y; Wong PM, 2013, AUTOPHAGY, V9, P124, DOI 10.4161/auto.23323; Yokota T, 2012, ANTI-CANCER AGENT ME, V12, P163, DOI 10.2174/187152012799014968; Zhao MT, 2011, CELL METAB, V13, P119, DOI 10.1016/j.cmet.2011.01.009	28	16	16	2	6	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	SEP	2015	10	3					1583	1588		10.3892/ol.2015.3417			6	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CQ9GZ	WOS:000360923000060	26622714	Green Published, gold			2022-04-25	
J	Duangkumpha, K; Stoll, T; Phetcharaburanin, J; Yongvanit, P; Thanan, R; Techasen, A; Namwat, N; Khuntikeo, N; Chamadol, N; Roytrakul, S; Mulvenna, J; Mohamed, A; Shah, AK; Hill, MM; Loilome, W				Duangkumpha, Kassaporn; Stoll, Thomas; Phetcharaburanin, Jutarop; Yongvanit, Puangrat; Thanan, Raynoo; Techasen, Anchalee; Namwat, Nisana; Khuntikeo, Narong; Chamadol, Nittaya; Roytrakul, Sittiruk; Mulvenna, Jason; Mohamed, Ahmed; Shah, Alok K.; Hill, Michelle M.; Loilome, Watcharin			Urine proteomics study reveals potential biomarkers for the differential diagnosis of cholangiocarcinoma and periductal fibrosis	PLOS ONE			English	Article							LYSOSOMAL MEMBRANE-GLYCOPROTEINS; EXPRESSION; CANCER; LAMP-1; OPISTHORCHIASIS; BIOGENESIS; AUTOPHAGY; PROTEINS; DAMAGE; COLON	Cholangiocarcinoma (CCA) is a primary malignant tumor of the epithelial lining of biliary track associated with endemic Opisthorchis viverrini (0v) infection in northeastern Thailand. Ov-associated periductal fibrosis (PDF) is the precancerous lesion for CCA, and can be detected by ultrasonography (US) to facilitate early detection. However, US cannot be used to distinguish PDF from cancer. Therefore, the objective of this study was to discover and qualify potential urine biomarkers for CCA detection in at-risk population. Biomarker discovery was conducted on pooled urine samples, 42 patients per group, with PDF or normal bile duct confirmed by ultrasound. After depletion of high abundance proteins, 338 urinary proteins were identified from the 3 samples (normal-US, PDF-US, CCA). Based on fold change and literature review, 70 candidate proteins were selected for qualification by multiple reaction monitoring mass spectrometry (MRM-MS) in 90 individual urine samples, 30 per group. An orthogonal signal correction projection to latent structures discriminant analysis (O-PLS-DA) multivariate model constructed from the 70 candidate biomarkers significantly discriminated CCA from normal and PDF groups (P = 0.003). As an independent validation, the expression of 3 candidate proteins was confirmed by immunohistochemistry in CCA tissues: Lysosome associated membrane glycoprotein 1 (LAMP1), lysosome associated membrane glycoprotein 2 (LAMP2) and cadherin-related family member 2 (CDHR2). Further evaluation of these candidate biomarkers in a larger cohort is needed to support their applicability in a clinical setting for screening and monitoring early CCA and for CCA surveillance.	[Duangkumpha, Kassaporn; Phetcharaburanin, Jutarop; Thanan, Raynoo; Namwat, Nisana; Loilome, Watcharin] Khon Kaen Univ, Dept Biochem, Fac Med, Khon Kaen, Thailand; [Duangkumpha, Kassaporn; Phetcharaburanin, Jutarop; Yongvanit, Puangrat; Techasen, Anchalee; Namwat, Nisana; Khuntikeo, Narong; Chamadol, Nittaya; Loilome, Watcharin] Khon Kaen Univ, Cholangiocarcinoma Res Inst, Khon Kaen, Thailand; [Stoll, Thomas; Mulvenna, Jason; Mohamed, Ahmed; Shah, Alok K.; Hill, Michelle M.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia; [Techasen, Anchalee] Khon Kaen Univ, Fac Associated Med Sci, Khon Kaen, Thailand; [Khuntikeo, Narong] Khon Kaen Univ, Dept Surg, Fac Med, Khon Kaen, Thailand; [Chamadol, Nittaya] Khon Kaen Univ, Dept Radiol, Fac Med, Khon Kaen, Thailand; [Roytrakul, Sittiruk] Natl Sci & Technol Dev Agcy, Natl Ctr Genet Engn & Biotechnol, Genome Inst, Prote Res Lab, Pathum Thani, Thailand		Loilome, W (corresponding author), Khon Kaen Univ, Dept Biochem, Fac Med, Khon Kaen, Thailand.; Loilome, W (corresponding author), Khon Kaen Univ, Cholangiocarcinoma Res Inst, Khon Kaen, Thailand.; Hill, MM (corresponding author), QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.	michelle.hill@qimrberghofer.edu.au; watloi@yahoo.com	Hill, Michelle Mei Chih/G-4417-2010; Shah, Alok/AAB-6629-2019; Mohamed, Ahmed/L-4998-2016; Loilome, Watcharin/AAW-6203-2021	Hill, Michelle Mei Chih/0000-0003-1134-0951; Shah, Alok/0000-0002-2687-1168; Mohamed, Ahmed/0000-0001-6507-5300; Roytrakul, Sittiruk/0000-0003-3696-8390; Stoll, Thomas/0000-0002-6275-3433	Thailand Research Fund through Royal Golden Jubilee Ph.D. Program [PHD/0145/2556]; Cholangiocarcinoma Screening and Care Program (CASCAP); Faculty of Medicine [IN 59340]; Thailand Research FundThailand Research Fund (TRF) [RSA5980013]	This work was supported by Thailand Research Fund through Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0145/2556) to W.L. and K.D., a grant from Cholangiocarcinoma Screening and Care Program (CASCAP) to W.L., the grant of Faculty of Medicine to K.D. (Grant No. IN 59340), a grant from the Thailand Research Fund (Grant No. RSA5980013) allocated to W.L.	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J	Xiong, Y; Xiong, YJ; Liu, DY; Shen, RR				Xiong, Yong; Xiong, Yi-Jia; Liu, Dong-Yang; Shen, Rong-Rong			Pancratistatin Inhibits the Growth of Colorectal Cancer Cells by Inducing Apoptosis, Autophagy, and G2/M Cell Cycle Arrest	MEDICAL SCIENCE MONITOR			English	Article						Apoptosis; Autophagy; Cell Cycle	NATURAL-PRODUCTS; MITOCHONDRIA	Background: Worldwide, colorectal cancer is ranked as the third most prevalent cancer. The natural compound, pancratistatin, extracted from the spider lily, has previously been shown to target apoptosis in cancer cells lines. This study aimed to investigate the effects of pancratistatin in human colorectal cancer cells in vitro. Material/Methods: Human colorectal cancer cell lines, including HTC-15 cells, were compared with a normal human colonic fibro- blast cell line, CDD-18Co. Cells were treated with increasing doses of pancratistatin. The MTT assay was used to assess cell viability. Fluorescence microscopy using DAPI and Annexin-V/propidium iodide (PI) was used to detect cell apoptosis. Cell autophagy was detected by electron microscopy. Cell migration was evaluated using a wound healing assay, and Western blot determined the expression levels of cell cycle proteins. Results: Pancratistatin inhibited the growth of the colorectal cancer cells with an IC50 ranging from 15-25 mu M, but had a limited effect in normal CCD-18Co cells, with an IC50 of >100 mu M. Pancratistatin reduced HCT-15 cell migration. Growth inhibition due to pancratistatin was associated with morphological changes of HCT-15 cells and included autophagy and apoptosis, and increased expression the autophagic proteins, LC3II, beclin-1, and Bax. Pancratistatin induced arrest of HCT-15 cells at G2/M of the cell cycle and inhibited phosphorylation of cdc2/cyclin-dependent kinase 1 (CDK1) and Cdc25c and the expression of cyclin B1. Conclusions: Pancratistatin inhibited the growth of colorectal cancer cells in vitro by inducing apoptosis, autophagy, and G2/M cell cycle arrest.	[Xiong, Yong; Liu, Dong-Yang; Shen, Rong-Rong] Shanghai Unvi Med & Hlth Sci, Shanghai Peoples Hosp East 6, Dept Gen Surg, Shanghai, Peoples R China; [Xiong, Yi-Jia] Shanghai Sixth Peoples Hosp, Dept Radiol, Shanghai, Peoples R China		Shen, RR (corresponding author), Shanghai Unvi Med & Hlth Sci, Shanghai Peoples Hosp East 6, Dept Gen Surg, Shanghai, Peoples R China.	RichieWattsfdv@yahoo.com					Aran V, 2016, CLIN COLORECTAL CANC, V15, P195, DOI 10.1016/j.clcc.2016.02.008; Arnold M, 2016, GUT, V2, P2; Griffin C, 2011, INT J ONCOL, V38, P1549, DOI 10.3892/ijo.2011.977; Griffin C, 2011, MOL CANCER THER, V10, P57, DOI 10.1158/1535-7163.MCT-10-0735; Guinney J, 2015, NAT MED, V21, P1350, DOI 10.1038/nm.3967; Harvey AL, 2015, NAT REV DRUG DISCOV, V14, P111, DOI 10.1038/nrd4510; Kekre N, 2005, CANCER CHEMOTH PHARM, V56, P29, DOI 10.1007/s00280-004-0941-8; Kondo Y, 2005, NAT REV CANCER, V5, P726, DOI 10.1038/nrc1692; McLachlan A, 2005, APOPTOSIS, V10, P619, DOI 10.1007/s10495-005-1896-x; Mutsuga M, 2002, BIOL PHARM BULL, V25, P223, DOI 10.1248/bpb.25.223; Newman DJ, 2016, J NAT PROD, V79, P629, DOI 10.1021/acs.jnatprod.5b01055; Pandey S, 2005, ARTIF CELL BLOOD SUB, V33, P279, DOI 10.1081/BIO-200066621; Patridge E, 2016, DRUG DISCOV TODAY, V21, P204, DOI 10.1016/j.drudis.2015.01.009; PETTIT GR, 1984, J CHEM SOC CHEM COMM, P1693, DOI 10.1039/c39840001693; Rinner U., 2004, ANGEW CHEM, V116, P5456; Siegel R, 2014, CA-CANCER J CLIN, V64, P104, DOI 10.3322/caac.21220; Van Cutsem E, 2016, ANN ONCOL, V27, P1386, DOI 10.1093/annonc/mdw235	17	2	2	2	12	INT SCIENTIFIC INFORMATION, INC	MELVILLE	150 BROADHOLLOW RD, STE 114, MELVILLE, NY 11747 USA	1643-3750			MED SCI MONITOR	Med. Sci. Monitor	AUG 12	2019	25						6015	6022		10.12659/MSM.916116			8	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	IQ0DX	WOS:000480422100003	31404056	Green Submitted, Green Published			2022-04-25	
J	Wu, H; Lu, XX; Wang, JR; Yang, TY; Li, XM; He, XS; Li, Y; Ye, WL; Wu, Y; Gan, WJ; Guo, PD; Li, JM				Wu, Hua; Lu, Xing-Xing; Wang, Jing-Ru; Yang, Tian-Yu; Li, Xiu-Ming; He, Xiao-Shun; Li, Yi; Ye, Wen-Long; Wu, Yong; Gan, Wen-Juan; Guo, Peng-Da; Li, Jian-Ming			TRAF6 inhibits colorectal cancer metastasis through regulating selective autophagic CTNNB1/beta-catenin degradation and is targeted for GSK3B/GSK3 beta-mediated phosphorylation and degradation	AUTOPHAGY			English	Article						Autophagy; colorectal cancer; CTNNB1; GSK3B; metastasis; TRAF6	TUMORIGENESIS; IMPAIRMENT; PROTEIN; CD40	Aberrant CTNNB1 signaling is one of the fundamental processes in cancers, especially colorectal cancer (CRC). Here, we reported that TRAF6, an E3 ubiquitin ligase important for inflammatory signaling, inhibited epithelial-mesenchymal transition (EMT) and CRC metastasis through driving a selective autophagic CTNNB1 degradation machinery. Mechanistically, TRAF6 interacted with MAP1LC3B/LC3B through its LC3-interacting region 'YxxL' and catalyzed K63-linked polyubiquitination of LC3B. The K63-linked ubiquitination of LC3B promoted the formation of the LC3B-ATG7 complex and was critical to the subsequent recognition of CTNNB1 by LC3B for the selective autophagic degradation. However, TRAF6 was phosphorylated at Thr266 by GSK3B in most clinical CRC, which triggered K48-linked polyubiquitination and degradation of TRAF6 and thereby attenuated its inhibitory activity towards the autophagy-dependent CTNNB1 signaling. Clinically, decreased expression of TRAF6 was associated with elevated GSK3B protein levels and activity and reduced overall survival in CRC patients. Pharmacological inhibition of GSK3B activity stabilized the TRAF6 protein, promoted CTNNB1 degradation, and effectively suppressed EMT and CRC metastasis. Thus, targeting TRAF6 and its pathway may be meaningful for treating advanced CRC.	[Wu, Hua; Li, Jian-Ming] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Pathol, Guangzhou 510120, Guangdong, Peoples R China; [Wu, Hua; Lu, Xing-Xing; Yang, Tian-Yu; Li, Xiu-Ming; Li, Yi; Ye, Wen-Long; Guo, Peng-Da; Li, Jian-Ming] Soochow Univ, Dept Pathol, Suzhou, Peoples R China; [Wang, Jing-Ru; He, Xiao-Shun; Gan, Wen-Juan] Soochow Univ, Dept Pathol, Affiliated Hosp 1, Suzhou, Peoples R China; [Wu, Yong] Soochow Univ, Affiliated Hosp 2, Dept Gen Surg, Suzhou, Peoples R China		Li, JM (corresponding author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Pathol, Guangzhou 510120, Guangdong, Peoples R China.	lijming3@mail.sysu.edu.cn	Wu, Hua/W-4204-2019				Bienz M, 2000, CELL, V103, P311, DOI 10.1016/S0092-8674(00)00122-7; Cao ZD, 1996, NATURE, V383, P443, DOI 10.1038/383443a0; Chen HZ, 2012, GUT, V61, P714, DOI 10.1136/gutjnl-2011-300783; Dower CM, 2017, CANCER RES, V77, P646, DOI 10.1158/0008-5472.CAN-15-3458; Feng LJ, 2017, AUTOPHAGY, V13, P686, DOI 10.1080/15548627.2017.1280207; Guo PD, 2016, CANCER RES, V76, P3813, DOI 10.1158/0008-5472.CAN-15-2882; Huang R, 2015, MOL CELL, V57, P456, DOI 10.1016/j.molcel.2014.12.013; Ishida T, 1996, J BIOL CHEM, V271, P28745, DOI 10.1074/jbc.271.46.28745; Jin SH, 2018, AUTOPHAGY, V14, P171, DOI 10.1080/15548627.2017.1393590; Klionsky DJ, 2016, AUTOPHAGY, V12, P1, DOI 10.1080/15548627.2015.1100356; Lamothe B, 2007, J BIOL CHEM, V282, P4102, DOI 10.1074/jbc.M609503200; Li YZ, 2017, AUTOPHAGY, V13, P1145, DOI 10.1080/15548627.2017.1320467; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Lomaga MA, 1999, GENE DEV, V13, P1015, DOI 10.1101/gad.13.8.1015; Mizushima N, 2007, ANNU REV NUTR, V27, P19, DOI 10.1146/annurev.nutr.27.061406.093749; Muzny DM, 2012, NATURE, V487, P330, DOI 10.1038/nature11252; Nazio F, 2013, NAT CELL BIOL, V15, P406, DOI 10.1038/ncb2708; Noda NN, 2010, FEBS LETT, V584, P1379, DOI 10.1016/j.febslet.2010.01.018; Petherick KJ, 2013, EMBO J, V32, P1903, DOI 10.1038/emboj.2013.123; Qu XP, 2003, J CLIN INVEST, V112, P1809, DOI 10.1172/JCI200320039; Rogov V, 2014, MOL CELL, V53, P167, DOI 10.1016/j.molcel.2013.12.014; Rong YF, 2014, MED ONCOL, V31, DOI 10.1007/s12032-014-0260-9; Sanchez-Tillo E, 2011, P NATL ACAD SCI USA, V108, P19204, DOI 10.1073/pnas.1108977108; Shi CS, 2010, AUTOPHAGY, V6, P986, DOI 10.4161/auto.6.7.13288; Starczynowski DT, 2011, J CLIN INVEST, V121, P4095, DOI 10.1172/JCI58818; Sun H, 2013, CANCER RES, V73, P4950, DOI 10.1158/0008-5472.CAN-13-0370; Tai HR, 2017, AUTOPHAGY, V13, P99, DOI 10.1080/15548627.2016.1247143; Thiery JP, 2009, CELL, V139, P871, DOI 10.1016/j.cell.2009.11.007; White E, 2012, NAT REV CANCER, V12, P401, DOI 10.1038/nrc3262; Wu H, 2016, J PATHOL, V238, P457, DOI 10.1002/path.4670; Xing C, 2016, CANCER RES, V76, P83, DOI 10.1158/0008-5472.CAN-14-3595	31	25	27	5	40	TAYLOR & FRANCIS INC	PHILADELPHIA	530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA	1554-8627	1554-8635		AUTOPHAGY	Autophagy	SEP 2	2019	15	9					1506	1522		10.1080/15548627.2019.1586250			17	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	IQ3DE	WOS:000480630300003	30806153	Green Published, Bronze			2022-04-25	
J	Hossain, KFB; Rahman, MM; Sikder, MT; Saito, T; Hosokawa, T; Kurasaki, M				Hossain, Kaniz Fatima Binte; Rahman, Md. Mostafizur; Sikder, Md. Tajuddin; Saito, Takeshi; Hosokawa, Toshiyuki; Kurasaki, Masaaki			Inhibitory effects of selenium on cadmium-induced cytotoxicity in PC12 cells via regulating oxidative stress and apoptosis	FOOD AND CHEMICAL TOXICOLOGY			English	Article						Glutathione; Glutathione peroxidase; Cytochrome c; Oxidative stress; Autophagy; Apoptosis	ACTIVATED PROTEIN-KINASE; COLORECTAL-CANCER CELLS; LEUKEMIA NB4 CELLS; SODIUM SELENITE; GLUTATHIONE-PEROXIDASE; SIGNALING PATHWAY; HUMAN HEALTH; DEATH; MECHANISM; TOXICITY	Purpose of this study is to investigate mechanism/s of cyto-protection by selenium (Na2SeO3; Se4+) against cadmium (CdCL2; Cd2+)-induced cytotoxicity using PCl2 cells. In addition, Se (5, 10, 20 and 40 mu M) and Cd (2.5, 5 and 10 mu M) -induced cytotoxicity is determined. Cytotoxicity assays and western blot analyses confirmed that Se (>= 10 mu M) promotes autophagic cell death via inhibition of mTOR activation and p62 accumulation due to increase of cellular oxidative stress. On the other hand, co-presence of non-toxic Se (5 mu M) and toxic Cd (5 mu M) showed to increase cell viability, glutathione and glutathione peroxidase 1 (GPx1) levels, and to decrease DNA fragmentation and lactate dehydrogenase (LDH) activity compared to Cd-treated (5 mu M) cells alone. Furthermore, western blot analyses of cytochrome c and ERK1 indicated that Cd-induced apoptotic cell death in PC12 cells. However, the co-exposure of Se with Cd significantly decreases the release of cytochrome c into cytosol from mitochondria, and up-regulates ERK1 protein to inhibit Cd-induced apoptosis. In conclusion, Se (>= 10 mu M) possess cytotoxicity in PC12 cells; however, co-presence of Se (5 mu M) with Cd (5 mu M) protects against Cd-induced apoptosis in PC12 cells due to inhibition of Cd-induced oxidative stress and subsequently suppression of mitochondrial apoptosis pathway.	[Hossain, Kaniz Fatima Binte; Rahman, Md. Mostafizur; Kurasaki, Masaaki] Hokkaido Univ, Grad Sch Environm Sci, Sapporo, Hokkaido 0600810, Japan; [Sikder, Md. Tajuddin; Saito, Takeshi] Hokkaido Univ, Lab Environm Hlth Sci, Fac Hlth Sci, Sapporo, Hokkaido 0600812, Japan; [Sikder, Md. Tajuddin; Kurasaki, Masaaki] Hokkaido Univ, Fac Environm Earth Sci, Grp Environm Adaptat Sci, Sapporo, Hokkaido 0600810, Japan; [Sikder, Md. Tajuddin] Jahangirnagar Univ, Dept Publ Hlth & Informat, Dhaka 1342, Bangladesh; [Hosokawa, Toshiyuki] Hokkaido Univ, Inst Adv Higher Educ, Res Div Higher Educ, Sapporo, Hokkaido 0600817, Japan		Kurasaki, M (corresponding author), Hokkaido Univ, Fac Environm Earth Sci, Grp Environm Adaptat Sci, Kita Ku, Kita 10,Nishi 5, Sapporo, Hokkaido 0600810, Japan.	kura@ees.hokudai.ac.jp	, 細川敏幸/A-3851-2012; Sikder, Tajuddin/AAK-4868-2020; Kurasaki, Masaaki/B-8207-2012; Rahman, Mostafizur/X-7420-2019; Hossain, Kaniz Fatima Binte/AAD-7902-2019; SAITO, TAKESHI/E-5950-2012	, 細川敏幸/0000-0002-4818-8968; Sikder, Tajuddin/0000-0002-5717-2263; Kurasaki, Masaaki/0000-0003-2125-095X; Rahman, Mostafizur/0000-0002-5290-3821; Hossain, Kaniz Fatima Binte/0000-0003-2922-9813; 			Abdulah R, 2011, INT J ONCOL, V39, P301, DOI 10.3892/ijo.2011.1035; Armstrong JS, 2002, CELL DEATH DIFFER, V9, P252, DOI 10.1038/sj.cdd.4400959; Battin EE, 2009, CELL BIOCHEM BIOPHYS, V55, P1, DOI 10.1007/s12013-009-9054-7; Brozmanova J, 2010, ARCH TOXICOL, V84, P919, DOI 10.1007/s00204-010-0595-8; Chatterjee A, 2013, NUTRIENTS, V5, P525, DOI 10.3390/nu5020525; Chen JJ, 2007, BIOFACTORS, V31, P55, DOI 10.1002/biof.5520310106; Chen L, 2008, FREE RADICAL BIO MED, V45, P1035, DOI 10.1016/j.freeradbiomed.2008.07.011; Chen L, 2008, J NEUROCHEM, V105, P251, DOI 10.1111/j.1471-4159.2007.05133.x; Chen X, 2012, MOLECULES, V17, P14565, DOI 10.3390/molecules171214565; Cheng Y, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0035104; Cummings Brian S, 2012, Curr Protoc Pharmacol, VChapter 12, DOI 10.1002/0471141755.ph1208s56; Cuypers A, 2010, BIOMETALS, V23, P927, DOI 10.1007/s10534-010-9329-x; Duran A, 2011, MOL CELL, V44, P134, DOI 10.1016/j.molcel.2011.06.038; El-Demerdash FM, 2001, J ENVIRON SCI HEAL B, V36, P489, DOI 10.1081/PFC-100104191; El-Sharaky AS, 2007, TOXICOLOGY, V235, P185, DOI 10.1016/j.tox.2007.03.014; El-Shenawy SMA, 2008, PHARMACOL REP, V60, P199; Elmore S, 2007, TOXICOL PATHOL, V35, P495, DOI 10.1080/01926230701320337; Fan TJ, 2005, ACTA BIOCH BIOPH SIN, V37, P719, DOI 10.1111/j.1745-7270.2005.00108.x; Finley JW, 2006, NUTR REV, V64, P146, DOI 10.1111/j.1753-4887.2006.tb00198.x; Fordyce F. 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APR	2018	114						180	189		10.1016/j.fct.2018.02.034			10	Food Science & Technology; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Food Science & Technology; Toxicology	GC4MH	WOS:000429758100020	29454865				2022-04-25	
J	Mira, A; Morello, V; Cespedes, MV; Perera, T; Comoglio, PM; Mangues, R; Michieli, P				Mira, Alessia; Morello, Virginia; Virtudes Cespedes, Maria; Perera, Timothy; Comoglio, Paolo M.; Mangues, Ramon; Michieli, Paolo			Stroma-derived HGF drives metabolic adaptation of colorectal cancer to angiogenesis inhibitors	ONCOTARGET			English	Article						colorectal cancer; HGF; anti-angiogenic therapy; resistance; tumor metabolism	HEPATOCYTE GROWTH-FACTOR; C-MET; GENE-EXPRESSION; GLUCOSE-UPTAKE; CELLS; MICROENVIRONMENT; XENOGRAFTS; RESISTANCE; THERAPIES; AUTOPHAGY	The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation. Starvation-induced apoptosis could be prevented by HGF, which promoted GLUT1-mediated glucose uptake, sustained glycolysis and activated autophagy. Pharmacological inhibition of GLUT1 in the presence of glucose killed tumor cells as effectively as glucose deprivation, and this effect was antagonized by HGF. Concomitant targeting of GLUT1 and HGF potently suppressed growth and dissemination of AI-resistant human tumors in human HGF knock-in SCID mice without exacerbating tumor hypoxia. These data suggest that stroma-derived HGF protects CRC cells against glucose starvation-induced apoptosis, promoting resistance to both AIs and anti-glycolytic agents. Combined inhibition of glucose metabolism and HGF/MET signaling ('anti-METabolic therapy') may represent a more effective CRC treatment compared to utterly blocking tumor blood supply.	[Mira, Alessia; Morello, Virginia; Comoglio, Paolo M.; Michieli, Paolo] IRCCS, FPO, Candiolo Canc Inst, Turin, Italy; [Morello, Virginia; Michieli, Paolo] Univ Turin, Med Sch, Dept Oncol, Turin, Italy; [Virtudes Cespedes, Maria; Mangues, Ramon] Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Barcelona, Spain; [Virtudes Cespedes, Maria; Mangues, Ramon] Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona, Spain; [Perera, Timothy] OCTIMET Oncol Ltd, Oxford, England		Michieli, P (corresponding author), IRCCS, FPO, Candiolo Canc Inst, Turin, Italy.; Michieli, P (corresponding author), Univ Turin, Med Sch, Dept Oncol, Turin, Italy.	paolo.michieli@ircc.it	Michieli, Paolo/A-2588-2011; Mangues, Ramon/J-6396-2014	Michieli, Paolo/0000-0002-3093-8871; Mangues, Ramon/0000-0003-2661-9525; Comoglio, Paolo/0000-0002-7056-5328; Morello, Virginia/0000-0002-3001-0993; Mira, Alessia/0000-0002-8456-8159	Associazione Italiana per la Ricerca sul Cancro (AIRC)Fondazione AIRC per la ricerca sul cancro [9970, 12798, 17489]; Instituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Commission; FEDEREuropean Commission [PI12/01861]; CIBER-BBN; Fondazione Umberto Veronesi FellowshipFondazione Umberto Veronesi	This work has been supported in part by the Associazione Italiana per la Ricerca sul Cancro (AIRC; 2010 Special Program in Molecular Clinical Oncology 5% #9970 to P.M. and P.M.C., 2012 IG #12798 and 2015 IG #17489 to P.M.), the Instituto de Salud Carlos III (co-funding from FEDER; grant PI12/01861 to R.M.), and CIBER-BBN (Intramural Grant Nanomets to R.M.). A.M. was supported by a Fondazione Umberto Veronesi Fellowship.	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J	Tan, YY; Ci, YP; Dai, XP; Wu, F; Guo, JP; Liu, DL; North, BJ; Huo, JR; Zhang, JF				Tan, Yuyong; Ci, Yanpeng; Dai, Xiangpeng; Wu, Fei; Guo, Jianping; Liu, Deliang; North, Brian J.; Huo, Jirong; Zhang, Jinfang			Cullin 3(SPOP) ubiquitin E3 ligase promotes the poly-ubiquitination and degradation of HDAC6	ONCOTARGET			English	Article						HDAC6; SPOP; Cullin 3; ubiquitination; tumorigenesis	HISTONE DEACETYLASE 6; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER-ASSOCIATED MUTANTS; TUMOR-SUPPRESSOR SPOP; PROSTATE-CANCER; ANDROGEN RECEPTOR; PROTEIN-TURNOVER; ACETYLATION; ACTIVATION; INHIBITOR	The histone deacetylase 6 (HDAC6) plays critical roles in human tumorigenesis and metastasis. As such, HDAC6-selective inhibitors have entered clinical trials for cancer therapy. However, the upstream regulator(s), especially ubiquitin E3 ligase(s), responsible for controlling the protein stability of HDAC6 remains largely undefined. Here, we report that Cullin 3(SPOP) earmarks HDAC6 for poly-ubiquitination and degradation. We found that the proteasome inhibitor MG132, or the Cullin-based E3 ligases inhibitor MLN4924, but not the autophagosome-lysosome inhibitor bafilomycin A1, stabilized endogenous HDAC6 protein in multiple cancer cell lines. Furthermore, we demonstrated that Cullin 3-based ubiquitin E3 ligase(s) primarily reduced the stability of HDAC6. Importantly, we identified SPOP, an adaptor protein of Cullin 3 family E3 ligases, specifically interacted with HDAC6, and promoted its poly-ubiquitination and subsequent degradation in cells. Notably, cancer-derived SPOP mutants disrupted their binding with HDAC6 and thereby failed to promote HDAC6 degradation. More importantly, increased cellular proliferation and migration in SPOP-depleted HCT116 colon cancer cells could be partly reversed by additional depletion of HDAC6, suggesting that HDAC6 is a key downstream effector for SPOP tumor suppressor function. Together, our data identify the tumor suppressor SPOP as an upstream negative regulator for HDAC6 stability, and SPOP loss-of-function mutations might lead to elevated levels of the HDAC6 oncoprotein to facilitate tumorigenesis and metastasis in various human cancers.	[Tan, Yuyong; Liu, Deliang; Huo, Jirong] Cent S Univ, Dept Gastroenterol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China; [Tan, Yuyong; Ci, Yanpeng; Dai, Xiangpeng; Wu, Fei; Guo, Jianping; North, Brian J.; Zhang, Jinfang] Harvard Med Sch, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA; [Ci, Yanpeng] Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150001, Peoples R China; [Wu, Fei] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai 200040, Peoples R China		Huo, JR (corresponding author), Cent S Univ, Dept Gastroenterol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China.; North, BJ; Zhang, JF (corresponding author), Harvard Med Sch, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.	bnorth@bidmc.harvard.edu; hjr198@hotmail.com; jzhang17@bidmc.harvard.edu	Wu, Fei/AAP-5721-2021	Wu, Fei/0000-0001-6689-6135	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AG052627]; Chinese National Key Disciplines [(2012)650]; Development and Reform Commission of Hunan Province [XFGTZ2014713]; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [K01AG052627] Funding Source: NIH RePORTER	We thank Dr. Wenyi Wei and Dr. Wenjian Gan for critical discussion and reading of the manuscript. B.J.N. was supported in part by NIH K01 grant AG052627. This work was partly supported by the Chinese National Key Disciplines [(2012)650] and Development and Reform Commission of Hunan Province (XFGTZ2014713 to D.L.).	Aldana-Masangkay GI, 2011, J BIOMED BIOTECHNOL, DOI 10.1155/2011/875824; An J, 2015, MOL CELL, V59, P904, DOI 10.1016/j.molcel.2015.07.025; An J, 2014, CELL REP, V6, P657, DOI 10.1016/j.celrep.2014.01.013; Nieto MA, 2016, CELL, V166, P21, DOI 10.1016/j.cell.2016.06.028; Barbieri CE, 2012, NAT GENET, V44, P685, DOI 10.1038/ng.2279; Batchu SN, 2016, CLIN SCI, V130, P987, DOI 10.1042/CS20160084; Berger MF, 2011, NATURE, V470, P214, DOI 10.1038/nature09744; Cook C, 2012, HUM MOL GENET, V21, P2936, DOI 10.1093/hmg/dds125; Duda DM, 2008, CELL, V134, P995, DOI 10.1016/j.cell.2008.07.022; Gan WJ, 2015, MOL CELL, V59, P917, DOI 10.1016/j.molcel.2015.07.026; Ganai SA, 2017, CURR DRUG TARGETS; Geng C, 2014, CANCER RES, V74, P5631, DOI 10.1158/0008-5472.CAN-14-0476; Geng C, 2013, P NATL ACAD SCI USA, V110, P6997, DOI 10.1073/pnas.1304502110; Genschik P, 2013, EMBO J, V32, P2307, DOI 10.1038/emboj.2013.173; Glozak MA, 2007, ONCOGENE, V26, P5420, DOI 10.1038/sj.onc.1210610; Gu SC, 2016, J BIOL CHEM, V291, P5396, DOI 10.1074/jbc.M115.713123; Han Y, 2009, BIOCHEM BIOPH RES CO, V383, P88, DOI 10.1016/j.bbrc.2009.03.147; Hernadez-Munoz I, 2005, P NATL ACAD SCI USA, V102, P7635, DOI 10.1073/pnas.0408918102; Hsieh TH, 2012, TOXICOL SCI, V128, P365, DOI 10.1093/toxsci/kfs163; Huang PY, 2017, ONCOTARGET, V8, P2694, DOI 10.18632/oncotarget.13738; Hubbert C, 2002, NATURE, V417, P455, DOI 10.1038/417455a; Jung SH, 2016, ONCOTARGET, V7, P69638, DOI 10.18632/oncotarget.11922; Kim MS, 2013, APMIS, V121, P626, DOI 10.1111/apm.12030; Klionsky DJ, 2008, AUTOPHAGY, V4, P849, DOI 10.4161/auto.6845; Kovacs JJ, 2005, MOL CELL, V18, P601, DOI 10.1016/j.molcel.2005.04.021; Kwon JE, 2006, J BIOL CHEM, V281, P12664, DOI 10.1074/jbc.M600204200; Lee DH, 1998, TRENDS CELL BIOL, V8, P397, DOI 10.1016/S0962-8924(98)01346-4; Li GQ, 2014, CANCER CELL, V25, P455, DOI 10.1016/j.ccr.2014.02.007; Li Y, 2016, HDACS HDACS HDAC INH, V6; Mobley RJ, 2017, CELL REP, V18, P2387, DOI 10.1016/j.celrep.2017.02.030; Petroski MD, 2005, NAT REV MOL CELL BIO, V6, P9, DOI 10.1038/nrm1547; Pugacheva EN, 2007, CELL, V129, P1351, DOI 10.1016/j.cell.2007.04.035; Ryu HW, 2017, CANCER LETT, V391, P162, DOI 10.1016/j.canlet.2017.01.033; Santo L, 2012, BLOOD, V119, P2579, DOI 10.1182/blood-2011-10-387365; Seidel C, 2015, EPIGENOMICS-UK, V7, P103, DOI [10.2217/EPI.14.69, 10.2217/epi.14.69]; Shan B, 2008, J BIOL CHEM, V283, P21065, DOI 10.1074/jbc.M802786200; Soucy TA, 2009, NATURE, V458, P732, DOI 10.1038/nature07884; Theurillat JPP, 2014, SCIENCE, V346, P85, DOI 10.1126/science.1250255; Wang ZW, 2014, NAT REV CANCER, V14, P233, DOI 10.1038/nrc3700; Williams KA, 2013, J BIOL CHEM, V288, P33156, DOI 10.1074/jbc.M113.472506; Wu F, 2017, CANCER LETT, V385, P207, DOI 10.1016/j.canlet.2016.10.021; Yang PH, 2013, DRUG DISCOV THER, V7, P233, DOI 10.5582/ddt.2013.v7.6.233; YOSHIMORI T, 1991, J BIOL CHEM, V266, P17707; Zhang LL, 2017, CANCER LETT, V390, P11, DOI 10.1016/j.canlet.2017.01.003; Zhang P, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.47; Zhang Q, 2006, DEV CELL, V10, P719, DOI 10.1016/j.devcel.2006.05.004; Zhang XH, 2007, MOL CELL, V27, P197, DOI 10.1016/j.molcel.2007.05.033; Zhuang M, 2009, MOL CELL, V36, P39, DOI 10.1016/j.molcel.2009.09.022	48	22	27	1	8	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA		1949-2553		ONCOTARGET	Oncotarget	JUL 18	2017	8	29					47890	47901		10.18632/oncotarget.18141			12	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	FA8KD	WOS:000405694000097	28599312	Green Published, Green Submitted, gold			2022-04-25	
J	Zheng, TL; Li, DP; Zhang, K; Guo, HZ; Cui, GH; Zhao, S				Zheng, Tianliang; Li, Deping; Zhang, Kai; Guo, Haizhou; Cui, Guanghui; Zhao, Song			Prognostic value of autophagy marker LC3 in esophageal cancer: a meta-analysis	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE			English	Article						Esophageal cancer; autophagy; microtubule-associated protein 1 light chain 3; prognosis; meta-analysis	SQUAMOUS-CELL CARCINOMA; PREDICTS POOR-PROGNOSIS; UNC-51-LIKE KINASE 1; COLORECTAL-CANCER; PROTEINS LC3; EXPRESSION; SURVIVAL; BECLIN-1; STATISTICS; APOPTOSIS	Objective: Autophagy played an important role in the carcinogenesis of esophageal cancer, and LC3 was a popular marker of autophagy. However, the association between LC3 and prognosis of esophageal cancer was controversial. We conducted this meta-analysis to systemically assess the prognostic value of LC3 in esophageal cancer. Materials and methods: Literature searches were performed in Embase and PubMed databases for eligible studies before June 30, 2016. Hazard ratio (HR) was pooled to assess the association of LC3 with overall survival (OS). Odds ratio (OR) was pooled to evaluate the correlation between LC3 and clinicopathological characteristics. Results: A total of six studies involving 775 patients were included for meta-analysis. The pooled result showed that the high LC3 level was significantly correlated with worse OS of esophageal cancer (HR=1.33, 95% CI 1.05-1.68; P=0.018). There was no correlation between LC3 and tumor grade (OR=0.96, 95% CI 0.68-1.36; P=0.822), lymph node involvement (OR=0.99, 95% CI 0.71-1.38; P=0.959) or TNM stage (OR=0.70, 95% CI 0.43-1.13; P=0.142). Conclusion: High LC3 level was correlated with worse prognosis of esophageal cancer, and LC3 might act as a promising autophagy-related prognostic marker of esophageal cancer.	[Zheng, Tianliang; Guo, Haizhou; Cui, Guanghui; Zhao, Song] Zhengzhou Univ, Affiliated Hosp 1, Dept Thorac Surg, Zhengzhou 450000, Peoples R China; [Zhang, Kai] Zhengzhou Univ, Affiliated Hosp 2, Dept Resp Med, Zhengzhou 450000, Peoples R China; [Li, Deping] Zhengzhou Hosp Tradit Chinese Med, Dept Pain Management, Zhengzhou 450000, Peoples R China		Zhao, S (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Thorac Surg, Zhengzhou 450000, Peoples R China.	zzuzhaosong@yahoo.com			Youth Innovation Fund Project of the First Affiliated Hospital of Zhengzhou University	This study was supported by the Youth Innovation Fund Project of the First Affiliated Hospital of Zhengzhou University.	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J. Clin. Exp. Med.		2016	9	11					21535	21541					7	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	EG7UD	WOS:000391260800114					2022-04-25	
J	Xian, ZY; Hu, B; Wang, T; Zeng, JY; Cai, JL; Zou, Q; Zhu, PX				Xian, Zhenyu; Hu, Bang; Wang, Ting; Zeng, Junyi; Cai, Jinlin; Zou, Qi; Zhu, Peixuan			lncRNA UCA1 Contributes to 5-Fluorouracil Resistance of Colorectal Cancer Cells Through miR-23b-3p/ZNF281 Axis	ONCOTARGETS AND THERAPY			English	Article						colorectal cancer; 5-FU; UCA1; miR-23b-3p; ZNF281; autophagy; apoptosis	LONG NONCODING RNA; HEPATOCELLULAR-CARCINOMA; POOR-PROGNOSIS; APOPTOSIS; AUTOPHAGY; PROLIFERATION; MICRORNA-23B; PROGRESSION; ACTIVATION; INVASION	Purpose: The chemoresistance of 5-fluorouracil (5-FU) limited the application of chemotherapy in colorectal cancer (CRC) treatment. Herein, we aimed to uncover the potential mechanism behind the 5-FU resistance of CRC cells. Methods: The abundance of long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1), microRNA-23b-3p (miR-23b-3p) and zinc finger protein 281 (ZNF281) was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cells. Western blot was conducted to examine autophagy-related proteins, apoptosis-associated proteins and ZNF281 in CRC tissues and cells. Cell counting kit-8 (CCK8) assay was performed to detect the viability and inhibitory concentration 50% (IC50) value of 5-FU of CRC cells. The apoptosis of CRC cells was measured by flow cytometry. The binding sites between miR-23b-3p and UCA1 or ZNF281 were predicted by miRcode and Starbase software, respectively, and the combination was confirmed by dual-luciferase reporter assay and RIP assay. Murine xenograft model was established to verify the role of UCA1 on the 5-FU resistance of CRC in vivo. Results: The 5-FU resistance of CRC was positively related to the level of UCA1 and autophagy. UCA1 accelerated the 5-FU resistance of CRC cells through facilitating autophagy and suppressing apoptosis. MiR-23b-3p was a target of UCA1 in 293T and CRC cells. The knockdown of miR-23b-3p reversed the inhibitory effects of UCA1 interference on the 5-FU resistance and autophagy and the promoting impact on the apoptosis of CRC cells. ZNF281 could bind to miR-23b-3p in 293T cells. MiR-23b-3p elevated the 5-FU sensitivity through down-regulating ZNF281 in CRC cells. UCA1 interference enhanced the 5-FU sensitivity of CRC through miR-23b-3p/ZNF281 axis in vivo. Conclusion: UCA1 mediated 5-FU resistance of CRC cells through facilitating autophagy and inhibiting apoptosis via miR-23b-3p/ZNF281 axis in vivo and in vitro.	[Xian, Zhenyu; Wang, Ting; Zeng, Junyi; Cai, Jinlin] Sun Yat Sen Univ, Affiliated Hosp 6, Graceland Med Ctr, Guangzhou, Guangdong, Peoples R China; [Hu, Bang; Zou, Qi] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Gastrointestinal & Anal Hosp, Guangzhou, Guangdong, Peoples R China; [Zhu, Peixuan] Guangzhou Gen Hosp Foresea Life Insurance, Int Med Ctr, 703 Xinchengdadao, Guangzhou 511300, Guangdong, Peoples R China		Zhu, PX (corresponding author), Guangzhou Gen Hosp Foresea Life Insurance, Int Med Ctr, 703 Xinchengdadao, Guangzhou 511300, Guangdong, Peoples R China.	zhupx@gzqhrsyy.com					Ambros V, 2004, NATURE, V431, P350, DOI 10.1038/nature02871; Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; Bian ZH, 2016, SCI REP-UK, V6, DOI 10.1038/srep23892; Calin GA, 2006, NAT REV CANCER, V6, P857, DOI 10.1038/nrc1997; Cesana M, 2011, CELL, V147, P358, DOI 10.1016/j.cell.2011.09.028; Croce CM, 2005, CELL, V122, P6, DOI 10.1016/j.cell.2005.06.036; Campos-Viguri GE, 2020, SCI REP-UK, V10, DOI 10.1038/s41598-020-60143-x; Fang Q, 2016, MED SCI MONITOR, V22, DOI 10.12659/MSM.900688; Hahn S, 2013, EMBO J, V32, P3079, DOI 10.1038/emboj.2013.236; Han Y, 2014, PATHOLOGY, V46, P396, DOI 10.1097/PAT.0000000000000125; Hu YR, 2017, MOL CANCER, V16, DOI 10.1186/s12943-017-0743-3; Huang J, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2013.541; Jonker FHW, 2015, DIS COLON RECTUM, V58, P931, DOI 10.1097/DCR.0000000000000432; Kallen AN, 2013, MOL CELL, V52, P101, DOI 10.1016/j.molcel.2013.08.027; Kou CH, 2016, ONCOL LETT, V12, P4838, DOI 10.3892/ol.2016.5265; Li JY, 2014, INT J CLIN EXP PATHO, V7, P7938; Li WP, 2014, FEBS LETT, V588, P1608, DOI 10.1016/j.febslet.2014.02.055; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Loftus JC, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0039818; PENG BH, 2019, J IMMUNOTHER CANCER, V8, DOI DOI 10.1186/S40425-019-0701-2; Qian Y, 2017, DIGEST DIS SCI, V62, P2011, DOI 10.1007/s10620-017-4611-1; Qin Chang-Jiang, 2019, Cell Physiol Biochem, V52, P1503, DOI 10.33594/000000104; Salvi A, 2009, FEBS J, V276, P2966, DOI 10.1111/j.1742-4658.2009.07014.x; Sun FF, 2019, MOL MED REP, V20, P3583, DOI 10.3892/mmr.2019.10588; Wang F, 2008, FEBS LETT, V582, P1919, DOI 10.1016/j.febslet.2008.05.012; Wang F, 2015, ONCOTARGET, V6, P7899, DOI 10.18632/oncotarget.3219; Wang HH, 2017, ONCOTARGET, V8, P64638, DOI 10.18632/oncotarget.18344; Wang K, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms4596; Wang M, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-1187-4; Wang XS, 2006, CLIN CANCER RES, V12, P4851, DOI 10.1158/1078-0432.CCR-06-0134; Wang ZX, 2008, STEM CELLS, V26, P2791, DOI 10.1634/stemcells.2008-0443; Wei HM, 2019, INT IMMUNOPHARMACOL, V73, P72, DOI 10.1016/j.intimp.2019.04.049; Xue YB, 2019, THORAC CANCER, V10, P1692, DOI 10.1111/1759-7714.13131; Yang T, 2018, GENE, V670, P114, DOI 10.1016/j.gene.2018.05.061; Yu XF, 2017, SCI REP-UK, V7, DOI 10.1038/srep42226; Zhang HH, 2015, CANCER LETT, V356, P781, DOI 10.1016/j.canlet.2014.10.029; Zhang L, 2017, BIOMED PHARMACOTHER, V96, P884, DOI 10.1016/j.biopha.2017.10.056; Zhang Y, 2018, J CELL BIOCHEM, V119, P6296, DOI 10.1002/jcb.26899	38	11	12	2	6	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2020	13						7571	7583		10.2147/OTT.S258727			13	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	MT3ZE	WOS:000554906400001	32801774	Green Published, gold			2022-04-25	
J	Liu, C; Ji, L; Song, X				Liu, Chao; Ji, Le; Song, Xue			Long non coding RNA UCA1 contributes to the autophagy and survival of colorectal cancer cells via sponging miR-185-5p to up-regulate the WISP2/beta-catenin pathway	RSC ADVANCES			English	Article							WNT/BETA-CATENIN PATHWAY; HEPATOCELLULAR-CARCINOMA; PREDICTIVE BIOMARKER; PANCREATIC-CANCER; POOR-PROGNOSIS; NONCODING RNAS; LUNG-CANCER; PROLIFERATION; MICRORNA-185; INHIBITION	The estimated number of new cases of colorectal cancer (CRC) will increase to 140250 in 2018 worldwide. The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has recently been shown to be dysregulated in CRC, which plays an important role in the progression of CRC. However, the biological role and the underling mechanism of UCA1 in the carcinogenesis of CRC remain unclear. Herein, we found that UCA1 was aberrantly upregulated in two CRC cell lines (SW620 and HT29) compared to colorectal cell CCD-18Co. UCA1 knockdown inhibited the apoptosis, growth and autophagy of CRC cell lines in vitro. Furthermore, UCA1 could act as an endogenous sponge by directly interacting with miR-185-5p and downregulation miR-185-5p expression. In addition, UCA1 could reverse the inhibitory effect of miR-185-5p on the growth and autophagy of CRC cells, which might be involved in the derepression of member 1 (WNT1)-inducible signaling pathway protein 2 (WISP2, a target gene of miR-185-5p) expression and the activation of the WISP2/beta-catenin signaling pathway. In vivo, the present study elucidates a novel UCA1-miR-185-5p-WISP2-Wnt/beta-catenin axis in CRC, which may help us to understand the pathogenesis and the feasibility of lncRNA-directed diagnosis and therapy of CRC.	[Liu, Chao; Ji, Le; Song, Xue] Yanan Univ, Affiliated Hosp, Dept Gastroenterol, 43 North St, Yanan 716000, Shaanxi, Peoples R China		Song, X (corresponding author), Yanan Univ, Affiliated Hosp, Dept Gastroenterol, 43 North St, Yanan 716000, Shaanxi, Peoples R China.	songxuedoctor@outlook.com					Ashworth C, 2018, NAT REV MATER, V3, DOI 10.1038/natrevmats.2017.92; Barreto SC, 2016, J BUON, V21, P1359; Bian ZH, 2016, SCI REP-UK, V6, DOI 10.1038/srep23892; Boehler M, 2011, J CANCER EDUC, V26, P147, DOI 10.1007/s13187-010-0161-3; Dai ZM, 2014, J NEUROSCI, V34, P8467, DOI 10.1523/JNEUROSCI.0311-14.2014; Dhar G, 2007, CANCER LETT, V254, P63, DOI 10.1016/j.canlet.2007.02.012; Dong-Xu W, 2015, INDIAN J CANCER, V52, P182, DOI 10.4103/0019-509X.186576; Fan Y, 2014, FEBS J, V281, P1750, DOI 10.1111/febs.12737; Gu W, 2014, ONCOL REP, V31, P397, DOI 10.3892/or.2013.2831; Han Y, 2014, PATHOLOGY, V46, P396, DOI 10.1097/PAT.0000000000000125; Hong HH, 2016, ONCOTARGET, V7, P44442, DOI 10.18632/oncotarget.10142; Ji JF, 2015, BRIT J CANCER, V113, P921, DOI 10.1038/bjc.2015.285; Ji JF, 2014, ONCOL REP, V31, P533, DOI 10.3892/or.2013.2909; Jing FY, 2017, TUMOR BIOL, V39, DOI 10.1177/1010428317703650; Lai K, 2014, J CLIN PATHOL, V67, P854, DOI 10.1136/jclinpath-2014-202529; Leal LF, 2011, J CLIN ENDOCR METAB, V96, P3106, DOI 10.1210/jc.2011-0363; Li K, 2016, ONCOL LETT, V11, P3896, DOI 10.3892/ol.2016.4481; Lu ZJ, 2014, MOL MED REP, V10, P2401, DOI 10.3892/mmr.2014.2562; Ni BB, 2015, INT J ONCOL, V47, P1329, DOI 10.3892/ijo.2015.3109; Nie W, 2016, CANCER LETT, V371, P99, DOI 10.1016/j.canlet.2015.11.024; Sebio A, 2014, EXPERT OPIN THER TAR, V18, P611, DOI 10.1517/14728222.2014.906580; Siegel RL, 2018, CA-CANCER J CLIN, V68, P7, DOI 10.3322/caac.21442; Tokura Y., 2017, B CHEM SOC JPN, V90, P967; Tomimaru Y, 2013, LIVER INT, V33, P1100, DOI 10.1111/liv.12188; Tuo YL, 2015, EUR REV MED PHARMACO, V19, P3403; Wang F, 2015, ONCOTARGET, V6, P7899, DOI 10.18632/oncotarget.3219; Wang HM, 2015, INT J CLIN EXP MED, V8, P11824; Wu MY, 2014, ONCOL REP, V32, P513, DOI 10.3892/or.2014.3266; Wu SH, 2015, INT J CLIN EXP PATHO, V8, P3882; Xu MD, 2014, MODERN PATHOL, V27, P1310, DOI 10.1038/modpathol.2014.33; Yang YX, 2016, ADV EXP MED BIOL, V937, P19, DOI 10.1007/978-3-319-42059-2_2; Zhang Z, 2015, ONCOGENE, V34, P4808, DOI 10.1038/onc.2014.404; Zhu YY, 2018, CANCER SCI, V109, P2235, DOI 10.1111/cas.13632	33	3	3	0	1	ROYAL SOC CHEMISTRY	CAMBRIDGE	THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND		2046-2069		RSC ADV	RSC Adv.		2019	9	25					14160	14166		10.1039/c8ra10468a			7	Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	HZ1WI	WOS:000468640100024		gold			2022-04-25	
J	Lan, SH; Lin, SC; Wang, WC; Yang, YC; Lee, JC; Lin, PW; Chu, ML; Lan, KY; Zuchini, R; Liu, HS; Wu, SY				Lan, Sheng-Hui; Lin, Shu-Ching; Wang, Wei-Chen; Yang, Yu-Chan; Lee, Jenq-Chang; Lin, Pei-Wen; Chu, Man-Ling; Lan, Kai-Ying; Zuchini, Roberto; Liu, Hsiao-Sheng; Wu, Shan-Ying			Autophagy Upregulates miR-449a Expression to Suppress Progression of Colorectal Cancer	FRONTIERS IN ONCOLOGY			English	Article						autophagy; miR-449a; FoxO1; colorectal cancer; tumorigenesis	C-MYC; TUMORIGENESIS; SURVIVAL; DISEASE; FOXO1; GENE	Many studies reported that microRNAs (miRNAs) target autophagy-related genes to affect carcinogenesis, however, autophagy-deficiency-related miRNA dysfunction in cancer development remains poorly explored. During autophagic progression, we identified miR-449a as the most up-regulated miRNA. MiR-449a expression was low in the tumor parts of CRC patient specimens and inversely correlated with tumor stage and metastasis with the AUC (area under the curve) of 0.899 and 0.736 as well as poor overall survival rate, indicating that miR-449a has the potential to be a prognostic biomarker. In the same group of CRC specimens, low autophagic activity (low Beclin 1 expression and high p62 accumulation) was detected, which was significantly associated with miR-449a expression. Mechanistic studies disclosed that autophagy upregulates miR-449a expression through degradation of the coactivator p300 protein which acetylates the transcription factor Forkhead Box O1 (FoxO1). Unacetylated FoxO1 translocated to the nucleus and bound to the miR-449a promoter to drive gene expression. Either activation of autophagy by the inducer or overexpression of exogenous miR-449a decreases the expression of target gene LEF-1 and cyclin D1, which lead to decreased proliferation, colony formation, migration, and invasion of CRC cells. Autophagy-miR-449a-tartet genes mediated suppression of tumor formation was further confirmed in the xenograft mouse model. In conclusion, this study reveals a novel mechanism wherein autophagy utilizes miR-449a-LEF1-cyclin D1 axis to suppress CRC tumorigenesis. Our findings open a new avenue toward prognosis and treatment of CRC patients by manipulating autophagy-miR-449a axis.	[Lan, Sheng-Hui; Lan, Kai-Ying] Natl Yang Ming Chiao Tung Univ, Dept Life Sci, Taipei, Taiwan; [Lan, Sheng-Hui; Lan, Kai-Ying] Natl Yang Ming Chiao Tung Univ, Inst Genome Sci, Taipei, Taiwan; [Lan, Sheng-Hui] Natl Yang Ming Chiao Tung Univ, Canc Progress Res Ctr, Taipei, Taiwan; [Lin, Shu-Ching; Wang, Wei-Chen; Yang, Yu-Chan; Liu, Hsiao-Sheng] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Coll Med, Tainan, Taiwan; [Lee, Jenq-Chang] Natl Cheng Kung Univ Hosp, Dept Surg, Coll Med, Tainan, Taiwan; [Lin, Pei-Wen; Chu, Man-Ling; Liu, Hsiao-Sheng] Kaohsiung Med Univ, Coll Med, Grad Inst Clin Med, Ctr Canc Res, Kaohsiung, Taiwan; [Zuchini, Roberto] Hosp Ctr Med, Dept Gastroenterol, Guatemala City, Guatemala; [Liu, Hsiao-Sheng] Kaohsiung Med Univ, Coll Med, Master Sci Program Trop Med, Kaohsiung, Taiwan; [Wu, Shan-Ying] Taipei Med Univ, Dept Microbiol & Immunol, Coll Med, Taipei, Taiwan; [Wu, Shan-Ying] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei, Taiwan		Liu, HS (corresponding author), Natl Cheng Kung Univ, Dept Microbiol & Immunol, Coll Med, Tainan, Taiwan.; Liu, HS (corresponding author), Kaohsiung Med Univ, Coll Med, Grad Inst Clin Med, Ctr Canc Res, Kaohsiung, Taiwan.; Liu, HS (corresponding author), Kaohsiung Med Univ, Coll Med, Master Sci Program Trop Med, Kaohsiung, Taiwan.; Wu, SY (corresponding author), Taipei Med Univ, Dept Microbiol & Immunol, Coll Med, Taipei, Taiwan.; Wu, SY (corresponding author), Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei, Taiwan.	hsliu713@kmu.edu.tw; shanyingwu@tmu.edu.tw		Wu, Shan-Ying/0000-0003-2380-5760	Ministry of Science and Technology, Taiwan, R.O.C.Ministry of Science and Technology, Taiwan [MOST 109-2314-B-038-119-MY2, MOST 104-2320-B-006-021-MY3]; Taipei Medical University [TMU108-AE1-B39]; Ministry of Health and WelfareMinistry of Health, Labour and Welfare, Japan [MOHW 106-TDU-B-211-124-003]; Kaohsiung Medical University Research Center Grant [KMU-TC108A04-0, KMU-TC108A04-2, KMU-TC109A04-1]	This study was supported by the grants from the Ministry of Science and Technology, Taiwan, R.O.C. (MOST 109-2314-B-038-119-MY2 to S-YW; MOST 104-2320-B-006-021-MY3 to H-SL), Taipei Medical University (TMU108-AE1-B39 to S-YW), Ministry of Health and Welfare (MOHW 106-TDU-B-211-124-003 to H-SL) and Kaohsiung Medical University Research Center Grant (KMU-TC108A04-0, KMU-TC108A04-2, and KMU-TC109A04-1 to H-SL).	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Oncol.	OCT 19	2021	11								738144	10.3389/fonc.2021.738144			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	WT4DP	WOS:000715816900001	34737955	gold, Green Published			2022-04-25	
J	Sun, SY; Hu, XT; Yu, XF; Zhang, YY; Liu, XH; Liu, YH; Wu, SH; Li, YY; Cui, SX; Qu, XJ				Sun, Shi-Yue; Hu, Xue-Tao; Yu, Xin-Feng; Zhang, Yue-Ying; Liu, Xiao-Hui; Liu, Yuan-Hang; Wu, Shu-Hua; Li, Yang-Yang; Cui, Shu-Xiang; Qu, Xian-Jun			Nuclear translocation of ATG5 induces DNA mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) via interacting with Mis18 alpha in colorectal cancer	BRITISH JOURNAL OF PHARMACOLOGY			English	Article						5-FU resistance; colorectal cancer; hypermethylation of MLH1 promoter CpG island; Mis18a; MMR-D/MSI; nuclear translocation of ATG5	REVISED BETHESDA GUIDELINES; MICROSATELLITE INSTABILITY; CENTROMERIC CHROMATIN; LIVER METASTASES; AUTOPHAGY; EXPRESSION; THERAPY; CARCINOMAS; MANAGEMENT; ADJUVANT	Background and Purpose It is well known that microsatellite instability-high (MSI-H) is associated with 5-fluorouracil (5-FU) resistance in colorectal cancer. MSI-H is the phenotype of DNA mismatch repair deficiency (MMR-D), mainly occurring due to hypermethylation of MLH1 promoter CpG island. However, the mechanisms of MMR-D/MSI-H are unclear. We aim to investigate the pathway of MMR-D/MSI-H involved in 5-FU resistance. Experimental Approach Human colorectal cancer specimens were diagnosed for MSI-H by immunohistochemistry and western blotting. Proteome microarray interactome assay was performed to screen nuclear proteins interacting with ATG5. Nuclear ATG5 and ATG5-Mis18 alpha overexpression were analysed in ATG5(high) colorectal cancer bearing mice. The methylation assay determined the hypermethylation of hMLH1 promoter CpG island in freshly isolated human colorectal cancer tissue samples and HT29(atg5) and SW480(atg5) cancer cells. Key Results In ATG5(high) colorectal cancer patients, 5-FU-based therapy resulted in nuclear translocation of ATG5, leading to MSI-H. Colorectal cancer in Atg5 Tg mice demonstrated 5-FU resistance, compared to Atg5(+/-) and WT mice. Proteome microarray assay identified Mis18 alpha, a protein localized on the centromere and a source for methylation of the underlying chromatin, which responded to the translocated nuclear ATG5 leading to ATG5-Mis18 alpha conjugate overexpression. This resulted in MLH1 deficiency due to hypermethylation of hMLH1 promoter CpG island, while the deletion of nuclear Mis18 alpha failed to induce ATG5-Mis18 alpha complex and MMR-D/MSI-H. Conclusions and Implications Nuclear ATG5 resulted in MMR-D/MSI-H through its interaction with Mis18 alpha in ATG5(high) colorectal cancer cells. We suggest that ATG5-Mis18 alpha or Mis18 alpha may be a therapeutic target for treating colorectal cancer.	[Sun, Shi-Yue; Hu, Xue-Tao; Yu, Xin-Feng; Liu, Xiao-Hui; Qu, Xian-Jun] Capital Med Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing, Peoples R China; [Sun, Shi-Yue] China Acad Chinese Med Sci, Inst Acu Moxibust, Beijing, Peoples R China; [Zhang, Yue-Ying] Shandong First Med Univ & Shandong Acad Med Sci, Dept Expt Pathol, Coll Basic Med Sci, Jinan, Peoples R China; [Liu, Yuan-Hang; Wu, Shu-Hua; Li, Yang-Yang] Hosp Bin Zhou Med Coll, Dept Pathol, Binzhou, Peoples R China; [Cui, Shu-Xiang] Capital Med Univ, Sch Publ Hlth, Toxicol & Sanit Chem, Beijing, Peoples R China		Qu, XJ (corresponding author), Capital Med Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing, Peoples R China.; Cui, SX (corresponding author), Capital Med Univ, Sch Publ Hlth, Toxicol & Sanit Chem, Beijing, Peoples R China.	sxccui@ccmu.edu.cn; qxj@ccmu.edu.cn			Beijing Municipal Commission of EducationBeijing Municipal Commission of Education [KZ201810025033]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872884, 81973350]; Natural Science Foundation of Beijing MunicipalityBeijing Natural Science Foundation	Beijing Municipal Commission of Education, Grant/Award Number: KZ201810025033; National Natural Science Foundation of China, Grant/Award Numbers: 81872884, 81973350; Natural Science Foundation of Beijing Municipality	Achilli P, 2021, INT J CANCER, V148, P161, DOI 10.1002/ijc.33203; Alexander SPH, 2019, BRIT J PHARMACOL, V176, pS229, DOI 10.1111/bph.14750; Alexander SPH, 2018, BRIT J PHARMACOL, V175, P407, DOI 10.1111/bph.14112; An CH, 2005, CLIN CANCER RES, V11, P656; Ashktorab H, 2005, INT J CANCER, V116, P914, DOI 10.1002/ijc.21062; Barchitta M, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20153842; Baretti M, 2018, CLIN COLORECTAL CANC, V17, pE489, DOI 10.1016/j.clcc.2018.03.010; Bayraktar S, 2010, CLIN COLORECTAL CANC, V9, P144, DOI 10.3816/CCC.2010.n.019; Benatti P, 2005, CLIN CANCER RES, V11, P8332, DOI 10.1158/1078-0432.CCR-05-1030; Chen LZ, 2019, INT J CLIN EXP PATHO, V12, P3685; Chen Y, 2013, MOL CELL PROTEOMICS, V12, P2804, DOI 10.1074/mcp.M112.025882; 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J. Pharmacol.	JUN	2021	178	11					2351	2369		10.1111/bph.15422		APR 2021	19	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	SB9SU	WOS:000645256900001	33645631				2022-04-25	
J	Rathore, B; Sunwoo, K; Jangili, P; Kim, J; Kim, JH; Huang, MN; Xiong, J; Sharma, A; Yang, ZG; Qu, JL; Kim, JS				Rathore, Bhowmira; Sunwoo, Kyoung; Jangili, Paramesh; Kim, Jiseon; Kim, Ji Hyeon; Huang, Meina; Xiong, Jia; Sharma, Amit; Yang, Zhigang; Qu, Junle; Kim, Jong Seung			Nanomaterial designing strategies related to cell lysosome and their biomedical applications: A review	BIOMATERIALS			English	Review						Lyososome; Nanomaterial; Diagnosis; Therapeutics; Endocytosis/non-endocyotic; Autophagy	NANOPARTICLES INDUCE AUTOPHAGY; COLORECTAL-CANCER CELLS; WALLED CARBON NANOTUBES; TARGETED DRUG-DELIVERY; MEMBRANE PERMEABILIZATION; DEATH; IMPAIRMENT; MECHANISM; PEPTIDES; GRAPHENE	Lysosomes, an important organelle of eukaryotic cells, are covered with the cell membrane and contain an array of degradative enzymes. The disrupt in lysosomal functions may lead to the development of severe diseases. In nanotechnology, nanomaterials working mechanism and its biomedical output are highly dependent on the lysosomes as it plays a crucial role in intracellular transport. Several nanomaterials specifically designed for lysosome-related actions are highly advantageous in trafficking and delivering the loaded imaging/therapeutic agents. But for other applications, especially gene-based therapeutic delivery into the sub-organelles such as mitochondria and nucleus, lysosomal related degradation could be an obstacle to achieve a maximal therapeutic index. In order to understand the relationship between lysosomes and designed nanomaterials for kind of desired application in biomedical research, complete knowledge of their various designing strategies, size dependent or ligand supportive cellular uptake mechanisms, trafficking, and localizations in eukaryotic cells is highly desired. In this review, we intended to discuss various nanomaterial types that have been applied in biomedical applications based on lysosomal internalization and escape from endo/lysosomes and explored their related advantages/disadvantages. Additionally, we also deliberated nanomaterials direct translocation mechanism, their autophagic accumulation and the underlying mechanism to induced autophagy. Finally, some challenges and critical issues in current research from clinical application perspective has also been addressed. Great understanding of these factors will help in understanding and facilitating the development of safe and effective lysosomal related nanomaterial-based imaging/therapeutic systems for future applications.	[Rathore, Bhowmira; Huang, Meina; Xiong, Jia; Yang, Zhigang; Qu, Junle] Shenzhen Univ, Coll Phys & Optoelect Engn, Minist Educ & Guangdong Prov, Key Lab Optoelect Devices & Syst, Shenzhen 518060, Peoples R China; [Sunwoo, Kyoung; Jangili, Paramesh; Kim, Jiseon; Kim, Ji Hyeon; Sharma, Amit; Kim, Jong Seung] Korea Univ, Dept Chem, Seoul 02841, South Korea		Yang, ZG; Qu, JL (corresponding author), Shenzhen Univ, Coll Phys & Optoelect Engn, Minist Educ & Guangdong Prov, Key Lab Optoelect Devices & Syst, Shenzhen 518060, Peoples R China.; Sharma, A; Kim, JS (corresponding author), Korea Univ, Dept Chem, Seoul 02841, South Korea.	amitorg83@gmail.com; zhgyang@szu.edu.cn; jlqu@szu.edu.cn; jongskim@korea.ac.kr	Jangili, Paramesh/AAA-4652-2022; Sessler, Jonathan/AAY-7091-2021; Kim, Jong Seung/N-4504-2015; Sharma, Amit/F-7316-2018	Kim, Jong Seung/0000-0003-3477-1172; Sharma, Amit/0000-0003-2815-8208; PARAMESH, JANGILI/0000-0003-4220-8443; Sunwoo, Kyoung/0000-0003-0041-5022	National Research Foundation of KoreaNational Research Foundation of Korea [CRI 2018R1A3B1052702]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [61875131/61525503/61620106016/61835009/81727804]; National Basic Research Program of ChinaNational Basic Research Program of China [2015CB352005]; Guangdong Natural Science Foundation Innovation Team [2014A030312008]; National Key R&D Program of China [2017YFA0700500]; Guangdong Province [2015KGJHZ002/2016KCXTD007]; Shenzhen Basic Research Project [JCYJ20170818100931714/JCYJ20150930104948169/JCYJ20160328144746940/JCYJ20170412105003520]	This work was collaboratory supported by the National Research Foundation of Korea (CRI 2018R1A3B1052702, J.S.K); the National Natural Science Foundation of China (61875131/61525503/61620106016/61835009/81727804); the National Basic Research Program of China (2015CB352005); Guangdong Natural Science Foundation Innovation Team (2014A030312008); the National Key R&D Program of China (2017YFA0700500); Guangdong Province (2015KGJHZ002/2016KCXTD007) and Shenzhen Basic Research Project (JCYJ20170818100931714/JCYJ20150930104948169/JCYJ20160328144746940/JCYJ20170412105003520).	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J	Kaneko, M; Nozawa, H; Hiyoshi, M; Tada, N; Murono, K; Nirei, T; Emoto, S; Kishikawa, J; Iida, Y; Sunami, E; Tsuno, NH; Kitayama, J; Takahashi, K; Watanabe, T				Kaneko, Manabu; Nozawa, Hiroaki; Hiyoshi, Masaya; Tada, Noriko; Murono, Koji; Nirei, Takako; Emoto, Shigenobu; Kishikawa, Junko; Iida, Yuuki; Sunami, Eiji; Tsuno, Nelson H.; Kitayama, Joji; Takahashi, Koki; Watanabe, Toshiaki			Temsirolimus and chloroquine cooperatively exhibit a potent antitumor effect against colorectal cancer cells	JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY			English	Article						Temsirolimus; Chloroquine; Colorectal cancer; mTOR; Autophagy; Angiogenesis	HISTONE DEACETYLASE INHIBITOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; MALIGNANT GLIOMA-CELLS; MAMMALIAN TARGET; RAD001 EVEROLIMUS; INDUCED APOPTOSIS; INDUCED AUTOPHAGY; MTOR INHIBITORS; RAPAMYCIN; GROWTH	Temsirolimus (TEM) is a novel, water-soluble mammalian target of rapamycin (mTOR) inhibitor that has shown activity against a wide range of cancers in preclinical models, but its efficacy against colorectal cancer (CRC) has not been fully explored. We evaluated the antitumor effect of TEM in CRC cell lines (CaR-1, HT-29, Colon26) in vitro and in vivo. In vitro, cell growth inhibition was assessed using a MTS assay. Apoptosis induction and cell cycle effects were measured using flow cytometry. Modulation of mTOR signaling was measured using immunoblotting. Antitumor activity as a single agent was evaluated in a mouse subcutaneous tumor model of CRC. The effects of adding chloroquine, an autophagy inhibitor, to TEM were evaluated in vitro and in vivo. In vitro, TEM was effective in inhibiting the growth of two CRC cell lines with highly activated AKT, possibly through the induction of G1 cell cycle arrest via a reduction in cyclin D1 expression, whereas TEM reduced HIF-1 alpha and VEGF in all three cell lines. In a mouse subcutaneous tumor model, TEM inhibited the growth of tumors in all cell lines, not only through direct growth inhibition but also via an anti-angiogenic effect. We also explored the effects of adding chloroquine, an autophagy inhibitor, to TEM. Chloroquine significantly potentiated the antitumor activity of TEM in vitro and in vivo. Moreover, the combination therapy triggered enhanced apoptosis, which corresponded to an increased Bax/Bcl-2 ratio. Based on these data, we propose TEM with or without chloroquine as a new treatment option for CRC.	[Kaneko, Manabu; Nozawa, Hiroaki; Hiyoshi, Masaya; Tada, Noriko; Murono, Koji; Nirei, Takako; Emoto, Shigenobu; Kishikawa, Junko; Iida, Yuuki; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki] Univ Tokyo, Dept Surg Oncol, Fac Med, Bunkyo Ku, Tokyo 1138655, Japan; [Tsuno, Nelson H.; Takahashi, Koki] Univ Tokyo, Dept Transfus Med, Fac Med, Bunkyo Ku, Tokyo 1138655, Japan		Kaneko, M (corresponding author), Univ Tokyo, Dept Surg Oncol, Fac Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.	m.kaneko@fancy.ocn.ne.jp	Murono, Koji/AAC-3958-2020				Altomare I, 2011, ONCOLOGIST, V16, P1131, DOI 10.1634/theoncologist.2011-0078; Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; Bellodi C, 2009, J CLIN INVEST, V119, P1109, DOI 10.1172/JCI35660; Bursch W, 1996, CARCINOGENESIS, V17, P1595, DOI 10.1093/carcin/17.8.1595; Carew JS, 2007, BLOOD, V110, P313, DOI 10.1182/blood-2006-10-050260; Carew JS, 2011, TARGET ONCOL, V6, P17, DOI 10.1007/s11523-011-0167-8; Carew JS, 2011, J BIOL CHEM, V286, P6602, DOI 10.1074/jbc.M110.151324; Carew JS, 2010, J CELL MOL MED, V14, P2448, DOI 10.1111/j.1582-4934.2009.00832.x; Chau I, 2009, BRIT J CANCER, V100, P1704, DOI 10.1038/sj.bjc.6605061; Chen TH, 2005, PHARMACOL RES, V51, P329, DOI 10.1016/j.phrs.2004.10.004; Del Bufalo D, 2006, CANCER RES, V66, P5549, DOI 10.1158/0008-5472.CAN-05-2825; Ding ZB, 2011, CLIN CANCER RES, V17, P6229, DOI 10.1158/1078-0432.CCR-11-0816; Fan CD, 2006, BIOORGAN MED CHEM, V14, P3218, DOI 10.1016/j.bmc.2005.12.035; Guba M, 2005, TRANSPL INT, V18, P89, DOI 10.1111/j.1432-2277.2004.00026.x; Guo XL, 2013, J MOL MED, V91, P473, DOI 10.1007/s00109-012-0966-0; Hayun R, 2009, LEUKEMIA LYMPHOMA, V50, P625, DOI 10.1080/10428190902789181; Hu YL, 2012, AUTOPHAGY, V8, P979, DOI 10.4161/auto.20232; Hu YL, 2012, CANCER RES, V72, P1773, DOI 10.1158/0008-5472.CAN-11-3831; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Jiang PD, 2008, CELL PHYSIOL BIOCHEM, V22, P431, DOI 10.1159/000185488; Kanzawa T, 2003, CANCER RES, V63, P2103; Kanzawa T, 2004, CELL DEATH DIFFER, V11, P448, DOI 10.1038/sj.cdd.4401359; Kapoor A, 2009, CANCER-AM CANCER SOC, V115, P3618, DOI 10.1002/cncr.24409; Kim DD, 2012, EXPERT OPIN INV DRUG, V21, P1775, DOI 10.1517/13543784.2012.721353; Lagneaux L, 2002, LEUKEMIA LYMPHOMA, V43, P1087, DOI 10.1080/10428190290021506; Lane HA, 2009, CLIN CANCER RES, V15, P1612, DOI 10.1158/1078-0432.CCR-08-2057; Mabuchi S, 2007, CLIN CANCER RES, V13, P4261, DOI 10.1158/1078-0432.CCR-06-2770; Mabuchi S, 2007, CANCER RES, V67, P2408, DOI 10.1158/0008-5472.CAN-06-4490; Manegold PC, 2008, CLIN CANCER RES, V14, P892, DOI 10.1158/1078-0432.CCR-07-0955; Miyake N, 2012, ONCOL REP, V28, P848, DOI 10.3892/or.2012.1855; Nguyen SA, 2012, CURR TREAT OPTION ON, V13, P71, DOI 10.1007/s11864-011-0180-2; Nozawa H, 2007, CANCER LETT, V251, P105, DOI 10.1016/j.canlet.2006.11.008; Paglin S, 2001, CANCER RES, V61, P439; Park BC, 2008, TOXICOL LETT, V178, P52, DOI 10.1016/j.toxlet.2008.02.003; Phung TL, 2006, CANCER CELL, V10, P159, DOI 10.1016/j.ccr.2006.07.003; Rao R, 2012, MOL CANCER THER, V11, P973, DOI 10.1158/1535-7163.MCT-11-0979; Semela D, 2007, J HEPATOL, V46, P840, DOI 10.1016/j.jhep.2006.11.021; Shinohara ET, 2005, ONCOGENE, V24, P5414, DOI 10.1038/sj.onc.1208715; Sun SY, 2005, CANCER RES, V65, P7052, DOI 10.1158/0008-5472.CAN-05-0917; Takeuchi H, 2005, CANCER RES, V65, P3336, DOI 10.1158/0008-5472.CAN-04-3640; Van Cutsem E, 2010, ANN ONCOL, V21, pv93, DOI 10.1093/annonc/mdq222; Wan XL, 2006, NEOPLASIA, V8, P394, DOI 10.1593/neo.05820; Zhang JF, 2007, TRANSPL IMMUNOL, V17, P162, DOI 10.1016/j.trim.2006.12.003; Zheng YZ, 2009, CANCER INVEST, V27, P286, DOI 10.1080/07357900802427927; Zhu Keyi, 2009, Proceedings of the American Association for Cancer Research Annual Meeting, V50, P451, DOI 10.1038/onc.2009.343	45	19	20	2	17	SPRINGER	NEW YORK	ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES	0171-5216	1432-1335		J CANCER RES CLIN	J. Cancer Res. Clin. Oncol.	MAY	2014	140	5					769	781		10.1007/s00432-014-1628-0			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AF0WA	WOS:000334434000008	24619662				2022-04-25	
J	Dutta, N; Pemmaraju, DB; Ghosh, S; Ali, A; Mondal, A; Majumder, C; Nelson, VK; Mandal, SC; Misra, AK; Rengan, AK; Ravichandiran, V; Che, CT; Gurova, KV; Gudkov, AV; Pal, M				Dutta, Naibedya; Pemmaraju, Deepak Bharadwaj; Ghosh, Suvranil; Ali, Asif; Mondal, Ayan; Majumder, Chirantan; Nelson, Vinod K.; Mandal, Subhash C.; Misra, Anup K.; Rengan, Aravind K.; Ravichandiran, Velyutham; Che, Chun-Tao; Gurova, Katerina, V; Gudkov, Andrei, V; Pal, Mahadeb			Alkaloid-rich fraction of Ervatamia coronaria sensitizes colorectal cancer through modulating AMPK and mTOR signalling pathways	JOURNAL OF ETHNOPHARMACOLOGY			English	Article						Ervatamia coronaria; Alkaloid fraction; Colorectal cancer; Autophagy activator; mTOR inhibitor	INDOLE ALKALOIDS; CELL-GROWTH; AUTOPHAGY; P53; PHOSPHORYLATION; CONSTITUENTS; METABOLISM; TARGETS; LEAVES	Ethnopharmacological relevance: Ervatamia coronaria, a popular garden plant in India and some other parts of the world is known traditionally for its anti-inflammatory and anti-cancer properties. The molecular bases of these functions remain poorly understood. Aim of the study: Efficacies of the existing therapies for colorectal cancer (CRC) are limited by their lifethreatening side effects and unaffordability. Therefore, identifying a safer, efficient, and affordable therapeutic is urgent. We studied the anti-CRC activity of an alkaloid-rich fraction of E. coronaria leaf extracts (AFE) and associated underlying mechanism. Materials and methods: Activity guided solvant fractionation was adopted to identify the activity in AFE. Different cell lines, and tumor grown in syngeneic mice were used to understand the anti-CRC effect. Methodologies such as LCMS, MTT, RT-qPCR, immunoblot, immunohistochemistry were employed to understand the molecular basis of its activity. Results: We showed that AFE, which carries about six major compounds, is highly toxic to colorectal cancer (CRC) cells. AFE induced cell cycle arrest at G1 phase and p21 and p27 genes, while those of CDK2, CDK-4, cyclin-D, and cyclin-E genes were downregulated in HCT116 cells. It predominantly induced apoptosis in HCT116p53+/+ cells while the HCT116p53-/- cells under the same treatment condition died by autophagy. Notably, AFE induced upregulation of AMPK phosphorylation, and inhibition of both of the mTOR complexes as indicated by inhibition of phosphorylation of S6K1, 4EBP1, and AKT. Furthermore, AFE inhibited mTOR-driven conversion of cells from reversible cell cycle arrest to senescence (geroconversion) as well as ERK activity. AFE activity was independent of ROS produced, and did not primarily target the cellular DNA or cytoskeleton. AFE also efficiently regressed CT26-derived solid tumor in Balb/c mice acting alone or in synergy with 5FU through inducing autophagy as a major mechanism of action as indicated by upregulation of Beclin 1 and phospho-AMPK, and inhibition of phospho-S6K1 levels in the tumor tissue lysates. Conclusion: AFE induced CRC death through activation of both apoptotic and autophagy pathways without affecting the normal cells. This study provided a logical basis for consideration of AFE in future therapy regimen to overcome the limitations associated with existing anti-CRC chemotherapy.	[Dutta, Naibedya; Pemmaraju, Deepak Bharadwaj; Ghosh, Suvranil; Ali, Asif; Mondal, Ayan; Majumder, Chirantan; Misra, Anup K.; Pal, Mahadeb] Bose Inst, Div Mol Med, P1-12 CIT Scheme VIIM, Kolkata, India; [Pemmaraju, Deepak Bharadwaj; Rengan, Aravind K.] IIT, Dept Biomed Engn, Hyderabad, India; [Nelson, Vinod K.; Mandal, Subhash C.] Jadavpur Univ, Dept Pharmaceut Technol, Kolkata, India; [Ravichandiran, Velyutham] Natl Inst Pharmaceut Res & Educ NIPER, Kolkata, India; [Che, Chun-Tao] Univ Illinois, Dept Pharmaceut Sci, Chicago, IL USA; [Gurova, Katerina, V; Gudkov, Andrei, V] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY USA; [Pemmaraju, Deepak Bharadwaj] Natl Inst Pharmaceut Educ & Res, Dept Pharmacol & Toxicol, Gauhati, India		Pal, M (corresponding author), Bose Inst, Div Mol Med, P1-12 CIT Scheme VIIM, Kolkata, India.	palmahadeb@gmail.com		Pemmaraju, Deepak Bharadwaj/0000-0002-6588-1481; Mandal, Subhash Chandra/0000-0002-9079-489X	ICMR SRF fellowship; DBTDepartment of Biotechnology (DBT) India; SERBDepartment of Science & Technology (India)Science Engineering Research Board (SERB), India; Bose InstituteDepartment of Science & Technology (India)	We thank Sibsankar Roy, Samit Adhya, Manikuntala Kundu, Gopal Chakrabarti for sharing antibodies. We thank Sanghamitra Raha, and Srabani Pal for their constant support. We thank Rahul L Gajbhiye for his help in LCMS analysis. ND is a recipient of ICMR SRF fellowship. DP was supported by funds from DBT. SG is a CSIR adhoc senior research fellow. We thank SERB, DBT and Bose Institute for financial support.	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Ethnopharmacol.	JAN 30	2022	283								114666	10.1016/j.jep.2021.114666		NOV 2021	12	Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine	WW6QK	WOS:000718038400004	34592338				2022-04-25	
J	Wu, JC; Tsai, ML; Lai, CS; Lo, CY; Ho, CT; Wang, YJ; Pan, MH				Wu, Jia-Ching; Tsai, Mei-Ling; Lai, Ching-Shu; Lo, Chih-Yu; Ho, Chi-Tang; Wang, Ying-Jan; Pan, Min-Hsiung			Polymethoxyflavones prevent benzo[a]pyrene/dextran sodium sulfate-induced colorectal carcinogenesis through modulating xenobiotic metabolism and ameliorate autophagic defect in ICR mice	INTERNATIONAL JOURNAL OF CANCER			English	Article						polycyclic aromatic hydrocarbons; polymethoxyflavones; colorectal cancer; autophagic defect; microbiota	POLYCYCLIC AROMATIC-HYDROCARBONS; NATURAL DIETARY COMPOUNDS; IN-VIVO; SIGNALING PATHWAY; DNA-ADDUCTS; CANCER-RISK; MICROBIOTA; CELLS; MODEL; TETRAHYDROCURCUMIN	Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental carcinogenic pollutants and they have become an important issue in food contamination. Dietary intake of PAHs has been recognized as a major route of human exposure. However, the mechanisms behind dietary PAH-induced colorectal cancer (CRC) remain unclear. Several studies have shown that polymethoxyflavones (PMFs) are effective in preventing carcinogen-induced CRC or colitis. In this study, we investigated the preventive effect of PMFs on benzo[a]pyrene/dextran sulfate sodium (BaP/DSS)-induced colorectal tumorigenesis in ICR mice. We found that PMFs significantly prevented BaP/DSS-induced colorectal tumor formation. BaP mutagenic metabolite and DNA adducts were found to be reduced in colonic tissue in the PMFs-treated groups through the modulation of BaP metabolism. At the molecular level, the results of RNA-sequencing indicated that PMFs ameliorated BaP/DSS-induced abnormal molecular mechanism change including activated inflammation, downregulated anti-oxidation targets, and induced metastasis genes. The autophagic defect caused by BaP/DSS-induced tumorigenesis was improved by pretreatment with PMFs. We found BaP/DSS-induced CRC may be a Wnt/beta-catenin independent process. Additionally, consumption of PMFs extracts also altered the composition of gut microbiota and made it similar to that in the control group by increasing butyrate-producing probiotics and decreasing CRC-related bacteria. BaP in combination with DSS significantly induced colorectal tumorigenesis through induced DNA adduct formation, abnormal gene expression, and imbalanced gut microbiota composition. PMFs were a powerful preventive agent that suppressed BaP/DSS-induced CRC via modulating multiple pathways as well as ameliorating autophagic defect. These results demonstrated for the first time the chemopreventive efficacy and comprehensive mechanisms of dietary PMFs for preventing BaP/DSS-induced colorectal carcinogenesis.	[Wu, Jia-Ching; Wang, Ying-Jan] Natl Cheng Kung Univ, Coll Med, Dept Environm & Occupat Hlth, Tainan 704, Taiwan; [Tsai, Mei-Ling; Lai, Ching-Shu] Natl Kaohsiung Marine Univ, Dept Seafood Sci, Kaohsiung 811, Taiwan; [Lo, Chih-Yu] Natl Chiayi Univ, Dept Food Sci, 300 Syuefu Rd, Chiayi 600, Taiwan; [Ho, Chi-Tang] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA; [Wang, Ying-Jan] Natl Cheng Kung Univ, Coll Med, Dept Food Safety Hyg & Risk Management, Tainan 704, Taiwan; [Wang, Ying-Jan] Taipei Med Univ, Grad Inst Clin Med, Coll Med, Taipei 110, Taiwan; [Pan, Min-Hsiung] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan; [Pan, Min-Hsiung] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung, Taiwan; [Pan, Min-Hsiung] Natl Taiwan Univ, Inst Food Sci & Technol, 1,Sect 4,Roosevelt Rd, Taipei 10617, Taiwan		Pan, MH (corresponding author), Natl Taiwan Univ, Inst Food Sci & Technol, 1,Sect 4,Roosevelt Rd, Taipei 10617, Taiwan.; Wang, YJ (corresponding author), Natl Cheng Kung Univ, Med Coll, Dept Environm & Occupat Hlth, 138 Sheng Li Rd, Tainan 70428, Taiwan.	yjwang@mail.ncku.edu.tw; mhpan@ntu.edu.tw	Pan, Min-Hsiung/AAT-8865-2021	Pan, Min-Hsiung/0000-0002-5188-7030	Ministry of Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [105-2320-B-002-031-MY3, 105-2628-B-002-003-MY3]	Grant sponsor: Ministry of Science and Technology; Grant numbers: 105-2320-B-002-031-MY3, 105-2628-B-002-003-MY3	Baird WM, 2005, ENVIRON MOL MUTAGEN, V45, P106, DOI 10.1002/em.20095; Bansal V, 2015, ENVIRON INT, V84, P26, DOI 10.1016/j.envint.2015.06.016; Baxter NT, 2014, MICROBIOME, V2, DOI 10.1186/2049-2618-2-20; Bishehsari F, 2014, WORLD J GASTROENTERO, V20, P6055, DOI 10.3748/wjg.v20.i20.6055; Boffetta P, 1997, CANCER CAUSE CONTROL, V8, P444, DOI 10.1023/A:1018465507029; Bruner SD, 2016, CLIN PHARMACOL THER, V99, P585, DOI 10.1002/cpt.348; Caporaso JG, 2011, P NATL ACAD SCI USA, V108, P4516, DOI 10.1073/pnas.1000080107; Chen WG, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0039743; da Costa J, 2009, AM J DENT, V22, P92; Duchartre Y, 2016, CRIT REV ONCOL HEMAT, V99, P141, DOI 10.1016/j.critrevonc.2015.12.005; Eid HM, 2017, FRONT PHARMACOL, V8, DOI 10.3389/fphar.2017.00387; Galluzzi L, 2015, EMBO J, V34, P856, DOI 10.15252/embj.201490784; Hadizadeh F., 2017, GUT; Hakura A, 1998, MUTAT RES-FUND MOL M, V398, P123, DOI 10.1016/S0027-5107(97)00248-0; Hakura A, 2013, PYRENE CHEM PROPERTI, P43; Kabatkova M, 2015, MUTAGENESIS, V30, P565, DOI 10.1093/mutage/gev019; Kahl CR, 2003, ENDOCR REV, V24, P719, DOI 10.1210/er.2003-0008; Kim H, 2017, J NUTR BIOCHEM, V43, P107, DOI 10.1016/j.jnutbio.2017.02.005; Lai CS, 2011, MOL NUTR FOOD RES, V55, P1819, DOI 10.1002/mnfr.201100290; Leone A, 2017, OXID MED CELL LONGEV, V2017, DOI 10.1155/2017/2597581; Li SY, 2017, ONCOL REP, V38, P1637, DOI 10.3892/or.2017.5849; Long AS, 2016, TOXICOL APPL PHARM, V290, P31, DOI 10.1016/j.taap.2015.11.010; Lucas C, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18061310; Ma YN, 2015, ENVIRON INT, V84, P7, DOI 10.1016/j.envint.2015.07.006; Nebert DW, 2013, MOL PHARMACOL, V84, P304, DOI 10.1124/mol.113.086637; Omar Al-Hassi H, 2017, GUT; Owusu Daniel, 2015, Int J High Risk Behav Addict, V4, pe23424, DOI 10.5812/ijhrba.4(2)2015.23424; Pan MH, 2008, CHEM SOC REV, V37, P2558, DOI 10.1039/b801558a; Pan MH, 2011, MOL NUTR FOOD RES, V55, P32, DOI 10.1002/mnfr.201000412; Park SM, 2016, MOL CELL, V62, P479, DOI 10.1016/j.molcel.2016.04.011; Peran L, 2005, WORLD J GASTROENTERO, V11, P5185; Schwab C, 2014, ISME J, V8, P1101, DOI 10.1038/ismej.2013.223; Shabalala S, 2017, LIFE SCI, V180, P160, DOI 10.1016/j.lfs.2017.05.003; Shangguan HD, 2015, BIORESOURCE TECHNOL, V193, P456, DOI 10.1016/j.biortech.2015.06.151; Sonoda J, 2015, J TOXICOL PATHOL, V28, P109, DOI 10.1293/tox.2014-0061; Tanaka Takuji, 2009, J Carcinog, V8, P5; Tang YX, 2009, MOL CANCER THER, V8, P458, DOI 10.1158/1535-7163.MCT-08-0885; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; Turati F, 2012, EUR J CLIN NUTR, V66, P517, DOI 10.1038/ejcn.2011.217; Van RT, 2017, MICROBIOL SPECTR, V5; Wells K, 2017, SURG CLIN N AM, V97, P605, DOI 10.1016/j.suc.2017.01.009; Wu JC, 2017, J FOOD DRUG ANAL, V25, P176, DOI 10.1016/j.jfda.2016.10.019; Wu JC, 2015, MOL NUTR FOOD RES, V59, P2511, DOI 10.1002/mnfr.201500373; Wu JC, 2011, MOL NUTR FOOD RES, V55, P1646, DOI 10.1002/mnfr.201100454; Yamashiro K, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0171521; Yin XD, 2016, ONCOTARGET, V7, P51720, DOI 10.18632/oncotarget.10102; Zelinkova Z, 2015, POLYCYCL AROMAT COMP, V35, P248, DOI 10.1080/10406638.2014.918550; Zeng S, 2017, MOL CANC THER; Zhu J, 2014, J APPL MICROBIOL, V117, P208, DOI 10.1111/jam.12499; Zuo J, 2014, BMC GENOMICS, V15, DOI 10.1186/1471-2164-15-880	50	11	12	5	43	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0020-7136	1097-0215		INT J CANCER	Int. J. Cancer	APR 15	2018	142	8					1689	1701		10.1002/ijc.31190			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FW3CX	WOS:000425184800021	29197069	Bronze			2022-04-25	
J	Ruan, LH; Liu, WF; Yang, YH; Chu, ZJ; Yang, C; Yang, TB; Sun, JJ				Ruan, Longhui; Liu, Weifeng; Yang, Yanhui; Chu, Zhijie; Yang, Cheng; Yang, Tianbao; Sun, Junjun			TRIM16 overexpression inhibits the metastasis of colorectal cancer through mediating Snail degradation	EXPERIMENTAL CELL RESEARCH			English	Article						TRIM16; EMT; Colorectal cancer; Cell migration; Ubiquitination	FAMILY PROTEINS; EMT; AUTOPHAGY; ROLES	Tripartite motif containing 16 (TRIM16) is a member of the tripartite motif protein family and functions as a potential tumor suppressor in several cancers. However, the specific function and clinical significance of TRIM16 in colorectal cancer (CRC) remains unclear. In this study, we observed that low TRIM16 expression was detected frequently in primary colorectal cancer (CRC) tissues and was closely associated with a better prognosis. Functional studies demonstrate that TRIM16 overexpression notably inhibits the metastasis abilities of CRC in vivo and in vitro. Mechanistically, our results demonstrated that TRIM16 directly bound and ubiquitinated Snail family transcriptional repressor 1 (Snail), an important transcriptional factor of the epithelial-mesenchymal transition (EMT) process suppressing the EMT in CRC. Additionally, our data revealed that the inhibition effect of TRIM16 on cancer metastasis was dependent on Snail degradation. Collectively, our study is the first to report that TRIM16 plays a crucial anti-tumor role in CRC tumorigenesis. We also provided novel evidence that TRIM16 might act as a prognostic and therapeutic target to assess and inhibit CRC progression.	[Sun, Junjun] Henan Univ Sci & Technol, Affiliated Hosp 1, Luoyang 471003, Peoples R China; Henan Univ Sci & Technol, Coll Clin Med, Luoyang 471003, Peoples R China		Sun, JJ (corresponding author), Henan Univ Sci & Technol, Affiliated Hosp 1, Luoyang 471003, Peoples R China.	lyhnkjdx@163.com			Natural Science Foundation of Henan Province [152300410205]	The authors gratefully acknowledge the financial assistance provided by the Natural Science Foundation of Henan Province (152300410205).	Aiello NM, 2019, J EXP MED, V216, P1016, DOI 10.1084/jem.20181827; Nieto MA, 2016, CELL, V166, P21, DOI 10.1016/j.cell.2016.06.028; Nieto MA, 2013, SCIENCE, V342, P708, DOI 10.1126/science.1234850; Bakir B, 2020, TRENDS CELL BIOL, V30, P764, DOI 10.1016/j.tcb.2020.07.003; Brabletz T, 2018, NAT REV CANCER, V18, P128, DOI 10.1038/nrc.2017.118; Dongre A, 2019, NAT REV MOL CELL BIO, V20, P69, DOI 10.1038/s41580-018-0080-4; Hatakeyama S, 2017, TRENDS BIOCHEM SCI, V42, P297, DOI 10.1016/j.tibs.2017.01.002; Huo XW, 2015, BIOCHEM BIOPH RES CO, V460, P1021, DOI 10.1016/j.bbrc.2015.03.144; Jena KK, 2018, EMBO J, V37, DOI 10.15252/embj.201798358; Kim PY, 2013, APOPTOSIS, V18, P639, DOI 10.1007/s10495-013-0813-y; Kow AWC, 2019, J GASTROINTEST ONCOL, V10, P1274, DOI 10.21037/jgo.2019.08.06; Li LL, 2016, INT J ONCOL, V48, P1639, DOI 10.3892/ijo.2016.3398; Li YC, 2020, FRONT ONCOL, V9, DOI 10.3389/fonc.2019.01525; Liu HLC, 1998, MOL ENDOCRINOL, V12, P1733, DOI 10.1210/me.12.11.1733; Lv W, 2020, BIOCHEM BIOPH RES CO, V529, P799, DOI 10.1016/j.bbrc.2020.05.187; Nagy Z, 2020, SCI REP-UK, V10, DOI 10.1038/s41598-020-76722-x; Noren A, 2016, EUR J CANCER, V53, P105, DOI 10.1016/j.ejca.2015.10.055; Ozato K, 2008, NAT REV IMMUNOL, V8, P849, DOI 10.1038/nri2413; Pastushenko I, 2019, TRENDS CELL BIOL, V29, P212, DOI 10.1016/j.tcb.2018.12.001; Pohl C, 2019, SCIENCE, V366, P818, DOI 10.1126/science.aax3769; Qi L, 2016, INT J MOL MED, V38, P1734, DOI 10.3892/ijmm.2016.2774; Siegel RL, CA-CANCER J CLIN, V71, P7; Spirina LV, 2018, B EXP BIOL MED+, V166, P237, DOI 10.1007/s10517-018-4322-4; Wang Y, 2019, ADV EXP MED BIOL, V1206, P527, DOI 10.1007/978-981-15-0602-4_25; Wang YF, 2013, CURR CANCER DRUG TAR, V13, P963, DOI 10.2174/15680096113136660102; Yang J, 2020, NAT REV MOL CELL BIO, V21, P341, DOI 10.1038/s41580-020-0237-9; Yao JT, 2016, ONCOL REP, V35, P1204, DOI 10.3892/or.2015.4437; Zhao Y, 2020, FRONT CELL DEV BIOL, V8; Zhao Y, 2020, EXP CELL RES, V397, DOI 10.1016/j.yexcr.2020.112336	29	0	0	1	2	ELSEVIER INC	SAN DIEGO	525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA	0014-4827	1090-2422		EXP CELL RES	Exp. Cell Res.	SEP 1	2021	406	1							112735	10.1016/j.yexcr.2021.112735		JUL 2021	11	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	TZ6OL	WOS:000684590000009	34265287				2022-04-25	
J	Kim, MJ; Koo, JE; Han, GY; Kim, B; Lee, YS; Ahn, C; Kim, CW				Kim, Min-Jung; Koo, Jeong-Eun; Han, Gi-Yeon; Kim, Buyun; Lee, Yoo-Sun; Ahn, Chiyoung; Kim, Chan-Wha			Dual-Blocking of PI3K and mTOR Improves Chemotherapeutic Effects on SW620 Human Colorectal Cancer Stem Cells by Inducing Differentiation	JOURNAL OF KOREAN MEDICAL SCIENCE			English	Article						Cancer Stem Cells; PI3K; mTOR; Drug Resistance; Differentiation Therapy	BREAST-CANCER; PATHWAY; RAPAMYCIN; INHIBITORS; THERAPY; IDENTIFICATION; NVP-BEZ235; RESISTANCE; AUTOPHAGY; TARGET	Cancer stem cells (CSCs) have tumor initiation, self-renewal, metastasis and chemoresistance properties in various tumors including colorectal cancer. Targeting of CSCs may be essential to prevent relapse of tumors after chemotherapy. Phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signals are central regulators of cell growth, proliferation, differentiation, and apoptosis. These pathways are related to colorectal tumorigenesis. This study focused on PI3K and mTOR pathways by inhibition which initiate differentiation of SW620 derived CSCs and investigated its effect on tumor progression. By using rapamycin, LY294002, and NVP-BEZ235, respectively, PI3K and mTOR signals were blocked independently or dually in colorectal CSCs. Colorectal CSCs gained their differentiation property and lost their sternness properties most significantly in dual -blocked CSCs. After treated with anti-cancer drug (paclitaxel) on the differentiated CSCs cell viability, self-renewal ability and differentiation status were analyzed. As a result dual-blocking group has most enhanced sensitivity for anti-cancer drug. Xenograft tumorigenesis assay by using immunodeficiency mice also shows that dual-inhibited group more effectively increased drug sensitivity and suppressed tumor growth compared to single-inhibited groups. Therefore it could have potent anti-cancer effects that dual blocking of PI3K and mTOR induces differentiation and improves chemotherapeutic effects on SW620 human colorectal CSCs.	[Kim, Min-Jung; Koo, Jeong-Eun; Han, Gi-Yeon; Kim, Buyun; Lee, Yoo-Sun; Kim, Chan-Wha] Korea Univ, Coll Life Sci & Biotechnol, Dept Biotechnol, 145 Anam Ro, Seoul 02841, South Korea; [Kim, Min-Jung; Ahn, Chiyoung] Minist Food & Drug Safety, Cheongju, South Korea		Kim, CW (corresponding author), Korea Univ, Coll Life Sci & Biotechnol, Dept Biotechnol, 145 Anam Ro, Seoul 02841, South Korea.	cwkim@korea.ac.kr			Ministry of Trade, Industry and Energy [1147890]	This work was supported by Ministry of Trade, Industry and Energy (1147890, 2014)	Alison MR, 2012, CANCER TREAT REV, V38, P589, DOI 10.1016/j.ctrv.2012.03.003; Barker N, 2007, NATURE, V449, P1003, DOI 10.1038/nature06196; Botchkina G, 2013, CANCER LETT, V338, P127, DOI 10.1016/j.canlet.2012.04.006; Choi KS, 2005, BIOCHEM BIOPH RES CO, V330, P1299, DOI 10.1016/j.bbrc.2005.03.111; Dean M, 2005, NAT REV CANCER, V5, P275, DOI 10.1038/nrc1590; Dontu G, 2003, CELL PROLIFERAT, V36, P59, DOI 10.1046/j.1365-2184.36.s.1.6.x; Dubrovska A, 2010, CLIN CANCER RES, V16, P5692, DOI 10.1158/1078-0432.CCR-10-1601; Engelman JA, 2009, NAT REV CANCER, V9, P550, DOI 10.1038/nrc2664; Faivre S, 2006, NAT REV DRUG DISCOV, V5, P671, DOI 10.1038/nrd2062; Fan QW, 2006, CANCER CELL, V9, P341, DOI 10.1016/j.ccr.2006.03.029; Fang DD, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0067258; Guertin DA, 2007, CANCER CELL, V12, P9, DOI 10.1016/j.ccr.2007.05.008; Hay N, 2005, CANCER CELL, V8, P179, DOI 10.1016/j.ccr.2005.08.008; Jordan CT, 2006, NEW ENGL J MED, V355, P1253, DOI 10.1056/NEJMra061808; Katso R, 2001, ANNU REV CELL DEV BI, V17, P615, DOI 10.1146/annurev.cellbio.17.1.615; Kim DD, 2012, EXPERT OPIN INV DRUG, V21, P1775, DOI 10.1517/13543784.2012.721353; Koehl GE, 2010, ONCOGENE, V29, P1553, DOI 10.1038/onc.2009.435; Lee EK, 2010, J PROTEOME RES, V9, P5108, DOI 10.1021/pr100378z; Lin SJ, 2015, ONCOTARGET, V6, P39329, DOI 10.18632/oncotarget.5744; Liu PX, 2009, NAT REV DRUG DISCOV, V8, P627, DOI 10.1038/nrd2926; Lobo NA, 2007, ANNU REV CELL DEV BI, V23, P675, DOI 10.1146/annurev.cellbio.22.010305.104154; Maira SM, 2008, MOL CANCER THER, V7, P1851, DOI 10.1158/1535-7163.MCT-08-0017; O'Brien CA, 2007, NATURE, V445, P106, DOI 10.1038/nature05372; Osaki M, 2004, APOPTOSIS, V9, P667, DOI 10.1023/B:APPT.0000045801.15585.dd; Palozza P, 2009, CANCER LETT, V283, P108, DOI 10.1016/j.canlet.2009.03.031; Pandurangan AK, 2013, ASIAN PAC J CANCER P, V14, P2201, DOI 10.7314/APJCP.2013.14.4.2201; Petrelli A, 2015, ONCOTARGET, V6, P2315, DOI 10.18632/oncotarget.2962; Ricci-Vitiani L, 2007, NATURE, V445, P111, DOI 10.1038/nature05384; Rich JN, 2007, CANCER RES, V67, P8980, DOI 10.1158/0008-5472.CAN-07-0895; Sabatini DM, 2006, NAT REV CANCER, V6, P729, DOI 10.1038/nrc1974; Serra V, 2008, CANCER RES, V68, P8022, DOI 10.1158/0008-5472.CAN-08-1385; Siegel R, 2012, CA-CANCER J CLIN, V62, P10, DOI 10.3322/caac.20138; Slattery ML, 2010, CARCINOGENESIS, V31, P1604, DOI 10.1093/carcin/bgq142; Takeuchi H, 2005, CANCER RES, V65, P3336, DOI 10.1158/0008-5472.CAN-04-3640; Tang C, 2007, FASEB J, V21, P3777, DOI 10.1096/fj.07-8560rev; Vivanco I, 2002, NAT REV CANCER, V2, P489, DOI 10.1038/nrc839; YATSCOFF RW, 1993, THER DRUG MONIT, V15, P478, DOI 10.1097/00007691-199312000-00004	37	10	11	0	13	KOREAN ACAD MEDICAL SCIENCES	SEOUL	302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA	1011-8934	1598-6357		J KOREAN MED SCI	J. Korean Med. Sci.	MAR	2016	31	3					360	+		10.3346/jkms.2016.31.3.360			13	Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine	DG2LN	WOS:000371898700006	26955235	Green Published, Green Submitted, gold			2022-04-25	
J	Rahman, FU; Ali, A; Duong, HQ; Khan, IU; Bhatti, MZ; Li, ZT; Wang, H; Zhang, DW				Rahman, Faiz-Ur; Ali, Amjad; Duong, Hong-Quan; Khan, Inam Ullah; Bhatti, Muhammad Zeeshan; Li, Zhan-Ting; Wang, Hui; Zhang, Dan-Wei			ONS-donor ligand based Pt(II) complexes display extremely high anticancer potency through autophagic cell death pathway	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						ONS-Donor Pt(II) complexes; In vitro cytotoxicity; Caspase 3/7 activation; Autophagy; E. Coli growth	IN-VITRO ANTICANCER; PLATINUM(II) COMPLEXES; ESCHERICHIA-COLI; CISPLATIN; GROWTH; INHIBITION; RESISTANCE; PHENANTHRIPLATIN; EXPRESSION; DIVISION	The current study unveils ONS-donor ligand based Pt(II) complexes with unusual anticancer potency showing higher anticancer effect as compared to cisplatin. This series of Pt(lI)(R-salicylaldimine)Cl (C1a-C4a) (R = 5-H, 5-CH3, F, 3-CH3O) complexes were prepared in single step in good isolated yields from commercially available materials. The chloride ancillary ligand of "a" series (C1a-C4a) was replaced with 4-picoline and "b" series of four complexes Pt(II)(R-salicylaldimine)(4-picoline)BF4 (C1b-C4b) (R = 5-H, 5-CH3, F, 3-CH3O) was obtained. All these complexes were characterized by different structure elucidation techniques. Among these, the structures of C1a, C2a, C2b and Cab were determined in solid state by single crystal X-ray analysis. We found quick aquation of "a" series of complexes in DMSO/water mixture that was well investigated by H-1 NMNR, LCMS and ESI-MS, while "b" series of these complexes was quite stable over a month as described by the 1H NMNR in DMSO/D2O mixture. This ONS-donor ligand based class of Pt(11) complexes showed unusual anticancer potency in non-small cell lung cancer A549, colorectal cancer HT-29 and triple negative breast cancer MDA-MB-231 cells. These Pt(II) complexes induced PARP cleavage and significantly inhibited colony formation ability of cancer cells. Mechanistically, we found reduced aggressive growth of cancer cells by the induction of autophagic cell death via LC3-I/LC3-II expression and recruitment of LC3B to autophagosomal membrane. These complexes induced p21 expression, that suggested their potentials to suppress cell cycle progression. Significant activation of Caspase3/7-dependent apoptotic signaling was observed in cancer cells treated with these Pt(II) complexes. Morphological changes of cancer cells suggested their potentials to modulate epithelial-mesenchymal-transition (EMT) like features of cancer cells. Gel electrophoresis study revealed their interaction with plasmid DNA. Similarly, strong growth retardation effect and filamentous morphology was observed in Escherichia coli (E. coli). These ONS-donor Pt(II) complexes possessed strong anticancer effect in multiple human cancer cells via activation of multiple pathways for apoptotic and autophagic cell death. (C) 2018 Elsevier Masson SAS. All rights reserved.	[Rahman, Faiz-Ur] Shanghai Univ, Dept Chem, Ctr Supramol Mat & Catalysis, Shanghai 200444, Peoples R China; [Rahman, Faiz-Ur; Li, Zhan-Ting; Wang, Hui; Zhang, Dan-Wei] Fudan Univ, Dept Chem, 2005 Songhu Rd, Shanghai 200438, Peoples R China; [Ali, Amjad; Bhatti, Muhammad Zeeshan] East China Normal Univ, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China; [Ali, Amjad] CECOS Univ IT & Emerging Sci, Inst Integrat Biosci, Peshawar, Kpk, Pakistan; [Duong, Hong-Quan] Duy Tan Univ, Inst Res & Dev, K7-25 Quang Trung, Danang 550000, Vietnam; [Khan, Inam Ullah] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Lab Mol Immunol, 220 Handan Rd, Shanghai 200433, Peoples R China; [Bhatti, Muhammad Zeeshan] Natl Univ Med Sci, Dept Biol Sci, Rawalpindi 46000, Pakistan		Wang, H; Zhang, DW (corresponding author), Fudan Univ, Dept Chem, 2005 Songhu Rd, Shanghai 200438, Peoples R China.	wanghui@fudan.edu.cn; zhangdw@fudan.edu.cn	Li, Zhan-Ting/V-7552-2017; Rahman, Faiz-Ur/S-4598-2019; Bhatti, Muhammad Zeeshan/ACS-5136-2022	Li, Zhan-Ting/0000-0003-3954-0015; Rahman, Faiz-Ur/0000-0002-4006-8881; Bhatti, Muhammad Zeeshan/0000-0003-0532-0532	Ministry of Science and Technology of ChinaMinistry of Science and Technology, China [2013CB834501]; Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [13NM1400200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21102017]; China postdoctoral association	The authors acknowledge the Ministry of Science and Technology of China (2013CB834501), The Science and Technology Commission of Shanghai Municipality (13NM1400200), the National Natural Science Foundation of China (No. 21102017) and China postdoctoral association for providing postdoctoral fellowship.	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J. Med. Chem.	FEB 15	2019	164						546	561		10.1016/j.ejmech.2018.12.052			16	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Pharmacology & Pharmacy	HK8EE	WOS:000458221400036	30622026				2022-04-25	
J	Chaeichi-Tehrani, N; Ferns, GA; Hassanian, SM; Khazaei, M; Avan, A				Chaeichi-Tehrani, Negin; Ferns, Gordon A.; Hassanian, Seyed Mahdi; Khazaei, Majid; Avan, Amir			The Therapeutic Potential of Targeting Autophagy in the Treatment of Cancer	CURRENT CANCER DRUG TARGETS			English	Review						Autophagy; lysosomes; pharmacologic agents; gastrointestinal cancers; therapeutic potential; chemotherapeutic drug	HEPATOCELLULAR-CARCINOMA CELLS; PANCREATIC-CANCER; INDUCED APOPTOSIS; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; PHOSPHATIDYLINOSITOL 3'-KINASE; INHIBITS AUTOPHAGY; STEM-CELLS; GROWTH; ADENOCARCINOMA	Autophagy is a mechanism by which unwanted cellular components are degraded through a pathway that involves the lysosomes and contributes to several pathological conditions such as cancer. Gastrointestinal cancers affect the digestive organs from the esophagus to the anus and are among the most commonly diagnosed cancers globally. The modulation of autophagy using pharmacologic agents offers a great potential for cancer therapy. In this review, some commonly used compounds, together with their molecular target and the mechanism through which they stimulate or block the autophagy pathway, as well as their therapeutic benefit in treating patients with gastrointestinal cancers, are summarized.	[Chaeichi-Tehrani, Negin; Hassanian, Seyed Mahdi; Avan, Amir] Mashhad Univ Med Sci, Fac Med, Student Res Comm, Mashhad, Razavi Khorasan, Iran; [Chaeichi-Tehrani, Negin; Hassanian, Seyed Mahdi; Khazaei, Majid; Avan, Amir] Mashhad Univ Med Sci, Metab Syndrome Res Ctr, Mashhad, Razavi Khorasan, Iran; [Avan, Amir] Mashhad Univ Med Sci, Dept Med Genet, Mashhad, Razavi Khorasan, Iran; [Avan, Amir] Mashhad Univ Med Sci, Fac Med, Mashhad, Razavi Khorasan, Iran; [Ferns, Gordon A.] Brighton & Sussex Med Sch, Dept Med Educ, Brighton, Sussex, England		Khazaei, M (corresponding author), Mashhad Univ Med Sci, Fac Med, Student Res Comm, Mashhad, Razavi Khorasan, Iran.	avana@mums.ac.ir			Mashhad University of Medical Sciences	This study was supported by a grant awarded to Amir Avan by the Mashhad University of Medical Sciences grant No:	Akkoc Y, 2018, TURK J GASTROENTEROL, V29, P270, DOI 10.5152/tjg.2018.150318; Al-Bari MAA, 2015, J ANTIMICROB CHEMOTH, V70, P1608, DOI 10.1093/jac/dkv018; Amaravadi RK, 2012, AUTOPHAGY, V8, P1383, DOI 10.4161/auto.20958; 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Cancer Drug Targets		2021	21	9					725	736		10.2174/1568009621666210601113144			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	XO7LW	WOS:000730363400001	34077348				2022-04-25	
J	Su, T; Zhu, JC; Sun, RQ; Zhang, HH; Huang, QH; Zhang, XD; Du, RL; Qiu, LQ; Cao, RH				Su, Tong; Zhu, Jiongchang; Sun, Rongqin; Zhang, Huihui; Huang, Qiuhua; Zhang, Xiaodong; Du, Runlei; Qiu, Liqin; Cao, Rihui			Design, synthesis and biological evaluation of new quinoline derivatives as potential antitumor agents	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						Synthesis; Quinoline derivative; Antitumor; Autophagy; ATG5	COLORECTAL-CANCER; AUTOPHAGY; MECHANISM	A series of new quinoline derivatives was designed, synthesized and evaluated for their antiproliferative activity. The results demonstrated that compounds 11p, lls, 11v, llx and 11y exhibited potent anti proliferative activity with 10(50) value of lower than 10 mu M against seven human tumor cell lines, and N-(3methoxypheny1)-7- (3-phenylpropoxy)quinolin-4-amine 11x was found to be the most potent anti proliferative agent against HCT-116, RKO, A2780 and Hela cell lines with an 10(50) value of 2.56, 3.67, 3.46 and 2.71 mu M, respectively. The antitumor efficacy of the representative compound 11x in mice was also evaluated, and the results showed that compound 11x effectively inhibited tumor growth and decreased tumor weight in animal models. Further investigation on mechanism of action indicated that compound llx could inhibit colorectal cancer growth through ATG5-depenent autophagy pathway. Therefore, these quinoline derivatives are a new class of molecules that have the potential to be developed as new antitumor drugs. 2019 Elsevier Masson SAS. All rights reserved.	[Zhu, Jiongchang; Sun, Rongqin; Huang, Qiuhua; Qiu, Liqin; Cao, Rihui] Sun Yat Sen Univ, Sch Chem, 135 Xin Gang West Rd, Guangzhou 510275, Guangdong, Peoples R China; [Su, Tong; Zhang, Xiaodong; Du, Runlei] Wuhan Univ, Coll Life Sci, 299 Ba Yi Rd, Wuchang 430072, Peoples R China; [Zhang, Huihui] Hunan Normal Univ, Sch Med, Key Lab Study & Discovery Small Targeted Mol Huna, Changsha 410013, Hunan, Peoples R China		Cao, RH (corresponding author), Sun Yat Sen Univ, Sch Chem, 135 Xin Gang West Rd, Guangzhou 510275, Guangdong, Peoples R China.	caorihui@mail.sysu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872271]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [S2013010012138, 2016A030313349]; Research Foundation of Education Bureau of Hunan Province [1613161]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [413000099]; Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund Project [cxpy2017005]	This work was supported by grants from National Natural Science Foundation of China [81872271], the Natural Science Foundation of Guangdong Province [S2013010012138 and 2016A030313349], Research Foundation of Education Bureau of Hunan Province[1613161] and the Fundamental Research Funds for the Central Universities [413000099] and Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund Project [cxpy2017005].	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J. Med. Chem.	SEP 15	2019	178						154	167		10.1016/j.ejmech.2019.05.088			14	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Pharmacology & Pharmacy	IQ3PR	WOS:000480664100013	31181480				2022-04-25	
J	Lee, SH; Moon, HJ; Lee, YS; Kang, CD; Kim, SH				Lee, Su-Hoon; Moon, Hyun-Jung; Lee, Young-Shin; Kang, Chi-Dug; Kim, Sun-Hee			Potentiation of TRAIL-induced cell death by nonsteroidal anti-inflammatory drug in human hepatocellular carcinoma cells through the ER stress-dependent autophagy pathway	ONCOLOGY REPORTS			English	Article						hepatocellular carcinoma; TRAIL; non-steroidal anti-inflammatory drug; autophagy; CD44; c-FLIP; endoplasmic reticulum stress	COLON-CANCER CELLS; INDUCED APOPTOSIS; C-FLIP; UP-REGULATION; DUAL ROLE; EXPRESSION; CHOP; DEGRADATION; COMBINATION; CROSSTALK	Hepatocellular carcinoma (HCC) is the most commonly diagnosed primary liver malignancy. The limited success with relapse of the disease in HCC therapy is frequently associated with the acquired resistance to anticancer drugs. To develop a strategy and design for overcoming the resistance of HCC cells to TNF-related apoptosis inducing ligand (TRAIL)-induced cell death, we evaluated the efficacy of a non-steroidal anti-inflammatory drug (NSAID) in combination with TRAIL against TRAIL-resistant HCC cells expressing a high level of CD44. We revealed by MTT and western blotting, respectively, that celecoxib (CCB), an NSAID, and 2,5-dimethyl celecoxib (DMC), a non-cyclooxygenase (COX)-2 inhibitor analog of CCB, were able to sensitize TRAIL-resistant HCC cells to TRAIL, implicating a COX-independent mechanism. CCB dose-dependently enhanced LC3-II and reduced p62 levels through AMPK activation and inhibition of the Akt/mTOR pathway and upregulated expression of ATF4/CHOP, leading to activation of endoplasmic reticulum (ER) stress-dependent autophagy. The TRAIL sensitization capacity of CCB in TRAIL-resistant HCC cells was abrogated by an ER stress inhibitor. In addition, we also revealed by flow cytometry and western blotting, respectively, that accelerated downregulation of TRAIL-mediated c-FLIP expression, DR5 activation and CD44 degradation/downregulation by NSAID resulted in activation of caspases and poly(ADP-ribose) polymerase (PARP), leading to the sensitization of TRAIL-resistant HCC cells to TRAIL and thereby reversal of TRAIL resistance. From these results, we propose that NSAID in combination with TRAIL may improve the antitumor activity of TRAIL in TRAIL-resistant HCC, and this approach may serve as a novel strategy that maximizes the therapeutic efficacy of TRAIL for clinical application.	[Lee, Su-Hoon; Moon, Hyun-Jung; Lee, Young-Shin; Kang, Chi-Dug; Kim, Sun-Hee] Pusan Natl Univ, Dept Biochem, Sch Med, Yangsan 626870, Gyeongsangnam D, South Korea		Kang, CD; Kim, SH (corresponding author), Pusan Natl Univ, Dept Biochem, Sch Med, Yangsan 626870, Gyeongsangnam D, South Korea.	kcdshbw@pusan.ac.kr; ksh7738@pusan.ac.kr			Pusan National UniversityPusan National University	The present study was supported by Pusan National University Research Grant, 2019.	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Rep.	SEP	2020	44	3					1136	1148		10.3892/or.2020.7662			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NF8SU	WOS:000563563700027	32705218	hybrid, Green Published			2022-04-25	
J	Shi, XF; Zhang, HY; Jin, WD; Liu, WC; Yin, HJ; Li, YX; Dong, HJ				Shi, Xiafei; Zhang, Hongyu; Jin, Wendong; Liu, Weichao; Yin, Huijuan; Li, Yingxin; Dong, Huajiang			Metronomic photodynamic therapy with 5-aminolevulinic acid induces apoptosis and autophagy in human SW837 colorectal cancer cells	JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY			English	Article						Metronomic photodynamic therapy; Apoptosis; Autophagy; Colorectal cancer; 5-Aminolevulinic acid (ALA)	FLUENCE RATE; FEASIBILITY; GLIOMA; MODEL	Metronomic photodynamic therapy (mPDT) has emerged as an attractive treatment for the selective destruction of tumor cells by induction of apoptosis. Here, we compared the effects of mPDT and acute photodynamic therapy (aPDT) on human SW837 colorectal cancer (CRC) cells. CRC cells were subjected to mPDT using various exposure durations, concentrations of 5-aminolevulinic acid (ALA), fluence rates and energy densities. The effects were compared with those induced by aPDT. We found that apoptosis and autophagy were earlier induced to a greater extent by mPDT than by the same dose applied as aPDT. The survival rates for mPDT vs. aPDT were 35.2%, 32.4%, 27.6%, 31.6% vs. 85.7%, 71.1%, 67.8%, 42.1% after 3, 6, 12, and 24 h PDT, respectively. For the same time points, the apoptotic rates for mPDT vs. aPDT were 43.2%, 47.3%, 54.7%, and 50.3% vs. 14.6%, 17.6%, 27.1%, and 53.2%, respectively. mPDT induced a peak rate of autophagy of 20.0% at 3 h, whereas aPDT induced two smaller peaks at 3 h (14.1%) and 12 h (15.8%). Advanced autophagosomes were more abundant in mPDT- than aPDT-treated cells and appeared earlier after mPDT (3 h) than after aPDT (3-12 h). Western Bloting results showed that the ratio of LC3B-II/beta - actin at 3 h was higher (1.04 times) after mPDT than aPDT. Collectively, these datas indicated that ALA-mPDT was more effective than the same dose of ALA-aPDT at inducing SW837 CRC cell death via apoptosis and autophagy. Thus, mPDT may be a superior choice than aPDT for the treatment of human CRC.	[Shi, Xiafei; Jin, Wendong; Liu, Weichao; Yin, Huijuan; Li, Yingxin] Chinese Acad Med Sci, Peking Union Med Coll, Inst Biomed Engn, Lab Laser Med, Tianjin 300192, Peoples R China; [Zhang, Hongyu] Shanxi Prov Tumor Hosp, PETCT Ctr, Taiyuan 030013, Shanxi, Peoples R China; [Dong, Huajiang] Logist Univ Chinese Peoples Armed Police Forces, Tianjin 300309, Peoples R China		Yin, HJ; Li, YX (corresponding author), Chinese Acad Med Sci, Peking Union Med Coll, Inst Biomed Engn, Lab Laser Med, Tianjin 300192, Peoples R China.	yinhj@bme.cams.cn; yingxinli2005@126.com			Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province	We thank the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province for support.	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Photochem. Photobiol. B-Biol.	SEP	2019	198								111586	10.1016/j.jphotobiol.2019.111586			9	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	IY4JM	WOS:000486357300018	31437760				2022-04-25	
J	Singh, MP; Khaket, TP; Bajpai, VK; Alfarraj, S; Kim, SG; Chen, L; Huh, YS; Han, YK; Kang, SC				Singh, Mahendra Pal; Khaket, Tejinder Pal; Bajpai, Vivek K.; Alfarraj, Saleh; Kim, Se-Gie; Chen, Lei; Huh, Yun Suk; Han, Young-Kyu; Kang, Sun Chul			Morin Hydrate Sensitizes Hepatoma Cells and Xenograft Tumor towards Cisplatin by Downregulating PARP-1-HMGB1 Mediated Autophagy	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						apoptosis; autophagy; cisplatin; HMGB1; morin hydrate	HEPATOCELLULAR-CARCINOMA; CANCER CELLS; DNA-DAMAGE; COLORECTAL-CANCER; INHIBITION; APOPTOSIS; STRESS; RESISTANT; DEATH; HMGB1	The cross-talk between apoptosis and autophagy influences anticancer drug sensitivity and cellular death in various cancer cell lines. However, the fundamental mechanisms behind this phenomenon are still unidentified. We demonstrated anti-cancerous role of cisplatin (CP) and morin hydrate (Mh) as an individual and/or in combination (CP-Mh) in hepatoma cells and tumor model. Exposure of CP resulted in the production of intracellular reactive oxygen species (ROS)-mediated cellular vacuolization, expansion of mitochondria membrane and activation of endoplasmic reticulum (ER)-stress. Consequently, Cyt c translocation led to the increase of Bax/Bcl-2 ratio, which simultaneously triggered caspase-mediated cellular apoptosis. In addition, CP-induced PARP-1 activation led to ADP-ribosylation of HMGB1, which consequently developed autophagy as evident by the LC3I/II ratio. Chemically-induced inhibition of autophagy marked by increased cell death signified a protective role of autophagy against CP treatment. CP-Mh abrogates the PARP-1 expression and significantly reduced HMGB1-cytoplasmic translocation with subsequent inhibition of the HMGB1-Beclin1 complex formation. In the absence of PARP-1, a reduced HMGB1 mediated autophagy was observed followed by induced caspase-dependent apoptosis. To confirm the role of PARP-1-HMGB1 signaling in autophagy, we used the PARP-1 inhibitor, 4-amino-1,8-naphthalimide (ANI), HMGB1 inhibitor, ethyl pyruvate (EP), autophagy inhibitors, 3-methyl adenine (3-MA) and bafilomycin (baf) and small interfering RNAs (siRNA) to target Atg5 in combination of CP and Mh. Exposure to these inhibitors enhanced the sensitivity of HepG2 cells to CP. Collectively, our findings indicate that CP-Mh in combination served as a prominent regulator of autophagy and significant inducer of apoptosis that maintains a homeostatic balance towards HepG2 cells and the subcutaneous tumor model.	[Singh, Mahendra Pal; Kang, Sun Chul] Daegu Univ, Dept Biotechnol, Gyongsan 38453, Gyeongbuk, South Korea; [Singh, Mahendra Pal] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA; [Khaket, Tejinder Pal] Ohio State Univ, Dept Radiat Oncol, Columbus, OH 43210 USA; [Bajpai, Vivek K.; Han, Young-Kyu] Dongguk Univ Seoul, Dept Energy & Mat Engn, 30 Pildong Ro 1 Gil, Seoul 04620, South Korea; [Alfarraj, Saleh] King Saud Univ, Coll Sci, Zool Dept, Riyadh 11451, Saudi Arabia; [Kim, Se-Gie] Daegu Catholic Univ, Dept Pharmaceut Engn, Gyeongsan 38430, Gyeongbuk, Saudi Arabia; [Chen, Lei] Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China; [Huh, Yun Suk] Inha Univ, Biohybrid Syst Res Ctr BSRC, Dept Biol Engn, 100 Inha Ro, Incheon 22212, South Korea		Kang, SC (corresponding author), Daegu Univ, Dept Biotechnol, Gyongsan 38453, Gyeongbuk, South Korea.; Han, YK (corresponding author), Dongguk Univ Seoul, Dept Energy & Mat Engn, 30 Pildong Ro 1 Gil, Seoul 04620, South Korea.; Chen, L (corresponding author), Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China.	mahendra.rathore9@gmail.com; tejkhaket@gmail.com; vbiotech04@gmail.com; salfarraj@hotmail.com; sgkim7@cu.ac.kr; chenlei841114@hotmail.com; yunsuk.huh@inha.ac.kr; ykenergy@dongguk.edu; sckang@daegu.ac.kr	Singh, Mahendra Pal/J-8391-2019	Huh, Yun Suk/0000-0003-1612-4473	National Research Foundation of South Korea (NRF) [016R1A2B4009227, 2016H1D3A1938249, 2017R1D1A1B03036569, RSP-2020/7]; King Saud University, Riyadh, Saudi ArabiaKing Saud University [RSP-2020/7]	This research was funded by the National Research Foundation of South Korea (NRF) - 016R1A2B4009227, 2016H1D3A1938249, and 2017R1D1A1B03036569 grants. This research was funded by the Researchers Supporting Project Number (RSP-2020/7), King Saud University, Riyadh, Saudi Arabia.	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J. Mol. Sci.	NOV	2020	21	21							8253	10.3390/ijms21218253			24	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	OQ8VA	WOS:000589052800001	33158052	Green Published, gold			2022-04-25	
J	Soni, M; Patel, Y; Markoutsa, E; Jie, CF; Liu, S; Xu, PS; Chen, HX				Soni, Mithil; Patel, Yogin; Markoutsa, Eleni; Jie, Chunfa; Liu, Shou; Xu, Peisheng; Chen, Hexin			Autophagy, Cell Viability, and Chemoresistance Are Regulated By miR-489 in Breast Cancer	MOLECULAR CANCER RESEARCH			English	Article							HEPATOCELLULAR-CARCINOMA; MULTIDRUG-RESISTANCE; COLORECTAL-CANCER; TUMOR-GROWTH; LAPTM4B; INHIBITION; CHEMOTHERAPY; PROLIFERATION; CONTRIBUTES; SUPPRESSION	It is postulated that the complexity and heterogeneity in cancer may hinder most efforts that target a single pathway. Thus, discovery of novel therapeutic agents targeting multiple pathways, such as miRNAs, holds promise for future cancer therapy. One such miRNA, miR-489, is downregulated in a majority of breast cancer cells and several drug-resistant breast cancer cell lines, but its role and underlying mechanism for tumor suppression and drug resistance needs further investigation. The current study identifies autophagy as a novel pathway targeted by miR-489 and reports Unc-51 like autophagy activating kinase 1 (ULK1) and lysosomal protein transmembrane 4 beta (LAPTM4B) to be direct targets of miR-489. Furthermore, the data demonstrate autophagy inhibition and LAPTM4B downregulation as a major mechanism responsible for miR-489-mediated doxorubicin sensitization. Finally, miR-489 and LAPTM4B levels were inversely correlated in human tumor clinical specimens, and more importantly, miR-489 expression levels predict overall survival in patients with 8q22 amplification (the region in which LAPTM4B resides). Implications: These findings expand the understanding of miR-489-mediated tumor suppression and chemosensitization in and suggest a strategy for using miR-489 as a therapeutic sensitizer in a defined subgroup of resistant breast cancer patients. (C) 2018 AACR.	[Soni, Mithil; Patel, Yogin; Liu, Shou; Chen, Hexin] Univ South Carolina, Dept Biol Sci, 715 Sumter St,PSC621, Columbia, SC 29205 USA; [Soni, Mithil; Patel, Yogin; Liu, Shou; Chen, Hexin] Univ South Carolina, Ctr Colon Canc Res, Columbia, SC 29208 USA; [Markoutsa, Eleni; Xu, Peisheng] Univ South Carolina, South Carolina Coll Pharm, Dept Drug Discovery & Biomed Sci, Columbia, SC 29208 USA; [Jie, Chunfa] Des Moines Univ, Biomed Sci Program, Sci, Des Moines, IA USA		Chen, HX (corresponding author), Univ South Carolina, Dept Biol Sci, 715 Sumter St,PSC621, Columbia, SC 29205 USA.	hchen@biol.sc.edu	chen, hexin/F-1714-2011		NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [5R01 CA178386-04, 1R15CA188847-01A1, 1R01AG054839-01A1]; USC ASPIRE-1 grant; USC ASPIRE postdoctoral fellowship; USC SPARC graduate fellowship; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA178386, R15CA188847] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG054839] Funding Source: NIH RePORTER	The authors thank Dr. Thomas Blom and Dr. Elina Ikonen for providing LAPTM4B-mCherry and pcDNA-3xFLAG-LAPTM4B vectors, Dr. Jayanta Debnath for mCherry-EGFP-LC3B (Addgene # 22418) vector, and Dr. Do-Hyung Kim for HA-ULK1 vector (Addgene # 31963). This work was partially supported by the NIH grant (5R01 CA178386-04) and the USC ASPIRE-1 grant (to H. Chen), the NIH grants (1R15CA188847-01A1 and 1R01AG054839-01A1; to P. Xu), the USC ASPIRE postdoctoral fellowship (to S. Liu), and the USC SPARC graduate fellowship (to M. Soni).	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Cancer Res.	SEP	2018	16	9					1348	1360		10.1158/1541-7786.MCR-17-0634			13	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	GS9HI	WOS:000444027800003	29784669	Green Accepted, Bronze			2022-04-25	
J	Hong, EH; Heo, EY; Song, JH; Kwon, BE; Lee, JY; Park, Y; Kim, J; Chang, SY; Chin, YW; Jeon, SM; Ko, HJ				Hong, Eun-Hye; Heo, Eun-Young; Song, Jae-Hyoung; Kwon, Bo-Eun; Lee, Jae-Young; Park, Yaejeong; Kim, Jinwoong; Chang, Sun-Young; Chin, Young-Won; Jeon, Sang-Min; Ko, Hyun-Jeong			Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells	ONCOTARGET			English	Article						trans-scirpusin A; colorectal cancer cells; AMPK; autophagy; apoptosis	IN-VIVO; POLYPHENOLIC COMPOUNDS; BREAST-CANCER; RESVERATROL; DIMER; TUMORIGENESIS; INHIBITION; EXPRESSION; PREVENTION; RESPONSES	Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabelliferL. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-a mRNA in tumor tissue and Her2specific Ab (antibody) production. More importantly, we found that TSA overcomes the tumor-associated immunosuppressive microenvironment by reducing the number of CD25+ FoxP3+ regulatory T cells and myeloid-derived suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated Her2/CT26 cells, based on the increased level of the mammalian autophagy protein LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5' AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated AMPK activation and inhibition of mTORC1 pathway might be associated with autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double positive results, and TUNELpositive cells. Finally, we found that the combined treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a greater extent than docetaxel alone. Therefore, we propose the use of TSA for supplementary anticancer therapy to support anti-neoplastic drugs, such as docetaxel, by inducing apoptosis in cancer cells and resulting in the induction of neighborhood anti-cancer immunity.	[Hong, Eun-Hye; Heo, Eun-Young; Song, Jae-Hyoung; Kwon, Bo-Eun; Lee, Jae-Young; Ko, Hyun-Jeong] Kangwon Natl Univ, Coll Pharm, Lab Microbiol & Immunol, Chunchon 24341, Gangwon Do, South Korea; [Chang, Sun-Young] Ajou Univ, Coll Pharm, Lab Microbiol, Suwon 16499, Gyeonggi Do, South Korea; [Chang, Sun-Young; Jeon, Sang-Min] Ajou Univ, RIPST, Suwon 16499, Gyeonggi Do, South Korea; [Jeon, Sang-Min] Ajou Univ, Coll Pharm, Lab Canc Signaling & Metab Network, Suwon 16499, Gyeonggi Do, South Korea; [Park, Yaejeong; Kim, Jinwoong] Seoul Natl Univ, Coll Pharm, Seoul 08826, South Korea; [Park, Yaejeong; Kim, Jinwoong] Seoul Natl Univ, Res Inst Pharmaceut Sci, Seoul 08826, South Korea; [Chin, Young-Won] Dongguk Univ Seoul, Coll Pharm, Goyang 10326, Gyeonggi Do, South Korea; [Chin, Young-Won] Dongguk Univ Seoul, Integrated Res Inst Drug Dev, Goyang 10326, Gyeonggi Do, South Korea; [Ko, Hyun-Jeong] Adv Inst Convergence Technol, Convergence Res Ctr Funct Plant Prod, Suwon 16229, Gyeonggi Do, South Korea		Ko, HJ (corresponding author), Kangwon Natl Univ, Coll Pharm, Lab Microbiol & Immunol, Chunchon 24341, Gangwon Do, South Korea.; Jeon, SM (corresponding author), Ajou Univ, RIPST, Suwon 16499, Gyeonggi Do, South Korea.; Jeon, SM (corresponding author), Ajou Univ, Coll Pharm, Lab Canc Signaling & Metab Network, Suwon 16499, Gyeonggi Do, South Korea.; Ko, HJ (corresponding author), Adv Inst Convergence Technol, Convergence Res Ctr Funct Plant Prod, Suwon 16229, Gyeonggi Do, South Korea.	smjeon@ajou.ac.kr; hjko@kangwon.ac.kr	Jeon, Sang-Min/I-7917-2018	Jeon, Sang-Min/0000-0002-0132-925X; Ko, Hyun-Jeong/0000-0002-3844-928X; Chin, Young-Won/0000-0001-6964-1779	Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2016R1A4A1010115]; Kangwon National University [520150291]; Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI15C0450]; National Research Foundation of Korea (NRF) grants - Ministry of Science, ICT and Future Planning [NRF-2015M2B2A6028602]	This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2016R1A4A1010115). This study was supported by the 2015 Research Grant from Kangwon National University (No. 520150291) and was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI15C0450). This study was supported by the National Research Foundation of Korea (NRF) grants funded by the Ministry of Science, ICT and Future Planning (No. NRF-2015M2B2A6028602).	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J	Peng, JQ; Wang, Q; Zhou, J; Zhao, SL; Di, P; Chen, Y; Tao, L; Du, QM; Shen, XC; Chen, Y				Peng, Jianqing; Wang, Qin; Zhou, Jia; Zhao, Shuli; Di, Pan; Chen, Yan; Tao, Ling; Du, Qianming; Shen, Xiangchun; Chen, Yi			Targeted Lipid Nanoparticles Encapsulating Dihydroartemisinin and Chloroquine Phosphate for Suppressing the Proliferation and Liver Metastasis of Colorectal Cancer	FRONTIERS IN PHARMACOLOGY			English	Article						chloroquine phosphate; lipid nanoparticles; colorectal cancer; liver metastasis; ROS; dihydroartemisinin	CELL-CYCLE ARREST; AUTOPHAGY; ARTEMISININ; ANGIOGENESIS; DERIVATIVES; FERROPTOSIS; INHIBITION; INDUCTION; GROWTH	Antimalarial drugs Dihydroartemisinin (DHA) and chloroquine phosphate (CQ) exhibit evident anti-cancer activity, particularly as combination therapy. DHA and CQ combination therapy has been proved to exhibit higher cytotoxic effect in tumor cells and lower toxicity to normal cells than combination of artemisinin derivatives (ARTs) and anticancer chemotherapy drugs. However, different physiochemical properties of DHA and CQ, leading to distinctive in vivo outcomes, considerably limited their synergistic effect in cancer treatment. Herein, we developed a lipid nanoparticle (LNP) for co-delivery of DHA and CQ to inhibit proliferation and metastasis of colorectal cancer. Considering the beneficial effects of acid/reactive oxide species (ROS)-sensitive phospholipids and targeting ligands for colorectal cancer cells, an RGD peptide-modified pH/ROS dual-sensitive LNP loaded with DHA and CQ (RLNP/DC) was prepared. It exhibited optimal cytotoxicity and suppression of invasion and metastasis in HCT116 cells in vitro, attributable to irreversible upregulation of intracellular ROS levels, downregulation of VEGF expression, and upregulation of paxillin expression. A mouse model of orthotopic metastasis of colorectal cancer was established to evaluate anti-proliferation and anti-metastasis effects of RLNP/DC in vivo. Thus, an optimized nanoplatform for DHA and CQ combination therapy was developed in this study that offered potential antitumor efficacy against colorectal cancer.	[Peng, Jianqing; Wang, Qin; Zhou, Jia; Di, Pan; Chen, Yan; Tao, Ling; Shen, Xiangchun; Chen, Yi] Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guiyang, Peoples R China; [Peng, Jianqing; Wang, Qin; Zhou, Jia; Di, Pan; Chen, Yan; Tao, Ling; Shen, Xiangchun; Chen, Yi] Guizhou Med Univ, High Efficacy Applicat Nat Med Resources Engn Ct, Sch Pharmaceut Sci, Guiyang, Peoples R China; [Zhao, Shuli; Du, Qianming] Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing, Peoples R China; [Zhao, Shuli; Du, Qianming] China Pharmaceut Univ, Sch Basic Med & Clin Pharm, Dept Clin Pharm, Nanjing, Peoples R China		Shen, XC; Chen, Y (corresponding author), Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guiyang, Peoples R China.; Shen, XC; Chen, Y (corresponding author), Guizhou Med Univ, High Efficacy Applicat Nat Med Resources Engn Ct, Sch Pharmaceut Sci, Guiyang, Peoples R China.; Du, QM (corresponding author), Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing, Peoples R China.; Du, QM (corresponding author), China Pharmaceut Univ, Sch Basic Med & Clin Pharm, Dept Clin Pharm, Nanjing, Peoples R China.	duqianming@njmu.edu.cn; shenxiangchun@126.com; chenyi_19890319@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81960647, 81702833]; Guizhou Provincial Natural Science Foundation [(2019)1255]; Excellent Young Talents Plan of Guizhou Medical University [2020-102, 2021-103]; High-level Overseas Talent Fund for Home Work from the Ministry of Human Resources and Social Security [RSBLXHGZ202001]; Foundation for Training Programs of Innovation and Entrepreneurship for Undergraduates of Guizhou Medical University [S202010660037]; Jiangsu Provincial Special Program of Medical Science [BE2019617]; Distinguished Young Scholars of Nanjing [JQX20008]	This work was financially supported by the National Natural Science Foundation of China (81960647, 81702833), the Guizhou Provincial Natural Science Foundation ((2019)1255), the Excellent Young Talents Plan of Guizhou Medical University (Nos. 2020-102, 2021-103), the High-level Overseas Talent Fund for Home Work from the Ministry of Human Resources and Social Security (RSBLXHGZ202001), the Foundation for Training Programs of Innovation and Entrepreneurship for Undergraduates of Guizhou Medical University (No. S202010660037), the Jiangsu Provincial Special Program of Medical Science (BE2019617), and the Distinguished Young Scholars of Nanjing (JQX20008).	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Pharmacol.	OCT 8	2021	12								720777	10.3389/fphar.2021.720777			17	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	WM2LE	WOS:000710921500001	34690764	Green Published, gold			2022-04-25	
J	Trincheri, NF; Follo, C; Nicotra, G; Peracchio, C; Castino, R; Isidoro, C				Trincheri, Nicol F.; Follo, Carlo; Nicotra, Giuseppina; Peracchio, Claudia; Castino, Roberta; Isidoro, Ciro			Resveratrol-induced apoptosis depends on the lipid kinase activity of Vps34 and on the formation of autophagolysosomes	CARCINOGENESIS			English	Article							CANCER CHEMOPREVENTIVE AGENT; ISOLATED RAT HEPATOCYTES; CELL-DEATH; AUTOPHAGOSOME FORMATION; PROTEIN-DEGRADATION; COLORECTAL-CANCER; INHIBITION; TUMORIGENESIS; ROLES; DIFFERENTIATION	In human colorectal DLD1 cancer cells, the dietary bioflavonoid resveratrol (RV) rapidly induced autophagy. This effect was reversible (on removal of the drug) and was associated with increased expression and cytosolic redistribution of the proteins Beclin1 and LC3 II. Supplementing the cells with asparagine (Asn) abrogated the Beclin-dependent autophagy. When applied acutely (2 h), RV was not toxic; however, reiterate chronic (48 h) exposure to RV eventually led to annexin V- and terminal deoxinucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cell death. This toxic effect was autophagy dependent, as it was prevented either by Asn, by expressing a dominant-negative lipid kinase-deficient class III phosphoinositide 3-phosphate kinase, or by RNA interference knockdown of Beclin1. Lamp2b silencing abolished the fusion of autophagosomes with lysosomes and preserved cell viability despite the ongoing formation of autophagosomes in cells chronically exposed to RV. The pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone inhibited RV-induced cell death, but not autophagy. These results uncover a novel pathway of RV cytotoxicity in which autophagy plays a dual role: (i) at first, it acts as a prosurvival stress response and (ii) at a later time, it switches to a caspase-dependent apoptosis pathway. The present data also indicate that genetic or epigenetic inactivation of autophagy proteins in cancer cells may confer resistance to RV-mediated killing.	[Trincheri, Nicol F.; Follo, Carlo; Nicotra, Giuseppina; Peracchio, Claudia; Castino, Roberta; Isidoro, Ciro] Univ Piemonte Orientale, Dipartimento Sci Med, Lab Patol Mol, I-28100 Novara, Italy		Isidoro, C (corresponding author), Univ Piemonte Orientale, Dipartimento Sci Med, Lab Patol Mol, Via Solaroli 17, I-28100 Novara, Italy.	isidoro@med.unipmn.it	Isidoro, Ciro/J-6063-2016	Isidoro, Ciro/0000-0002-5494-3034; Follo, Carlo/0000-0001-9711-2655			Abedin MJ, 2007, CELL DEATH DIFFER, V14, P500, DOI 10.1038/sj.cdd.4402039; Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; Bampton ETW, 2005, AUTOPHAGY, V1, P23, DOI 10.4161/auto.1.1.1495; Baur JA, 2006, NATURE, V444, P337, DOI 10.1038/nature05354; Baur JA, 2006, NAT REV DRUG DISCOV, V5, P493, DOI 10.1038/nrd2060; Boocock DJ, 2007, CANCER EPIDEM BIOMAR, V16, P1246, DOI 10.1158/1055-9965.EPI-07-0022; Bursch W, 2001, CELL DEATH DIFFER, V8, P569, DOI 10.1038/sj.cdd.4400852; Bursch W, 1996, CARCINOGENESIS, V17, P1595, DOI 10.1093/carcin/17.8.1595; Degenhardt K, 2006, CANCER CELL, V10, P51, DOI 10.1016/j.ccr.2006.06.001; Di Cristofano A, 2000, CELL, V100, P387, DOI 10.1016/S0092-8674(00)80674-1; Eskelinen Eeva-Liisa, 2006, Molecular Aspects of Medicine, V27, P495, DOI 10.1016/j.mam.2006.08.005; Fremont L, 2000, LIFE SCI, V66, P663, DOI 10.1016/S0024-3205(99)00410-5; Gonzalez-Polo RA, 2005, J CELL SCI, V118, P3091, DOI 10.1242/jcs.02447; Gusman J, 2001, CARCINOGENESIS, V22, P1111, DOI 10.1093/carcin/22.8.1111; HOYVIK H, 1991, J CELL BIOL, V113, P1305, DOI 10.1083/jcb.113.6.1305; Jang MS, 1997, SCIENCE, V275, P218, DOI 10.1126/science.275.5297.218; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Kessel D, 2007, CANCER LETT, V249, P294, DOI 10.1016/j.canlet.2006.09.009; Kihara A, 2001, EMBO REP, V2, P330, DOI 10.1093/embo-reports/kve061; Lee KW, 2006, BIOFACTORS, V26, P105, DOI 10.1002/biof.5520260202; Levine B, 2005, J CLIN INVEST, V115, P2679, DOI 10.1172/JCI26390; Liang C, 2006, NAT CELL BIOL, V8, P688, DOI 10.1038/ncb1426; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Liang YC, 2003, BIOCHEM PHARMACOL, V65, P1053, DOI 10.1016/S0006-2952(03)00011-X; MAHYAR R, 2002, BMC CANCER, V2, P27; Mahyar-Roemer M, 2001, INT J CANCER, V94, P615, DOI 10.1002/ijc.1516; MARTIN SJ, 1995, J EXP MED, V182, P1545, DOI 10.1084/jem.182.5.1545; Mizushima N, 2001, J CELL BIOL, V152, P657, DOI 10.1083/jcb.152.4.657; Mohan J, 2006, J BIOL CHEM, V281, P17599, DOI 10.1074/jbc.M602641200; Munafo DB, 2001, J CELL SCI, V114, P3619; OGIER D, 2003, BIOCHIM BIOPHYS ACTA, V2, P113; Opipari AW, 2004, CANCER RES, V64, P696, DOI 10.1158/0008-5472.CAN-03-2404; Qu XP, 2003, J CLIN INVEST, V112, P1809, DOI 10.1172/JCI200320039; Sale S, 2004, BRIT J CANCER, V90, P736, DOI 10.1038/sj.bjc.6601568; SCHATZKIN A, 1995, EUR J CANCER, V31A, P1198, DOI 10.1016/0959-8049(95)00138-9; Schneider Y, 2001, NUTR CANCER, V39, P102, DOI 10.1207/S15327914nc391_14; Schneider Y, 2000, CANCER LETT, V158, P85, DOI 10.1016/S0304-3835(00)00511-5; SEGLEN PO, 1982, P NATL ACAD SCI-BIOL, V79, P1889, DOI 10.1073/pnas.79.6.1889; SEGLEN PO, 1980, BIOCHIM BIOPHYS ACTA, V630, P103, DOI 10.1016/0304-4165(80)90141-5; SHENGKAN J, 2007, AUTOPHAGY, V3, P28; Suzuki K, 2001, EMBO J, V20, P5971, DOI 10.1093/emboj/20.21.5971; Tessitore L, 2000, CARCINOGENESIS, V21, P1619, DOI 10.1093/carcin/21.8.1619; Trincheri NF, 2007, CARCINOGENESIS, V28, P922, DOI 10.1093/carcin/bgl223; Wolter F, 2002, J NUTR, V132, P2082, DOI 10.1093/jn/132.7.2082; Wolter F, 2001, J NUTR, V131, P2197, DOI 10.1093/jn/131.8.2197; Yorimitsu T, 2005, CELL DEATH DIFFER, V12, P1542, DOI 10.1038/sj.cdd.4401765	46	87	90	0	5	OXFORD UNIV PRESS	OXFORD	GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND	0143-3334			CARCINOGENESIS	Carcinogenesis	FEB	2008	29	2					381	389		10.1093/carcin/bgm271			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	272AW	WOS:000253830800019	18048384	Bronze			2022-04-25	
J	Lee, HM; Choi, KC				Lee, Hae-Miru; Choi, Kyung-Chul			Cigarette smoke extract and isoprene resulted in the induction of apoptosis and autophagy in human placenta choriocarcinoma JEG-3 cells	ENVIRONMENTAL TOXICOLOGY			English	Article						cell cycle; cigarette smoke; EMT; isoprene; placenta choriocarcinoma	ENDOPLASMIC-RETICULUM STRESS; COLON-CANCER CELLS; KEAP1-NRF2 PATHWAY; MAINSTREAM SMOKE; ROS PRODUCTION; IN-VITRO; EXPOSURE; NRF2; ER; PHOSPHORYLATION	In this study, the effects of cigarette smoke (CS) on the induction of apoptosis via reactive oxygen species (ROS) production and endoplasmic reticulum stress (ER stress) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS and placenta development. Upon TUNEL assay, CS extract (3R4F; 0.3 and 2.1 M) increased JEG-3 apoptosis. Western blot assay revealed that the protein expressions of p53, Bax, and CCAAT-enhancer-binding protein homologous protein (CHOP) increased, while the levels of Bcl-2 were reduced following CS extract treatment. Moreover, 2,7-dichlorofluorescein diacetate (DCFH-DA) assay revealed increased ROS production. Upon 3-(4-5-dimethylthiazol-2-yl)-2.5-dyhphenyltetrazolium bromide (MTT) assay, isoprene (IP), one of ingredients of CS, deceased JEG-3 cell viability (10(-11) to 10(-6) M). After based on the MTT assay, two IP concentrations of 10(-11) and 10(-8) M were selected and the protein expressions of cyclin D1, cyclin E1, p21, and p27 decreased in response to IP. Furthermore, IP showed the greatest increase in autophagy at 24 hours and further induction of cell death at 72 hours upon monodansylacadaverine and TUNEL assay. Western blot analysis confirmed the increase in autophagy markers, LC3 and p62, as well as the increase or decrease of apoptosis markers p53, Bax, CHOP, and Bcl-2 in response to its treatments. In addition to confirming increases in ROS through DCFH-DA, we also confirmed the expression of Nrf2, an antioxidant marker, and the expression of Kelch-like ECH-associated protein 1 (KEAP1), which specifically degrades Nrf2, by Western blot. Taken together, these results indicate that CS and IP may inhibit the development of placenta via activation of ROS by inducing apoptosis and autophagy by affecting the expression of KEAP1, which regulates Nrf2 expression.	[Lee, Hae-Miru; Choi, Kyung-Chul] Chungbuk Natl Univ, Coll Vet Med, Lab Biochem & Immunol, Cheongju 28644, Chungbuk, South Korea		Choi, KC (corresponding author), Chungbuk Natl Univ, Coll Vet Med, Lab Biochem & Immunol, Cheongju 28644, Chungbuk, South Korea.	kchoi@cbu.ac.kr			Ministry of Food and Drug Safety (Korea)Ministry of Food & Drug Safety (MFDS) [14182MFDS977]	Ministry of Food and Drug Safety (Korea), Award/Grant number: 14182MFDS977.	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J	Kolap, RM; Datkhile, KD; Zimare, SB				Kolap, Rupali Mukesh; Datkhile, Kailash D.; Zimare, Saurabha Bhimrao			Bioprospecting of Lobelia nicotianifolia Roth. plant parts for antioxidant and cytotoxic activity and its phytoconstituents	PHARMACOGNOSY MAGAZINE			English	Article						Antioxidant; cytotoxic; HCT-15; HeLa; Lobelia nicotianifolia; MCF-7	IN-VITRO; ANTICANCER ACTIVITY; CANCER-CELLS; ACID; SESQUITERPENES; APOPTOSIS; AUTOPHAGY; GROWTH; ESTER; LEAF	Background: Though the Lobelia nicotianifolia Roth. is ethnobotanically important plant of India and Sri Lanka its phytoconstituents, antioxidant, and anticancer potential was not yet reported. Objective: The objective of this study is to analyze the phytoconstituents of plant parts of L. nicotianifolia and to determine its antioxidant and cytotoxic potential. Materials and Methods: The plant parts of L. nicotianifolia were extracted with different solvents and qualitative analysis revealed the presence of different phytoconstituents. Total phenolic content (TPC) and total flavonoid content (TFC) were recorded in all plant parts. The extracts were subjected to the antioxidant assays and the potent methanolic extracts were used for cytotoxicity study and further characterized by Fourier-transform infrared spectroscopy and liquid chromatography with a high resolution mass spectrometer (LC-HRMS). Results: The qualitative analysis showed the presence of a wide array of phytoconstituents in L. nicotianifolia plant parts. A significantly higher TPC, TFC, and antioxidant activities were seen in methanolic stem extract. Stem extract showed maximum cytotoxicity against human breast adenocarcinoma (MCF-7) and human cervical adenocarcinoma (HeLa) cell lines whereas, root extract had higher cytotoxicity against human colon adenocarcinoma (HCT-15) cells. The results of cell viability indicated that the methanolic extracts of L. nicotianifolia plant parts exhibited a range of cytotoxic activity in a concentration and time dependent manner against selected cancer cell lines. The LC-HRMS showed the presence of cytotoxic compounds comparatively higher in stem. Conclusion: The study confirms the antioxidant and cytotoxic potential of L. nicotianifolia. To understand the detailed mechanism of cytotoxicity of L. nicotianifolia, it is necessary to study the molecular mechanism involved in this study.	[Kolap, Rupali Mukesh; Zimare, Saurabha Bhimrao] Naoroji Godrej Ctr Plant Res, Lawkim Motor Campus, Shirwal, Maharashtra, India; [Datkhile, Kailash D.] Krishna Inst Med Sci Univ, Mol & Genet Lab, Satara, Maharashtra, India		Zimare, SB (corresponding author), Naoroji Godrej Ctr Plant Res, Lawkim Motor Campus, Shirwal, Maharashtra, India.	saurabhabot@gmail.com					Ahamed A, 2020, SAUDI J BIOL SCI, V27, P666, DOI 10.1016/j.sjbs.2019.11.043; Akar Z, 2017, J ENZYM INHIB MED CH, V32, P640, DOI 10.1080/14756366.2017.1284068; Alizadeh F, 2015, SM J PHARM THER, V1, P1; Arruebo Manuel, 2011, Cancers (Basel), V3, P3279, DOI 10.3390/cancers3033279; Aryal S, 2019, PLANTS-BASEL, V8, DOI 10.3390/plants8040096; Ashmawy AM, 2021, NAT PROD RES, V35, P4133, DOI 10.1080/14786419.2020.1736064; Aslam M.S., 2014, J CANC THER, V5, P817, DOI 10.4236/jct.2014.58089; Avato P, 2017, ANTI-CANCER AGENT ME, V17, P1508, DOI 10.2174/1871520617666170727152805; Bai LY, 2015, J FUNCT FOODS, V18, P368, DOI 10.1016/j.jff.2015.07.017; Baker MJ, 2014, NAT PROTOC, V9, P1771, DOI 10.1038/nprot.2014.110; Beccaria M, 2020, ANALYST, V145, P1129, DOI 10.1039/c9an02145k; Bendary E., 2013, Annals of Agricultural Science (Cairo), V58, P173, DOI 10.1016/j.aoas.2013.07.002; Bulle Saradamma, 2016, Pharmacogn Rev, V10, P43, DOI 10.4103/0973-7847.176575; Chang KC, 2003, PLANTA MED, V69, P667, DOI 10.1055/s-2003-41120; Chen HX, 2012, NAT PROD RES, V26, P2112, DOI 10.1080/14786419.2011.622275; Chen MW, 2014, CHIN J NAT MEDICINES, V12, P103, DOI 10.1016/S1875-5364(14)60016-9; Chua LS, 2019, MOLECULES, V24, DOI 10.3390/molecules24071416; Dai J, 2010, MOLECULES, V15, P7313, DOI 10.3390/molecules15107313; Dailey OD, 2011, ANTICANCER RES, V31, P3165; Denicolai E, 2014, ONCOTARGET, V5, P10934, DOI 10.18632/oncotarget.2541; Dilshad E, 2020, BIOCATAL AGR BIOTECH, V24, DOI 10.1016/j.bcab.2020.101539; Dobhal MP, 2004, J ORG CHEM, V69, P6165, DOI 10.1021/jo0491408; Durak T, 2020, ENVIRON EXP BOT, V169, DOI 10.1016/j.envexpbot.2019.103915; Feng XM, 2019, ONCOL LETT, V17, P4761, DOI 10.3892/ol.2019.10171; Folquitto DG, 2019, FITOTERAPIA, V134, P23, DOI 10.1016/j.fitote.2018.12.021; Ghosh S, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0082529; Guimarães Karina Carvalho, 2020, Braz. 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J	Swiderek, E; Kalas, W; Wysokinska, E; Pawlak, A; Rak, J; Strzadala, L				Swiderek, Ewelina; Kalas, Wojciech; Wysokinska, Edyta; Pawlak, Alicja; Rak, Janusz; Strzadala, Leon			The interplay between epigenetic silencing, oncogenic KRas and HIF-1 regulatory pathways in control of BNIP3 expression in human colorectal cancer cells	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						5-Aza-2 '-deoxycytidine; BNIP3; Colorectal cancer; HIF-1; Hypoxia; KRas	TRANSCRIPTIONAL REPRESSOR; COMBINED THERAPY; DNA METHYLATION; DEATH; AUTOPHAGY; HYPOXIA; PROTEIN; MITOCHONDRIAL; IRINOTECAN; RESISTANCE	Bcl-2/adenovirus E1B-19 kDa-interacting protein 3 (BNIP3) is an important mediator of cell survival and a member of the Bcl-2 family of proteins that regulate programmed cell death and autophagy. We have previously established a link between the expression of oncogenic HRas and up-regulation of BNIP3 and the control of autophagy in cancer cells. However, in view of varied expression of BNIP3 in different tumor types and emerging uncertainties as to the role of epigenetic silencing, oncogenic regulation and the role of BNIP3 in cancer are still poorly understood. In the present study we describe profound effect of KRas on the expression of methylated BNIP3 in colorectal cancer cells and explore the interplay between HIF-1, hypoxia pathway and oncogenic KRas in this context. We observed that BNIP3 mRNA remains undetectable in aggressive DLD-1 cells harboring G13D mutant KRAS and HT-29 colorectal cancer cells unless the cells are exposed to demethylating agents such as 5-aza-2'-deoxycytidine. Following this treatment BNIP3 expression remains uniquely dependent on the Ras activity. We found that hypoxia or pharmacological activation of HIF-1 alone contributes to, but is not sufficient for efficient induction of BNIP3 mRNA transcription in cells lacking mutant KRas activity. The up-regulation of BNIP3 by KRas in this setting is mediated by the MAPK pathway, and is attenuated by the respective inhibitors (PD98059, U0126). Thus, we demonstrate the novel mechanism where activity of Ras is essential for 5-aza-2'-deoxycytidine-mediated BNIP3 expression. Moreover, we found that 5-aza-2'-deoxycytidine-mediated or enforced up-regulation of BNIP3 in DLD-1 cells results in KRas-dependent resistance to 5-Fluorouracil. (C) 2013 Elsevier Inc. All rights reserved.	[Swiderek, Ewelina; Kalas, Wojciech; Wysokinska, Edyta; Pawlak, Alicja; Strzadala, Leon] Polish Acad Sci, Ludwik Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland; [Rak, Janusz] McGill Univ, Montreal Childrens Hosp Res Inst, Montreal, PQ H3A 2T5, Canada		Strzadala, L (corresponding author), Polish Acad Sci, Inst Immunol & Expt Therapy, Weigla 12, PL-53114 Wroclaw, Poland.	strzadal@iitd.pan.wroc.pl	Kałas, Wojciech/AAB-4469-2019	Kałas, Wojciech/0000-0003-2656-5192; Strzadala, Leon/0000-0002-7323-2254; Wysokinska, Edyta/0000-0003-1003-2463	NCN Grant [2011/01/B/NZ4/00938]	This work was supported by NCN Grant No. 2011/01/B/NZ4/00938.	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Biophys. Res. Commun.	NOV 29	2013	441	4					707	712		10.1016/j.bbrc.2013.10.098			6	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	272BH	WOS:000328434800003	24211581				2022-04-25	
J	Li, JX; Yan, Q; Liu, N; Zheng, WJ; Hu, M; Yu, ZM; Zhou, YD; Wang, XW; Liang, FX; Chen, R				Li, Jin-xiao; Yan, Qian; Liu, Na; Zheng, Wen-jiang; Hu, Man; Yu, Zhao-min; Zhou, Yu-dian; Wang, Xiong-wen; Liang, Feng-xia; Chen, Rui			The Prognostic Value of Autophagy-Related Markers Bclin-1 and LC-3 in Colorectal Cancers: A Systematic Review and Meta-analysis	EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE			English	Review							BECLIN 1; FAVORABLE PROGNOSIS; EXPRESSION; LC3; CARCINOMAS; GUIDELINES; PHYSIOLOGY; RELEVANCE; PROTEINS; PATTERNS	Objective. At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have demonstrated the correlation between autophagy microtubule-associated protein light chain 3 (LC-3), Beclin-1, and colorectal cancer (CRC). Since autophagy has dual regulatory roles in tumors, the results of this correlation are also uncertain. Hence, we summarized the relationship between Beclin-1, LC-3, and CRC using systematic reviews and meta-analysis to clarify their prognostic significance in it. Methods. PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched online up to April 1, 2019. The quality of the involving studies was assessed against the Newcastle-Ottawa Scale (NOS). Pooled hazard ratio (HR) and 95% confidence interval (CI) in a fixed or random effects model were used to assess the strength of correlation between Beclin-1, LC-3, and CRC. Results. A total of 9 articles were collected, involving 2,297 patients. Most literatures scored more than 6 points, suggesting that the quality of our including research was acceptable. Our finding suggested that the expression of Beclin-1 was not associated with overall survival (HR = 0.68, 95% CI (0.31-1.52), P=0.351). Nonetheless, LC-3 expression exerted significant impact on OS (HR = 0.51, 95% CI (0.35-0.74), P<0.05). Subgroup analysis exhibited that Beclin-1 expression was associated with OS at TNM stage III (HR = 0.04, 95% CI = 0.02-0.08, P<0.05), surgical treatment (HR = 1.53, 95% CI (1.15-2.02), P=0.003), and comprehensive treatment (HR = 0.27 95% CI (0.08-0.92), P=0.036), respectively. Similarly, the results showed the increased LC-3 expression in CRC was related to OS in multivariate analyses (HR = 0.44, 95% CI (0.34-0.57), P<0.05), stages (HR = 0.51, 95% CI (0.35-0.74), P<0.05), and comprehensive treatment (HR = 0.44, 95% CI (0.34-0.57), P<0.05). Conclusions. Autophagy-related proteins of LC-3 might be an important marker of CRC progression. However, since the number of the original studies was limited, more well-designed, large-scale, high-quality studies are warranted to provide more convincing and reliable information.	[Li, Jin-xiao; Hu, Man; Yu, Zhao-min; Chen, Rui] Huazhong Univ Sci & Technol, Dept Integrated Tradit Chinese & Western Med, Tongji Med Coll, Union Hosp, Wuhan 430022, Peoples R China; [Yan, Qian; Zheng, Wen-jiang] Guangzhou Univ Chinese Med, Guangzhou 510405, Peoples R China; [Liu, Na] Chengdu Univ Chinese Med, Dept Acupuncture & Moxibust, Chengdu 610075, Peoples R China; [Zhou, Yu-dian; Liang, Feng-xia] Hubei Univ Chinese Med, Dept Acupuncture & Moxibust, Wuhan 430065, Peoples R China; [Wang, Xiong-wen] Guangzhou Univ Tradit Chinese Med, Affiliated Hosp 1, Guangzhou 510405, Peoples R China		Chen, R (corresponding author), Huazhong Univ Sci & Technol, Dept Integrated Tradit Chinese & Western Med, Tongji Med Coll, Union Hosp, Wuhan 430022, Peoples R China.	962939252@qq.com; 20171101040@stu.gzucm.edu.cn; 1454542867@qq.com; 20171101136@stu.gzucm.edu.cn; 994485699@qq.com; 785773912@qq.com; 531245554@qq.com; awen681029@163.com; 315938821@qq.com; unioncr@163.com		Zheng, Wenjiang/0000-0001-5234-0339	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81774401, 81574065]	This meta-analysis was supported by the National Natural Science Foundation of China (Grant nos. 81774401 and 81574065).	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Med.	MAR 23	2020	2020								8475840	10.1155/2020/8475840			11	Integrative & Complementary Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine	LC0GU	WOS:000525010000001	32280357	Green Published, gold			2022-04-25	
J	Wang, YF; Xie, JY; Wang, H; Huang, HX; Xie, P				Wang, Yanfeng; Xie, Jianying; Wang, Hao; Huang, Haixia; Xie, Ping			Beclin-1 suppresses gastric cancer progression by promoting apoptosis and reducing cell migration	ONCOLOGY LETTERS			English	Article						Beclin-1; gastric cancer; tumorigenesis; apoptosis; migration	COLORECTAL-CANCER; 1 EXPRESSION; AUTOPHAGY; CARCINOMA; LC3; CHEMORADIATION; EFFICACY	To investigate Beclin-1 expression in gastric cancer and its clinical relevance, 60 samples were collected from patients with gastric carcinoma, which were subjected to immunohistochemical staining and analysis. Associations of Beclin-1 expression with the clinical parameters of the patients, including tumor size, histological differentiation and metastatic status, were examined by statistical analysis. The results demonstrated that Beclin-1 expression in gastric carcinoma tissue was significantly associated with the tumor, node, metastasis stage and tumor invasion status. Further experiments indicated that Beclin-1 overexpression promoted MKN-45 gastric cancer cell apoptosis and inhibited their migration. These data suggested that Beclin-1 was a suppressor of tumorigenesis in gastric cancer and a potential therapeutic target for patients with gastric cancer.	[Wang, Yanfeng] Heilongjiang Prov Land Reclamat Headquarter Gen H, Dept Pathol, Harbin 150088, Heilongjiang, Peoples R China; [Xie, Jianying; Huang, Haixia; Xie, Ping] King Med Diagnost Ctr, Dept Pathol, 3377 Kangxin Rd, Shanghai 201321, Peoples R China; [Wang, Hao] Heilongjiang Prov Land Reclamat Headquarter Gen H, Dept Phys Diagnost, Harbin 150088, Heilongjiang, Peoples R China		Xie, P (corresponding author), King Med Diagnost Ctr, Dept Pathol, 3377 Kangxin Rd, Shanghai 201321, Peoples R China.	xieping76@hotmail.com			Natural Science Foundation of Shanghai Health and Family Planning Commission [201540088]; China National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81370961]	The present study was supported by grants from the Natural Science Foundation of Shanghai Health and Family Planning Commission (grant no. 201540088) and the China National Natural Science Foundation of China (grant no. 81370961).	Burada F, 2015, WORLD J GASTRO ONCOL, V7, P271, DOI 10.4251/wjgo.v7.i11.271; Chen N, 2009, BBA-MOL CELL RES, V1793, P1516, DOI 10.1016/j.bbamcr.2008.12.013; Chen YS, 2013, PATHOL RES PRACT, V209, P562, DOI 10.1016/j.prp.2013.06.006; Fei BY, 2016, ONCOL LETT, V11, P2271, DOI 10.3892/ol.2016.4183; Gallagher LE, 2016, CELLS-BASEL, V5, DOI 10.3390/cells5020024; Geng ZH, 2016, AM J TRANSL RES, V8, P1886; Guo GF, 2011, WORLD J GASTROENTERO, V17, P4779, DOI 10.3748/wjg.v17.i43.4779; Hasima N, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.467; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Kongara S, 2010, MOL CANCER RES, V8, P873, DOI 10.1158/1541-7786.MCR-09-0494; Levine B, 2008, AUTOPHAGY, V4, P600, DOI 10.4161/auto.6260; Lian J, 2011, CELL DEATH DIFFER, V18, P60, DOI 10.1038/cdd.2010.74; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Lozy F, 2012, SEMIN CELL DEV BIOL, V23, P395, DOI 10.1016/j.semcdb.2012.01.005; Luo S, 2010, CELL DEATH DIFFER, V17, P268, DOI 10.1038/cdd.2009.121; Maiuri MC, 2007, EMBO J, V26, P2527, DOI 10.1038/sj.emboj.7601689; Mathew R, 2007, GENE DEV, V21, P1367, DOI 10.1101/gad.1545107; Miracco C, 2010, HUM PATHOL, V41, P503, DOI 10.1016/j.humpath.2009.09.004; Nikoletopoulou V, 2013, BBA-MOL CELL RES, V1833, P3448, DOI 10.1016/j.bbamcr.2013.06.001; Ozpolat B, 2015, CANCER MANAG RES, V7, P291, DOI 10.2147/CMAR.S34859; Pattingre S, 2005, CELL, V122, P927, DOI 10.1016/j.cell.2005.07.002; Qiu DM, 2014, BMC CANCER, V14, DOI 10.1186/1471-2407-14-327; Sakakura K, 2015, CANCER SCI, V106, P1, DOI [10.1111/cas.12559, 10.1111/cas.12579]; Tang JY, 2013, HUM PATHOL, V44, P2558, DOI 10.1016/j.humpath.2013.06.017; Wang YW, 2013, J ORAL PATHOL MED, V42, P557, DOI 10.1111/jop.12049; Washington K, 2010, ANN SURG ONCOL, V17, P3077, DOI 10.1245/s10434-010-1362-z; Weng JQ, 2014, ORAL ONCOL, V50, P983, DOI 10.1016/j.oraloncology.2014.06.020; Won KY, 2015, PATHOL RES PRACT, V211, P308, DOI 10.1016/j.prp.2014.11.005; Yue ZY, 2003, P NATL ACAD SCI USA, V100, P15077, DOI 10.1073/pnas.2436255100; Zaanan A, 2015, INT J CANCER, V137, P1498, DOI 10.1002/ijc.29496; Zhao GX, 2015, ANN MED, V47, P305, DOI 10.3109/07853890.2015.1040831; Zhao Y, 2014, TUMOR BIOL, V35, P1955, DOI 10.1007/s13277-013-1261-6	32	6	9	1	2	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	DEC	2017	14	6					6857	6862		10.3892/ol.2017.7046			6	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FP0LV	WOS:000417293400072	29163705	gold, Green Published			2022-04-25	
J	Zhu, JM; Chen, SS; Yang, BX; Mao, WD; Yang, X; Cai, J				Zhu, Jiamin; Chen, Shusen; Yang, Baixia; Mao, Weidong; Yang, Xi; Cai, Jing			Molecular mechanisms of lncRNAs in regulating cancer cell radiosensitivity	BIOSCIENCE REPORTS			English	Review							LONG NONCODING RNA; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN COLORECTAL-CANCER; ENHANCES RADIOSENSITIVITY; DOWN-REGULATION; LUNG-CANCER; NASOPHARYNGEAL CARCINOMA; RADIATION-RESISTANCE; TUMOR-CELLS; STEM-CELLS	Radiotherapy is one of the main modalities of cancer treatment. However, tumor recurrence following radiotherapy occurs in many cancer patients. A key to solving this problem is the optimization of radiosensitivity. In recent years, long non-coding RNAs (lncRNAs), which affect the occurrence and development of tumors through a variety of mechanisms, have become a popular research topic. LncRNAs have been found to influence radiosensitivity by regulating various mechanisms, including DNA damage repair, cell cycle arrest, apoptosis, cancer stem cells regulation, epithelial-mesenchymal transition, and autophagy. LncRNAs are expected to become a potential therapeutic target for radiotherapy in the future. This article reviews recent advances in the role and mechanism of lncRNAs in tumor radiosensitivity.	[Zhu, Jiamin; Mao, Weidong] Southeast Univ, Coll Med, Affiliated Jiangyin Hosp, Dept Oncol, 163 Shoushan Rd, Jiangyin 214400, Peoples R China; [Zhu, Jiamin; Chen, Shusen; Yang, Baixia; Cai, Jing] Nantong Univ, Affiliated Tumor Hosp, Nantong Tumor Hosp, Dept Radiat Oncol, Nantong 226321, Peoples R China; [Yang, Xi] Fudan Univ, Shanghai Med Coll, Dept Oncol, Dept Radiat Oncol,Shanghai Canc Ctr, Shanghai 200032, Peoples R China		Cai, J (corresponding author), Nantong Univ, Affiliated Tumor Hosp, Nantong Tumor Hosp, Dept Radiat Oncol, Nantong 226321, Peoples R China.; Yang, X (corresponding author), Fudan Univ, Shanghai Med Coll, Dept Oncol, Dept Radiat Oncol,Shanghai Canc Ctr, Shanghai 200032, Peoples R China.	ntgeorge@qq.com; cj7227@sina.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81703024]	This study was sponsored by grants from the National Natural Science Foundation of China [81703024].	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Zhang YY, 2016, NAT STRUCT MOL BIOL, V23, P522, DOI 10.1038/nsmb.3211; Zheng R, 2016, INT J RADIAT ONCOL, V96, P877, DOI 10.1016/j.ijrobp.2016.07.036; Zhou Y, 2019, MOL CELL BIOCHEM, V450, P125, DOI 10.1007/s11010-018-3379-8; Zou YM, 2018, EUR J CELL BIOL, V97, P369, DOI 10.1016/j.ejcb.2018.04.005	79	16	16	2	6	PORTLAND PRESS LTD	LONDON	CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND	0144-8463	1573-4935		BIOSCIENCE REP	Biosci. Rep.	AUG 28	2019	39		8						BSR20190590	10.1042/BSR20190590			9	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	IT6LX	WOS:000482987000001	31391206	Green Published, Green Submitted, gold			2022-04-25	
J	Sun, PF; Wang, HH; He, ZY; Chen, XY; Wu, QC; Chen, WK; Sun, ZR; Weng, ML; Zhu, MM; Ma, D; Miao, CH				Sun, Pengfei; Wang, Huihui; He, Zhiyong; Chen, Xiangyuan; Wu, Qichao; Chen, Wankun; Sun, Zhirong; Weng, Meilin; Zhu, Minmin; Ma, Duan; Miao, Changhong			Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages	ONCOTARGET			English	Article						fasting; tumor-associated macrophages; colorectal cancer; adenosine; autophagy	SUPPRESSOR-CELLS; AUTOPHAGY; RESTRICTION; PROGRESSION; BLOCKADE; OBESITY	Dietary restriction has been recognized as a healthy and natural therapy for cancer. It is reported that different forms of dietary restriction can promote antitumor immunity. However, it is not clear how fasting affects tumor-associated macrophages (TAMs). This study aims to investigate the relationship between fasting and antitumor immunity in terms of tumor-associated macrophages. In vivo, the results showed that alternate day fasting for 2 weeks inhibitted the tumor growth of mice without causing a reduction of body weight. Meanwhile, M2 polarization of tumor-associated macrophages in tumor tissues of alternate day fasting group was also decreased. In vitro, fasting induced the autophagy of CT26 cells, decreased the generation of extracellular adenosine by supressing the expression of CD73 in CT26 cells. Decreasing adenosine inhibitted M2 polarization of RAW264.7 cells through inactivating JAK1/STAT3 signal pathway in fasting condition. Eventually, the proliferation of CT26 cancer cells declined on account of fasting-facilitated antitumor immunity. These results suggested that fasting suppressed M2 polarization of tumorassociated macrophages to inhibit tumor growth through decreasing the level of adenosine in the tumor microenvironment both in vivo and in vitro. This process was associated with increasing autophagy of tumor cells.	[Sun, Pengfei; Wang, Huihui; He, Zhiyong; Chen, Xiangyuan; Wu, Qichao; Chen, Wankun; Sun, Zhirong; Weng, Meilin; Zhu, Minmin; Miao, Changhong] Fudan Univ, Shanghai Med Coll, Dept Anesthesiol, Shanghai Canc Ctr,Dept Oncol, Shanghai, Peoples R China; [Ma, Duan] Fudan Univ, Dept Biochem & Mol Biol,Inst Biomed Sci, Key Lab Metab & Mol Med,Sch Basic Med Sci, Collaborat Innovat Ctr Genet & Dev,Minist Educ, Shanghai, Peoples R China		Miao, CH (corresponding author), Fudan Univ, Shanghai Med Coll, Dept Anesthesiol, Shanghai Canc Ctr,Dept Oncol, Shanghai, Peoples R China.; Ma, D (corresponding author), Fudan Univ, Dept Biochem & Mol Biol,Inst Biomed Sci, Key Lab Metab & Mol Med,Sch Basic Med Sci, Collaborat Innovat Ctr Genet & Dev,Minist Educ, Shanghai, Peoples R China.	duanma@fudan.edu.cn; miaochh@aliyun.com	Ma, Duan/I-8330-2014		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81372101]	This work was is supported by the National Natural Science Foundation of China (No. 81372101).	Arranz A, 2012, P NATL ACAD SCI USA, V109, P9517, DOI 10.1073/pnas.1119038109; Bardou M, 2013, GUT, V62, P933, DOI 10.1136/gutjnl-2013-304701; Bianchi F, 2013, CELL TRANSPLANT, V22, P2063, DOI 10.3727/096368912X657855; Bianchi G, 2015, ONCOTARGET, V6, P11806, DOI 10.18632/oncotarget.3688; Cekic C, 2012, J IMMUNOL, V188, P198, DOI 10.4049/jimmunol.1101845; Chen WK, 2016, ONCOTARGET, V7, P78726, DOI 10.18632/oncotarget.12807; Csoka B, 2012, FASEB J, V26, P376, DOI 10.1096/fj.11-190934; D'Aronzo M, 2015, ONCOTARGET, V6, P18545, DOI 10.18632/oncotarget.4186; Gessi S, 2011, BBA-BIOMEMBRANES, V1808, P1400, DOI 10.1016/j.bbamem.2010.09.020; Hao NB, 2012, CLIN DEV IMMUNOL, DOI 10.1155/2012/948098; Hatfield SM, 2016, CURR OPIN PHARMACOL, V29, P90, DOI 10.1016/j.coph.2016.06.009; Ho TT, 2017, NATURE, V543, P205, DOI 10.1038/nature21388; Husain Z, 2013, J IMMUNOL, V191, P1486, DOI 10.4049/jimmunol.1202702; Iannone R, 2013, NEOPLASIA, V15, P1400, DOI 10.1593/neo.131748; Kang K, 2008, CELL METAB, V7, P485, DOI 10.1016/j.cmet.2008.04.002; Koscso B, 2013, J LEUKOCYTE BIOL, V94, P1309, DOI 10.1189/jlb.0113043; Lashinger LM, 2016, CANCER METAB, V4, DOI 10.1186/s40170-016-0158-4; Lee C, 2012, SCI TRANSL MED, V4, DOI 10.1126/scitranslmed.3003293; Leelatian N, 2017, CYTOM PART B-CLIN CY, V92, P68, DOI 10.1002/cyto.b.21481; LEVIN B, 1992, CANCER-AM CANCER SOC, V70, P1723, DOI 10.1002/1097-0142(19920915)70:4+<1723::AID-CNCR2820701612>3.0.CO;2-3; Luo JH, 2014, METHODS MOL BIOL, V1135, P357, DOI 10.1007/978-1-4939-0320-7_29; Ma DF, 2010, HUM PATHOL, V41, P1550, DOI 10.1016/j.humpath.2010.04.008; Mantovani A, 2002, TRENDS IMMUNOL, V23, P549, DOI 10.1016/S1471-4906(02)02302-5; Martinez-Useros J, 2016, J TRANSL MED, V14, DOI 10.1186/s12967-016-0772-5; Mendelsohn AR, 2014, REJUV RES, V17, P385, DOI 10.1089/rej.2014.1595; Mizushima N, 2004, MOL BIOL CELL, V15, P1101, DOI 10.1091/mbc.E03-09-0704; Morello S, 2016, ONCOIMMUNOLOGY, V5, DOI 10.1080/2162402X.2015.1108515; Ohta A, 2016, FRONT IMMUNOL, V7, DOI 10.3389/fimmu.2016.00109; Pietrocola F, 2016, CANCER CELL, V30, P147, DOI 10.1016/j.ccell.2016.05.016; Qian BZ, 2010, CELL, V141, P39, DOI 10.1016/j.cell.2010.03.014; Rao S, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms4056; Safdie F, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0044603; Sica A, 2006, EUR J CANCER, V42, P717, DOI 10.1016/j.ejca.2006.01.003; Van Blarigan EL, 2015, J CLIN ONCOL, V33, P1825, DOI 10.1200/JCO.2014.59.7799; van Niekerk G, 2016, FRONT ONCOL, V6, DOI 10.3389/fonc.2016.00242; Wei Q, 2013, PURINERG SIGNAL, V9, P271, DOI 10.1007/s11302-012-9350-3; White E, 2012, NAT REV CANCER, V12, P401, DOI 10.1038/nrc3262	37	30	31	5	21	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA		1949-2553		ONCOTARGET	Oncotarget	SEP 26	2017	8	43					74649	74660		10.18632/oncotarget.20301			12	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	FI2HT	WOS:000411760400106	29088814	Green Submitted, gold, Green Published			2022-04-25	
J	Han, Y; Xue, XF; Shen, HG; Guo, XB; Wang, X; Yuan, B; Guo, XP; Kuang, YT; Zhi, QM; Zhao, H				Han, Ye; Xue, Xiao-Feng; Shen, Hu-Gang; Guo, Xiao-Bo; Wang, Xu; Yuan, Bin; Guo, Xing-Po; Kuang, Yu-Ting; Zhi, Qiao-Ming; Zhao, Hong			Prognostic Significance of Beclin-1 Expression in Colorectal Cancer: a Meta-analysis	ASIAN PACIFIC JOURNAL OF CANCER PREVENTION			English	Article						Beclin-1; colorectal cancer; prognosis; meta-analysis	GASTRIC-CANCER; AUTOPHAGY; PROTEIN	Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers. However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed to evaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients. Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer and Chinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed to determine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were included in our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associated with poor prognosis in terms of tumor distant metastasis (OR=2.090, 95% CI=1.061-4.119, p=0.033) and overall survival (RR=1.422, 95% CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1 over-expression and tumor differentiation (OR=1.711, 95% CI=0.920-3.183, p=0.090). In addition, there was no evidence of publication bias as suggested by Egger's tests for tumor distant metastasis (p=1.000), differentiation (p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expression iss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as an efficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.	[Han, Ye; Xue, Xiao-Feng; Wang, Xu; Yuan, Bin; Guo, Xing-Po; Kuang, Yu-Ting; Zhi, Qiao-Ming; Zhao, Hong] Soochow Univ, Affiliated Hosp 1, Dept Gen Surg, Suzhou, Peoples R China; [Shen, Hu-Gang] Kunshan Hosp Tradit Chinese Med, Dept Gen Surg, Kunshan, Peoples R China; [Guo, Xiao-Bo] Shandong Univ, Prov Hosp, Dept Gastrointestinal Surg, Jinan 250100, Peoples R China		Zhi, QM (corresponding author), Soochow Univ, Affiliated Hosp 1, Dept Gen Surg, Suzhou, Peoples R China.	strexboy@163.com; zhaohong600@sina.com			National youthful Science Foundation of China [81201905, 81302147]; National Science Foundation of Jiangsu Province, China [BK20130270]	This study was supported by a grant from the National youthful Science Foundation of China (No. 81201905 and 81302147), the National Science Foundation of Jiangsu Province, China (No. BK20130270).	Ahn CH, 2007, APMIS, V115, P1344, DOI 10.1111/j.1600-0463.2007.00858.x; Cao Y, 2007, CELL RES, V17, P839, DOI 10.1038/cr.2007.78; Chen ZH, 2013, DIGEST DIS SCI, V58, P2887, DOI 10.1007/s10620-013-2732-8; Geng QR, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0045968; Guo GF, 2011, WORLD J GASTROENTERO, V17, P4779, DOI 10.3748/wjg.v17.i43.4779; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Kekelidze M, 2013, WORLD J GASTROENTERO, V19, P8502, DOI 10.3748/wjg.v19.i46.8502; Khiewkhern S, 2013, ASIAN PAC J CANCER P, V14, P3903, DOI 10.7314/APJCP.2013.14.6.3903; Kim HS, 2011, PATHOL RES PRACT, V207, P247, DOI 10.1016/j.prp.2011.02.007; Klionsky DJ, 2000, SCIENCE, V290, P1717, DOI 10.1126/science.290.5497.1717; Koneri K, 2007, ANTICANCER RES, V27, P1453; Koneri Kenji, 2003, Nihon Rinsho, V61 Suppl 7, P247; Koukourakis MI, 2010, BRIT J CANCER, V103, P1209, DOI 10.1038/sj.bjc.6605904; Li BX, 2009, AUTOPHAGY, V5, P303, DOI 10.4161/auto.5.3.7491; Maiuri MC, 2009, CELL DEATH DIFFER, V16, P87, DOI 10.1038/cdd.2008.131; Miracco C, 2007, INT J ONCOL, V30, P429; Mizushima N, 2008, NATURE, V451, P1069, DOI 10.1038/nature06639; Park JM, 2013, CANCER BIOL THER, V14, P100, DOI 10.4161/cbt.22954; Parmar MKB, 1998, STAT MED, V17, P2815, DOI 10.1002/(SICI)1097-0258(19981230)17:24<2815::AID-SIM110>3.0.CO;2-8; Song H, 2004, WORLD J GASTROENTERO, V10, P509, DOI 10.3748/wjg.v10.i4.509; Sui YQ, 2012, J CLIN EXP PATHOL, V28, P282; Tong GX, 2014, ASIAN PAC J CANCER P, V15, P1015, DOI 10.7314/APJCP.2014.15.2.1015; Xia P, 2013, TUMOR BIOL, V34, P3303, DOI 10.1007/s13277-013-1049-8; Zafar SY, 2013, CANCER-AM CANCER SOC, V119, P854, DOI 10.1002/cncr.27815; Zeng XH, 2006, J CELL SCI, V119, P259, DOI 10.1242/jcs.02735; Zhang HQ, 2013, ASIAN PAC J CANCER P, V14, P4685, DOI 10.7314/APJCP.2013.14.8.4685; Zois CE, 2009, AUTOPHAGY, V5, P442, DOI 10.4161/auto.5.4.7667	27	25	26	0	0	ASIAN PACIFIC ORGANIZATION CANCER PREVENTION	GYEONGGI-DO	APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA	1513-7368			ASIAN PAC J CANCER P	Asian Pac. J. Cancer Prev.		2014	15	11					4583	4587		10.7314/APJCP.2014.15.11.4583			5	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AK7VD	WOS:000338634900034	24969889	gold, Green Submitted			2022-04-25	
J	Tian, Y; Wang, KM; Fan, YR; Wang, Y; Sun, LQ; Wang, L; Wang, JR; Wang, ZX; Li, J; Ye, Y; Ji, GZ				Tian, Yun; Wang, Keming; Fan, Yingrui; Wang, Yan; Sun, Liqun; Wang, Li; Wang, Jirong; Wang, Zhaoxia; Li, Juan; Ye, Ying; Ji, Guozhong			Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway	NUTRIENTS			English	Article						colitis; colorectal cancer; glutamine; DEPTOR; mTOR signaling	INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; PREVENTS MUCOSAL INJURY; MTOR INHIBITOR; GROWTH; AUTOPHAGY; HYPERPERMEABILITY; TUMORIGENESIS; MODEL; MICE	Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.	[Tian, Yun; Wang, Keming; Fan, Yingrui; Wang, Li; Wang, Jirong; Wang, Zhaoxia; Li, Juan] Nanjing Med Univ, Dept Oncol, Affiliated Hosp 2, 121 Jiangjiayuan Rd, Nanjing 210011, Jiangsu, Peoples R China; [Wang, Yan] Nanjing Med Univ, Dept Pathol, Affiliated Hosp 2, 121 Jiangjiayuan Rd, Nanjing 210011, Jiangsu, Peoples R China; [Sun, Liqun] Nanjing Med Univ, Dept Intens Care Unit, Affiliated Hosp 2, 121 Jiangjiayuan Rd, Nanjing 210011, Jiangsu, Peoples R China; [Ye, Ying] Xuzhou Med Univ, Affiliated Hosp, Emergency Ctr, Xuzhou 221002, Peoples R China; [Ji, Guozhong] Nanjing Med Univ, Inst Digest Endoscopy, Affiliated Hosp 2, 121 Jiangjiayuan Rd, Nanjing 210011, Peoples R China; [Ji, Guozhong] Nanjing Med Univ, Med Ctr Digest Dis, Affiliated Hosp 2, 121 Jiangjiayuan Rd, Nanjing 210011, Peoples R China		Ji, GZ (corresponding author), Nanjing Med Univ, Inst Digest Endoscopy, Affiliated Hosp 2, 121 Jiangjiayuan Rd, Nanjing 210011, Peoples R China.; Ji, GZ (corresponding author), Nanjing Med Univ, Med Ctr Digest Dis, Affiliated Hosp 2, 121 Jiangjiayuan Rd, Nanjing 210011, Peoples R China.	summer.cloud@live.cn; drkemingwang@sina.cn; drfanyingrui@sohu.com; dryanwang@sina.com; lixiang@kplink.cn; drliqunsun@sina.com; rabbitwjr@126.com; zhaoxiawang88@hotmail.com; ljsmz1229@163.com; xzmcyy@163.com; drjiguozhong@sina.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81302110]; Nanjing Medical University [2014NJMUZD071]	This study was supported by funding from National Natural Science Foundation of China (Grant 81302110) and Funding from Nanjing Medical University (Grant 2014NJMUZD071).	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J	Kao, RH; Lai, GM; Chow, JM; Liao, CH; Zheng, YM; Tsai, WL; Hsia, S; Lai, IC; Lee, HL; Chuang, SE; Whang-Peng, J; Yao, CJ				Kao, Ruey-Ho; Lai, Gi-Ming; Chow, Jyh-Ming; Liao, Chien-Huang; Zheng, Yu-Mei; Tsai, Wei-Lun; Hsia, Simon; Lai, I-Chun; Lee, Hsin-Lun; Chuang, Shuang-En; Whang-Peng, Jacqueline; Yao, Chih-Jung			Opposite Regulation of CHOP and GRP78 and Synergistic Apoptosis Induction by Selenium Yeast and Fish Oil via AMPK Activation in Lung Adenocarcinoma Cells	NUTRIENTS			English	Article						selenium; fish oil; lung adenocarcinoma; ER stress; apoptosis	ENDOPLASMIC-RETICULUM STRESS; COLON-CANCER CELLS; PROTEIN-KINASE; GROWTH ARREST; FATTY-ACIDS; STEM-CELLS; ER STRESS; CHEMOPREVENTION; SUPPLEMENTATION; AUTOPHAGY	Selenium has been intensively studied for the use of cancer prevention and treatment. However, the clinical effects are still plausible. To enhance its efficacy, a combinational study of selenium yeast (SY) and fish oil (FO) was performed in A549, CL1-0, H1299, HCC827 lung adenocarcinoma (LADC) cells to investigate the enhancement in apoptosis induction and underlying mechanism. By sulforhodamine B staining, Western blot and flow cytometric assays, we found a synergism between SY and FO in growth inhibition and apoptosis induction of LADC cells. In contrast, the fetal lung fibroblast cells (MRC-5) were unsusceptible to this combination effect. FO synergized SY-induced apoptosis of A549 cells, accompanied with synergistic activation of AMP-activated protein kinase (AMPK) and reduction of Cyclooxygenase (COX)-2 and -catenin. Particularly, combining with FO not only enhanced the SY-elevated proapoptotic endoplasmic reticulum (ER) stress marker CCAAT/enhancer-binding protein homologous protein (CHOP), but also reduced the cytoprotective glucose regulated protein of molecular weight 78 kDa (GRP78). Consequently, the CHOP downstream targets such as phospho-JNK and death receptor 5 were also elevated, along with the cleavage of caspase-8, -3, and the ER stress-related caspase-4. Accordingly, inhibition of AMPK by compound C diminished the synergistic apoptosis induction, and elevated CHOP/GRP78 ratio by SY combined with FO. The AMPK-dependent synergism suggests the combination of SY and FO for chemoprevention and integrative treatment of LADC.	[Kao, Ruey-Ho; Lai, Gi-Ming; Chow, Jyh-Ming; Liao, Chien-Huang; Tsai, Wei-Lun; Whang-Peng, Jacqueline; Yao, Chih-Jung] Taipei Med Univ, Wan Fang Hosp, Canc Ctr, Taipei 11696, Taiwan; [Kao, Ruey-Ho; Lai, Gi-Ming; Chow, Jyh-Ming; Whang-Peng, Jacqueline] Taipei Med Univ, Wan Fang Hosp, Dept Internal Med, Div Hematol & Med Oncol, Taipei 11696, Taiwan; [Kao, Ruey-Ho; Lai, Gi-Ming; Whang-Peng, Jacqueline] Taipei Med Univ, Taipei Canc Ctr, Taipei 11031, Taiwan; [Kao, Ruey-Ho; Lai, Gi-Ming; Chow, Jyh-Ming; Yao, Chih-Jung] Taipei Med Univ, Coll Med, Sch Med, Dept Internal Med, Taipei 11031, Taiwan; [Lai, Gi-Ming; Chuang, Shuang-En] Natl Hlth Res Inst, Natl Inst Canc Res, Miaoli 35053, Taiwan; [Hsia, Simon] Taiwan Nutraceut Assoc, Taipei 10596, Taiwan; [Lai, I-Chun] Taipei Vet Gen Hosp, Dept Oncol, Div Radiat Oncol, Taipei 11217, Taiwan; [Lee, Hsin-Lun] Taipei Med Univ, Taipei Med Univ Hosp, Dept Radiat Oncol, Taipei 11031, Taiwan		Yao, CJ (corresponding author), Taipei Med Univ, Wan Fang Hosp, Canc Ctr, Taipei 11696, Taiwan.; Yao, CJ (corresponding author), Taipei Med Univ, Coll Med, Sch Med, Dept Internal Med, Taipei 11031, Taiwan.	rueykao@gmail.com; gminlai@nhri.org.tw; chow0803@yahoo.com.tw; a2639264@ms25.hinet.net; lilindr3@gmail.com; clairgg@hotmail.com; Dr.Simon.hsia@gmail.com; littlelai0114@gmail.com; b001089024@tmu.edu.tw; sechuang@nhri.org.tw; jqwpeng@nhri.org.tw; yaochihjung@gmail.com			Wan Fang Hospital; Taipei Medical University; New Health Products Co., Ltd., Taipei, Taiwan [W327]; Health and welfare surcharge of tobacco products [MOHW107-TDU-B-212-114020]; Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [MOST 104-2314-B-038-077-MY3]	This work was supported by the joint grant of Wan Fang Hospital, Taipei Medical University and New Health Products Co., Ltd., Taipei, Taiwan (Grant W327), Health and welfare surcharge of tobacco products (MOHW107-TDU-B-212-114020) and Ministry of Science and Technology, Taiwan (MOST 104-2314-B-038-077-MY3). This work was partially supported by the joint grant of Wan Fang Hospital, Taipei Medical University and New Health Products Co., Ltd., Taipei, Taiwan (Grant W327). Gi-Ming Lai and Chih-Jung Yao are the Principle Investigator and Co-Principle Investigator of the Grant W327, respectively.	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J	Zhang, LT; Lu, PF; Yan, LH; Yang, LJ; Wang, YT; Chen, JJ; Dai, J; Li, YH; Kang, ZM; Bai, T; Xi, YF; Xu, J; Sun, GQ; Yang, T				Zhang, Litao; Lu, Peifen; Yan, Lihong; Yang, Lijun; Wang, Yutao; Chen, Junjun; Dai, Jie; Li, Yahui; Kang, Zhiming; Bai, Tao; Xi, Yanfeng; Xu, Jun; Sun, Gongqin; Yang, Tao			MRPL35 Is Up-Regulated in Colorectal Cancer and Regulates Colorectal Cancer Cell Growth and Apoptosis	AMERICAN JOURNAL OF PATHOLOGY			English	Article							DNA-DAMAGE RESPONSE; MOLECULAR-MECHANISMS; OXIDATIVE STRESS; SODIUM SELENITE; ATM KINASE; P53; AUTOPHAGY; MITOCHONDRIA; ACTIVATION; DEATH	Mitochondrial ribosome proteins (MRPs), which are encoded by the nuclear genomic DNA, are important for mitochondrial-encoded protein synthesis and mitochondrial function. Emerging evidence suggests that several MRPs also exhibit important extra-mitochondrial. functions, such as involvement in apoptosis, protein biosynthesis, and signal transduction. In this study, we demonstrate a significant role of MRP L35 (MRPL35) in colorectal cancer (CRC). The expression of MRPL35 was higher in CRC tissues than in matched cancer-adjacent tissues and higher in CRC cells than in normal mucosal epithelial cells. Higher MRPL35 expression in CRC tissue correlated with shorter overall survival for CRC patients. In vitro, down-regulation of MRPL35 led to increased production of reactive oxygen species (ROS) together with DNA damage, loss of cell proliferation, G(2)/M arrest, a decrease in mitochondrial membrane potential, apoptosis, and autophagy induction. MRPL35 knockdown inhibited tumor proliferation in a CRC xenograft nude mouse model. Furthermore, overexpression of MRPL35 or treatment of cells with the ROS scavenger, N-acetyl cysteine, abrogated ROS production, cell cycle arrest, and apoptosis in vitro. These findings suggest that MRPL35 plays an essential role in the development of CRC and may be a potential therapeutic target for CRC.	[Zhang, Litao; Lu, Peifen; Yan, Lihong; Wang, Yutao; Chen, Junjun; Dai, Jie; Li, Yahui; Kang, Zhiming; Sun, Gongqin; Yang, Tao] Shanxi Med Univ, Dept Biochem & Mol Biol, Taiyuan, Shanxi, Peoples R China; [Yang, Lijun] Shanxi Med Univ, Dept Pharmacol, Taiyuan, Shanxi, Peoples R China; [Bai, Tao] Shanxi Med Univ, Affiliated Hosp 1, Dept Pathol, Taiyuan, Shanxi, Peoples R China; [Xi, Yanfeng] Shanxi Prov Canc Hosp, Dept Pathol, Taiyuan, Shanxi, Peoples R China; [Xu, Jun] Shanxi Grand Hosp, Dept Gen Surg, Taiyuan, Shanxi, Peoples R China; [Sun, Gongqin] Univ Rhode Isl, Dept Cell & Mol Biol, Kingston, RI 02881 USA		Yang, T (corresponding author), 56 Xinjian S Rd, Taiyuan 030001, Shanxi, Peoples R China.; Sun, GQ (corresponding author), 120 Flag Rd, Kingston, RI 02881 USA.	gongqinsun@uri.edu; yangtao056cn@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81101895, 81441021]; Shanxi Scholarship Council of China [2016-050]; Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi ProvinceScientific Research Foundation for the Returned Overseas Chinese Scholars [2014-779]	Supported by the National Natural Science Foundation of China grants 81101895 and 81441021, the Shanxi Scholarship Council of China grant 2016-050, and the Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province grant 2014-779.	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J	Bortnik, S; Gorski, SM				Bortnik, Svetlana; Gorski, Sharon M.			Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to Biomarkers	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						autophagy; cancer; biomarkers; immunohistochemistry	LIGHT-CHAIN 3B; BECLIN 1; PROGNOSTIC-SIGNIFICANCE; POOR-PROGNOSIS; COLORECTAL-CANCER; LUNG-CANCER; SELECTIVE INHIBITOR; MAMMALIAN AUTOPHAGY; MARKERS BECLIN-1; HIGH EXPRESSION	Autophagy, a lysosome-mediated intracellular degradation and recycling pathway, plays multiple context-dependent roles in tumorigenesis and treatment resistance. Encouraging results from various preclinical studies have led to the initiation of numerous clinical trials with the intention of targeting autophagy in various cancers. Accumulating knowledge of the particular mechanisms and players involved in different steps of autophagy regulation led to the ongoing discovery of small molecule inhibitors designed to disrupt this highly orchestrated process. However, the development of validated autophagy-related biomarkers, essential for rational selection of patients entering clinical trials involving autophagy inhibitors, is lagging behind. One possible source of biomarkers for this purpose is the autophagy machinery itself. In this review, we address the recent trends, challenges and advances in the assessment of the biomarker potential of clinically relevant autophagy proteins in human cancers.	[Bortnik, Svetlana; Gorski, Sharon M.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada; [Bortnik, Svetlana; Gorski, Sharon M.] Univ British Columbia, Interdisciplinary Oncol Program, Vancouver, BC V5Z 1L3, Canada; [Gorski, Sharon M.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada; [Gorski, Sharon M.] Simon Fraser Univ, Ctr Cell Biol Dev & Dis, Burnaby, BC V5A 1S6, Canada		Gorski, SM (corresponding author), BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.; Gorski, SM (corresponding author), Univ British Columbia, Interdisciplinary Oncol Program, Vancouver, BC V5Z 1L3, Canada.; Gorski, SM (corresponding author), Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.; Gorski, SM (corresponding author), Simon Fraser Univ, Ctr Cell Biol Dev & Dis, Burnaby, BC V5A 1S6, Canada.	sbortnik@bcgsc.ca; sgorski@bcgsc.ca	Gorski, Sharon M/E-9375-2012	Gorski, Sharon M/0000-0002-3821-8289	CIHR Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral AwardCanadian Institutes of Health Research (CIHR); University of British Columbia Four Year Doctoral Fellowship (4YF) Award; Avon Foundation for Women-Canada grant [OBC127216]; CIHRCanadian Institutes of Health Research (CIHR)	The authors thank Kevin C. Yang, Morgana Xu and Robert Camfield for helpful discussions and comments on the manuscript. S. Bortnik is supported by a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award, as well as the University of British Columbia Four Year Doctoral Fellowship (4YF) Award. The authors are grateful for support from CIHR in partnership with Avon Foundation for Women-Canada grant OBC127216.	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J. Mol. Sci.	JUL	2017	18	7							1496	10.3390/ijms18071496			16	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	FF2SJ	WOS:000408746800165	28696368	Green Published, Green Submitted, gold			2022-04-25	
J	Schonthal, AH				Schoenthal, Axel H.			Pharmacological targeting of endoplasmic reticulum stress signaling in cancer	BIOCHEMICAL PHARMACOLOGY			English	Review						Autophagy; Chemoresistance; GRP78 inhibitors; Yin-Yang principle	UNFOLDED PROTEIN RESPONSE; N-LINKED GLYCOSYLATION; DEPENDENT KINASE-1 INHIBITOR; GLUCOSE-REGULATED PROTEINS; CHAPERONE DOWN-REGULATOR; COLON-CARCINOMA CELLS; HUMAN-MELANOMA CELLS; NON-COXIB ANALOG; PHASE-I TRIAL; ER STRESS	The endoplasmic reticulum (ER) stress response constitutes a cellular process that can be triggered by a great variety of conditions that cause imbalances in intracellular homeostasis and threaten proper cell functioning. In response, the ER stress response activates an adaptive effort aimed at neutralizing these threats and reestablishing homeostasis. However, if these countermeasures are unsuccessful and severe imbalances persist, the ER stress response may abandon its pro-survival efforts and instead may initiate a pro-apoptotic program to eliminate the faulty cell for the benefit of the organism as a whole. Because vigorous growth of malignant tumors may create stressful conditions, such as hypoglycemia, hypoxia, or accumulation of misfolded proteins during revved up protein synthesis, the adaptive, pro-survival components of the ER stress response system (e.g., GRP78/BiP) are frequently found chronically activated in tumor cells. This differential to non-stressed normal. cells has been proposed to represent an Achilles' heel of tumor cells that may be exploitable by therapeutic intervention. In this model, the goal would be to further aggravate the pre-existing stress conditions in tumor cells with appropriate pharmacological agents, so that the already engaged pro-survival mechanism would be overwhelmed and the ER stress response forced to switch to its pro-apoptotic mode (e.g., CHOP/GADD153). This review will discuss the principle of pharmacological ER stress aggravation, and will present preclinical models with promise for cancer therapeutic applications. (C) 2012 Elsevier Inc. All rights reserved.	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Pharmacol.	MAR 1	2013	85	5			SI		653	666		10.1016/j.bcp.2012.09.012			14	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	090UB	WOS:000315004400008	23000916				2022-04-25	
J	Tan, KP; Ho, MY; Cho, HC; Yu, J; Hung, JT; Yu, ALT				Tan, Keng-Poo; Ho, Ming-Yi; Cho, Huan-Chieh; Yu, John; Hung, Jung-Tung; Yu, Alice Lin-Tsing			Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells	CELL DEATH & DISEASE			English	Article							COLON-CARCINOMA CELLS; ENDOPLASMIC-RETICULUM STRESS; BLOOD GROUP ANTIGENS; MEMBRANE-GLYCOPROTEINS; ADENOCARCINOMA CELLS; SURFACE EXPRESSION; PROTEINS; ADHESION; DIFFERENTIATION; PROLIFERATION	Alpha1,2-fucosyltransferases, FUT1 and FUT2, which transfer fucoses onto the terminal galactose of N-acetyl-lactosamine via alpha 1,2-linkage have been shown to be highly expressed in various types of cancers. A few studies have shown the involvement of FUT1 substrates in tumor cell proliferation and migration. Lysosome-associated membrane protein 1, LAMP-1, has been reported to carry alpha1,2-fucosylated Lewis Y (LeY) antigens in breast cancer cells, however, the biological functions of LeY on LAMP-1 remain largely unknown. Whether or not its family member, LAMP-2, displays similar modifications and functions as LAMP-1 has not yet been addressed. In this study, we have presented evidence supporting that both LAMP-1 and 2 are substrates for FUT1, but not FUT2. We have also demonstrated the presence of H2 and LeY antigens on LAMP-1 by a targeted nanoLC-MS3 and the decreased levels of fucosylation on LAMP-2 by MALDI-TOF analysis upon FUT1 knockdown. In addition, we found that the expression of LeY was substantial in less invasive ER+/PR+/HER - breast cancer cells (MCF-7 and T47D) but negligible in highly invasive triple-negative MDA-MB-231 cells, of which LeY levels were correlated with the levels of LeY carried by LAMP-1 and 2. Intriguingly, we also observed a striking change in the subcellular localization of lysosomes upon FUT1 knockdown from peripheral distribution of LAMP-1 and 2 to a preferential perinuclear accumulation. Besides that, knockdown of FUT1 led to an increased rate of autophagic flux along with diminished activity of mammalian target of rapamycin complex 1 (mTORC1) and enhanced autophagosome-lysosome fusion. This may be associated with the predominantly perinuclear distribution of lysosomes mediated by FUT1 knockdown as lysosomal positioning has been reported to regulate mTOR activity and autophagy. Taken together, our results suggest that downregulation of FUT1, which leads to the perinuclear localization of LAMP-1 and 2, is correlated with increased rate of autophagic flux by decreasing mTOR signaling and increasing autolysosome formation.	[Tan, Keng-Poo] Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei, Taiwan; [Tan, Keng-Poo; Ho, Ming-Yi; Cho, Huan-Chieh; Yu, John; Hung, Jung-Tung; Yu, Alice Lin-Tsing] Chang Gung Mem Hosp Linkou, Inst Stem Cell & Translat Canc Res, 5 Fuxing St, Taoyuan 333, Taiwan; [Yu, John; Yu, Alice Lin-Tsing] Chang Gung Univ, Taoyuan, Taiwan; [Yu, Alice Lin-Tsing] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA		Yu, ALT (corresponding author), Chang Gung Mem Hosp Linkou, Inst Stem Cell & Translat Canc Res, 5 Fuxing St, Taoyuan 333, Taiwan.	a1yu@ucsd.edu	yu, john/AAA-9255-2021	yu, alice/0000-0003-2444-0505; Yu, John/0000-0002-3237-4272	Chang Gung Medical Foundation [OMRPG3C0012]; Ministry of Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [MOST 103-2321-B-182A-005, MOST 104-2321-B-182A-003]; Academia SinicaAcademia Sinica - Taiwan	We were indebted to Dr Chuang-Yu Lin for his technical support of the TCS SP8 confocal microscope. We also thank Dr Chi-Huey Wong from Academia Sinica for providing fucose alkyne and biotinylated azido probe. This work was supported by grants from the Chang Gung Medical Foundation (OMRPG3C0012), Academia Sinica and Ministry of Science and Technology (MOST 103-2321-B-182A-005 and MOST 104-2321-B-182A-003).	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AUG	2016	7								e2347	10.1038/cddis.2016.243			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	DU2YP	WOS:000382077800001	27560716	Green Published, gold, Green Submitted			2022-04-25	
J	Li, G; Zhang, C; Liang, W; Zhang, YB; Shen, YH; Tian, XH				Li, Ge; Zhang, Chuang; Liang, Wei; Zhang, Yanbing; Shen, Yunheng; Tian, Xinhui			Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells	PHARMACEUTICAL BIOLOGY			English	Article						Connectivity map; synergistic effect; mechanism	DIABETES-MELLITUS; CYCLE ARREST; INHIBITION; APOPTOSIS; TARGET; GROWTH; MECHANISMS; COMPONENTS; AUTOPHAGY	Context: Berberine (BBR) is used to treat diarrhoea and gastroenteritis in the clinic. It was found to have anticolon cancer effects. Objective: To study the anticolon cancer mechanism of BBR by connectivity map (CMAP) analysis. Materials and methods: CMAP based mechanistic prediction was conducted by comparing gene expression profiles of 10 mu M BBR treated MCF-7 cells with that of clinical drugs such as helveticoside, ianatoside C, pyrvinium, gossypol and trifluoperazine. The treatment time was 12 h and two biological replications were performed. The DMSO-treated cells were selected as a control. The interaction between 100 mu M BBR and target protein was measured by cellular thermal shift assay. The protein expression of 1-9 mu M BBR treated SW480 cells were measured by WB assay. Apoptosis, cell cycle arrest, mitochondrial membrane potential (MMP) of 1-9 mu M BBR treated SW480 cells were measured by flow cytometry and Hoechst 33342 staining methods. Results: CMAP analysis found 14 Hsp90, HDAC, PI3K or mTOR protein inhibitors have similar functions with BBR. The experiments showed that BBR inhibited SW480 cells proliferation with IC50 of 3.436 mu M, induced apoptosis, autophage, MMP depolarization and arrested G1 phase of cell cycle at 1.0 mu M. BBR dose-dependently up-regulated PTEN, while inhibited Notch1, PI3K, Akt and mTOR proteins at 1.0-9.0 mu M (p < 0.05). BBR also acted synergistically with Hsp90 and HDAC inhibitor (0.01 mu M) in SW480 cells at 0.5 and 1.0 mu M. Discussion and conclusions: The integrative gene expression-based chemical genomic method using CMAP analysis may be applicable for mechanistic studies of other multi-targets drugs.	[Li, Ge; Liang, Wei; Tian, Xinhui] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai, Peoples R China; [Zhang, Chuang; Zhang, Yanbing] Zhengzhou Univ, Sch Pharm, Zhengzhou, Peoples R China; [Shen, Yunheng] Naval Med Univ, Sch Pharm, Shanghai, Peoples R China		Tian, XH (corresponding author), Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai, Peoples R China.	tianxinhui@126.com			Shanghai University of Traditional Chinese Medicine; The 13th College Students' Innovative Activity Project of SHUTCM; National Science and Technology Major Project of China [2018ZX09731016-005]	The work was supported by Grants from Shanghai University of Traditional Chinese Medicine, The 13th College Students' Innovative Activity Project of SHUTCM, and National Science and Technology Major Project of China [2018ZX09731016-005].	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Biol.	JAN 1	2021	59	1					21	30		10.1080/13880209.2020.1865407			10	Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy	PQ5SU	WOS:000606606200001	33417512	gold, Green Published			2022-04-25	
J	Xu, JW; Patel, NH; Saleh, T; Cudjoe, EK; Alotaibi, M; Wu, YL; Lima, S; Hawkridge, AM; Gewirtz, DA				Xu, Jingwen; Patel, Nipa H.; Saleh, Tareq; Cudjoe, Emmanuel K., Jr.; Alotaibi, Moureq; Wu, Yingliang; Lima, Santiago; Hawkridge, Adam M.; Gewirtz, David A.			Differential Radiation Sensitivity in p53 Wild-Type and p53-Deficient Tumor Cells Associated with Senescence but not Apoptosis or (Nonprotective) Autophagy	RADIATION RESEARCH			English	Article							COLORECTAL-CANCER CELLS; ACCELERATED SENESCENCE; CARCINOMA-CELLS; GROWTH ARREST; INHIBITION; THERAPY; RADIOTHERAPY; CONTRIBUTES; BIOMARKERS; DEATH	Studies of radiation interaction with tumor cells often focus on apoptosis as an end point; however, clinically relevant doses of radiation also promote autophagy and senescence. Moreover, functional p53 has frequently been implicated in contributing to radiation sensitivity through the facilitation of apoptosis. To address the involvement of apoptosis, autophagy, senescence and p53 status in the response to radiation, the current studies utilized isogenic H460 non-small cell lung cancer cells that were either p53-wild type (H460wt) or null (H460crp53). As anticipated, radiosensitivity was higher in the H460wt cells than in the H460crp53 cell line; however, this differential radiation sensitivity did not appear to be a consequence of apoptosis. Furthermore, radiosensitivity did not appear to be reduced in association with the promotion of autophagy, as autophagy was markedly higher in the H460wt cells. Despite radiosensitization by chloroquine in the H460wt cells, the radiation-induced autophagy proved to be essentially nonprotective, as inhibition of autophagy via 3-methyl adenine (3-MA), bafilomycin A1 or ATG5 silencing failed to alter radiation sensitivity or promote apoptosis in either the H460wt or H460crp53 cells. Radiosensitivity appeared to be most closely associated with senescence, which occurred earlier and to a greater extent in the H460wt cells. This finding is consistent with the in-depth proteomics analysis on the secretomes from the H460wt and H460crp53 cells (with or without radiation exposure) that showed no significant association with radioresistance-related proteins, whereas several senescence-associated secretory phenotype (SASP) factors were upregulated in H460wt cells relative to H460crp53 cells. Taken together, these findings indicate that senescence, rather than apoptosis, plays a central role in determination of radiosensitivity; furthermore, autophagy is likely to have minimal influence on radiosensitivity under conditions where autophagy takes the nonprotective form. (C) 2018 by Radiation Research Society	[Xu, Jingwen; Wu, Yingliang] Shenyang Pharmaceut Univ, Dept Pharmacol & Toxicol, Shenyang, Liaoning, Peoples R China; [Patel, Nipa H.; Saleh, Tareq; Gewirtz, David A.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus, Richmond, VA 23298 USA; [Patel, Nipa H.; Saleh, Tareq; Gewirtz, David A.] Virginia Commonwealth Univ, Dept Med, Med Coll Virginia Campus, Richmond, VA 23298 USA; [Cudjoe, Emmanuel K., Jr.; Hawkridge, Adam M.] Virginia Commonwealth Univ, Dept Pharmacotherapy & Outcome Sci, Med Coll Virginia Campus, Richmond, VA 23298 USA; [Cudjoe, Emmanuel K., Jr.; Hawkridge, Adam M.] Virginia Commonwealth Univ, Dept Pharmaceut, Med Coll Virginia Campus, Richmond, VA 23298 USA; [Lima, Santiago] Virginia Commonwealth Univ, Dept Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA; [Patel, Nipa H.; Saleh, Tareq; Lima, Santiago; Hawkridge, Adam M.; Gewirtz, David A.] Virginia Commonwealth Univ, Massey Canc Ctr, 401 Coll St, Richmond, VA 23298 USA; [Alotaibi, Moureq] King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh, Saudi Arabia		Gewirtz, DA (corresponding author), Virginia Commonwealth Univ, Massey Canc Ctr, 401 Coll St, Richmond, VA 23298 USA.	david.gewirtz@vcuhealth.org	Saleh, Tareq/AGY-9225-2022; Patel, Nipa/AAK-3632-2021	Cudjoe, Emmanuel/0000-0003-1258-4034; Saleh, Tareq/0000-0002-2878-1107	Office of the Assistant Secretary of Defense for Health Affairs through the Breast Cancer Research Program [W81XWH-14-1-0088]; Massey Center Support Grant [P30 CA016059]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K22 CA187314]; China Scholarship CouncilChina Scholarship Council; NIH-NCI Cancer Center Flow Cytometry Shared Resource; NIH-NCI Cancer CenterUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30 CA016059]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [K22CA187314, P30CA016059] Funding Source: NIH RePORTER	Work in Dr. Gewirtz's laboratory was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Breast Cancer Research Program (grant no. W81XWH-14-1-0088 to DAG) and a Massey Center Support Grant (no. P30 CA016059). Santiago Lima was supported by the National Institutes of Health (grant no. K22 CA187314). We gratefully acknowledge financial support (JX) from the China Scholarship Council. Services and products in support of the research project were generated by the VCU Massey Cancer Center Flow Cytometry Shared Resource, supported in part, with funding from NIH-NCI Cancer Center Support Grant no. P30 CA016059.	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Res.	NOV	2018	190	5					538	557		10.1667/RR15099.1			20	Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging	HC8WE	WOS:000452084900009	30132722	Green Accepted			2022-04-25	
J	Wang, JH; Xing, YJ; Wang, YY; He, YD; Wang, LT; Peng, SH; Yang, LF; Xie, JQ; Li, XT; Qiu, WW; Yi, ZF; Liu, MY				Wang, Jinhua; Xing, Yajing; Wang, Yingying; He, Yundong; Wang, Liting; Peng, Shihong; Yang, Lianfang; Xie, Jiuqing; Li, Xiaotao; Qiu, Wenwei; Yi, Zhengfang; Liu, Mingyao			A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH			English	Article						Colorectal cancer; Cancer stem-like; BMI-1	SURVIVORSHIP STATISTICS; MESENCHYMAL TRANSITION; SELF-RENEWAL; IN-VITRO; CELLS; METASTASIS; EXPRESSION; SURVIVAL; GROWTH; CHEMOTHERAPY	Background Cancer-initiating cell (CIC), a functionally homogeneous stem-like cell population, is resonsible for driving the tumor maintenance and metastasis, and is a source of chemotherapy and radiation-therapy resistance within tumors. Targeting CICs self-renewal has been proposed as a therapeutic goal and an effective approach to control tumor growth. BMI-1, a critical regulator of self-renewal in the maintenance of CICs, is identified as a potential target for colorectal cancer therapy. Methods Colorectal cancer stem-like cell lines HCT116 and HT29 were used for screening more than 500 synthetic compounds by sulforhodamine B (SRB) cell proliferation assay. The candidate compound was studied in vitro by SRB cell proliferation assay, western blotting, cell colony formation assay, quantitative real-time PCR, flow cytometry analysis, and transwell migration assay. Sphere formation assay and limiting dilution analysis (LDA) were performed for measuring the effect of compound on stemness properties. In vivo subcutaneous tumor growth xenograft model and liver metastasis model were performed to test the efficacy of the compound treatment. Student's t test was applied for statistical analysis. Results We report the development and characterization of a small molecule inhibitor QW24 against BMI-1. QW24 potently down-regulates BMI-1 protein level through autophagy-lysosome degradation pathway without affecting the BMI-1 mRNA level. Moreover, QW24 significantly inhibits the self-renewal of colorectal CICs in stem-like colorectal cancer cell lines, resulting in the abrogation of their proliferation and metastasis. Notably, QW24 significantly suppresses the colorectal tumor growth without obvious toxicity in the subcutaneous xenograft model, as well as decreases the tumor metastasis and increases mice survival in the liver metastasis model. Moreover, QW24 exerts a better efficiency than the previously reported BMI-1 inhibitor PTC-209. Conclusions Our preclinical data show that QW24 exerts potent anti-tumor activity by down-regulating BMI-1 and abrogating colorectal CICs self-renewal without obvious toxicity in vivo, suggesting that QW24 could potentially be used as an effective therapeutic agent for clinical colorectal cancer treatment.	[Wang, Jinhua; Xing, Yajing; He, Yundong; Peng, Shihong; Xie, Jiuqing; Yi, Zhengfang; Liu, Mingyao] East China Normal Univ, East China Normal Univ & Shanghai Fengxian Dist C, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200241, Peoples R China; [Wang, Jinhua; Xing, Yajing; He, Yundong; Peng, Shihong; Xie, Jiuqing; Yi, Zhengfang; Liu, Mingyao] East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China; [Wang, Yingying; Wang, Liting; Yang, Lianfang; Qiu, Wenwei; Yi, Zhengfang] East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China; [Li, Xiaotao] Baylor Coll Med, Dept Mol & Cellular Biol, Dan L Duncan Canc Ctr, Houston, TX 77030 USA		Yi, ZF; Liu, MY (corresponding author), East China Normal Univ, East China Normal Univ & Shanghai Fengxian Dist C, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200241, Peoples R China.; Yi, ZF; Liu, MY (corresponding author), East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China.; Qiu, WW; Yi, ZF (corresponding author), East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China.	wangjh91@163.com; wwqiu@chem.ecnu.edu.cn; zfyi@bio.ecnu.edu.cn; myliu@bio.ecnu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472788, 81773204, 81330049]; Major State Basic Research Development Program of ChinaNational Basic Research Program of China [2015CB910400]; Shanghai Science and Technology Council [18ZR1411200]; National Key R&D Program of China [2018YFA0507000]; Innovation program of Shanghai municipal education commissionInnovation Program of Shanghai Municipal Education Commission [2017-01-07-00-05-E00011]; ECNU public platform for Innovation	This work was partially supported by National Natural Science Foundation of China (No. 81472788, No. 81773204, No. 81330049), Major State Basic Research Development Program of China (2015CB910400), Shanghai Science and Technology Council (Grant 18ZR1411200), National Key R&D Program of China (2018YFA0507000), Innovation program of Shanghai municipal education commission (2017-01-07-00-05-E00011 to M.L.) and ECNU public platform for Innovation (011).	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Exp. Clin. Cancer Res.	OCT 22	2019	38	1							422	10.1186/s13046-019-1392-8			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	JG1VG	WOS:000491864700001	31640758	Green Published, gold			2022-04-25	
J	Wang, F; Xia, XJ; Yang, CY; Shen, JL; Mai, JH; Kim, HC; Kirui, D; Kang, Y; Fleming, JB; Koay, EJ; Mitra, S; Ferrari, M; Shen, HF				Wang, Feng; Xia, Xiaojun; Yang, Chunying; Shen, Jianliang; Mai, Junhua; Kim, Han-Cheon; Kirui, Dickson; Kang, Ya'an; Fleming, Jason B.; Koay, Eugene J.; Mitra, Sankar; Ferrari, Mauro; Shen, Haifa			SMAD4 Gene Mutation Renders Pancreatic Cancer Resistance to Radiotherapy through Promotion of Autophagy	CLINICAL CANCER RESEARCH			English	Article							TUMOR-SUPPRESSOR GENE; DUCTAL ADENOCARCINOMA; ADJUVANT RADIOTHERAPY; GENOMIC INSTABILITY; COLORECTAL-CANCER; CELLS; TRIAL; CARCINOMA; THERAPY; CHEMOTHERAPY	Purpose: Understanding the mechanism of radioresistance could help develop strategies to improve therapeutic response of patients with PDAC. The SMAD4 gene is frequently mutated in pancreatic cancer. In this study, we investigated the role of SMAD4 deficiency in pancreatic cancer cells' response to radiotherapy. Experimental Design: We downregulated SMAD4 expression with SMAD4 siRNA or SMAD4 shRNA and overexpressed SMAD4 in SMAD4 mutant pancreatic cancer cells followed by clonogenic survival assay to evaluate their effects on cell radioresistance. To study the mechanism of radioresistance, the effects of SMAD4 loss on reactive oxygen species (ROS) and autophagy were determined by flow cytometry and immunoblot analysis, respectively. Furthermore, we measured radioresistance by clonogenic survival assay after treatment with autophagy inhibitor (Chloroquine) and ROS inhibitor (N-acetyl-L-cysteine) in SMAD4-depleted pancreatic cancer cells. Finally, the effects of SMAD4 on radioresistance were also confirmed in an orthotopic tumor model derived from SMAD4-depleted Panc-1 cells. Results: SMAD4-depleted pancreatic cancer cells were more resistant to radiotherapy based on clonogenic survival assay. Overexpression of wild-type SMAD4 in SMAD4-mutant cells rescued their radiosensitivity. Radioresistance mediated by SMAD4 depletion was associated with persistently higher levels of ROS and radiation-induced autophagy. Finally, SMAD4 depletion induced in vivo radioresistance in Panc-1-derived orthotopic tumor model (P = 0.038). More interestingly, we observed that the protein level of SMAD4 is inversely correlated with autophagy in orthotopic tumor tissue samples. Conclusions: Our results demonstrate that defective SMAD4 is responsible for radioresistance in pancreatic cancer through induction of ROS and increased level of radiation-induced autophagy. (C) 2018 AACR.	[Wang, Feng; Xia, Xiaojun; Shen, Jianliang; Mai, Junhua; Kim, Han-Cheon; Kirui, Dickson; Ferrari, Mauro; Shen, Haifa] Houston Methodist Res Inst, Dept Nanomed, Houston, TX USA; [Wang, Feng] Tongji Univ, Peoples Hosp Shanghai 10, Dept Gastroenterol, Shanghai, Peoples R China; [Xia, Xiaojun] Sun Yat Sen Univ, State Key Lab Oncol South China, Dept Expt Med, Ctr Canc, Guangzhou, Guangdong, Peoples R China; [Yang, Chunying; Mitra, Sankar] Houston Methodist Res Inst, Dept Radiat Oncol, Houston, TX USA; [Kang, Ya'an; Fleming, Jason B.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA; [Koay, Eugene J.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA; [Ferrari, Mauro] Weill Cornell Med Coll, Dept Med, New York, NY USA; [Shen, Haifa] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY USA; [Shen, Haifa] Houston Methodist Canc Ctr, Houston, TX USA		Shen, HF (corresponding author), Houston Methodist Res Inst, 6670 Bertner Ave,R8-214, Houston, TX 77030 USA.	hshen@houstonmethodist.org			NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01CA193880, U54CA143837, U54CA210181]; Department of DefenseUnited States Department of Defense [W81XWH-12-1-0414]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31771497, 81472578]; Ernest Cockrell Jr. Presidential Distinguished Chair; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [U54CA143837, R01CA193880, U54CA210181] Funding Source: NIH RePORTER	The authors acknowledge financial support from the following sources: NIH grants (Nos. 1R01CA193880, U54CA143837, and U54CA210181), Department of Defense grants (No. W81XWH-12-1-0414), National Natural Science Foundation of China (No. 31771497, 81472578), and the Ernest Cockrell Jr. Presidential Distinguished Chair.	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Cancer Res.	JUL 1	2018	24	13					3176	3185		10.1158/1078-0432.CCR-17-3435			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GL6DS	WOS:000437270800023	29602802	Bronze, Green Accepted			2022-04-25	
J	Zhu, HB; Klement, JD; Lu, CW; Redd, PS; Yang, DF; Smith, AD; Poschel, DB; Zou, J; Liu, D; Wang, PG; Ostrov, D; Coant, N; Hannun, YA; Colby, AH; Grinstaff, MW; Liu, KB				Zhu, Huabin; Klement, John D.; Lu, Chunwan; Redd, Priscilla S.; Yang, Dafeng; Smith, Alyssa D.; Poschel, Dakota B.; Zou, Juan; Liu, Ding; Wang, Peng George; Ostrov, David; Coant, Nicolas; Hannun, Yusuf A.; Colby, Aaron H.; Grinstaff, Mark W.; Liu, Kebin			Asah2 Represses the p53-Hmox1 Axis to Protect Myeloid-Derived Suppressor Cells from Ferroptosis	JOURNAL OF IMMUNOLOGY			English	Article							CANCER; DEATH; CERAMIDE; METABOLISM; SPHINGOLIPIDS; PATHOGENESIS; FACILITATE; AUTOPHAGY; PROMOTES; PD-L1	Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that massively accumulate under pathological conditions to suppress T cell immune response. Dysregulated cell death contributes to MDSC accumulation, but the molecular mechanism underlying this cell death dysregulation is not fully understood. In this study, we report that neutral ceramidase (N-acylsphingosine amidohydrolase [ASAH2]) is highly expressed in tumor-infiltrating MDSCs in colon carcinoma and acts as an MDSC survival factor. To target ASAH2, we performed molecular docking based on human ASAH2 protein structure. Enzymatic inhibition analysis of identified hits determined NC06 as an ASAH2 inhibitor. Chemical and nuclear magnetic resonance analysis determined NC06 as 7-chloro-2-(3-chloroanilino)pyrano[3,4-e][1,3]oxazine-4,5-dione. NC06 inhibits ceramidase activity with an IC50 of 10.16-25.91 mu M for human ASAH2 and 18.6-30.2 mu M for mouse Asah2 proteins. NC06 induces MDSC death in a dosedependent manner, and inhibition of ferroptosis decreased NC06-induced MDSC death. NC06 increases glutathione synthesis and decreases lipid reactive oxygen species to suppress ferroptosis in MDSCs. Gene expression profiling identified the p53 pathway as the Asah2 target in MDSCs. Inhibition of Asah2 increased p53 protein stability to upregulate Hmox1 expression to suppress lipid reactive oxygen species production to suppress ferroptosis inMDSCs. NC06 therapy increases MDSC death and reduces MDSC accumulation in tumor-bearing mice, resulting in increased activation of tumor-infiltrating CTLs and suppression of tumor growth in vivo. Our data indicate that ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway inMDSCs in the tumor microenvironment. Targeting ASAH2 with NC06 to induce MDSC ferroptosis is potentially an effective therapy to suppress MDSC accumulation in cancer immunotherapy.	[Zhu, Huabin; Klement, John D.; Lu, Chunwan; Redd, Priscilla S.; Yang, Dafeng; Smith, Alyssa D.; Poschel, Dakota B.; Liu, Kebin] Med Coll Georgia, Dept Biochem & Mol Biol, 1410 Laney Walker Blvd, Augusta, GA 30912 USA; [Zhu, Huabin; Klement, John D.; Lu, Chunwan; Redd, Priscilla S.; Yang, Dafeng; Smith, Alyssa D.; Poschel, Dakota B.; Liu, Kebin] Med Coll Georgia, Georgia Canc Ctr, Augusta, GA 30912 USA; [Zhu, Huabin; Klement, John D.; Lu, Chunwan; Redd, Priscilla S.; Yang, Dafeng; Smith, Alyssa D.; Poschel, Dakota B.; Liu, Kebin] Charlie Norwood VA Med Ctr, Augusta, GA 30904 USA; [Zou, Juan] Augusta Univ, Dept Chem & Phys, Augusta, GA 30912 USA; [Liu, Ding; Wang, Peng George] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA; [Ostrov, David] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA; [Coant, Nicolas; Hannun, Yusuf A.] SUNY Stony Brook, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA; [Colby, Aaron H.] Ion Pharmaceut, Brookline, MA 02445 USA; [Colby, Aaron H.; Grinstaff, Mark W.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA		Liu, KB (corresponding author), Med Coll Georgia, Dept Biochem & Mol Biol, 1410 Laney Walker Blvd, Augusta, GA 30912 USA.	Kliu@augusta.edu		Zhu, Huabin/0000-0002-4557-795X; COANT, Nicolas/0000-0001-9237-2132	National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 CA133085, R01 CA227433, F30 CA226436, F31 CA257212]; U.S. Department of Veterans Affairs GrantUS Department of Veterans Affairs [CX001364]	This work was supported by National Institutes of Health (NIH) Grants R01 CA133085 and R01 CA227433 (to K.L.), F30 CA226436 (to J.D.K.), and F31 CA257212 (to A.D.S.), and U.S. Department of Veterans Affairs Grant CX001364 (to K.L.).	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Immunol.	MAR 15	2021	206	6					1395	1404		10.4049/jimmunol.2000500			10	Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Immunology	QU6XN	WOS:000627424200024	33547170	Bronze, Green Accepted			2022-04-25	
J	Geremia, A; Sartori, R; Baraldo, M; Nogara, L; Balmaceda, V; Dumitras, GA; Ciciliot, S; Scalabrin, M; Nolte, H; Blaauw, B				Geremia, Alessia; Sartori, Roberta; Baraldo, Martina; Nogara, Leonardo; Balmaceda, Valeria; Dumitras, Georgia Ana; Ciciliot, Stefano; Scalabrin, Marco; Nolte, Hendrik; Blaauw, Bert			Activation of Akt-mTORC1 signalling reverts cancer-dependent muscle wasting	JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE			English	Article; Early Access						Cancer cachexia; mTOR; Raptor; Akt; Muscle growth; Skeletal muscle force	CACHEXIA; PREVENTS; FORCE	Background Cancer-related muscle wasting occurs in most cancer patients. An important regulator of adult muscle mass and function is the Akt-mTORC1 pathway. While Akt-mTORC1 signalling is important for adult muscle homeostasis, it is also a major target of numerous cancer treatments. Which role Akt-mTORC1 signalling plays during cancer cachexia in muscle is currently not known. Here, we aimed to determine how activation or inactivation of the pathway affects skeletal muscle during cancer cachexia. Methods We used inducible, muscle-specific Raptor ko (mTORC1) mice to determine the effect of reduced mTOR signalling during cancer cachexia. On the contrary, in order to understand if skeletal muscles maintain their anabolic capacity and if activation of Akt-mTORC1 signalling can reverse cancer cachexia, we generated mice in which we can inducibly activate Akt specifically in skeletal muscles. Results We found that mTORC1 signalling is impaired during cancer cachexia, using the Lewis lung carcinoma and C26 colon cancer model, and is accompanied by a reduction in protein synthesis rates of 57% (P < 0.01). Further reduction of mTOR signalling, as seen in Raptor ko animals, leads to a 1.5-fold increase in autophagic flux (P > 0.001), but does not further increase muscle wasting. On the other hand, activation of Akt-mTORC1 signalling in already cachectic animals completely reverses the 15-20% loss in muscle mass and force (P < 0.001). Interestingly, Akt activation only in skeletal muscle completely normalizes the transcriptional deregulation observed in cachectic muscle, despite having no effect on tumour size or spleen mass. In addition to stimulating muscle growth, it is also sufficient to prevent the increase in protein degradation normally observed in muscles from tumour-bearing animals. Conclusions Here, we show that activation of Akt-mTORC1 signalling is sufficient to completely revert cancer-dependent muscle wasting. Intriguingly, these results show that skeletal muscle maintains its anabolic capacities also during cancer cachexia, possibly giving a rationale behind some of the beneficial effects observed in exercise in cancer patients.	[Geremia, Alessia; Sartori, Roberta; Baraldo, Martina; Nogara, Leonardo; Balmaceda, Valeria; Dumitras, Georgia Ana; Ciciliot, Stefano; Scalabrin, Marco; Blaauw, Bert] Veneto Inst Mol Med VIMM, Via Orus 1, Padua, Italy; [Geremia, Alessia; Baraldo, Martina; Nogara, Leonardo; Dumitras, Georgia Ana; Scalabrin, Marco; Blaauw, Bert] Univ Padua, Dept Biomed Sci, Padua, Italy; [Nolte, Hendrik] Max Planck Inst Biol Ageing, Cologne, Germany		Blaauw, B (corresponding author), Veneto Inst Mol Med VIMM, Via Orus 1, Padua, Italy.	bert.blaauw@unipd.it		Sartori, Roberta/0000-0002-2763-9838; BLAAUW, BERT/0000-0002-4167-5106	French Muscular Dystrophy Association [Association Francaise contre les Myopathies (AFMTelethon)] [21865]; Associazione Italiana per la Ricerca sul Cancro (AIRC)Fondazione AIRC per la ricerca sul cancro [20406]; University of Padua (Universita degli Studi di Padova) (STARSMyoAktivation)	This work was supported by grants from the French Muscular Dystrophy Association [Association Francaise contre les Myopathies (AFMTelethon) to B.B., No. 21865], University of Padua (Universita degli Studi di Padova) (STARSMyoAktivation to B.B.), and Associazione Italiana per la Ricerca sul Cancro (AIRC) 20406 to B.B.	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Cachexia Sarcopenia Muscle												10.1002/jcsm.12854		NOV 2021	14	Geriatrics & Gerontology; Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	Geriatrics & Gerontology; General & Internal Medicine	WS0NL	WOS:000714886900001	34741441	gold, Green Published			2022-04-25	
J	Yang, Y; Feng, MY; Bai, LL; Zhang, MX; Zhou, KX; Liao, WT; Lei, WT; Zhang, N; Huang, JX; Li, Q				Yang, Yang; Feng, Mingyang; Bai, LiangLiang; Zhang, Mengxi; Zhou, Kexun; Liao, Weiting; Lei, Wanting; Zhang, Nan; Huang, Jiaxing; Li, Qiu			The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer	FRONTIERS IN ONCOLOGY			English	Article						colorectal cancer; autophagy; gene; lncRNA; prognosis; immune	IMMUNOTHERAPY	Cellular autophagy plays an important role in the occurrence and development of colorectal cancer (CRC). Whether autophagy-related genes and lncRNAs can be used as ideal markers in CRC is still controversial. The purpose of this study is to identify novel treatment and prognosis markers of CRC. We downloaded transcription and clinical data of CRC from the GEO (GSE40967, GSE12954, GSE17536) and TCGA database, screened for differentially autophagy-related genes (DEAGs) and lncRNAs, constructed prognostic model, and analyzed its relationship with immune infiltration. TCGA and GEO datasets (GSE12954 and GSE17536) were used to validate the effect of the model. Oncomine database and Human Protein Atlas verified the expression of DEAGs. We obtained a total of 151 DEAGs in three verification sets collaboratively. Then we constructed a risk prognostic model through Lasso regression to obtain 15 prognostic DEAGs from the training set and verified the risk prognostic model in three verification sets. The low-risk group survived longer than the high-risk group. Age, gender, pathological stage, and TNM stage were related to the prognostic risk of CRC. On the other hand, BRAF status, RFS event, and tumor location are considered as most significant risk factors of CRC in the training set. Furthermore, we found that the immune score of the low-risk group was higher. The content of CD8 + T cells, active NK cells, macrophages M0, macrophages M1, and active dendritic cells was noted more in the high-risk group. The content of plasma cells, resting memory CD4 + T cells, resting NK cells, resting mast cells, and neutrophil cells was higher in the low-risk group. After all, the Oncomine database and immunohistochemistry verified that the expression level of most key autophagy-related genes was consistent with the results that we found. In addition, we obtained six lncRNAs co-expressed with DEAGs from the training set and found that the survival time was longer in the low-risk group. This finding was verified in the verification set and showed same trend to the results mentioned above. In the final analysis, these results indicate that autophagy-related genes and lncRNAs can be used as prognostic and therapeutic markers for CRC.	[Yang, Yang; Feng, Mingyang; Bai, LiangLiang; Zhang, Mengxi; Zhou, Kexun; Liao, Weiting; Lei, Wanting; Zhang, Nan; Huang, Jiaxing; Li, Qiu] Sichuan Univ, West China Hosp, Canc Ctr, Dept Med Oncol, Chengdu, Sichuan, Peoples R China; [Yang, Yang; Feng, Mingyang; Bai, LiangLiang; Zhang, Mengxi; Zhou, Kexun; Liao, Weiting; Lei, Wanting; Zhang, Nan; Huang, Jiaxing; Li, Qiu] Sichuan Univ, West China Biomed Big Data Ctr, Chengdu, Sichuan, Peoples R China		Li, Q (corresponding author), Sichuan Univ, West China Hosp, Canc Ctr, Dept Med Oncol, Chengdu, Sichuan, Peoples R China.; Li, Q (corresponding author), Sichuan Univ, West China Biomed Big Data Ctr, Chengdu, Sichuan, Peoples R China.	fbqiu9@163.com					Arai H, 2019, CANCER TREAT REV, V81, DOI 10.1016/j.ctrv.2019.101912; Bernardini JP, 2017, ONCOGENE, V36, P1315, DOI 10.1038/onc.2016.302; Brody H, 2015, NATURE, V521, pS1, DOI 10.1038/521S1a; Burada F, 2015, WORLD J GASTRO ONCOL, V7, P271, DOI 10.4251/wjgo.v7.i11.271; Chang WT, 2017, MOLECULES, V22, DOI 10.3390/molecules22050854; Chi HC, 2016, AUTOPHAGY, V12, P2271, DOI 10.1080/15548627.2016.1230583; Christensen JG, 2020, J INTERN MED, V288, P183, DOI 10.1111/joim.13057; Dekker E, 2019, LANCET, V394, P1467, DOI 10.1016/S0140-6736(19)32319-0; Demarchi F, 2007, AUTOPHAGY, V3, P235, DOI 10.4161/auto.3661; Deshpande M, 2020, CANCERS, V12, DOI 10.3390/cancers12113319; El-Zaatari M, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.00051; Fan JQ, 2018, THERANOSTICS, V8, P5784, DOI 10.7150/thno.29035; Gauthier A, 2013, HEPATOL RES, V43, P147, DOI 10.1111/j.1872-034X.2012.01113.x; Gmeiner WH, 2020, CANCERS, V12, DOI 10.3390/cancers12061641; Gozuacik D, 2006, AUTOPHAGY, V2, P74, DOI 10.4161/auto.2.2.2459; Guo L, 2020, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.01052; Guo PT, 2017, MOL MED REP, V15, P724, DOI 10.3892/mmr.2016.6049; Heldring N, 2014, NEURO-ONCOLOGY, V16, P241, DOI 10.1093/neuonc/not214; Jo YK, 2018, ANTICANCER RES, V38, P271, DOI 10.21873/anticanres.12218; Kang LM, 2021, J NEUROL, V268, P3269, DOI 10.1007/s00415-020-09942-w; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Kim BK, 2018, BRIT J CANCER, V119, P1347, DOI 10.1038/s41416-018-0289-1; Kimmelman AC, 2017, CELL METAB, V25, P1037, DOI 10.1016/j.cmet.2017.04.004; Koustas E, 2019, CANCERS, V11, DOI 10.3390/cancers11040533; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Li CG, 2020, ANN TRANSL MED, V8, DOI 10.21037/atm.2020.02.173; Li ZD, 2019, GENE, V691, P106, DOI 10.1016/j.gene.2018.11.099; Lichtenstern CR, 2020, CELLS-BASEL, V9, DOI 10.3390/cells9030618; Lin SC, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1303-z; Lin TY, 2020, AUTOPHAGY, V16, P1296, DOI 10.1080/15548627.2019.1671643; Ma J, 2020, J CELL MOL MED, V24, P6472, DOI 10.1111/jcmm.15298; Majidzadeh H, 2020, COLLOID SURFACE B, V194, DOI 10.1016/j.colsurfb.2020.111188; Marmol I, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18010197; Mokarram P, 2017, AUTOPHAGY, V13, P781, DOI 10.1080/15548627.2017.1290751; Molina-Cerrillo J, 2020, CANCERS, V12, DOI 10.3390/cancers12061571; Natarajan S, 2018, MOL MED REP, V18, P4147, DOI 10.3892/mmr.2018.9404; Olino K, 2020, SEMIN CANCER BIOL, V65, P114, DOI 10.1016/j.semcancer.2020.01.001; Oliver GR, 2015, CLIN CHEM, V61, P124, DOI 10.1373/clinchem.2014.224360; Onorati AV, 2018, CANCER-AM CANCER SOC, V124, P3307, DOI 10.1002/cncr.31335; Pietrantonio F, 2020, CANCER TREAT REV, V82, DOI 10.1016/j.ctrv.2019.101935; Qaderi SM, 2020, EJSO-EUR J SURG ONC, V46, P1779, DOI 10.1016/j.ejso.2020.06.017; Sheikh-Zeineddini N, 2020, EUR J PHARMACOL, V870, DOI 10.1016/j.ejphar.2019.172821; Shih JH, 2020, NUCLEIC ACIDS RES, V48, P1175, DOI 10.1093/nar/gkz1149; Steyerberg EW, 2014, EUR HEART J, V35, P1925, DOI 10.1093/eurheartj/ehu207; Tang ZB, 2018, INT J NANOMED, V13, P2907, DOI 10.2147/IJN.S159388; Thongchot S, 2018, MOL CARCINOGEN, V57, P1735, DOI 10.1002/mc.22893; Wiener Z, 2014, CELL REP, V8, P1943, DOI 10.1016/j.celrep.2014.08.034; Wu YH, 2018, SIGNAL TRANSDUCT TAR, V3, DOI 10.1038/s41392-018-0031-8; Xu Y, 2020, AUTOPHAGY, V16, P3, DOI 10.1080/15548627.2019.1603547; Yan LL, 2018, TOXICOL LETT, V295, P153, DOI 10.1016/j.toxlet.2018.06.1066; Zhang L, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.139; Zhao YL, 2018, FOOD FUNCT, V9, P4548, DOI [10.1039/c8fo00850g, 10.1039/C8FO00850G]; Zhou BR, 2020, SEMIN CANCER BIOL, V66, P89, DOI 10.1016/j.semcancer.2019.03.002	53	2	2	2	2	FRONTIERS MEDIA SA	LAUSANNE	AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND	2234-943X			FRONT ONCOL	Front. Oncol.	MAR 11	2021	11								582040	10.3389/fonc.2021.582040			16	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	RC0AS	WOS:000632467000001	33777735	gold, Green Published			2022-04-25	
J	Giatromanolaki, A; Sivridis, E; Mendrinos, S; Koutsopoulos, AV; Koukourakis, MI				Giatromanolaki, Alexandra; Sivridis, Efthimios; Mendrinos, Savvas; Koutsopoulos, Anastasios V.; Koukourakis, Michael I.			Autophagy proteins in prostate cancer: Relation with anaerobic metabolism and Gleason score	UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS			English	Article						Autophagy; LC3A; LC3B; p62; LDH5; Prostate cancer	COLORECTAL-CANCER; CARCINOMAS; SURVIVAL; HYPOXIA; CELLS; LC3; EXPRESSION; PROGNOSIS; PATTERNS; THERAPY	Objectives: Up-regulation of autophagy provides an important survival mechanism to normal and malignant cells residing in a hypoxic and unfavorable nutritional environment. Yet, its role in the biology of prostate cancer remains poorly understood. Methods: In this study we investigated the expression of four major autophagy proteins, namely the microtubule-associated protein 1 light chain 3A (LC3A), LC3B. Beclin 1. and p62, together with an enzyme of anaerobic metabolism, the lactate dehydrogenase 5 (LDH5), in relation to Gleason score and extraprostatic invasion. A series of 96 prostate adenocarcinomas was examined using immunohistochemical techniques and appropriate antibodies. Results: The LC3A protein was expressed in the form of "stone-like" structures, and diffuse cytoplasmic staining. the LC3B reactivity was solely cytoplasmic, whereas that of p62 and LDH5 was both cytoplasmic and nuclear. A median count of 0.90 "stone-like" structures per 200x optical field (range 0-3.6) was highly associated with a high Gleason score. Similarly, a strong cytoplasmic LC3A, LC3B, and p62 expression, when extensive (present in >50% tumor cells per section), was significantly associated with LDH5 and a high Gleason score. In addition, extensive cytoplasmic p62 expression was related with LC3A and B reactivity and also with extraprostatic invasion. Extensive Beclin-1 expression was significantly linked with extraprostatic invasion and also with p62 and LDH5 expression. Conclusions: Immunohistochemical detection of autophagy proteins may potentially prove to be useful as prognostic markers and a tool for the stratification of patients in therapeutic trials targeting autophagy in prostate cancer. (C) 2014 Elsevier Inc. All rights reserved.	[Giatromanolaki, Alexandra; Sivridis, Efthimios; Koutsopoulos, Anastasios V.] Democritus Univ Thrace, Univ Gen Hosp Alexandroupolis, Dept Pathol, Alexandroupolis, Greece; [Koukourakis, Michael I.] Democritus Univ Thrace, Univ Gen Hosp Alexandroupolis, Dept Radiotherapy Oncol, Alexandroupolis, Greece; [Mendrinos, Savvas] Div Pathol Integrated Med Profess, New York, NY USA		Giatromanolaki, A (corresponding author), Democritus Univ Thrace, Univ Gen Hosp Alexandroupolis, Dept Pathol, Alexandroupolis, Greece.	agiatrom@med.duth.gr	Koutsopoulos, Anastasios/AAO-9498-2020	Koutsopoulos, Anastasios/0000-0002-8430-7565	Tumor and Angiogenesis Research Group	The study was financially supported by the Tumor and Angiogenesis Research Group.	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Oncol.-Semin. Orig. Investig.	JAN	2014	32	1								10.1016/j.urolonc.2013.04.003			8	Oncology; Urology & Nephrology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Urology & Nephrology	AX9SW	WOS:000347243300062	23787295				2022-04-25	
J	Zhou, ZH; Wang, QL; Mao, LH; Li, XQ; Liu, P; Song, JW; Liu, X; Xu, F; Lei, J; He, S				Zhou, Zhi-Hang; Wang, Qing-Liang; Mao, Lin-Hong; Li, Xiao-Qin; Liu, Peng; Song, Jin-Wen; Liu, Xue; Xu, Feng; Lei, Jing; He, Song			Chromatin accessibility changes are associated with enhanced growth and liver metastasis capacity of acid-adapted colorectal cancer cells	CELL CYCLE			English	Article						Colorectal cancer; acidosis; chromatin accessibility; NFIB; metastasis	GLUTAMINE-METABOLISM; MELANOMA-CELLS; PH; DRIVES; MICROENVIRONMENT; TRANSCRIPTION; PROGRESSION; AUTOPHAGY; BREAST; NFIB	The acidic extracellular microenvironment, namely acidosis, is a biochemical hallmark of solid tumors. However, the tumorigenicity, metastatic potential, gene expression profile and chromatin accessibility of acidosis-adapted colorectal cancer cells remain unknown. The colorectal cancer cell SW620 was cultured in acidic medium (pH 6.5) for more than 3 months to be acidosis-adapted (SW620-AA). In comparison to parental cells, SW620-AA cells exhibit enhanced tumorigenicity and liver metastatic potential in vivo. Following mRNA and lncRNA expression profiling, we validated that OLMF1, NFIB, SMAD9, DGKB are upregulated, while SESN2, MAP1B, UTRN, PCDH19, IL18, LMO2, CNKSR3, GXYLT2 are downregulated in SW620-AA cells. The differentially expressed mRNAs were significantly enriched in DNA remodeling-associated pathways including HDACs deacetylate histones, SIRT1 pathway, DNA methylation, DNA bending complex, and RNA polymerase 1 chain elongation. Finally, chromatin accessibility evaluation by ATAC-sequencing revealed that the differentially opened peaks were enriched in pathways such as small cell lung cancer, pathways in cancer, ErbB signaling, endometrial cancer, and chronic myeloid leukemia, which were mainly distributed in intergenic regions and introns. These results suggest that the chromatin accessibility changes are correlated with enhanced growth and liver metastasis capacity of acid-adapted colorectal cancer cells.	[Zhou, Zhi-Hang; Mao, Lin-Hong; Li, Xiao-Qin; Xu, Feng; Lei, Jing; He, Song] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing, Peoples R China; [Zhou, Zhi-Hang] 309th Hosp PLA, Dept Pathol, Beijing, Peoples R China; [Wang, Qing-Liang] Chongqing Med Univ, Affiliated Hosp 2, Dept Pathol, Chongqing, Peoples R China; [Liu, Peng] Gen Hosp Guangzhou Mil Command, Chest Pain Ctr, Dept Emergency, Guangzhou, Guangdong, Peoples R China; [Song, Jin-Wen] 302nd Hosp PLA, Treatment & Res Ctr Infect Dis, Beijing, Peoples R China; [Liu, Xue] Jining Med Univ, Basic Sci Sch, Dept Pathol, Jining, Shandong, Peoples R China		He, S (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing, Peoples R China.	hedoctor65@sina.com	zhou, zhi-hang/AAA-4010-2021	Song, Jin-Wen/0000-0002-8582-8012; Zhou, Zhihang/0000-0003-1356-9872; Liu, Peng/0000-0002-3394-971X	National Natural Science Fund for Youth [81602097]; Beijing Municipal Natural Science FoundationBeijing Natural Science Foundation [7182162]; Beijing Nova ProjectBeijing Municipal Science & Technology Commission [Z181100006218016]	This study was funded by the National Natural Science Fund for Youth [No. 81602097]; Beijing Municipal Natural Science Foundation [7182162]; Beijing Nova Project [Z181100006218016].	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J	Mahalingam, D; Mita, M; Sarantopoulos, J; Wood, L; Amaravadi, RK; Davis, LE; Mita, A; Curiel, TJ; Espitia, CM; Nawrocki, ST; Giles, FJ; Carew, JS				Mahalingam, Devalingam; Mita, Monica; Sarantopoulos, John; Wood, Leslie; Amaravadi, Ravi K.; Davis, Lisa E.; Mita, Alain; Curiel, Tyler J.; Espitia, Claudia M.; Nawrocki, Steffan T.; Giles, Francis J.; Carew, Jennifer S.			Combined autophagy and HDAC inhibition A phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors	AUTOPHAGY			English	Article						autophagy; cancer; clinical trial; hydroxychloroquine; vorinostat	HISTONE DEACETYLASE INHIBITORS; TARGETING AUTOPHAGY; CANCER-TREATMENT; CELL-DEATH; THERAPY; MECHANISMS; RESISTANCE; MODEL; SAHA	We previously reported that inhibition of autophagy significantly augmented the anticancer activity of the histone deacetylase (HDAC) inhibitor vorinostat (VOR) through a cathepsin D-mediated mechanism. We thus conducted a first-in-human study to investigate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and VOR in patients with advanced solid tumors. Of 27 patients treated in the study, 24 were considered fully evaluable for study assessments and toxicity. Patients were treated orally with escalating doses of HCQ daily (QD) (d 2 to 21 of a 21-d cycle) in combination with 400 mg VOR QD (d one to 21). Treatment-related adverse events (AE) included grade 1 to 2 nausea, diarrhea, fatigue, weight loss, anemia, and elevated creatinine. Grade 3 fatigue and/or myelosuppression were observed in a minority of patients. Fatigue and gastrointestinal AE were dose-limiting toxicities. Six-hundred milligrams HCQ and 400 mg VOR was established as the maximum tolerated dose and recommended phase II regimen. One patient with renal cell carcinoma had a confirmed durable partial response and 2 patients with colorectal cancer had prolonged stable disease. The addition of HCQ did not significantly impact the PK profile of VOR. Treatment-related increases in the expression of CDKN1A and CTSD were more pronounced in tumor biopsies than peripheral blood mononuclear cells. Based on the safety and preliminary efficacy of this combination, additional clinical studies are currently being planned to further investigate autophagy inhibition as a new approach to increase the efficacy of HDAC inhibitors.	[Mahalingam, Devalingam; Mita, Monica; Sarantopoulos, John; Wood, Leslie; Mita, Alain; Curiel, Tyler J.; Espitia, Claudia M.; Nawrocki, Steffan T.; Giles, Francis J.; Carew, Jennifer S.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA; [Mita, Monica; Mita, Alain] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA; [Amaravadi, Ravi K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA; [Amaravadi, Ravi K.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA; [Davis, Lisa E.] Univ Sci, Philadelphia, PA USA; [Giles, Francis J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA; [Carew, Jennifer S.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA		Carew, JS (corresponding author), Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.	mahalingam@uthscsa.edu; carewj@ccf.org			NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21CA139476, P30CA054174]; Merck, Inc.Merck & Company; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R21CA139476, P30CA054174] Funding Source: NIH RePORTER	This research was supported by NIH grants R21CA139476 (FG) and P30CA054174 (TC). The authors would like to thank Merck, Inc. for providing vorinostat in support of this study.	Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; Amaravadi RK, 2011, CLIN CANCER RES, V17, P654, DOI 10.1158/1078-0432.CCR-10-2634; Carew JS, 2008, CANCER LETT, V269, P7, DOI 10.1016/j.canlet.2008.03.037; Carew JS, 2008, CANCER RES, V68, P4783, DOI 10.1158/0008-5472.CAN-07-6483; Carew JS, 2007, AUTOPHAGY, V3, P464, DOI 10.4161/auto.4311; Carew JS, 2007, BLOOD, V110, P313, DOI 10.1182/blood-2006-10-050260; Carew Jennifer S, 2012, Cancer Manag Res, V4, P357, DOI 10.2147/CMAR.S26133; Carew JS, 2011, J BIOL CHEM, V286, P6602, DOI 10.1074/jbc.M110.151324; Carew Jennifer S, 2008, Biologics, V2, P201; Carew JS, 2010, J CELL MOL MED, V14, P2448, DOI 10.1111/j.1582-4934.2009.00832.x; Guo JY, 2011, GENE DEV, V25, P460, DOI 10.1101/gad.2016311; Janku F, 2011, NAT REV CLIN ONCOL, V8, P528, DOI 10.1038/nrclinonc.2011.71; Kelly WK, 2005, J CLIN ONCOL, V23, P3923, DOI 10.1200/JCO.2005.14.167; Lane AA, 2009, J CLIN ONCOL, V27, P5459, DOI 10.1200/JCO.2009.22.1291; Lazova R, 2012, CLIN CANCER RES, V18, P370, DOI 10.1158/1078-0432.CCR-11-1282; Lee JH, 2012, ADV CANCER RES, V116, P39, DOI 10.1016/B978-0-12-394387-3.00002-1; Lin Y, 2001, Biostatistics, V2, P203, DOI 10.1093/biostatistics/2.2.203; McAfee Q, 2012, P NATL ACAD SCI USA, V109, P8253, DOI 10.1073/pnas.1118193109; Parise RA, 2006, J CHROMATOGR B, V840, P108, DOI 10.1016/j.jchromb.2006.04.044; Pfaffl MW, 2001, NUCLEIC ACIDS RES, V29, DOI 10.1093/nar/29.9.e45; Rangwala R, 2014, AUTOPHAGY, V10, P1391, DOI 10.4161/auto.29119; Rangwala R, 2014, AUTOPHAGY, V10, P1369, DOI 10.4161/auto.29118; Rao R, 2012, MOL CANCER THER, V11, P973, DOI 10.1158/1535-7163.MCT-11-0979; Robey RW, 2011, MOL PHARMACEUT, V8, P2021, DOI 10.1021/mp200329f; Rosenfeld MR, 2014, AUTOPHAGY, V10, P1359, DOI 10.4161/auto.28984; Rubinsztein DC, 2012, NAT REV DRUG DISCOV, V11, P709, DOI 10.1038/nrd3802; Shao YF, 2004, P NATL ACAD SCI USA, V101, P18030, DOI 10.1073/pnas.0408345102; Spiegel S, 2012, ONCOGENE, V31, P537, DOI 10.1038/onc.2011.267; Therasse P, 2000, J NATL CANCER I, V92, P205, DOI 10.1093/jnci/92.3.205; Torgersen ML, 2013, BLOOD, V122, P2467, DOI 10.1182/blood-2013-05-500629; Trotti A, 2003, SEMIN RADIAT ONCOL, V13, P176, DOI 10.1016/S1053-4296(03)00031-6; Vogl DT, 2014, AUTOPHAGY, V10, P1380, DOI 10.4161/auto.29264; White E, 2012, NAT REV CANCER, V12, P401, DOI 10.1038/nrc3262; Yang ZF, 2010, CURR OPIN CELL BIOL, V22, P124, DOI 10.1016/j.ceb.2009.11.014	34	184	187	2	21	LANDES BIOSCIENCE	AUSTIN	1806 RIO GRANDE ST, AUSTIN, TX 78702 USA	1554-8627	1554-8635		AUTOPHAGY	Autophagy	AUG	2014	10	8					1403	1414		10.4161/auto.29231			12	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	AN0HU	WOS:000340266200006	24991835	Green Published, Bronze			2022-04-25	
J	Meng, CQ; Zhou, X; Teng, YH; Wu, CN; Wu, J; Tian, F; Zhou, Y; Zou, X; Wang, RP				Meng, Chunqin; Zhou, Xue; Teng, Yuhao; Wu, Cunen; Wu, Jian; Tian, Fang; Zhou, Yao; Zou, Xi; Wang, Ruiping			Mechanisms of Raddeanin A-induced autophagy and apoptosis in human colorectal cancer cells	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE			English	Article						Raddeanin A; autophagy; apoptosis; HCT116 cells; induce		Several studies have confirmed that the Chinese medicine Raddeanin A (RA), which is extracted from the plant Anemone raddeana Regel, can inhibit the proliferation of a variety of tumor cell lines. Previously, our team demonstrated that RA could induce apoptosis and autophagy in human gastric cancer cells. Objective: This experiment was intended to explore whether RA can induce autophagy and apoptosis in human colorectal cancer HCT116 cells and to investigate the mechanisms and relationship between autophagy and apoptosis. Methods: Cell proliferation was detected via MTT assay. Transmission electron microscope was used to observe autophagosomes as a marker for autophagy. Apoptosis was examined via Hoechst 33258 staining. Flowcytometry was used to calculate the rate of apoptosis. The expression of related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. Results: Cell viability gradually decreased with an increase of drug concentration and disposal time. This result indicated that RA could significantly inhibit the growth of HCT116 cells in a manner that was both time-and concentration dependent. RA induced autophagy and apoptosis in HCT116 cells. RT-PCR and western blot showed that the expression of genes and proteins related to autophagy increased. Moreover, the expression of proteins that suppress apoptosis decreased while pro-apoptotic protein levels increased. The expression of proteins involved in the PI3K-AKT-mTOR signaling pathway also decreased, while caspase-8 and 9 levels increased. Compared with RA treatment alone, the apoptosis rate decreased when HCT116 cells were treated with RA and hydroxychloroquine (HCQ) together. However, when RA and rapamycin (RAPA) were given together, the apoptosis rate increased. Conclusion: RA induces autophagy by regulating the PI3K-AKT-mTOR signaling pathway and apoptosis through intrinsic and extrinsic pathways. Autophagy induced by RA in HCT116 cells can promote cell apoptosis.	[Meng, Chunqin; Teng, Yuhao; Wu, Jian; Tian, Fang; Zou, Xi; Wang, Ruiping] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Tradit Chinese Med, Dept Oncol, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China; [Meng, Chunqin; Wu, Cunen; Zhou, Yao] Nanjing Univ Chinese Med, Dept Clin Med Coll 1, Nanjing 210023, Jiangsu, Peoples R China; [Zhou, Xue] Nanjing Hosp Tradit Chinese Med, Dept Acupuncture, Nanjing 210029, Jiangsu, Peoples R China		Zou, X; Wang, RP (corresponding author), Nanjing Univ Chinese Med, Affiliated Hosp, Dept Oncol, Nanjing 210029, Jiangsu, Peoples R China.	zxvery@162.com; wrp61@163.com		Teng, YU-hao/0000-0002-1475-1599	State Administration of Traditional Chinese Medicine of China [JDZX2012087]; Jiangsu Provincial Commission of Health and Family Planning [BJ14013]; Talent Project of Traditional Chinese Medicine in Jiangsu Province [LJ200908]; Innovation Project Research of Ordinary University in Jiangsu Province [KYLX16_ 1145]; People Pro-gramme of the European Union's Seventh Framework Programme (FP7) under REA grant [PIRSES-GA-2013-61258]	This work was supported by the State Administration of Traditional Chinese Medicine of China (grant# JDZX2012087), Jiangsu Provincial Commission of Health and Family Planning (grant# BJ14013), Talent Project of Traditional Chinese Medicine in Jiangsu Province (No. LJ200908), the Innovation Project Research of Ordinary University in Jiangsu Province (No. KYLX16_ 1145), and the People Pro-gramme of the European Union's Seventh Framework Programme (FP7/2007-2013/under REA grant agreement No. PIRSES-GA-2013-61258: China and Europe taking care of healthcare solutions.	Dayou L, 2005, ACAD PERIODICAL CHAN, V19, P71; Guan YY, 2015, PHYTOMEDICINE, V22, P103, DOI 10.1016/j.phymed.2014.11.008; Hui L., 2013, RES EFFECT AKT BETTA; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Kihara A, 2001, J CELL BIOL, V152, P519, DOI 10.1083/jcb.152.3.519; Li BX, 2010, CHIN J CLIN, V4, P395; Mathew R, 2007, NAT REV CANCER, V7, P961, DOI 10.1038/nrc2254; Mokarram P, 2017, AUTOPHAGY, V13, P781, DOI 10.1080/15548627.2017.1290751; Price TJ, 2017, LANCET ONCOL, V18, P157, DOI 10.1016/S1470-2045(17)30002-5; Qian S, 2014, CHEM PHARM BULL, V62, P779, DOI 10.1248/cpb.c14-00138; Teng YH, 2016, EVID-BASED COMPL ALT, V2016, DOI 10.1155/2016/9406758; US Cancer Statistics Working Group, 2010, US CANC STAT USCS 19; Wang Ming-Kui, 2008, Ai Zheng, V27, P910; Xiaoyi W., 2004, CHINESE J ANAL CHEM, V32, P587; Xue G, 2013, BIOCHEM BIOPH RES CO, V439, P196, DOI 10.1016/j.bbrc.2013.08.060; Yanagisawa H, 2003, CELL DEATH DIFFER, V10, P798, DOI 10.1038/sj.cdd.4401246; Yang JW, 2013, RES RELATIONSHIP MEC, P12; Yee KS, 2009, CELL DEATH DIFFER, V16, P1135, DOI 10.1038/cdd.2009.28; Yoshida H, 1998, CELL, V94, P739, DOI 10.1016/S0092-8674(00)81733-X; [张嘉岷 Zhang Jiamin], 2003, [中国新药杂志, Chinese Journal New Drugs], V12, P191; Zhongjie Z, 2004, CHINESE PHARM J, V39, P493; 刘丹, 2014, [中药药理与临床, Pharmacology and Clinics of Chinese Materia Medica], V30, P49	22	0	0	0	1	E-CENTURY PUBLISHING CORP	MADISON	40 WHITE OAKS LN, MADISON, WI 53711 USA	1940-5901			INT J CLIN EXP MED	Int. J. Clin. Exp. Med.		2017	10	11					15766	15774					9	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	FO5IA	WOS:000416885900102					2022-04-25	
J	Kang, KB; Zhu, CJ; Yong, SK; Gao, QH; Wong, MC				Kang, Khong Bee; Zhu, Congju; Yong, Sook Kwin; Gao, Qiuhan; Wong, Meng Cheong			Enhanced sensitivity of celecoxib in human glioblastoma cells: Induction of DNA damage leading to p53-dependent G(1) cell cycle arrest and autophagy	MOLECULAR CANCER			English	Article							COX-2 INHIBITOR CELECOXIB; COLON-CARCINOMA CELLS; U87MG GLIOMA-CELLS; DOWN-REGULATION; CANCER-CELLS; IN-VITRO; CYCLOOXYGENASE-2 INHIBITORS; INDUCED APOPTOSIS; STRAND BREAKS; TUMOR-GROWTH	Background: Selective cyclooxygenase (COX)-2 inhibitors elicit anti-proliferative responses in various tumours, however the underlying anti-tumour mechanisms are unclear. Mutational inactivation of the tumour suppressor p53 gene is frequent in malignant gliomas. The role of p53 mutation in the anti-tumour responses of the selective COX-2 inhibitor celecoxib in human glioblastoma cells is unknown. In this study, we used human glioblastoma cells with various p53 status; U87MG (with high and low p53 functional levels), LN229 (functional p53) and U373MG (mutant p53) cells. Inhibition of p53 was achieved in U87MG cells transfected with E6 oncoprotein (U87MG-E6) and treated with pifithrin-alpha, a reversible inhibitor of p53 (U87MG-PFT). We investigated whether the anti-glioblastoma responses of celecoxib were p53-dependent, and whether celecoxib induced DNA damage leading to p53-dependent G(1) cell cycle arrest, followed by autophagy or apoptosis. Results: Our findings demonstrated that celecoxib concentration-dependently reduced glioblastoma cell viability, following 24 and 72 hours of treatment. Inhibition of functional p53 in glioblastoma cells significantly reduced the anti-proliferative effect of celecoxib. In U87MG cells, celecoxib (8 and 30 mu M) significantly induced DNA damage and inhibited DNA synthesis, corresponding with p53 activation. Celecoxib induced G(1)-phase cell cycle arrest, accompanied with p21 activation in U87MG cells. Cell cycle progression of U87MG-E6 and U87MG-PFT cells was not affected by celecoxib. In parallel, celecoxib induced G(1) cell cycle arrest in LN229 cells, but not in U373MG cells. Autophagy was induced by celecoxib in U87MG and LN229 cells, as shown by the significantly greater population of acridine orange-stained cells and increased levels of LC3-II protein (in comparison with non-treated controls). Celecoxib did not induce significant autophagy in U87MG-PFT, U87MG-E6 and U373MG cells, which lack functional p53. Regardless of p53 status, celecoxib caused no significant difference in apoptosis level of U87MG, U87MG-PFT, U87MG-E6 and U373MG cells. Conclusion: Our findings reveal that p53 increases human glioblastoma sensitivity to celecoxib. Celecoxib inhibits glioblastoma cell viability by induction of DNA damage, leading to p53-dependent G(1) cell cycle arrest and p53-dependent autophagy, but not apoptosis.	[Kang, Khong Bee; Zhu, Congju; Yong, Sook Kwin; Gao, Qiuhan; Wong, Meng Cheong] Natl Canc Ctr, Humphrey Oei Inst Canc Res, Div Med Sci, Brain Tumour Res Lab, Singapore 169610, Singapore		Kang, KB (corresponding author), Natl Canc Ctr, Humphrey Oei Inst Canc Res, Div Med Sci, Brain Tumour Res Lab, 11 Hosp Dr, Singapore 169610, Singapore.	dmskkb@nccs.com.sg; dmszcj@nccs.com.sg; nmsyskg@nccs.com.sg; chrisgqh@yahoo.com.sg; dmswmc@nccs.com.sg	ZHU, CONGJU/H-6369-2011		Singhealth Foundation, SingaporeSingHealth [SHF/FG023/2004]; Singapore Millennium Foundation, Singapore.Singapore Millennium Foundation	The authors would like to thank A/Prof. Russell Pieper (UCSF Comprehensive Cancer Centre, San Francisco, CA) for providing the stable transfectant U87MG-E6 cells, and Yin Ling Wong for technical assistance in performing part of the cell viability assays. This study was supported by a grant from Singhealth Foundation, Singapore (SHF/FG023/2004). K. B. Kang was a recipient of the Post-doctoral Research Fellowship from the Singapore Millennium Foundation, Singapore.	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Cancer	AUG 25	2009	8								66	10.1186/1476-4598-8-66			16	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	496DS	WOS:000269950000001	19706164	gold, Green Published			2022-04-25	
J	Jiang, YW; Xiao, LB; Fu, WW; Tang, YX; Lertnimitphun, P; Kim, N; Zheng, CW; Tan, HS; Lu, Y; Xu, HX				Jiang, Yiwen; Xiao, Lianbo; Fu, Wenwei; Tang, Yuexun; Lertnimitphun, Peeraphong; Kim, Nami; Zheng, Changwu; Tan, Hongsheng; Lu, Yue; Xu, Hongxi			Gaudichaudione H Inhibits Inflammatory Responses in Macrophages and Dextran Sodium Sulfate-Induced Colitis in Mice	FRONTIERS IN PHARMACOLOGY			English	Article						gaudichaudione H; macrophages; colitis; nitric oxide; nuclear factor-kappa B; mitogen-activated protein kinases	LPS-INDUCED INFLAMMATION; NF-KAPPA-B; SIGNALING PATHWAYS; NITRIC-OXIDE; ACTIVATION; GARCINIA; MECHANISMS; EXPRESSION; RECEPTORS; INDUCTION	Macrophages-involved inflammation is considered to induce the damage in various diseases. Herein, novel therapeutics inhibiting over-activation of macrophages could prove an effective strategy to prevent inflammation-related diseases. Gaudichaudione H (GH), which is a natural small molecular compound isolated from Garcinia oligantha Merr. (Clusiaceae) has previously been demonstrated its anti-cancer effects on several cancer cell lines. However, no report has been published about the anti-inflammatory effect of GH to date. This study aims to examine the anti-inflammatory effects and potential molecular mechanism of GH, and provide new insights toward the treatment of inflammation. GH inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, cytokine interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) production, and messenger RNA (mRNA) expression to attenuate inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells or stimulated bone marrow-derived macrophages (BMDMs). GH inhibited nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) pathways, the nuclear translocation of transcription factors NF-kappa B and activator protein 1 (AP-1), as well as upstream signaling of the toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) pathway in stimulated macrophages. Furthermore, the result of the intracellular signaling array showed that the phosphorylation of adenosine 5'-monophosphate-activated protein kinase-alpha (AMPK alpha), proline-rich Akt substrate of 40 kDa (PRAS40), and p38 could be down regulated by GH in BMDMs, indicating that the mechanism by which GH inhibited inflammation may be also associated with the energy metabolism pathway, PRAS40-mediated NF-kappa B pathway, cell proliferation, apoptosis, and autophagy, etc. In addition, GH alleviated dextran sodium sulfate (DSS)-induced colitis in mice by ameliorating weight loss, stool consistency change, blood in the stool, and colon shortening. GH decreased the protein and mRNA levels of IL-6 and TNF-alpha, iNOS and COX-2 mRNA expression, the activation of NF-kappa B and MAPK pathways, the phosphorylation of AMPK alpha and PRAS40, histological damage, and infiltration of macrophages in the colons of mice with DSS-induced colitis. Taken together, our results support that GH exerts the anti-inflammatory effects in macrophages in vitro through regulation of NF-kappa B and MAPK pathways, and DSS-induced colitis mouse model in vivo. These findings suggest that GH may be a promising candidate in treating macrophage-related inflammatory disease.	[Jiang, Yiwen; Fu, Wenwei; Tang, Yuexun; Lertnimitphun, Peeraphong; Kim, Nami; Zheng, Changwu; Tan, Hongsheng; Lu, Yue; Xu, Hongxi] Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai, Peoples R China; [Xiao, Lianbo] Shanghai Acad Chinese Med Sci, Guanghua Integrat Med Hosp, Inst Arthrit Res, Shanghai, Peoples R China		Lu, Y; Xu, HX (corresponding author), Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai, Peoples R China.	lvyue126@hotmail.com; xuhongxi88@gmail.com	Xu, Hongxi/AAC-2799-2020; Zheng, Changwu/P-5319-2014	Zheng, Changwu/0000-0002-0869-8314; Xu, Hongxi/0000-0001-6238-4511	National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81803545, 81602990]; Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning; Three-year development plan project for Traditional Chinese Medicine [ZY(2018-2020)-CCCX-2001-02]	This work was financially sponsored by grants from the National Natural Science Foundation of China (NSFC) Grants 81803545 and 81602990; Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning; the Three-year development plan project for Traditional Chinese Medicine (ZY(2018-2020)-CCCX-2001-02) for financial support.	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JAN 17	2020	10								1561	10.3389/fphar.2019.01561			17	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	KH8OY	WOS:000510911300001	32009962	gold, Green Published			2022-04-25	
J	Liu, CC; DeRoo, EP; Stecyk, C; Wolsey, M; Szuchnicki, M; Hagos, EG				Liu, Changchang; DeRoo, Elise P.; Stecyk, Catherine; Wolsey, Margaret; Szuchnicki, Mateusz; Hagos, Engda G.			Impaired autophagy in mouse embryonic fibroblasts null for Kruppel-like Factor 4 promotes DNA damage and increases apoptosis upon serum starvation	MOLECULAR CANCER			English	Article						Kruppel-like Factor 4; Autophagy; Apoptosis; Mammalian target of rapamycin; DNA damage; Mouse embryonic fibroblasts; Autophagy related genes	TRANSCRIPTION FACTOR KLF4; TUMOR-SUPPRESSOR GENE; COLORECTAL-CANCER; DOWN-REGULATION; CELL-DEATH; MTOR; TUMORIGENESIS; MACROAUTOPHAGY; INHIBITION; KRUPPEL-LIKE-FACTOR-4	Background: Autophagy is a major cellular process by which cytoplasmic components such as damaged organelles and misfolded proteins are recycled. Although low levels of autophagy occur in cells under basal conditions, certain cellular stresses including nutrient depletion, DNA damage, and oxidative stress are known to robustly induce autophagy. Kruppel-like factor 4 (KLF4) is a zinc-finger transcription factor activated during oxidative stress to maintain genomic stability. Both autophagy and KLF4 play important roles in response to stress and function in tumor suppression. Methods: To explore the role of KLF4 on autophagy in mouse embryonic fibroblasts (MEFs), we compared wild-type with Klf4 deficient cells. To determine the levels of autophagy, we starved MEFs for different times with Earle's balanced salts solution (EBSS). Rapamycin was used to manipulate mTOR activity and autophagy. The percentage of cells with gamma-H2AX foci, a marker for DNA damage, and punctate pattern of GFP-LC3 were counted by confocal microscopy. The effects of the drug treatments, Klf4 overexpression, or Klf4 transient silencing on autophagy were analyzed using Western blot. Trypan Blue assay and flow cytometry were used to study cell viability and apoptosis, respectively. qPCR was also used to assay basal and the effects of Klf4 overexpression on Atg7 expression levels. Results: Here our data suggested that Klf4(-/-) MEFs exhibited impaired autophagy, which sensitized them to cell death under nutrient deprivation. Secondly, DNA damage in Klf4-null MEFs increased after treatment with EBSS and was correlated with increased apoptosis. Thirdly, we found that Klf4(-/-) MEFs showed hyperactive mTOR activity. Furthermore, we demonstrated that rapamycin reduced the increased level of mTOR in Klf4-/-MEFs, but did not restore the level of autophagy. Finally, re-expression of Klf4 in Klf4 deficient MEFs resulted in increased levels of LC3II, a marker for autophagy, and Atg7 expression level when compared to GFP-control transfected Klf4(-/-) MEFs. Conclusion: Taken together, our results strongly suggest that KLF4 plays a critical role in the regulation of autophagy and suppression of mTOR activity. In addition, we showed that rapamycin decreased the level of mTOR in Klf4(-/-) MEFs, but did not restore autophagy. This suggests that KLF4 regulates autophagy through both mTOR-dependent and independent mechanisms. Furthermore, for the first time, our findings provide novel insights into the mechanism by which KLF4 perhaps prevents DNA damage and apoptosis through activation of autophagy.	[Liu, Changchang; DeRoo, Elise P.; Stecyk, Catherine; Wolsey, Margaret; Szuchnicki, Mateusz; Hagos, Engda G.] Colgate Univ, Dept Biol, Hamilton, NY 13346 USA; [DeRoo, Elise P.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA; [DeRoo, Elise P.] Harvard Univ, Sch Med Sch, Boston, MA 02115 USA; [Stecyk, Catherine] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA 01536 USA		Hagos, EG (corresponding author), Colgate Univ, Dept Biol, 13 Oak Dr,Olin Hall 205A, Hamilton, NY 13346 USA.	ehagos@colgate.edu	, ehagos/AAY-8486-2020		Colgate University Research Council	This work was supported in part by Picker Research Fellowship and Major Grant from Colgate University Research Council. We acknowledge the lab of Dr. Vincent W. Yang (Stony Brook Medical School, NY) for providing KLF4-GFP and GFP constructs. The authors would also like to thank Dr. Kenneth Belanger for critically reviewing the manuscript.	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Cancer	MAY 6	2015	14								101	10.1186/s12943-015-0373-6			13	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	CH3NZ	WOS:000353938700001	25944097	gold, Green Published			2022-04-25	
J	Astanina, E; Bussolino, F; Doronzo, G				Astanina, Elena; Bussolino, Federico; Doronzo, Gabriella			Multifaceted activities of transcription factor EB in cancer onset and progression	MOLECULAR ONCOLOGY			English	Review						angiogenesis; autophagy; cell&#8208; cycle; lysosome; metabolism; tumor microenvironment	RENAL-CELL CARCINOMA; REGULATING LYSOSOMAL BIOGENESIS; INNATE IMMUNE-RESPONSE; AMINO-ACID LEVELS; FACTOR TFEB; RAG GTPASES; DEPENDENT REGULATION; COLORECTAL-CANCER; TUMOR-SUPPRESSOR; AUTOPHAGY	Transcription factor EB (TFEB) represents an emerging player in cancer biology. Together with microphthalmia-associated transcription factor, transcription factor E3 and transcription factor EC, TFEB belongs to the microphthalmia family of bHLH-leucine zipper transcription factors that may be implicated in human melanomas, renal and pancreatic cancers. TFEB was originally described as being translocated in a juvenile subset of pediatric renal cell carcinoma; however, whole-genome sequencing reported that somatic mutations were sporadically found in many different cancers. Besides its oncogenic activity, TFEB controls the autophagy-lysosomal pathway by recognizing a recurrent motif present in the promoter regions of a set of genes that participate in lysosome biogenesis; furthermore, its dysregulation was found to have a crucial pathogenic role in different tumors by modulating the autophagy process. Other than regulating cancer cell-autonomous responses, recent findings indicate that TFEB participates in the regulation of cellular functions of the tumor microenvironment. Here, we review the emerging role of TFEB in regulating cancer cell behavior and choreographing tumor-microenvironment interaction. Recognizing TFEB as a hub of network of signals exchanged within the tumor between cancer and stroma cells provides a fresh perspective on the molecular principles of tumor self-organization, promising to reveal numerous new and potentially druggable vulnerabilities.	[Astanina, Elena; Bussolino, Federico; Doronzo, Gabriella] Univ Torino, Dept Oncol, Sp 142,Km 3.95, I-10060 Candiolo, Italy; [Astanina, Elena; Bussolino, Federico; Doronzo, Gabriella] Candiolo Canc Inst IRCCS FPO, Candiolo, Italy		Bussolino, F (corresponding author), Univ Torino, Dept Oncol, Sp 142,Km 3.95, I-10060 Candiolo, Italy.	Federico.bussolino@unito.it	Doronzo, Gabriella/AAC-4953-2022; Bussolino, Federico/K-2500-2016	Doronzo, Gabriella/0000-0002-3693-8178; Bussolino, Federico/0000-0002-5348-1341	AIRC - Associazione Italiana Per la Ricerca sul CancroFondazione AIRC per la ricerca sul cancro [22910]; Regione PiemonteRegione Piemonte [A1907A]; Ministero dell'Universita e della RicercaMinistry of Education, Universities and Research (MIUR) [2017237P5X]; FPRC 5xmille 2016 MIUR (Biofilm); ERA-Net Transcan2 [TRS-2018-00000689]; Fondazione CRTFondazione CRT	This work was supported by AIRC - Associazione Italiana Per la Ricerca sul Cancro (grant 22910), Regione Piemonte (grant A1907A, Deflect), Fondazione CRT, Ministero dell'Universita e della Ricerca (PRIN 2017, grant 2017237P5X), FPRC 5xmille 2016 MIUR (Biofilm) and ERA-Net Transcan2 (grant TRS-2018-00000689) to FB.	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Oncol.	FEB	2021	15	2					327	346		10.1002/1878-0261.12867		DEC 2020	20	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	QB6TZ	WOS:000601107800001	33252196	gold, Green Published			2022-04-25	
J	Wu, SH; Sun, CB; Li, YY; Gao, XQ; He, S; Li, TY; Tian, D				Wu Shuhua; Sun Chenbo; Li Yangyang; Gao Xiangqian; He Shuang; Li Tangyue; Tian Dong			Autophagy-related genes Raptor, Rictor, and Beclin1 expression and relationship with multidrug resistance in colorectal carcinoma	HUMAN PATHOLOGY			English	Article						Colorectal cancer; MDR; Raptor; Rictor; Beclin1; Prognosis	MAMMALIAN TARGET; DEGRADATION; INHIBITION	This study aims to evaluate the relationship between the expressions of autophagy-related genes Raptor, Rictor, and Beclin1 and the expression of multidrug resistance (MDR) gene in colorectal cancer (CRC) patients. Immunohistochemistry and real-time polymerase chain reaction were used to detect the protein and messenger RNA expressions of mammalian target of rapamycin (mTOR), Raptor, Rictor, Beclin1, light chain 3 (LC3), and MDR-1 in 279 CRC specimens. Patients were followed up annually by telephone or at an outpatient clinic. Results revealed that the protein and messenger RNA expressions of Beclin1, LC3, mTOR, Raptor, Rictor, and MDR-1 in CRC are significantly higher than in adjacent tissues. LC3 expression in poorly differentiated CRC is higher than that in well-differentiated CRC, and the expression of mTOR, Raptor, Rictor, and LC3 in lymph node metastasis is higher than that obtained in the absence of lymph node metastasis. The expression of LC3 is positively correlated with those of Beclin1 and Rictor and negatively correlated with Raptor and mTOR in CRC. The expression of Raptor is negatively correlated with Rictor. The expression of MDR-1 is positively correlated with those of Beclin1, LC3, and Rictor and negatively correlated with Raptor and mTOR. Kaplan-Meier analysis revealed that the 5-year survival rate of patients without lymph node metastasis; positive expression of Rictor, Beclin1, and LC3; and negative expression of Raptor and mTOR were higher than those with these characteristics. To conclude, the expressions of Beclin1, Raptor, and Rictor are related to the development and progression of colorectal carcinoma and MDR. (C) 2015 Elsevier Inc. All rights reserved.	[Wu Shuhua; Li Yangyang; Gao Xiangqian; He Shuang; Tian Dong] Binzhou Med Univ Hosp, Dept Pathol, Binzhou 256603, Shandong, Peoples R China; [Sun Chenbo; Li Tangyue] Binzhou Med Univ, Dept Pathol, Binzhou 256603, Shandong, Peoples R China		Wu, SH (corresponding author), Binzhou Med Univ Hosp, Dept Pathol, Binzhou 256603, Shandong, Peoples R China.	wsh6108@126.com; dongtianbz@163.com			Scientific and Technological Project of Shandong Province, Binzhou, China	This work was supported by Scientific and Technological Project of Shandong Province, Binzhou, China.	Cao Y, 2007, CELL RES, V17, P839, DOI 10.1038/cr.2007.78; El-Readi MZ, 2010, EUR J PHARMACOL, V626, P139, DOI 10.1016/j.ejphar.2009.09.040; Eum KH, 2011, MOL CELLS, V31, P231, DOI 10.1007/s10059-011-0034-6; Fu X, 2013, BREAST S2, pS12; Guertin DA, 2007, CANCER CELL, V12, P9, DOI 10.1016/j.ccr.2007.05.008; Gulhati P, 2009, CLIN CANCER RES, V15, P7207, DOI 10.1158/1078-0432.CCR-09-1249; Jemal A, 2009, CA-CANCER J CLIN, V59, P225, DOI 10.3322/caac.20006; Jung CH, 2010, FEBS LETT, V584, P1287, DOI 10.1016/j.febslet.2010.01.017; Kohli L, 2013, AUTOPHAGY, V9, P1438, DOI 10.4161/auto.25837; Kristensen AR, 2008, MOL CELL PROTEOMICS, V7, P2419, DOI 10.1074/mcp.M800184-MCP200; Li N, 2013, BIOCHEM BIOPH RES CO, V439, P187, DOI 10.1016/j.bbrc.2013.08.065; Lin CJ, 2012, FREE RADICAL BIO MED, V52, P377, DOI 10.1016/j.freeradbiomed.2011.10.487; Ming HY, 2014, PLOS ONE, V9; National Comprehensive Cancer Network, 2015, NCCN CLIN PRACT GUID; Shu JY, 2011, PLOS ONE, V6; Tanida I, 2005, AUTOPHAGY, V1, P84, DOI 10.4161/auto.1.2.1697; Teimoori-Toolabi L, 2015, ANTI-CANCER DRUG, V26, P187, DOI 10.1097/CAD.0000000000000175; Vlahakis A, 2014, AUTOPHAGY, V10, P2085, DOI 10.4161/auto.36262; Wang XR, 2008, CANCER RES, V68, P7409, DOI 10.1158/0008-5472.CAN-08-1522; Wen FF, 2014, INT J CLIN EXP PATHO, V7, P8295; Xu N, 2012, BIOCHEM BIOPH RES CO, V423, P826, DOI 10.1016/j.bbrc.2012.06.048; Zheng ZZ, 2012, AUTOPHAGY, V8, P1; Zhi HC, 2013, DIGEST DIS SCI, V58, P2887	23	35	42	0	13	W B SAUNDERS CO-ELSEVIER INC	PHILADELPHIA	1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA	0046-8177	1532-8392		HUM PATHOL	Hum. Pathol.	NOV	2015	46	11					1752	1759		10.1016/j.humpath.2015.07.016			8	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	CV6DJ	WOS:000364360600022	26363527				2022-04-25	
J	Cao, J; Bhatnagar, S; Wang, JW; Qi, XY; Prabha, S; Panyam, J				Cao, Jin; Bhatnagar, Shubhmita; Wang, Jiawei; Qi, Xueyong; Prabha, Swayam; Panyam, Jayanth			Cancer stem cells and strategies for targeted drug delivery	DRUG DELIVERY AND TRANSLATIONAL RESEARCH			English	Review						Cancer stem cells (CSCs); Drug delivery system; Anti-tumor therapy; Drug-resistance; Cancer biology	ACUTE MYELOID-LEUKEMIA; OVERCOME MULTIDRUG-RESISTANCE; FACILITATED AUTOPHAGY INHIBITION; HUMAN PANCREATIC-CANCER; BREAST-CANCER; ABC TRANSPORTERS; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; HYALURONIC-ACID; P-GLYCOPROTEIN	Cancer stem cells (CSCs) are a small proportion of cancer cells with high tumorigenic activity, self-renewal ability, and multilineage differentiation potential. Standard anti-tumor therapies including conventional chemotherapy, radiation therapy, and molecularly targeted therapies are not effective against CSCs, and often lead to enrichment of CSCs that can result in tumor relapse. Therefore, it is hypothesized that targeting CSCs is key to increasing the efficacy of cancer therapies. In this review, CSC properties including CSC markers, their role in tumor growth, invasiveness, metastasis, and drug resistance, as well as CSC microenvironment are discussed. Further, CSC-targeted strategies including the use of targeted drug delivery systems are examined.	[Cao, Jin; Qi, Xueyong] Jiangsu Univ, Sch Pharm, Zhenjiang 212013, Jiangsu, Peoples R China; [Cao, Jin; Bhatnagar, Shubhmita; Wang, Jiawei; Prabha, Swayam; Panyam, Jayanth] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA; [Bhatnagar, Shubhmita; Panyam, Jayanth] Temple Univ, Sch Pharm, Philadelphia, PA 19140 USA; [Prabha, Swayam] Temple Univ, Lewis Katz Sch Med, Canc Res & Mol Biol, Philadelphia, PA 19140 USA; [Prabha, Swayam] Temple Univ, Lewis Katz Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA; [Wang, Jiawei] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA		Panyam, J (corresponding author), Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA.; Panyam, J (corresponding author), Temple Univ, Sch Pharm, Philadelphia, PA 19140 USA.	jayanth.panyam@temple.edu	Bhatnagar, Shubhmita/ABB-8557-2021	Bhatnagar, Shubhmita/0000-0002-2721-9307	Community of Pharmaceutical Development (CPD), Office of Discovery and Translation (ODAT) at the University of Minnesota; Randy Shaver Foundation; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01EB019893]	Funding was provided by the Community of Pharmaceutical Development (CPD), Office of Discovery and Translation (ODAT) at the University of Minnesota, the Randy Shaver Foundation, and NIH R01EB019893.	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Transl. Res.	OCT	2021	11	5					1779	1805		10.1007/s13346-020-00863-9		OCT 2020	27	Instruments & Instrumentation; Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Instruments & Instrumentation; Research & Experimental Medicine; Pharmacology & Pharmacy	UO0VO	WOS:000582087400001	33095384				2022-04-25	
J	Zhao, YZ; Zhang, YY; Han, H; Fan, RP; Hu, Y; Zhong, L; Kou, JP; Yu, BY				Zhao Ya-Zheng; Zhang Yuan-Yuan; Han Han; Fan Rui-Ping; Hu Yang; Zhong Liang; Kou Jun-Ping; Yu Bo-Yang			Advances in the antitumor activities and mechanisms of action of steroidal saponins	CHINESE JOURNAL OF NATURAL MEDICINES			English	Article						Steroidal saponins; Tumor; Mechanism	COLORECTAL-CANCER CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; REVERSES MULTIDRUG-RESISTANCE; DWARF LILYTURF TUBER; PARIS SAPONIN; IN-VITRO; P38 MAPK; HEPATOCELLULAR-CARCINOMA; INHIBITS GROWTH; OPHIOPOGONIN B	The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.	[Zhao Ya-Zheng; Zhang Yuan-Yuan; Han Han; Fan Rui-Ping; Hu Yang; Zhong Liang; Kou Jun-Ping; Yu Bo-Yang] China Pharmaceut Univ, Dept Complex Prescript Tradit Chinese Med, Jiangsu Key Lab TCM Evaluat & Translat Res, Nanjing 211198, Jiangsu, Peoples R China		Kou, JP; Yu, BY (corresponding author), China Pharmaceut Univ, Dept Complex Prescript Tradit Chinese Med, Jiangsu Key Lab TCM Evaluat & Translat Res, Nanjing 211198, Jiangsu, Peoples R China.	junpingkou@cpu.edu.cn; boyangyu59@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81503295]; 2011 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education; Priority Academic Program Development of Jiangsu Higher Education Institutions; Jiangsu Province 2011 Plan for Collaborative Innovation	This work was supported by the National Natural Science Foundation of China (No. 81503295), 2011 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education, a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Jiangsu Province 2011 Plan for Collaborative Innovation.	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J	Gong, WY; Zhao, ZX; Liu, BJ; Lu, LW; Dong, JC				Gong, Wei-Yi; Zhao, Zheng-Xiao; Liu, Bao-Jun; Lu, Lin-Wei; Dong, Jing-Cheng			Exploring the chemopreventive properties and perspectives of baicalin and its aglycone baicalein in solid tumors	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Review						Baicalin; Baicalein; Solid tumor; Bioavailability	CELLS IN-VITRO; EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL-CANCER CELLS; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; DOWN-REGULATION; SCUTELLARIA-BAICALENSIS; CYCLE ARREST; 12-LIPOXYGENASE INHIBITION; MATRIX METALLOPROTEINASES	Solid tumors contain a huge mass of malignant tumors other than hematological malignancies. Novel therapies based on bio-safe agents against solid tumors are urgently required. Baicalin and its aglycone baicalein, the major bioactive flavones derived from Scutellaria baicalensis, have potential roles in the management of cancer. The chemopreventive properties governed by baicalin and baicalein were multifold, via apoptosis induction, autophagy triggering, cell cycle arrest, inhibition of 12-lipoxygenase and metastasis suppression. However, their poor solubility and low oral bioavailability severely limited the clinical application. This extensive review focused on the promising anti-cancer activities of baicalin and baicalein and new techniques to improve their bioavailability. (C) 2016 Elsevier Masson SAS. All rights reserved.	[Gong, Wei-Yi; Zhao, Zheng-Xiao; Liu, Bao-Jun; Lu, Lin-Wei; Dong, Jing-Cheng] Fudan Univ, Huashan Hosp, Dept Integrat Med, 12 Middle Wulumiqi Rd, Shanghai, PR, Peoples R China; [Gong, Wei-Yi; Zhao, Zheng-Xiao; Liu, Bao-Jun; Lu, Lin-Wei; Dong, Jing-Cheng] Fudan Univ, Inst Integrat Med, 12 Middle Wulumuqi Rd, Shanghai, PR, Peoples R China		Dong, JC (corresponding author), Fudan Univ, Huashan Hosp, Dept Integrat Med, 12 Middle Wulumiqi Rd, Shanghai, PR, Peoples R China.; Dong, JC (corresponding author), Fudan Univ, Inst Integrat Med, 12 Middle Wulumuqi Rd, Shanghai, PR, Peoples R China.	jcdong2004@126.com		Dong, Jingcheng/0000-0002-5194-367X	National Natural Science Foundation for Distinguished Young Scholars of ChinaNational Natural Science Foundation of China (NSFC)National Science Fund for Distinguished Young Scholars [81403148]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81673916]; Development Project of Shanghai Peak Disciplines -Integrative Medicine [20150407]	This study was funded by grants from National Natural Science Foundation for Distinguished Young Scholars of China (Grant No. 81403148), National Natural Science Foundation of China (Grant No. 81673916) and Development Project of Shanghai Peak Disciplines -Integrative Medicine (Grant No. 20150407).	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J. Med. Chem.	JAN 27	2017	126						844	852		10.1016/j.ejmech.2016.11.058			9	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	EO6LP	WOS:000396804600064	27960146				2022-04-25	
J	Schroll, MM; LaBonia, GJ; Ludwig, KR; Hummon, AB				Schroll, Monica M.; LaBonia, Gabriel J.; Ludwig, Katelyn R.; Hummon, Amanda B.			Glucose Restriction Combined with Autophagy Inhibition and Chemotherapy in HCT 116 Spheroids Decreases Cell Clonogenicity and Viability Regulated by Tumor Suppressor Genes	JOURNAL OF PROTEOME RESEARCH			English	Article						nutrient restriction; autophagy; chloroquine; colorectal cancer; proteomics; iTRAQ; MALDI imaging mass spectrometry; three-dimensional cell culture	MASS-SPECTROMETRY; NUCLEAR-PROTEIN; NUTRIENT RESTRICTION; DIFFERENT REGIONS; IN-VITRO; CANCER; CHLOROQUINE; METABOLISM; IRINOTECAN; THERAPY	Drug resistance is a prevalent phenomenon that decreases the efficacy of cancer treatments and contributes to cancer progression and metastasis. Weakening drug-resistant cancer cells prior to chemotherapy is a potential strategy to combat chemoresistance. One approach to damage resistant cancer cells is modulation of nutritional intake. The combination of nutrient restriction with targeted compound treatment results in pronounced molecular changes. This study provides valuable information about augmenting existing chemotherapeutic regimes with simultaneous glucose restriction and autophagy inhibition in colorectal cancer cells. In this study, we explore the chemical pathways that drive the cellular response to nutrient restriction, autophagy inhibition, and the chemotherapy irinotecan using global quantitative proteomics and imaging mass spectrometry. We determined that significant pathways were altered including autophagy and metabolism via glycplysis, gluconeogenesis, and sucrose degradation. We also found that period circadian clock 2 (PER2), a tumor suppressor protein, was significantly up-regulated only when glucose was restricted with autophagy inhibition and chemotherapy. The upstream regulators of these differentially regulated pathways were determined to have implications in cancer, showing an increase in tumor suppressor proteins and a decrease in nuclear protein 1 (NUPR1) an important protein in chemoresistance. We also evaluated the phenotypic response of these cells and discovered autophagy inhibition and chemotherapy treatment increased apoptosis and decreased cell Clonogenicity and viability. When glucose restriction was combined with autophagy inhibition and chemotherapy, all of the phenotypic results were intensified. In sum, our results indicate that glucose metabolism is of great importance in the ability of cancer cells to survive chemotherapy. By weakening cancer cells with glucose restriction and autophagy inhibition prior to chemotherapy, cancer cells become more sensitive to therapy.	[Hummon, Amanda B.] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA; Univ Notre Dame, Harper Canc Res Inst, Notre Dame, IN 46556 USA		Hummon, AB (corresponding author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA.	ahummon@nd.edu		Hummon, Amanda/0000-0002-1969-9013	National Institutes of Health Training Grant - Chemistry Biochemistry Biology Interface ProgramUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32GM075762]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01GM110406]; National Science Foundation (CAREER Award)National Science Foundation (NSF) [CHE-1351595]; National Science FoundationNational Science Foundation (NSF) [1625944]; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [T32GM075762, R01GM110406] Funding Source: NIH RePORTER	M.S. was supported by National Institutes of Health Training Grant - Chemistry Biochemistry Biology Interface Program (T32GM075762). A.B.H. was supported by the National Institutes of Health (R01GM110406) and the National Science Foundation (CAREER Award, CHE-1351595). The UltrafleXtreme instrument (MALDI-TOF-TOF) was acquired through National Science Foundation award #1625944. We gratefully acknowledge the assistance of Dr. Susan Skube for her edits and the Notre Dame Mass Spectrometry and Proteomics Facility (MSPF).	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Proteome Res.	AUG	2017	16	8					3009	3018		10.1021/acs.jproteome.7b00293			10	Biochemical Research Methods	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	FD1OY	WOS:000407307800030	28650662	Green Accepted			2022-04-25	
J	Weidner, P; Sohn, M; Gutting, T; Friedrich, T; Gaiser, T; Magdeburg, J; Kienle, P; Ruh, H; Hopf, C; Behrens, HM; Rocken, C; Hanoch, T; Seger, R; Ebert, MPA; Burgermeister, E				Weidner, Philip; Soehn, Michaela; Gutting, Tobias; Friedrich, Teresa; Gaiser, Timo; Magdeburg, Julia; Kienle, Peter; Ruh, Hermelindis; Hopf, Carsten; Behrens, Hans-Michael; Roecken, Christoph; Hanoch, Tamar; Seger, Rony; Ebert, Matthias P. A.; Burgermeister, Elke			Myotubularin-related protein 7 inhibits insulin signaling in colorectal cancer	ONCOTARGET			English	Article						colorectal cancer; insulin; MTMR7; phosphatase; myotubularin	GASTRIC-CANCER; METAANALYSIS; PROGRESSION; RECURRENCE; CAVEOLIN-1; EXPRESSION; MUTATIONS; AUTOPHAGY; GENOMICS; FAMILY	Phosphoinositide (PIP) phosphatases such as myotubularins (MTMs) inhibit growth factor receptor signaling. However, the function of myotubularin-related protein 7 (MTMR7) in cancer is unknown. We show that MTMR7 protein was down-regulated with increasing tumor grade (G), size (T) and stage (UICC) in patients with colorectal cancer (CRC) (n=1786). The presence of MTMR7 in the stroma correlated with poor prognosis, whereas MTMR7 expression in the tumor was not predictive for patients' survival. Insulin reduced MTMR7 protein levels in human CRC cell lines, and CRC patients with type 2 diabetes mellitus (T2DM) or loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) had an increased risk for MTMR7 loss. Mechanistically, MTMR7 lowered PIPs and inhibited insulin-mediated AKT-ERK1/2 signaling and proliferation in human CRC cell lines. MTMR7 provides a novel link between growth factor signaling and cancer, and may thus constitute a potential marker or drug target for human CRC.	[Weidner, Philip; Soehn, Michaela; Gutting, Tobias; Friedrich, Teresa; Ebert, Matthias P. A.; Burgermeister, Elke] Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Dept Med 2, D-68167 Mannheim, Germany; [Gaiser, Timo] Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Inst Pathol, D-68167 Mannheim, Germany; [Magdeburg, Julia; Kienle, Peter] Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Dept Surg, D-68167 Mannheim, Germany; [Ruh, Hermelindis; Hopf, Carsten] Mannheim Univ Appl Sci, ABIMAS Res Ctr, D-68163 Mannheim, Germany; [Behrens, Hans-Michael; Roecken, Christoph] Univ Kiel, Inst Pathol, D-24105 Kiel, Germany; [Hanoch, Tamar; Seger, Rony] Weizmann Inst Sci, Dept Biol Regulat, I-7610001 Rehovot, Israel		Burgermeister, E (corresponding author), Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Dept Med 2, D-68167 Mannheim, Germany.	elke.burgermeister@medma.uni-heidelberg.de	Röcken, Christoph/A-9239-2010; Hopf, Carsten/A-3275-2015	Röcken, Christoph/0000-0002-6989-8002; Hopf, Carsten/0000-0003-0802-6451	Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) [Ca158]; Israel's Ministry of Science, Technology and Space (MOST); DKFZ-MOST [Ca158]; Deutsche KrebshilfeDeutsche Krebshilfe [108287, 111086]; Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [BU2285]; Land Baden-Wurttemberg (ZO IV); EFRE (ZAFH ABIMAS); DFGGerman Research Foundation (DFG)European Commission [SFB 824, TP B1]; ZOBEL (Center of Geriatric Biology and Oncology); Land Baden-Wurttemberg (Perspektivforderung)	This work was supported in part by grants to EB and RS from the Cooperation Program in Cancer Research (Ca158) of the Deutsches Krebsforschungszentrum (DKFZ) and Israel's Ministry of Science, Technology and Space (MOST). MS was granted a doctoral fellowship within this program (DKFZ-MOST: Ca158). EB received additional funds from Deutsche Krebshilfe (#108287; #111086) and Deutsche Forschungsgemeinschaft (DFG) (BU2285). CH was funded by Land Baden-Wurttemberg (ZO IV) and EFRE (ZAFH ABIMAS). ME was funded by DFG (SFB 824, TP B1), ZOBEL (Center of Geriatric Biology and Oncology) and Land Baden-Wurttemberg (Perspektivforderung).	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J	Lou, J; Yang, XX; Shan, WX; Jin, Z; Ding, JH; Hu, YX; Liao, QS; Du, Q; Xie, R; Xu, JY				Lou, Jun; Yang, Xiaoxu; Shan, Weixi; Jin, Zhe; Ding, Jianhong; Hu, Yanxia; Liao, Qiushi; Du, Qian; Xie, Rui; Xu, Jingyu			Effects of calcium-permeable ion channels on various digestive diseases in the regulation of autophagy	MOLECULAR MEDICINE REPORTS			English	Review						calcium; autophagy; ion channel; calcium signaling; digestive system diseases	ENDOPLASMIC-RETICULUM STRESS; GASTRIC-CANCER; HELICOBACTER-PYLORI; COLORECTAL-CANCER; CA2+; PANCREATITIS; CARCINOMA; INHIBITION; MECHANISM; APOPTOSIS	Autophagy is a process of degradation and catabolism in cells. By removing damaged or dysfunctional organelles, autophagy interacts with the ubiquitin-proteasome degradation system to jointly regulate cell function and energy homeostasis. Since autophagy plays a key role in physiology, disorders of the autophagy mechanism are associated with various diseases. Therefore, thorough understanding of the autophagy regulatory mechanism are crucially important in the diagnosis and treatment of diseases. To date, ion channels may affect the development and treatment of diseases by regulating autophagy, especially calcium-permeable ion channels, in the process of digestive system diseases. However, the mechanism by which calcium ions and their channels regulate autophagy is still poorly understood, thus emphasizing the need for further research in this field. The present review intends to discuss the association, mechanism and application of calcium ions, their channels and autophagy in the occurrence and development of digestive system diseases.	[Lou, Jun; Yang, Xiaoxu; Shan, Weixi; Jin, Zhe; Ding, Jianhong; Hu, Yanxia; Liao, Qiushi; Du, Qian; Xie, Rui; Xu, Jingyu] Zunyi Med Univ, Affiliated Hosp, Dept Gastroenterol, 149 Dalian Rd, Zunyi 563003, Guizhou, Peoples R China		Xie, R; Xu, JY (corresponding author), Zunyi Med Univ, Affiliated Hosp, Dept Gastroenterol, 149 Dalian Rd, Zunyi 563003, Guizhou, Peoples R China.	xr19841029@aliyun.com; xujingyu_gzzy@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81970541]; Graduate Research Fund Project of Guizhou Province [(2019) 088]	This study was supported by research grants from the National Natural Science Foundation of China (grant no. 81970541 to JY); and the Graduate Research Fund Project of Guizhou Province [grant no. YJSCXJH (2019) 088 to XXY].	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Med. Rep.	SEP	2021	24	3							680	10.3892/mmr.2021.12319			11	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	TV2RI	WOS:000681572200001	34318907				2022-04-25	
J	Chen, GQ; Gong, RH; Yang, DJ; Zhang, G; Lu, AP; Yan, SC; Lin, SH; Bian, ZX				Chen, Guo-Qing; Gong, Rui-Hong; Yang, Da-Jian; Zhang, Ge; Lu, Ai-Ping; Yan, Siu-Cheong; Lin, Shu-Hai; Bian, Zhao-Xiang			Halofuginone dually regulates autophagic flux through nutrient-sensing pathways in colorectal cancer	CELL DEATH & DISEASE			English	Article							CALORIC RESTRICTION MIMETICS; KINASE ULK1; METABOLISM; MTOR; AMPK; PHOSPHORYLATION; INDUCTION; TARGETS; COMPLEX; STRESS	Autophagy has a key role in metabolism and impacts on tumorigenesis. Our previous study found that halofuginone (HF) exerts anticancer activity in colorectal cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. But whether and how HF regulates autophagy and metabolism to inhibit cancer growth remains an open question. Here, we unveil that HF activates ULK1 by downregulation of its phosphorylation site at Ser757 through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux under nutrient-rich condition. On the other hand, HF inactivates ULK1 by downregulation of its phosphorylation sites at Ser317 and Ser777 through LKB1/AMPK signaling pathway, resulting in autophagic inhibition under nutrient-poor condition. Furthermore, Atg7-dependent autophagosome formation is also induced under nutrient-rich condition or blocked in nutrient-poor environment, respectively, upon HF treatment. More interestingly, we also found that HF inhibits glycolysis under nutrient-rich condition, whereas inhibits gluconeogenesis under nutrient-poor condition in an Atg7-dependent manner, suggesting that autophagy has a pivotal role of glucose metabolism upon HF treatment. Subsequent studies showed that HF treatment retarded tumor growth in xenograft mice fed with either standard chow diet or caloric restriction through dual regulation of autophagy in vivo. Together, HF has a dual role in autophagic modulation depending on nutritional conditions for anti-CRC.	[Chen, Guo-Qing; Gong, Rui-Hong; Zhang, Ge; Lu, Ai-Ping; Lin, Shu-Hai; Bian, Zhao-Xiang] Hong Kong Baptist Univ, Sch Chinese Med, Ctr Clin Res Chinese Med, Lab Brain & Gut Res, Hong Kong, Hong Kong, Peoples R China; [Chen, Guo-Qing; Yang, Da-Jian] Chongqing Acad Chinese Mat Med, Chongqing, Peoples R China; [Yan, Siu-Cheong] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Kowloon, Hong Kong, Peoples R China; [Lin, Shu-Hai] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Tumor Microenvironm & Inflammat, Dept Biochem & Mol Cell Biol, 280 S Chongqing Rd, Shanghai 200025, Peoples R China		Lin, SH; Bian, ZX (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Tumor Microenvironm & Inflammat, Dept Biochem & Mol Cell Biol, 280 S Chongqing Rd, Shanghai 200025, Peoples R China.	slin@shsmu.edu.cn; bzxiang@hkbu.edu.hk	Zhang, Ge/K-9118-2019	Zhang, Ge/0000-0002-7807-7695; Yan, Siu-cheoong/0000-0001-7486-3069; chen, guoqing/0000-0002-3671-5257; Lin, Shuhai/0000-0002-4782-5320	Chongqing Science & Technology CommissionNatural Science Foundation Project of CQ CSTC [cstc2016jcyjA0071]; Hong Kong Research Grants Council/General Research FundHong Kong Research Grants Council [12104415]; National NaturalScience Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21377106]	This work was financially supported by Chongqing Science & Technology Commission (No. cstc2016jcyjA0071) to G-QC, Hong Kong Research Grants Council/General Research Fund (No. 12104415) to Z-X B, and the National NaturalScience Foundation of China (No. 21377106) to S-HL.	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MAY	2017	8								e2789	10.1038/cddis.2017.203			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	EW0QG	WOS:000402195700055	28492544	Green Published, gold			2022-04-25	
J	Chen, YQ; Zhu, WT; Lin, CY; Yuan, ZW; Li, ZH; Yan, PK				Chen, Yi-Qing; Zhu, Wen-Ting; Lin, Cai-Yan; Yuan, Zhong-Wen; Li, Zhen-Hua; Yan, Peng-Ke			Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer	INTERNATIONAL JOURNAL OF NANOMEDICINE			English	Article						rapamycin liposomes; 5-fluorouracil; Akt/mTOR; P53; colorectal cancer	CYTOTOXICITY; MICELLES; NANOPARTICLES; ACTIVATION; CISPLATIN; AUTOPHAGY	Background: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer. Methods: We prepared the rapamycin liposomes using the ethanol injection method. The cellular uptake and biodistribution were detected by LC-MS and in vivo imaging system. MTT assay, transwell migration experiment, flow cytometry, and Western blot analysis evaluated the antitumor effect of rapamycin liposomes in vitro. Furthermore, HCT-116 tumor-bearing mice were used to assess the therapeutic efficacy of rapamycin liposomes in vivo. Results: The prepared rapamycin liposomes had a particle size of 100 +/- 5.5 nm and with a narrow size distribution. In vitro cellular uptake experiments showed that the uptake of rapamycin liposomes by colorectal cells was higher than that of free rapamycin. Subsequently, in vivo imaging experiments also demonstrated that rapamycin liposomes exhibited higher tumor accumulation. Therefore, the ability of rapamycin liposomes to inhibit tumor proliferation, migration and to induce tumor apoptosis is superior to that of free rapamycin. We also demonstrated in vivo good antitumor efficacy of the rapamycin liposomes in HCT-116 xenograft mice. In addition, rapamycin liposomes and 5-FU can synergistically improve the efficacy of colorectal cancer via the Akt/mTOR and P53 pathways. Conclusion: Collectively, rapamycin liposomes are a potential treatment for colorectal cancer, as it not only improves rapamycin's antitumor effect but also synergistically enhances 5-FU's chemotherapy effect.	[Chen, Yi-Qing; Zhu, Wen-Ting; Lin, Cai-Yan; Yuan, Zhong-Wen; Li, Zhen-Hua; Yan, Peng-Ke] Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou 510150, Peoples R China		Yan, PK (corresponding author), Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou 510150, Peoples R China.	gysyypk@126.com		Yan, PengKe/0000-0002-8356-2986	Science and Technology Major Project Foundation of Guangzhou of Guangdong [201604020166]; Guangzhou Science and Technology Program key projects [201903010014]	This work was supported by the Science and Technology Major Project Foundation of Guangzhou of Guangdong (Grant-in-Aid 201604020166) and Guangzhou Science and Technology Program key projects (No. 201903010014).	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J. Nanomed.		2021	16						269	281		10.2147/IJN.S270939			13	Nanoscience & Nanotechnology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics; Pharmacology & Pharmacy	PR9RR	WOS:000607568400001	33469286	gold, Green Published			2022-04-25	
J	Chen, YS; Yang, Z; Deng, B; Wu, DJ; Quan, YJ; Min, ZJ				Chen, Yusheng; Yang, Zhou; Deng, Bo; Wu, Dejun; Quan, Yingjun; Min, Zhijun			Interleukin 1 beta/1RA axis in colorectal cancer regulates tumor invasion, proliferation and apoptosis via autophagy	ONCOLOGY REPORTS			English	Article						interleukin 1 beta; interleukin 1RA; autophagy; epithelial-mesenchymal transformation; colorectal cancer	GENE-EXPRESSION; INFLAMMATION; ACTIVATION; IL-6; EMT	Interleukin (IL)-1 beta is a member of the IL-1 family of proteins. IL-1 receptor antagonist (IL-1RA) is an agent that binds to the IL-1 receptor, preventing IL-1 from transmitting signals to cells. The present study aimed to identify the role of the IL-1 beta/1RA axis in epithelial-mesenchymal transition (EMT), cell invasion, migration, proliferation and clone formation in colorectal cancer (CRC) and to determine its underlying mechanisms of action. Significantly increased expression of both IL-1 beta and IL-1RA was identified in CRC patient data uploaded in The Cancer Genome Atlas database, and in tumor tissues when compared with matched control tissue. High expression of IL-1 beta was associated with an increased rate of overall survival and recurrence-free survival. Further research revealed that the IL-1 beta gene was co-expressed with the IL-1RA gene in tumors of CRC patients. It was additionally determined that recombinant human (rh)IL-1 beta suppressed autophagy as well as EMT in HCT-116 cells compared with control-treated cells, whereas rhIL-1RA exhibited the opposite effect. In addition, autophagy activator rapamycin (RAPA) rescued the inhibition of EMT in rhIL-1 beta-treated HCT-116 cells. Moreover, rhIL-1 beta inhibited cell invasion, migration, proliferation and colony-formation ability, when compared with a control treatment. Compared with a control treatment rhIL-1RA promoted cell invasion, migration, proliferation, but had no effect on clone formation ability. Furthermore, both rhIL-1RA and RAPA rescued inhibition of cell invasion, migration and clone formation ability in rhIL-1 beta-treated HCT-116 cells. RAPA, but not rhIL-1RA, rescue inhibited proliferation in rhIL-1 beta-treated HCT-116 cells compared with controls. In addition, it was confirmed that rhIL-1 beta inhibited the growth of subcutaneous xenografts in nude mice, when compared with control treatments. These results indicated that upregulation of the IL-1 beta/1RA axis in CRC regulated EMT, cell invasion and migration, proliferation and clone formation via autophagy.	[Chen, Yusheng; Yang, Zhou; Wu, Dejun; Min, Zhijun] Fudan Univ, Pudong Med Ctr, Dept Gen Surg, Shanghai Pudong Hosp, 2800 Gongwei Rd, Shanghai 201399, Peoples R China; [Deng, Bo] Shanghai Jiao Tong Univ, Div Nephrol, Shanghai Peoples Hosp 9, Sch Med, Shanghai 200011, Peoples R China; [Quan, Yingjun] Shanghai Jiao Tong Univ, Sch Med, Dept Gen Surg, Tongren Hosp, 1111 Xianxia Rd, Shanghai 200050, Peoples R China		Min, ZJ (corresponding author), Fudan Univ, Pudong Med Ctr, Dept Gen Surg, Shanghai Pudong Hosp, 2800 Gongwei Rd, Shanghai 201399, Peoples R China.; Quan, YJ (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Dept Gen Surg, Tongren Hosp, 1111 Xianxia Rd, Shanghai 200050, Peoples R China.	qyjasmine@126.com; minzhijun@126.com			Puxiu Medical Talents Training Program of Pudong Hospital [PX201702]	The present study was funded by Puxiu Medical Talents Training Program of Pudong Hospital (grant no. PX201702).	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Rep.	MAR	2020	43	3					908	918		10.3892/or.2020.7475			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	KU3CB	WOS:000519584500015	32020215	hybrid, Green Published			2022-04-25	
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Using co-immunoprecipitation and proteomic analysis, we identified some of the interacting partners of ANT in several normal tissues and human cancer cell lines. During chemotherapy-induced apoptosis, some of these interactions were constant (e g. ANT-VDAC), whereas others changed strongly concomitantly with the dissipation of the mitochondrial transmembrane potential and until nuclear degradation occurred (e.g. Bax, Bcl-2, subunits of the respiratory chain, a subunit of the phosphatase PP2A, phospholipase PLC beta 4 and IP3 receptor). In addition, a glutathione-S-transferase (GST) interacts with ANT in normal tissue, in colon carcinoma cells and in vitro. This interaction is lost during apoptosis induction, suggesting that GST behaves as an endogenous repressor of PTPC and ANT pore opening. Thus, ANT is connected to mitochondrial proteins as well as to proteins from other organelles such as the endoplasmic reticulum forming a dynamic polyprotein complex. Changes within this ANT interactome coordinate the lethal response of cells to apoptosis induction.	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J	Wu, X; Zhou, Z; Xu, S; Liao, CL; Chen, X; Li, B; Peng, JW; Li, D; Yang, LF				Wu, Xia; Zhou, Zhuan; Xu, San; Liao, Chaoliang; Chen, Xi; Li, Bo; Peng, Jinwu; Li, Dan; Yang, Lifang			Extracellular vesicle packaged LMP1-activated fibroblasts promote tumor progression via autophagy and stroma-tumor metabolism coupling	CANCER LETTERS			English	Article						Latent membrane protein 1; Extracellular vesicle; Cancer-associated fibroblast; Reverse Warburg effect; Nasopharyngeal carcinoma	CANCER-ASSOCIATED FIBROBLASTS; EPSTEIN-BARR-VIRUS; METASTATIC NICHE FORMATION; NASOPHARYNGEAL CARCINOMA; COLORECTAL-CANCER; EXOSOMES; GLYCOLYSIS; INITIATE; THERAPY; GROWTH	Several reports have demonstrated that Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1), which is transferred by extracellular vesicles (EVs) or exosomes, can promote cancer progression. However, its mechanism is still not fully understood. In the present study, we demonstrated that EV packaged LMP1 can activate normal fibroblasts (NFs) into cancer-associated fibroblasts (CAFs). The NF-kappa B p65 pathway is the key signal that promotes the activation of NFs to CAFs in nasopharyngeal carcinoma (NPC). In activated CAFs, aerobic glycolysis and autophagy were increased. Moreover, glucose uptake and lactate production were decreased, and mitochondrial activity in tumor cells was enhanced, which supported the Reverse Warburg Effect (RWE). During this process, upregulation of MCT4 in CAFs and MCT1 in tumor cells was observed. The NF-kappa B p65 pathway also plays an important role in the regulation of MCT4. Furthermore, co-culture with CAFs promoted the proliferation, migration and radiation resistance of NPC cells. And EV packaged LMP1 promoted tumor proliferation and pre-metastatic niche formation by activating CAFs in vivo. Our findings indicate that EV packaged LMP1-activated CAFs promote tumor progression via autophagy and stroma-tumor metabolism coupling.	[Wu, Xia; Zhou, Zhuan; Xu, San; Liao, Chaoliang; Yang, Lifang] Cent South Univ, Xiangya Hosp, Dept Oncol, Key Lab Carcinogenesis & Canc Invas,Minist Educ, Changsha, Peoples R China; [Wu, Xia; Zhou, Zhuan; Xu, San; Liao, Chaoliang; Yang, Lifang] Cent South Univ, Sch Basic Med Sci, Canc Res Inst, Changsha, Peoples R China; [Chen, Xi; Li, Dan] Hunan Univ, Coll Biol, Inst Mol Med & Oncol, Changsha, Peoples R China; [Li, Bo; Peng, Jinwu] Cent South Univ, Xiangya Hosp, Dept Pathol, Changsha, Peoples R China		Yang, LF (corresponding author), Cent South Univ, Xiangya Rd 110, Changsha 410078, Peoples R China.; Li, D (corresponding author), Hunan Univ, Tianma Rd 27, Changsha 410082, Peoples R China.	sw_ld@hnu.edu.cn; yanglifang@csu.edu.cn		yang, lifang/0000-0002-3012-8350	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81372182, 81672761]; Natural Science Foundation of Hunan Province, ChinaNatural Science Foundation of Hunan Province [2018JJ2545]	This work was supported by the grants from the National Natural Science Foundation of China (No. 81372182, 81672761) and the Natural Science Foundation of Hunan Province, China (2018JJ2545).	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MAY 28	2020	478						93	106		10.1016/j.canlet.2020.03.004			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	LD2MV	WOS:000525868400010	32160975				2022-04-25	
J	Xu, ZJ; Yan, YL; Qian, L; Gong, ZC				Xu, Zhijie; Yan, Yuanliang; Qian, Long; Gong, Zhicheng			Long non-coding RNAs act as regulators of cell autophagy in diseases (Review)	ONCOLOGY REPORTS			English	Review						lncRNAs; autophagy; autophagy-associated diseases; molecular mechanism; cancers	VASCULAR ENDOTHELIAL-CELLS; DOWN-REGULATION; CANCER-CELLS; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; LUNG-CANCER; MICRORNA; APOPTOSIS; PROLIFERATION; PVT1	Identification of long non-coding RNAs (lncRNAs) has provided a substantial increase in our understanding of the non-coding transcriptome. Studies have revealed a crucial function of IncRNAs in the modulation of cell autophagy in vitro and in vivo, further contributing to the hallmarks of disease phenotypes. These findings have profoundly altered our understanding of disease pathobiology, and may lead to the emergence of new biological concepts underlying autophagy-associated diseases, such as the carcinomas. Studies on the molecular mechanism of the lncRNA-autophagy axis may offer additional avenues for therapeutic intervention and biomarker assessment. In this review, we discuss recent findings on the multiple molecular roles of regulatory IncRNAs in the signaling pathways of cell autophagy. The emerging knowledge in this rapidly advancing field will offer novel insights into human diseases, especially cancers.	[Xu, Zhijie] Cent S Univ, Xiangya Hosp, Dept Pathol, Changsha 410008, Hunan, Peoples R China; [Xu, Zhijie] Cent S Univ, Sch Basic Med, Dept Pathol, Changsha 410008, Hunan, Peoples R China; [Yan, Yuanliang; Qian, Long; Gong, Zhicheng] Cent S Univ, Xiangya Hosp, Dept Pharm, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China; [Yan, Yuanliang; Qian, Long; Gong, Zhicheng] Cent S Univ, Inst Hosp Pharm, Changsha 410008, Hunan, Peoples R China		Gong, ZC (corresponding author), Cent S Univ, Xiangya Hosp, Dept Pharm, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.	gongzhicheng2013@163.com	Yan, Yuanliang/K-7149-2019	Xu, Zhijie/0000-0003-2047-883X	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572946]; Changsha Science and Technology Project [k1508024-31]; Clinical and Rehabilitation Research Foundation of Xiangya Hospital Beidaweiming	This study was supported by the National Natural Science Foundation of China (no. 81572946), the Changsha Science and Technology Project (no. k1508024-31), and the Clinical and Rehabilitation Research Foundation of Xiangya Hospital Beidaweiming.	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Rep.	MAR	2017	37	3					1359	1366		10.3892/or.2017.5416			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EN7MJ	WOS:000396186600007	28184916	Green Submitted, Green Published, hybrid			2022-04-25	
J	Feng, Y; Gao, YJ; Wang, DY; Xu, ZH; Sun, WX; Ren, P				Feng, Ye; Gao, Yongjian; Wang, Dayu; Xu, Zhonghang; Sun, Weixuan; Ren, Ping			Autophagy Inhibitor (LY294002) and 5-fluorouracil (5-FU) Combination-Based Nanoliposome for Enhanced Efficacy Against Esophageal Squamous Cell Carcinoma	NANOSCALE RESEARCH LETTERS			English	Article						Esophageal cancer; 5-fluorouracil; Autophagy inhibitor; Apoptosis; Liposome	COLORECTAL-CANCER CELLS; ANTICANCER LIPID NANOPARTICLES; DRUG-DELIVERY SYSTEMS; GROWTH-INHIBITION; SOLID TUMORS; APOPTOSIS; CLEAVAGE	In this study, 5-fluorouracil (5-FU) and LY294002 (LY)-loaded PEGylated nanoliposome was prepared to target esophageal squamous cell carcinoma (ESCC). The particles were characterized in terms of physicochemical and biological parameters. The co-delivery of autophagy inhibitor and chemotherapeutic drug in a single carrier was successfully accomplished. The two components from 5-FU and LY-loaded PEGylated nanoliposome (FLNP) released in a controlled manner with LY relatively released faster compared to that of 5-FU. FLNP showed a receptor-mediated cellular uptake that will allow the gradual release of drug in the acidic environment The cellular uptake of nanoparticles (NP) was further confirmed by FACS analysis. The combination of 5-FU and LY resulted in higher cytotoxic effect compared to that of individual drugs. Most importantly, FLNP exhibited a significantly higher anticancer effect in cancer cells compared to that of free cocktail combinations. The faster release of LY from FLNP leads to autophagy inhibition that improves the sensitivity of cancer cells towards 5-FU, resulting in more cell death. Consistently, FLNP induced a greater apoptosis (similar to 48%) of cancer cells compared to that of any other groups. Western blot analysis clearly showed that 5-FU and LY individually increased the expression of caspase-3 and PARP, while as expected FLNP induced a remarkable expression of these protein markers indicating the superior anticancer effect. We believe that the programmed release of autophagy inhibitor and chemotherapeutic drug from a single nanocarrier will increase the prospect of anticancer therapy in ESCC.	[Feng, Ye; Gao, Yongjian; Wang, Dayu; Xu, Zhonghang; Sun, Weixuan] Jilin Univ, China Japan Friendship Hosp, Dept Gastrointestinal Surg, Changchun 130033, Jilin, Peoples R China; [Ren, Ping] Jilin Univ, Dept Thorac Surg, Hosp 1, Changchun 130033, Jilin, Peoples R China		Ren, P (corresponding author), Jilin Univ, Dept Thorac Surg, Hosp 1, Changchun 130033, Jilin, Peoples R China.	zhaoke8618@126.com; pingren1962@yahoo.com			First Hospital of Jilin University, Changchun China	This study was supported from the grant of The First Hospital of Jilin University, Changchun China.	Allen TM, 2013, ADV DRUG DELIVER REV, V65, P36, DOI 10.1016/j.addr.2012.09.037; Casiano CA, 1998, CELL DEATH DIFFER, V5, P183, DOI 10.1038/sj.cdd.4400336; Chen MQ, 2014, J CHIN MED ASSOC, V77, P562, DOI 10.1016/j.jcma.2014.05.014; Grem JL, 2000, INVEST NEW DRUG, V18, P299, DOI 10.1023/A:1006416410198; Han WD, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0028491; Kumar Priyank, 2012, Cells, V1, P558, DOI 10.3390/cells1030558; Li Q, 2015, LIFE SCI, V127, P106, DOI 10.1016/j.lfs.2015.01.028; Longley DB, 2003, NAT REV CANCER, V3, P330, DOI 10.1038/nrc1074; Luo KJ, 2012, ANN THORAC SURG, V93, P1682, DOI 10.1016/j.athoracsur.2012.01.102; Meng L, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0033434; Mohan A, 2016, EUR J PHARM BIOPHARM, V99, P73, DOI 10.1016/j.ejpb.2015.11.017; Ramasamy T, 2015, CHEM COMMUN, V51, P5758, DOI 10.1039/c5cc00482a; Ramasamy T, 2017, J CONTROL RELEASE, V258, P226, DOI 10.1016/j.jconrel.2017.04.043; Ramasamy T, 2017, ACTA BIOMATER, V48, P131, DOI 10.1016/j.actbio.2016.10.034; Ramasamy T, 2014, ACTA BIOMATER, V10, P5116, DOI 10.1016/j.actbio.2014.08.021; Sheen JH, 2011, CANCER CELL, V19, P613, DOI 10.1016/j.ccr.2011.03.012; Soldani C, 2001, EXP CELL RES, V269, P193, DOI 10.1006/excr.2001.5293; Sun LL, 2015, INT J CANCER, V136, pE569, DOI 10.1002/ijc.29211; Sundaramoorthy P, 2016, ACTA BIOMATER, V42, P220, DOI 10.1016/j.actbio.2016.07.006; Sundaramoorthy P, 2015, COLLOID SURFACE B, V135, P793, DOI 10.1016/j.colsurfb.2015.08.039; Thant AA, 2008, ANTICANCER RES, V28, P3579; Tokunaga E, 2000, EUR J CANCER, V36, P1998, DOI 10.1016/S0959-8049(00)00200-8; Tong D, 2000, ORAL ONCOL, V36, P236, DOI 10.1016/S1368-8375(99)00079-2; Wilson TR, 2006, ANN ONCOL, V17, pX315, DOI 10.1093/annonc/mdl280	24	27	27	3	11	SPRINGEROPEN	LONDON	CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND	1556-276X			NANOSCALE RES LETT	Nanoscale Res. Lett.	OCT 17	2018	13								325	10.1186/s11671-018-2716-x			9	Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics; Materials Science; Physics	GX5CT	WOS:000447759800001	30328537	Green Published, gold			2022-04-25	
J	You, LJ; Geng, H; Yang, XF; Wei, GL; Zhu, YD; Ge, GB; Lei, M; Wang, DD				You, Li-Jiao; Geng, Huan; Yang, Xiao-Fang; Wei, Gui-Lin; Zhu, Ya-Di; Ge, Guang-Bo; Lei, Ming; Wang, Dan-Dan			The comparison analysis of polyphyllin I and its analogues induced apoptosis of colon and lung cancer cells via mitochondrial dysfunction	BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY			English	Article						cell apoptosis; Chonglou; comparison analysis; mitochondrial dysfunction; polyphyllin I and its analogues	ROS; AUTOPHAGY; SAPONINS	Polyphyllin I (PPI) and its analogues, including polyphyllin II (PPII), polyphyllin VI (PPVI) and polyphyllin VII (PPVII), are major bioactive compounds isolated from the Chinese herb Chonglou. However, the susceptibilities of PPI and its analogues towards the different cell lines are diversified and the mechanisms are not fully clarified. Thus, the present study aimed to investigate the cytotoxicity of PPI and its analogues on two different cell lines, as well as to explore the underlying mechanisms of these agents via inducing mitochondrial dysfunction. The results showed that PPI and its analogues were cytotoxic agents towards both A549 and HT-29 cells, with IC50 values ranged from 1.0 to 4.5 mu mol/L. Further investigations demonstrated that they decreased the mitochondrial membrane potentials of both A549 and HT-29 cells in a dose-dependent manner. Among all tested compounds, PPVI and PPI induced the most obvious changes in Ca2+ haemostasis in these two cell lines. In addition, they could induce the accumulation of ROS in cells and down-regulated the Bcl-2 expression, up-regulated the Bax expression and induced the activity of cleaved caspase-3 in cells. Collectively, our findings clearly demonstrated the cytotoxic differences and mechanisms of PPI and its analogues induced cell apoptosis and could partially explain the anticancer effects of these natural constituents in Chonglou.	[You, Li-Jiao; Geng, Huan; Yang, Xiao-Fang; Zhu, Ya-Di; Lei, Ming] Shanghai Univ TCM, Peoples Hosp 7, Shanghai 200137, Peoples R China; [You, Li-Jiao; Geng, Huan; Wei, Gui-Lin; Zhu, Ya-Di; Ge, Guang-Bo; Wang, Dan-Dan] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China		Lei, M (corresponding author), Shanghai Univ TCM, Peoples Hosp 7, Shanghai 200137, Peoples R China.; Wang, DD (corresponding author), Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China.	leiming6891@163.com; wangdandan801@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81973649, 81922070, 82073813, 81803489]; Three-year Action Plan of Shanghai TCM Development [ZY-(201-2020)-CCCX-5001]; National Key Research and Development Program of China [2020YFC0845400, 2017YFC1700200, 2017YFC1702000]; Outstanding Clinical Discipline Project of Shanghai Pudong [PWYgy201801]; Leading Medical Talent Training Program of Pudong Health Bureau of Shanghai [PWR12019-02]; National Science and Technology Major Project of China [2018ZX09731016]; Shanghai University of Traditional Chinese Medicine "Postgraduate Innovation Training Project" [Y2021022]	National Natural Science Foundation of China, Grant/Award Number: 81973649, 81922070, 82073813 and 81803489; Three-year Action Plan of Shanghai TCM Development, Grant/Award Number: ZY-(201-2020)-CCCX-5001; National Key Research and Development Program of China, Grant/Award Number: 2020YFC0845400, 2017YFC1700200 and 2017YFC1702000; Outstanding Clinical Discipline Project of Shanghai Pudong, Grant/Award Number: PWYgy201801; Leading Medical Talent Training Program of Pudong Health Bureau of Shanghai, Grant/Award Number: PWR12019-02; National Science and Technology Major Project of China, Grant/Award Number: 2018ZX09731016; Shanghai University of Traditional Chinese Medicine "Postgraduate Innovation Training Project", Grant/Award Number: Y2021022	Amoedo ND, 2014, INT J BIOCHEM CELL B, V51, P53, DOI 10.1016/j.biocel.2014.03.009; Bagkos G, 2014, MED HYPOTHESES, V83, P175, DOI 10.1016/j.mehy.2014.05.001; Banjara S, 2020, BIOMOLECULES, V10, DOI 10.3390/biom10010128; Chang JL, 2015, J ETHNOPHARMACOL, V170, P117, DOI 10.1016/j.jep.2015.05.006; Chen J, 2020, BIOMED RES INT, V2020, DOI 10.1155/2020/2328401; Deng XH, 2020, INT J BIOL SCI, V16, P1403, DOI 10.7150/ijbs.41768; Escobar ML, 2019, J HISTOCHEM CYTOCHEM, V67, P873, DOI 10.1369/0022155419881127; Fitzmaurice C, 2019, JAMA ONCOL, V5, P1749, DOI 10.1001/jamaoncol.2019.2996; Gu LH, 2016, ONCOL LETT, V12, P4969, DOI 10.3892/ol.2016.5348; Han WH, 2015, INT J CLIN EXP MED, V8, P20664; Jiang SY, 2019, INT J ONCOL, V54, P1933, DOI 10.3892/ijo.2019.4785; Lee BZ, 2020, J MICROBIOL BIOTECHN, V30, P1214, DOI 10.4014/jmb.2006.06022; Lin LT, 2019, MOLECULES, V24, DOI 10.3390/molecules24112102; Liu GB, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18020367; Long J., 2020, BIOMED RES INT, V2020, P1; Luo QH, 2018, BIOMED RES INT, V2018, DOI 10.1155/2018/5241941; Manouchehri N, 2019, IRAN J PHARM RES, V18, P1445, DOI 10.22037/ijpr.2019.1100711; NavaneethaKrishnan S, 2020, ONCOGENE, V39, P2797, DOI 10.1038/s41388-020-1188-5; Pang DJ, 2020, BIOL OPEN, V9, DOI 10.1242/bio.046854; Park J, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21176229; Perrone M, 2020, INT REV CEL MOL BIO, V350, P119, DOI 10.1016/bs.ircmb.2019.11.002; Ramadan MA, 2019, CYTOTECHNOLOGY, V71, P461, DOI 10.1007/s10616-018-0287-4; Salehi F, 2020, INT J BIOL MACROMOL, V164, P3645, DOI 10.1016/j.ijbiomac.2020.08.084; Salimi A, 2015, REDOX BIOL, V6, P461, DOI 10.1016/j.redox.2015.08.021; Siu FM, 2008, PROTEOMICS, V8, P3105, DOI 10.1002/pmic.200700829; Sola-Riera C, 2020, PLOS PATHOG, V16, DOI 10.1371/journal.ppat.1008297; Teng JF, 2020, CANCERS, V12, DOI 10.3390/cancers12010193; Tveden-Nyborg P, 2021, BASIC CLIN PHARMACOL, V128, P4, DOI 10.1111/bcpt.13492; Vandamme M, 2012, INT J CANCER, V130, P2185, DOI 10.1002/ijc.26252; Wang WP, 2019, J CELL PHYSIOL, V234, P7078, DOI 10.1002/jcp.27462; Xu XH, 2016, MOLECULES, V21, DOI 10.3390/molecules21101326; Yan Y., 2019, ONCOL REP, V41, P3005; Yuan YL, 2019, DRUG DES DEV THER, V13, P3091, DOI 10.2147/DDDT.S194961; Zhang Denglu, 2018, Curr Urol, V11, P144, DOI 10.1159/000447209; Zhang J, 2015, MED SCI MONITOR, V21, P2535, DOI 10.12659/MSM.895084; Zhou L, 2020, BMC MUSCULOSKEL DIS, V21, DOI 10.1186/s12891-020-3077-z; Zorov DB, 2014, PHYSIOL REV, V94, P909, DOI 10.1152/physrev.00026.2013	37	1	1	2	5	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1742-7835	1742-7843		BASIC CLIN PHARMACOL	Basic Clin. Pharmacol. Toxicol.	JUL	2021	129	1					15	25		10.1111/bcpt.13596		MAY 2021	11	Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy; Toxicology	SP1VJ	WOS:000649975500001	33915023				2022-04-25	
J	Lorente, J; Velandia, C; Leal, JA; Garcia-Mayea, Y; Lyakhovich, A; Kondoh, H; LLeonart, ME				Lorente, Juan; Velandia, Carolina; Leal, Jose A.; Garcia-Mayea, Yoelsis; Lyakhovich, Alex; Kondoh, Hiroshi; LLeonart, Matilde E.			The interplay between autophagy and tumorigenesis: exploiting autophagy as a means of anticancer therapy	BIOLOGICAL REVIEWS			English	Review						autophagy; cancer; cancer stem cells; oxidative stress; therapy	UNFOLDED PROTEIN RESPONSE; CANCER-CELLS; INDUCED APOPTOSIS; MITOCHONDRIAL DYSFUNCTION; COLORECTAL-CANCER; ATG PROTEINS; INHIBITION; METABOLISM; SURVIVAL; TUMORS	In wild-type cells, autophagy represents a tumour-suppressor mechanism, and dysfunction of the autophagy machinery increases genomic instability, DNA damage, oxidative stress and stem/progenitor expansion, which are events associated with cancer onset. Autophagy occurs at a basal level in all cells depending on cell type and cellular microenvironment. However, the role of autophagy in cancer is diverse and can promote different outcomes even in a single tumour. For example, in hypoxic tumour regions, autophagy emerges as a protective mechanism and allows cancer cell survival. By contrast, in cancer cells surrounding the tumour mass, the induction of autophagy by radio- or chemotherapy promotes cell death and significantly reduces the tumour mass. Importantly, inhibition of autophagy compromises tumorigenesis by mechanisms that are not entirely understood. The aim of this review is to explain the apparently contradictory role of autophagy as a mechanism that both promotes and inhibits tumorigenesis using different models. The induction/inhibition of autophagy as a mechanism for cancer treatment is also discussed.	[Lorente, Juan; Velandia, Carolina; Leal, Jose A.; Garcia-Mayea, Yoelsis; Lyakhovich, Alex; LLeonart, Matilde E.] Vall dHebron Hosp, Pathol Dept, Biomed Res Canc Stem Cell Grp, Barcelona 08035, Spain; [Lorente, Juan; Velandia, Carolina] Vall dHebron Hosp, Otolaryngol Dept, Barcelona 08035, Spain; [Kondoh, Hiroshi] Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Kyoto 6068507, Japan		LLeonart, ME (corresponding author), Vall dHebron Hosp, Pathol Dept, Biomed Res Canc Stem Cell Grp, Barcelona 08035, Spain.	matilde.lleonart@vhir.org	LLeonart, Matilde E./Q-2662-2019; Mayea, Yoelsis Garcia/AAI-5845-2021; Lyakhovich, Alex/B-4410-2008	LLeonart, Matilde E./0000-0002-6196-7405; Mayea, Yoelsis Garcia/0000-0002-9395-7471; Lyakhovich, Alex/0000-0002-8279-4697	Instituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Commission [PI12/01104, PI15/01262]; European Regional Development Fund (ERDF)European Commission; Marie Curie - COFUND program, Spain [INCOMED - GA 267128]; Vall d'Hebron Institut de Recerca (VHIR)	This work was supported by grants from the Instituto de Salud Carlos III (grant PI12/01104 and PI15/01262 (M.E.LL.) cofinanced by the European Regional Development Fund (ERDF). M.E.LL. is a FIS investigator (Instituto de Salud Carlos III, ref. CP03/00101). A.L. received support from the Marie Curie - COFUND program (INCOMED - GA 267128), Spain. Y.G.-M. is funded by a Vall d'Hebron Institut de Recerca (VHIR), fellowship.	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Rev.	FEB	2018	93	1					152	165		10.1111/brv.12337			14	Biology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics	FS7GK	WOS:000419965700008	28464404				2022-04-25	
J	Zhu, Y; Huang, SM; Chen, SY; Chen, JX; Wang, ZQ; Wang, YD; Zheng, HX				Zhu, Yin; Huang, Shimiao; Chen, Shengyuan; Chen, Jiaxuan; Wang, Zhiqing; Wang, Yadong; Zheng, Haoxuan			SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial-mesenchymal transition by beta-catenin and Beclin1/autophagy signaling in colorectal cancer	CELL DEATH & DISEASE			English	Article							MULTIDRUG-RESISTANCE; INITIATING CELLS; CHROMOSOME 17Q; AUTOPHAGY; METASTASIS; EXPRESSION; PATHWAY; ACTIVATION; SUPPRESSION; PROGRESSION	Sex-determining region Y-box2 (SOX2), a master regulator of embryonic and induced pluripotent stem cells, drives cancer stem cells (CSCs) properties, fuels tumor initiation, and contributes to tumor aggressiveness. Our previous study has demonstrated the oncogenic role of SOX2 in colorectal cancer (CRC). In this study, we sought to elucidate the underlying mechanisms. Cell function experiments were performed to detect chemoresistance, proliferation, stemness, migration, and invasion in vitro. Chromatin immunoprecipitation, co-immunoprecipitation, luciferase reporter assay, and immunofluorescence were performed to explore the regulation of ABCC2, beta-catenin, and Beclin1 by SOX2. The carcinogenic role of SOX2-beta-catenin/Beclin1-ABCC2 axis in vivo was analyzed by CRC tissues and xenograft models. Here, we reported that SOX2 sustained chemoresistance by transcriptional activation of ABCC2 expression. Suppressing either beta-catenin or autophagy signaling curbed SOX2-driven chemoresistance, stemness, and epithelial-mesenchymal transition (EMT). Mechanistically, SOX2 combined with beta-catenin and increased its nuclear expression and transcriptional activity. Transcriptional activation of Beclin1 expression by SOX2 consequently activating autophagy and inducing malignant phenotype. Furthermore, overexpression of beta-catenin or Beclin1 facilitated ABCC2 expression. The clinical analyses showed that high expression of ABCC2 and Beclin1 were positively correlated with SOX2 and were associated with poor prognosis in CRC patients. Finally, xenograft models revealed that inhibition of SOX2 expression and autophagy restrained tumor growth and chemoresistance in vivo. Conclusively, we demonstrated a novel mechanism by which the SOX2-beta-catenin/Beclin1/autophagy signaling axis regulates chemoresistance, stemness, and EMT in CRC. Our findings provide novel insights into CRC carcinogenesis and may help develop potential therapeutic candidates for CRC.	[Zhu, Yin; Huang, Shimiao; Chen, Shengyuan; Chen, Jiaxuan; Wang, Zhiqing; Wang, Yadong; Zheng, Haoxuan] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou, Peoples R China		Zheng, HX (corresponding author), Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou, Peoples R China.	haoxuan.zheng@qq.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773191]; National Major New Drug Creation Science and Technology Major Special Fund Funding Project [2020ZX09201017]; Guangdong Gastrointestinal Disease Research Center [2017B020209003]	The present work was supported by the National Natural Science Foundation of China (No. 81773191), National Major New Drug Creation Science and Technology Major Special Fund Funding Project (No. 2020ZX09201017), and Guangdong Gastrointestinal Disease Research Center (No. 2017B020209003).	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MAY 5	2021	12	5							449	10.1038/s41419-021-03733-5			16	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	SK5HZ	WOS:000656247600003	33953166	gold, Green Published			2022-04-25	
J	Raufi, AG; Liguori, NR; Carlsen, L; Parker, C; Borrero, LH; Zhang, SL; Tian, XB; Louie, A; Zhou, LL; Seyhan, AA; El-Deiry, WS				Raufi, Alexander G.; Liguori, Nicholas R.; Carlsen, Lindsey; Parker, Cassandra; Hernandez Borrero, Liz; Zhang, Shengliang; Tian, Xiaobing; Louie, Anna; Zhou, Lanlan; Seyhan, Attila A.; El-Deiry, Wafik S.			Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma	FRONTIERS IN PHARMACOLOGY			English	Review						autophagy; pancreatic cancer; MEK inhibitors; ONC212; chloroquine; Atg5; LC3; beclin 1	ENDOPLASMIC-RETICULUM STRESS; HYPOXIA-INDUCIBLE FACTOR; SMALL-MOLECULE NSC59984; COLORECTAL-CANCER; CELL-SURVIVAL; RESTORES P53; ER STRESS; TRANSLATIONAL CONTROL; ANTITUMOR-ACTIVITY; KINASE ULK1	Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by early metastasis, late detection, and poor prognosis. Progress towards effective therapy has been slow despite significant efforts. Novel treatment approaches are desperately needed and autophagy, an evolutionary conserved process through which proteins and organelles are recycled for use as alternative energy sources, may represent one such target. Although incompletely understood, there is growing evidence suggesting that autophagy may play a role in PDAC carcinogenesis, metastasis, and survival. Early clinical trials involving autophagy inhibiting agents, either alone or in combination with chemotherapy, have been disappointing. Recently, evidence has demonstrated synergy between the MAPK pathway and autophagy inhibitors in PDAC, suggesting a promising therapeutic intervention. In addition, novel agents, such as ONC212, have preclinical activity in pancreatic cancer, in part through autophagy inhibition. We discuss autophagy in PDAC tumorigenesis, metabolism, modulation of the immune response, and preclinical and clinical data with selected autophagy modulators as therapeutics.	[Raufi, Alexander G.; Liguori, Nicholas R.; Carlsen, Lindsey; Parker, Cassandra; Hernandez Borrero, Liz; Zhang, Shengliang; Tian, Xiaobing; Louie, Anna; Zhou, Lanlan; Seyhan, Attila A.; El-Deiry, Wafik S.] Brown Univ, Warren Alpert Med Sch, Lab Translat Oncol & Expt Canc Therapeut, Providence, RI 02912 USA; [Raufi, Alexander G.; El-Deiry, Wafik S.] Lifespan Hlth Syst & Brown Univ, Dept Med, Div Hematol Oncol, Providence, RI 02912 USA; [Raufi, Alexander G.; Carlsen, Lindsey; Zhang, Shengliang; Tian, Xiaobing; Zhou, Lanlan; Seyhan, Attila A.; El-Deiry, Wafik S.] Lifespan Hlth Syst & Brown Univ, Joint Program Canc Biol, Providence, RI 02912 USA; [Raufi, Alexander G.; Carlsen, Lindsey; Zhang, Shengliang; Tian, Xiaobing; Zhou, Lanlan; Seyhan, Attila A.; El-Deiry, Wafik S.] Brown Univ, Ctr Canc, Providence, RI 02912 USA; [Liguori, Nicholas R.] Temple Univ, Lewis Katz Sch Med, Philadelphia, PA 19122 USA; [Carlsen, Lindsey; Hernandez Borrero, Liz; El-Deiry, Wafik S.] Brown Univ, Pathobiol Grad Program, Warren Alpert Med Sch, Providence, RI 02912 USA; [Parker, Cassandra; Louie, Anna] Brown Univ, Dept Surg, Warren Alpert Med Sch, Providence, RI 02912 USA; [Zhang, Shengliang; Tian, Xiaobing; Zhou, Lanlan; Seyhan, Attila A.; El-Deiry, Wafik S.] Brown Univ, Dept Pathol & Lab Med, Warren Alpert Med Sch, Providence, RI 02912 USA		Raufi, AG; El-Deiry, WS (corresponding author), Brown Univ, Warren Alpert Med Sch, Lab Translat Oncol & Expt Canc Therapeut, Providence, RI 02912 USA.; Raufi, AG; El-Deiry, WS (corresponding author), Lifespan Hlth Syst & Brown Univ, Dept Med, Div Hematol Oncol, Providence, RI 02912 USA.; Raufi, AG; El-Deiry, WS (corresponding author), Lifespan Hlth Syst & Brown Univ, Joint Program Canc Biol, Providence, RI 02912 USA.; Raufi, AG; El-Deiry, WS (corresponding author), Brown Univ, Ctr Canc, Providence, RI 02912 USA.; El-Deiry, WS (corresponding author), Brown Univ, Pathobiol Grad Program, Warren Alpert Med Sch, Providence, RI 02912 USA.; El-Deiry, WS (corresponding author), Brown Univ, Dept Pathol & Lab Med, Warren Alpert Med Sch, Providence, RI 02912 USA.	wafik@brown.edu; 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Pharmacol.	NOV 30	2021	12								751568	10.3389/fphar.2021.751568			16	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	XO0ZK	WOS:000729923200001	34916936	gold, Green Published			2022-04-25	
J	Wang, L; Mai, ZH; Zhao, MX; Wang, B; Yu, S; Wang, XP; Chen, TS				Wang, Lu; Mai, Zihao; Zhao, Mengxin; Wang, Bin; Yu, Si; Wang, Xiaoping; Chen, Tongsheng			Aspirin induces oncosis in tumor cells	APOPTOSIS			English	Article						Aspirin; Oncosis; Bcl-XL; ATP depletion; Caspase-3	MITOCHONDRIAL PERMEABILITY TRANSITION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MEDIATED INTRINSIC PATHWAY; COLON-CANCER; INDUCED APOPTOSIS; CONTROLLED-TRIAL; NECROSIS; ACETAMINOPHEN; ACTIVATION; PREVENTION	In contrast to the well-known anti-tumor mechanisms of aspirin in inducing apoptosis or autophagy, we here for the first time report oncosis induced by aspirin in tumor cells. In vitro and in vivo analysis showed that aspirin induced compromised Bcl-XL level and subsequent ATP depletion. Overexpression of CFP-Bcl-XL in Hela and A549 cells observably inhibited aspirin-induced ATP depletion and almost completely inhibited the aspirin-induced cells bubbling, while pharmacological inhibition of endogenous Bcl-XL activity by ABT-737 remarkably promoted aspirin-induced ATP depletion and cells bubbling, suggesting the key inhibitory role of Bcl-XL in aspirin-induced oncosis. Overexpression of Bax/Bad significantly promoted aspirin-induced oncosis. In addition, cells cultured in a glucose-free medium with low ATP level exhibited higher percentage of bubbling cells than the cells cultured in a glucose medium with high ATP level under aspirin treatment, indicating the important role of ATP depletion in aspirin-induced oncosis. Furthermore, caspase-3 was demonstrated to be not involved in aspirin-induced oncosis. Animal studies showed that aspirin treatment significantly inhibited tumors growth, but did not induce toxicities to mice. Collectively, aspirin inhibits tumors growth in mice and induces oncosis in which the compromised Bcl-XL and intracellular ATP depletion play a dominant role, which provides insights into the therapeutic strategy of aspirin in oncology.	[Wang, Lu; Mai, Zihao; Wang, Bin; Yu, Si; Chen, Tongsheng] South China Normal Univ, MOE Key Lab Laser Life Sci, Guangzhou 510631, Guangdong, Peoples R China; [Wang, Lu; Mai, Zihao; Wang, Bin; Yu, Si; Chen, Tongsheng] South China Normal Univ, Coll Biophoton, Guangzhou 510631, Guangdong, Peoples R China; [Zhao, Mengxin; Wang, Xiaoping] Jinan Univ, Affiliated Hosp 1, Dept Pain Management, Guangzhou 5610632, Guangdong, Peoples R China		Chen, TS (corresponding author), South China Normal Univ, MOE Key Lab Laser Life Sci, Guangzhou 510631, Guangdong, Peoples R China.; Chen, TS (corresponding author), South China Normal Univ, Coll Biophoton, Guangzhou 510631, Guangdong, Peoples R China.; Wang, XP (corresponding author), Jinan Univ, Affiliated Hosp 1, Dept Pain Management, Guangzhou 5610632, Guangdong, Peoples R China.	txp2938@jnu.edu.cn; chentsh@scnu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [61875056, 61527825, 81572184]	This work was supported by the National Natural Science Foundation of China (Grant Nos. 61875056, 61527825 and 81572184).	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J	Yang, HZ; Ma, Y; Zhou, Y; Xu, LM; Chen, XJ; Ding, WB; Zou, HB				Yang, Hao-Zheng; Ma, Yi; Zhou, Yan; Xu, Long-Mei; Chen, Xiao-Jing; Ding, Wen-Bin; Zou, Han-Bing			Autophagy contributes to the enrichment and survival of colorectal cancer stem cells under oxaliplatin treatment	CANCER LETTERS			English	Article						Colorectal cancer; Autophagy; Cancer stem cells; Chemoresistance	INITIATING CELLS; INHIBITION; MAINTENANCE; PROMOTES; INDUCTION; VIABILITY; PATHWAY; CD44	Currently, chemoresistance is an important cause of treatment failure in colorectal cancer. Cancer stem cells, which are a population of multi-potent cells with the capacity to self-renew and differentiate, have been found to participate in chemoresistance. In the present study, the chemotherapeutic drug oxaliplatin induced autophagy in colorectal cancer cell lines, which in turn protected cancer cells from apoptosis. Further results showed that oxaliplatin-induced autophagy enriched the population of colorectal CSCs and participated in maintaining the sternness of colorectal CSCs, thus making the cells more resistant to chemotherapy. Taken together, the results indicate that autophagy might enhance the chemoresistance of colorectal cancer cells by protecting the stemness and chemoresistance of colorectal CSCs. Our study demonstrates that autophagy plays a pro-survival role in colorectal CSCs subjected to oxaliplatin. Therefore, targeting autophagy may be considered as a potential therapeutic strategy to address chemoresistance in the treatment of colorectal cancer. (C) 2015 Elsevier Ireland Ltd. All rights reserved.	[Yang, Hao-Zheng; Zhou, Yan; Xu, Long-Mei; Chen, Xiao-Jing; Ding, Wen-Bin; Zou, Han-Bing] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Cent Lab, Shanghai 200127, Peoples R China; [Ma, Yi] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Biobank, Shanghai 200127, Peoples R China		Ding, WB (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Cent Lab, Shanghai 200127, Peoples R China.	wbding@shsmu.edu.cn; coolice0917@163.com			Science and Technology Commission of Shanghai Municipality and Renji hospital [124119a1300, 12DZ2295005]; Shanghai JiaoTong University School of Medicine [RJZZ14-009]	This work was supported by the Science and Technology Commission of Shanghai Municipality (124119a1300; 12DZ2295005) and Renji hospital, Shanghai JiaoTong University School of Medicine (RJZZ14-009).	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MAY 28	2015	361	1					128	136		10.1016/j.canlet.2015.02.045			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CF6OH	WOS:000352675500016	25749420				2022-04-25	
J	de Oliveira, MR; Nabavi, SF; Nabavi, SM; Jardim, FR				de Oliveira, Marcos Roberto; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Jardim, Fernanda Rafaela			Omega-3 polyunsaturated fatty acids and mitochondria, back to the future	TRENDS IN FOOD SCIENCE & TECHNOLOGY			English	Review						Omega-3 fatty acids; Mitochondria; Antioxidant; Apoptosis; Mitochondrial biogenesis	COLON-CANCER CELLS; ENDOPLASMIC-RETICULUM STRESS; ACTIVATED PROTEIN-KINASES; ALPHA-LINOLENIC ACID; DOCOSAHEXAENOIC ACID; EICOSAPENTAENOIC ACID; OXIDATIVE STRESS; INDUCED APOPTOSIS; FISH-OIL; CYTOCHROME-C	Background: Mitochondrion, a double-membrane bound organelle, plays a critical role in eukaryotic cells energy production. Further to its role as ATP-producing factory, mitochondrion has distinct role in a number of cellular functions including calcium and redox signaling, apoptosis, and autophagy. Extensive studies showed the crucial role of mitochondrial dysfunction in pathophysiology of different diseases such as cardiovascular diseases, neurodegenerative diseases, among others. Recently extensive evidences report the promising effects of omega-3 polyunsaturated fatty acids on mitochondrial structure and functions as well as mitochondrial diseases. Scope and approach: In this paper, we critically review the available evidences on beneficial role of omega-3 polyunsaturated fatty acids on mitochondrial dynamic and biogenesis. We also discuss about chemistry, source, and bioavailability of omega-3 polyunsaturated fatty acids. Key findings and conclusions: These findings lead to an upsurge of interest in finding a new effective therapeutic strategy based on targeting mitochondrial dysfunction for above-mentioned diseases. Recently, a great body of evidences obtained from experimental studies shows the promising role of omega-3 polyunsaturated fatty acids on mitochondrial function and dynamics. Different clinical trials have also addressed the promising role of omega-3 polyunsaturated fatty acids on different disease and these facts may be related to its favorable effects on mitochondria. (C) 2017 Elsevier Ltd. All rights reserved.	[de Oliveira, Marcos Roberto] Fed Univ Mato Grosso UFMT, Dept Chem, ICET, Ave Fernando Correa da Costa 2367, BR-78060900 Cuiaba, MT, Brazil; [Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad] Baqiyatallah Univ Med Sci, Appl Biotechnol Res Ctr, POB 19395-5487, Tehran, Iran; [Jardim, Fernanda Rafaela] Forens Inst, IGP, Dept Pericias Labs, Forens Toxicol Div,Postmortem Toxicol Sect, Ave Ipiranga 1807, BR-90160093 Porto Alegre, RS, Brazil		de Oliveira, MR (corresponding author), Fed Univ Mato Grosso UFMT, Dept Chem, ICET, Ave Fernando Correa da Costa 2367, BR-78060900 Cuiaba, MT, Brazil.; Nabavi, SM (corresponding author), Baqiyatallah Univ Med Sci, Appl Biotechnol Res Ctr, POB 19395-5487, Tehran, Iran.	mrobioq@yahoo.com.br; Nabavi208@gmail.com	Nabavi, Seyed Mohammad/G-5335-2010; Nabavi, Seyed Fazel/A-2223-2010; de Oliveira, Marcos Roberto/D-7470-2015	Nabavi, Seyed Mohammad/0000-0001-8859-5675; de Oliveira, Marcos Roberto/0000-0003-2414-6605			Agrawal R, 2014, BBA-MOL BASIS DIS, V1842, P535, DOI 10.1016/j.bbadis.2013.12.004; Anderson BM, 2009, LIPIDS HEALTH DIS, V8, DOI 10.1186/1476-511X-8-33; Arita K, 2001, BIOCHEM PHARMACOL, V62, P821, DOI 10.1016/S0006-2952(01)00723-7; Arterburn LM, 2006, AM J CLIN NUTR, V83, p1467S, DOI 10.1093/ajcn/83.6.1467S; Ascenzi P, 2015, IUBMB LIFE, V67, P98, DOI 10.1002/iub.1350; Atamna H, 2012, BIOFACTORS, V38, P158, DOI 10.1002/biof.197; Barrow CJ, 2009, J FUNCT FOOD, V1, P38, DOI 10.1016/j.jff.2008.09.006; Bays HE, 2007, AM J CARDIOL, V99, p35C, DOI 10.1016/j.amjcard.2006.11.020; BELURY MA, 1995, NUTR REV, V53, P83; Berbusse GW, 2016, FRONT CELL NEUROSCI, V10, DOI 10.3389/fncel.2016.00179; Birben E, 2012, WORLD ALLERGY ORGAN, V5, P9, DOI 10.1097/WOX.0b013e3182439613; Bo L, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0152216; Bourre J M, 2004, J Nutr Health Aging, V8, P163; Brenna JT, 2009, PROSTAG LEUKOTR ESS, V80, P85, DOI 10.1016/j.plefa.2009.01.004; Brown GC, 2003, MOL NEUROBIOL, V27, P325, DOI 10.1385/MN:27:3:325; Bu JY, 2016, OXID MED CELL LONGEV, V2016, DOI 10.1155/2016/6906712; Burdge GC, 2005, REPROD NUTR DEV, V45, P581, DOI 10.1051/rnd:2005047; Cadet JL, 2005, NEUROTOX RES, V8, P199, DOI 10.1007/BF03033973; Calabrese V, 2001, NEUROCHEM RES, V26, P739, DOI 10.1023/A:1010955807739; Calder PC, 2013, BRIT J CLIN PHARMACO, V75, P645, DOI 10.1111/j.1365-2125.2012.04374.x; Cameron RB, 2016, J MED CHEM, V59, P10411, DOI 10.1021/acs.jmedchem.6b00669; Candas D, 2014, ANTIOXID REDOX SIGN, V20, P1599, DOI 10.1089/ars.2013.5305; Cansell M, 2003, LIPIDS, V38, P551, DOI 10.1007/s11745-003-1341-0; Cao J, 2006, CLIN CHEM, V52, P2265, DOI 10.1373/clinchem.2006.072322; Capo X, 2015, EUR J NUTR, V54, P35, DOI 10.1007/s00394-014-0683-2; Casanova E, 2014, J NUTR BIOCHEM, V25, P1003, DOI 10.1016/j.jnutbio.2014.05.003; Casanova E, 2014, BBA-BIOENERGETICS, V1837, P783, DOI 10.1016/j.bbabio.2014.01.014; Cavaliere G, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0149033; Cederbaum AI, 2001, FREE RADICAL BIO MED, V31, P1539, DOI 10.1016/S0891-5849(01)00743-2; Chen Q, 1997, J BIOL CHEM, V272, P14532, DOI 10.1074/jbc.272.23.14532; Chen Y, 2014, BIOCATAL AGR BIOTECH, V3, P38, DOI 10.1016/j.bcab.2013.08.007; Chenevier-Gobeaux C, 2006, INFLAMM RES, V55, P483, DOI 10.1007/s00011-006-6036-8; Cicero AFG, 2009, CURR VASC PHARMACOL, V7, P330, DOI 10.2174/157016109788340659; Cieslik M, 2013, NEUROCHEM INT, V62, P626, DOI 10.1016/j.neuint.2013.02.016; Collins ML, 2014, FOOD CHEM TOXICOL, V72, P162, DOI 10.1016/j.fct.2014.07.021; Colquhoun A, 2001, CELL BIOCHEM FUNCT, V19, P97, DOI 10.1002/cbf.902; Colquhoun A, 2001, BBA-MOL CELL BIOL L, V1533, P207, DOI 10.1016/S1388-1981(01)00136-6; Colquhoun A, 2009, J UROLOGY, V181, P1885, DOI 10.1016/j.juro.2008.11.092; Cortie CH, 2012, INT J MOL SCI, V13, P15447, DOI 10.3390/ijms131115447; Crane FL, 2008, BIOFACTORS, V32, P5, DOI 10.1002/biof.5520320102; Crnkovic S, 2012, FREE RADICAL BIO MED, V52, P1786, DOI 10.1016/j.freeradbiomed.2012.02.036; Cui ZG, 2014, CHEM-BIOL INTERACT, V215, P46, DOI 10.1016/j.cbi.2014.03.005; Dabkowski ER, 2013, CARDIOVASC DRUG THER, V27, P499, DOI 10.1007/s10557-013-6487-4; Davidson MH, 2013, CURR OPIN LIPIDOL, V24, P467, DOI 10.1097/MOL.0000000000000019; de Oliveira M. 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J	Foth, M; McMahon, M				Foth, Mona; McMahon, Martin			Autophagy Inhibition in BRAF-Driven Cancers	CANCERS			English	Review						BRAF; MEK1; 2; autophagy; targeted therapy; drug resistance; metabolism	ENDOPLASMIC-RETICULUM STRESS; MUTANT COLORECTAL-CANCER; ADVANCED SOLID TUMORS; PHASE-I TRIAL; ACQUIRED-RESISTANCE; MELANOMA-CELLS; ONCOGENIC KRAS; MAPK PATHWAY; RAG GTPASES; BRAF(V600E) INHIBITION	Simple Summary BRAF is a protein kinase that is frequently mutationally activated in cancer. Mutant BRAF can be pharmacologically inhibited, which in combination with blockade of its direct effector, MEK1/2, is an FDA-approved therapeutic strategy for several BRAF-mutated cancer patients, such as melanoma, non-small-cell lung carcinoma, and thyroid cancer. However, therapy resistance is a major clinical challenge, highlighting the need for comprehensive investigations on the biological causes of such resistance, as well as to develop novel therapeutic strategies to improve patient survival. Autophagy is a cellular recycling process, which has been shown to allow cancer cells to escape from BRAF inhibition. Combined blockade of autophagy and BRAF signaling is a novel therapeutic strategy that is currently being tested in clinical trials. This review describes the relationship between BRAF-targeted therapy and autophagy regulation and discusses possible future treatment strategies. Several BRAF-driven cancers, including advanced BRAF(V600E/K)-driven melanoma, non-small-cell lung carcinoma, and thyroid cancer, are currently treated using first-line inhibitor combinations of BRAF(V600E) plus MEK1/2. However, despite the success of this vertical inhibition strategy, the durability of patient response is often limited by the phenomenon of primary or acquired drug resistance. It has recently been shown that autophagy, a conserved cellular recycling process, is increased in BRAF-driven melanoma upon inhibition of BRAF(V600E) signaling. Autophagy is believed to promote tumor progression of established tumors and also to protect cancer cells from the cytotoxic effects of chemotherapy. To this end, BRAF inhibitor (BRAFi)-resistant cells often display increased autophagy compared to responsive lines. Several mechanisms have been proposed for BRAFi-induced autophagy, such as activation of the endoplasmic reticulum (ER) stress gatekeeper GRP78, AMP-activated protein kinase, and transcriptional regulation of the autophagy regulating transcription factors TFEB and TFE3 via ERK1/2 or mTOR inhibition. This review describes the relationship between BRAF-targeted therapy and autophagy regulation, and discusses possible future treatment strategies of combined inhibition of oncogenic signaling plus autophagy for BRAF-driven cancers.	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J	Filfan, M; Sandu, RE; Zavaleanu, AD; Gresita, A; Glavan, DG; Olaru, DG; Popa-Wagner, A				Filfan, Madalina; Sandu, Raluca Elena; Zavaleanu, Alexandra-Daniela; Gresita, Andrei; Glavan, Daniela-Gabriela; Olaru, Denissa-Greta; Popa-Wagner, Aurel			Autophagy in aging and disease	ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY			English	Review						autophagy; aging; polyamines; neurodegenerative diseases; cancer	HEPATITIS-C VIRUS; UNFOLDED PROTEIN RESPONSE; CELL-DEATH; MAMMALIAN AUTOPHAGY; OXIDATIVE STRESS; SELF-DIGESTION; LIFE-SPAN; SPERMIDINE; APOPTOSIS; INDUCTION	Autophagy is a catabolic degradation system used to destroy and recycle the unnecessary or damaged components of a cell. Autophagy is present at a basal level in all mammals and is regulated by some conditions, such as oxidative stress, starvation or hypoxia. In aged tissues, increased but also decreased expression of autophagy-specific proteins, Beclin 1, LC3, Atg5 and Atg7 has been reported. Likewise, it could be shown that the lifespan of yeast, nematodes and flies is prolonged by pharmacologically stimulated autophagy using exogenous administered spermidine. Autophagy is potentially implicated in acute lung injury and sepsis, two main causes of morbidity and mortality worldwide. Finally, a quite recent study supports the hypothesis that autophagy might be useful in vascular disease prevention by stimulating cholesterol efflux, which leads to inhibition of necrotic core formation and lipid accumulation. Since autophagy is also implicated in neuroprotection, in Alzheimer's and Huntington's disease animal models and many others normal and pathological states, including immunity, diabetes mellitus, different kind of tumors, colorectal cancer, different inflammations, lung diseases, neurodegenerative diseases, autophagy is of interest to many biomedical researchers.	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J	Tamura, N; Hirano, K; Kishino, K; Hashimoto, K; Amano, O; Shimada, J; Sakagami, H				Tamura, Nozomi; Hirano, Kumi; Kishino, Kaori; Hashimoto, Ken; Amano, Osamu; Shimada, Jun; Sakagami, Hiroshi			Analysis of Type of Cell Death Induced by Topoisomerase Inhibitor SN-38 in Human Oral Squamous Cell Carcinoma Cell Lines	ANTICANCER RESEARCH			English	Article						SN-38; irinotecan; oral sqamous cell carcinoma; apoptosis; autophagy; topoisomerase inhibitors; HSC-2; HSC-4 cells	1ST-LINE TREATMENT; COLORECTAL-CANCER; INDUCED APOPTOSIS; PHASE-II; IRINOTECAN; CYTOTOXICITY; CHEMOTHERAPY; AUTOPHAGY; FLUOROURACIL; PROTEIN	Despite frequent use of topoisomerase inhibitors (TIs) as antitumor agents, their application to oral squamous cell carcinoma (OSCC) has not been reported. We investigated three inhibitors of topoisomerase 1 [camptothecin, irinotecan, SN-38 (active metabolite of irinotecan)] and two inhibitors of topoisomerase II (etoposide, teniposide) for their cytotoxicity towards a total of 15 human tumor cell lines and normal cultured cells. All TIs exhibited higher cytotoxicity towards tumor cell lines (OSCC, glioblastoma, myelogenous leukemia) as compared with normal mesenchymal (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and epithelial cells (skin keratinocytes). Among TIs, SN-38 had the highest cytotoxicity towards OSCC cell lines, with a tumor specificity index of 1321 compared to mesenchymal cells and 22 compared with epithelial cells. SN-38 induced different types of cell death in two OSCC cell lines: apoptosis (caspase-3 activation and internucleosomal DNA fragmentation) in HSC-2 cells and autophagy (formation of autophagosome and secondary lysosome) in HSC-4 cells. The cell death of HSC-2 and HSC-4 cells was significantly inhibited by pre-treatment with caspase inhibitor (Z-VAD-FMK) and autophagy inhibitors (3-methyladenine, bafilomycin A1), respectively. The present study demonstrated that SN-38 is highly cytotoxic to OSCC cell lines, regardless of the type of induced cell death, suggesting its future application for chemotherapy of OSCC.	[Kishino, Kaori; Hashimoto, Ken; Sakagami, Hiroshi] Meikai Univ, Sch Dent, Div Pharmacol, Sakado, Saitama 3500283, Japan; [Tamura, Nozomi; Hirano, Kumi; Shimada, Jun] Meikai Univ, Sch Dent, Div Oral & Maxillofacial Surg, Sakado, Saitama 3500283, Japan; [Amano, Osamu] Meikai Univ, Sch Dent, Div Anat, Sakado, Saitama 3500283, Japan		Sakagami, H (corresponding author), Meikai Univ, Sch Dent, Div Pharmacol, Sakado, Saitama 3500283, Japan.	sakagami@dent.meikai.ac.jp		Sakagami, Hiroshi/0000-0001-8001-2121	Ministry of Education, Science, Sports and Culture of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [19592156]	This study was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan (Sakagami, No.19592156). The Authors acknowledge Drs. Kunii and Kanda for their technical assistance.	Bhattacharya A, 2008, NEOPLASIA, V10, P857, DOI 10.1593/neo.08424; Broker LE, 2005, CLIN CANCER RES, V11, P3155, DOI 10.1158/1078-0432.CCR-04-2223; Chabner B. A., 2006, GOODMAN GILMANS PHAR, P1315; de Gramont A, 2000, J CLIN ONCOL, V18, P2938, DOI 10.1200/JCO.2000.18.16.2938; DERBNATH J, 2005, AUTOPHAGY, V1, P66; Douillard JY, 2000, LANCET, V355, P1041, DOI 10.1016/S0140-6736(00)02034-1; Dunn William A. Jr., 1994, Trends in Cell Biology, V4, P139, DOI 10.1016/0962-8924(94)90069-8; Fujisawa S, 2002, TOXICOLOGY, V177, P39, DOI 10.1016/S0300-483X(02)00194-4; GUPTA M, 1995, BBA-GENE STRUCT EXPR, V1262, P1, DOI 10.1016/0167-4781(95)00029-G; Han JY, 2005, CANCER-AM CANCER SOC, V104, P2759, DOI 10.1002/cncr.21563; Hanley K, 1999, J INVEST DERMATOL, V113, P788, DOI 10.1046/j.1523-1747.1999.00743.x; HSIANG YH, 1989, CANCER RES, V49, P5077; HUSAIN I, 1994, CANCER RES, V54, P539; Ideo A, 2009, ANTICANCER RES, V29, P175; Ishihara M, 2006, ANTICANCER RES, V26, P2883; Jin SK, 2006, AUTOPHAGY, V2, P80, DOI 10.4161/auto.2.2.2460; Kantoh K, 2010, IN VIVO, V24, P843; Kishino K, 2008, ANTICANCER RES, V28, P2577; Otsuki S, 2011, TOXICOLOGY, V287, P131, DOI 10.1016/j.tox.2011.06.007; Pectasides D, 2002, EUR J CANCER, V38, P1194, DOI 10.1016/S0959-8049(02)00027-8; Robey RW, 2007, CANCER METAST REV, V26, P39, DOI 10.1007/s10555-007-9042-6; Takeba Y, 2007, BIOL PHARM BULL, V30, P1400, DOI 10.1248/bpb.30.1400; Takeba Y, 2007, J PHARMACOL SCI, V104, P232, DOI 10.1254/jphs.FP0070442; Wu YC, 2009, BIOCHEM BIOPH RES CO, V382, P451, DOI 10.1016/j.bbrc.2009.03.051; Wu YT, 2010, J BIOL CHEM, V285, P10850, DOI 10.1074/jbc.M109.080796; YANAGISAWASHIOTA F, 1995, ANTICANCER RES, V15, P259	26	11	11	0	3	INT INST ANTICANCER RESEARCH	ATHENS	EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE	0250-7005			ANTICANCER RES	Anticancer Res.	NOV	2012	32	11					4823	4832					10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	043EA	WOS:000311524500025	23155248				2022-04-25	
J	Gu, MC; Gao, YL; Chang, PY				Gu, Meichen; Gao, Yanli; Chang, Pengyu			KRAS Mutation Dictates the Cancer Immune Environment in Pancreatic Ductal Adenocarcinoma and Other Adenocarcinomas	CANCERS			English	Review						KRAS gene; pancreatic ductal adenocarcinoma; cancer immunity; immune checkpoint blockade	PACLITAXEL NAB-P; STEREOTACTIC BODY RADIOTHERAPY; CONSENSUS MOLECULAR SUBTYPES; GEMCITABINE GEM; MUTANT KRAS; PHASE-I; IMMUNOTHERAPY; COMBINATION; CELLS; TREMELIMUMAB	Simple Summary The vast majority of patients with pancreatic ductal adenocarcinomas harbor KRAS mutations in their tumors. Functionally, mutated KRAS is not only dedicated to tumor cell proliferation, survival and invasiveness, but also causing the immunosuppression in this cancer. In this situation, current data indicating the therapeutic effects of immune checkpoint inhibitors on pancreatic ductal adenocarcinomas are still not satisfying. In order to reflect the present bottleneck of immune checkpoint inhibitors in managing this cancer, we mainly provide information associated with the mechanism by which KRAS mutations establish the immunosuppressive milieus in pancreatic ductal adenocarcinomas. Together with other advances in this field, future directions to overcome the KRAS mutation-induced immunosuppression in pancreatic ductal adenocarcinomas are raised as well. Meanwhile, lung adenocarcinomas and colorectal adenocarcinomas are enumerated to compare with pancreatic ductal adenocarcinomas, aiming to indicate the specificity of KRAS mutations in dictating tumoral immune milieus among these cancers. Generally, patients with pancreatic ductal adenocarcinoma, especially those with wide metastatic lesions, have a poor prognosis. Recently, a breakthrough in improving their survival has been achieved by using first-line chemotherapy, such as gemcitabine plus nab-paclitaxel or oxaliplatin plus irinotecan plus 5-fluorouracil plus calcium folinate. Unfortunately, regimens with high effectiveness are still absent in second- or later-line settings. In addition, although immunotherapy using checkpoint inhibitors definitively represents a novel method for metastatic cancers, monotherapy using checkpoint inhibitors is almost completely ineffective for pancreatic ductal adenocarcinomas largely due to the suppressive immune milieu in such tumors. Critically, the genomic alteration pattern is believed to impact cancer immune environment. Surprisingly, KRAS gene mutation is found in almost all pancreatic ductal adenocarcinomas. Moreover, KRAS mutation is indispensable for pancreatic carcinogenesis. On these bases, a relationship likely exists between this oncogene and immunosuppression in this cancer. During pancreatic carcinogenesis, KRAS mutation-driven events, such as metabolic reprogramming, cell autophagy, and persistent activation of the yes-associated protein pathway, converge to cause immune evasion. However, intriguingly, KRAS mutation can dictate a different immune environment in other types of adenocarcinoma, such as colorectal adenocarcinoma and lung adenocarcinoma. Overall, the KRAS mutation can drive an immunosuppression in pancreatic ductal adenocarcinomas or in colorectal carcinomas, but this mechanism is not true in KRAS-mutant lung adenocarcinomas, especially in the presence of TP53 inactivation. As a result, the response of these adenocarcinomas to checkpoint inhibitors will vary.	[Gu, Meichen; Chang, Pengyu] First Hosp Jilin Univ, Dept Radiat Oncol & Therapy, Changchun 130021, Peoples R China; [Gao, Yanli] First Hosp Jilin Univ, Dept Pediat Ultrasound, Changchun 130021, Peoples R China		Chang, PY (corresponding author), First Hosp Jilin Univ, Dept Radiat Oncol & Therapy, Changchun 130021, Peoples R China.	gumc20@mails.jlu.edu.cn; gaoyanli@jlu.edu.cn; changpengyu@jlu.edu.cn		Gu, Meichen/0000-0002-3236-7785	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81874254]; Scientific and Technological Developing Scheme Foundation of Jilin Province [20200201400JC]; Foundation of Scientific Research Planning Project of the 13th Five-year Plan of Jilin Provincial Department of Education [JJKH20201043KJ]	This work was supported by National Natural Science Foundation of China [Grant No. 81874254], by Scientific and Technological Developing Scheme Foundation of Jilin Province [Grant No. 20200201400JC], and by Foundation of Scientific Research Planning Project of the 13th Five-year Plan of Jilin Provincial Department of Education [Grant No. JJKH20201043KJ].	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J	Ardakani, AA; Ghader, A; Asgari, H; Keshavarz, M; Tazehmahalleh, FE; Arae, MHM; Malekzadeh, M; Ghaznavi, H; Shakeri-Zadeh, A				Ardakani, Ali Abbasian; Ghader, Alireza; Asgari, Hamid; Keshavarz, Marzieh; Tazehmahalleh, Fatemeh Ebrahimi; Arae, Mohammad Hosein Majles; Malekzadeh, Malekeh; Ghaznavi, Habib; Shakeri-Zadeh, Ali			The capability of nonlinear optical characteristics as a predictor for cellular uptake of nanoparticles and cell damage	PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY			English	Article						Nanotechnology; Cell damage; Z-Scan; Nonlinear optical characteristics; Refractive index	CISPLATIN; CANCER; CHEMOTHERAPY; DOXORUBICIN; SCATTERING; AUTOPHAGY	Current methods for determining the cellular effects of a treatment modality need expensive materials and much time to provide a researcher with results. The aim of this study was to evaluate the potential of nonlinear optical characteristics of cancer cells using Z-scan technique to monitor the level of cellular uptake and cell damage caused by a nanotechnology based treatment modality. Two nanocomplexes were synthesized and characterized. The first one was made of alginate hydrogel co-loaded with cisplatin and gold nanoparticles (AuNPs) named as ACA nanocomplex. The second one, named as AA nanocomplex, was the same as ACA, but without cisplatin and this AA nanocomplex was considered as the control for ACA. Different groups of CT26 mouse colon cancer cell line received various treatments of cisplatin, ACA, and AA nanocomplexes and then the samples were prepared for Z-scan studies. The MTT assay was used to evaluate the cytotoxicity induced by different treatment modalities. Transmission electron microscopy (TEM) and inductively coupled plasma-mass spectrometry (ICP-MS) were used for qualitative and quantitative assessments of the level of AuNPs cellular uptake. The trend of nonlinear optical properties changes for treated cells was in agreement with MTT, TEM and ICP-MS results. Z-scan technique was able to successfully indicate the occurrence of cell damage. It was also capable to determine the intensity of cell damage induced by ACA nanocomplex in comparison to free cisplatin. Furthermore, Z-scan results showed that it was able to discriminate the differences of optical properties of the cells incubated with ACA nanocomplex for various incubation times. Nonlinear optical characteristics of a cell may be considered as a reliable indicator to predict the level of cellular effects induced by a nanotechnology based treatment modality. The protocol suggested in this article does not waste materials, not take much time to provide the results, and it is inexpensive technique.	[Ardakani, Ali Abbasian; Ghader, Alireza; Asgari, Hamid; Shakeri-Zadeh, Ali] IUMS, Finetech Med Res Ctr, Tehran, Iran; [Ardakani, Ali Abbasian; Ghader, Alireza; Malekzadeh, Malekeh; Shakeri-Zadeh, Ali] IUMS, Sch Med, Med Phys Dept, Tehran, Iran; [Keshavarz, Marzieh] Shiraz Univ Med Sci, Sch Med, Dept Med Phys, Tehran, Iran; [Tazehmahalleh, Fatemeh Ebrahimi] Univ Hosp Cologne, Cologne, Germany; [Arae, Mohammad Hosein Majles] Kharazmi Univ, ASRC, Biophoton Lab, Dept Phys, Karaj, Iran; [Ghaznavi, Habib] Zahedan Univ Med Sci ZaUMS, Zahedan, Iran		Ghaznavi, H; Shakeri-Zadeh, A (corresponding author), IUMS, Tehran, Iran.	dr.ghaznavi@zaums.ac.ir; shakeriz@iums.ac.ir	ghaznavi, habib/H-2293-2017; Ardakani, Ali Abbasian/A-2228-2015	Ardakani, Ali Abbasian/0000-0001-7536-0973; Ghader, Alireza/0000-0002-6100-0261	Ministry of Health & Medical Education (MOHME) of Iran; Zahedan University of Medical Sciences [7970]	All supports received from the Ministry of Health & Medical Education (MOHME) of Iran are acknowledged. This study was also supported by Zahedan University of Medical Sciences (grant number 7970).	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SEP	2019	27						442	448		10.1016/j.pdpdt.2019.07.023			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IW3HH	WOS:000484870600073	31362112				2022-04-25	
J	Orienti, I; Francescangeli, F; De Angelis, ML; Fecchi, K; Bongiorno-Borbone, L; Signore, M; Peschiaroli, A; Boe, A; Bruselles, A; Costantino, A; Eramo, A; Salvati, V; Sette, G; Contavalli, P; Zolla, L; Oki, T; Kitamura, T; Spada, M; Giuliani, A; Baiocchi, M; La Torre, F; Melino, G; Tartaglia, M; De Maria, R; Zeuner, A				Orienti, Isabella; Francescangeli, Federica; De Angelis, Maria Laura; Fecchi, Katia; Bongiorno-Borbone, Lucilla; Signore, Michele; Peschiaroli, Angelo; Boe, Alessandra; Bruselles, Alessandro; Costantino, Angelita; Eramo, Adriana; Salvati, Valentina; Sette, Giovanni; Contavalli, Paola; Zolla, Lello; Oki, Toshihiko; Kitamura, Toshio; Spada, Massimo; Giuliani, Alessandro; Baiocchi, Marta; La Torre, Filippo; Melino, Gerry; Tartaglia, Marco; De Maria, Ruggero; Zeuner, Ann			A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors	CELL DEATH & DISEASE			English	Article							PHASE-I TRIAL; LOW-DOSE TAMOXIFEN; CANCER STEM-CELLS; DIHYDROCERAMIDE DESATURASE; HIGH-RISK; ORAL FENRETINIDE; NEUROBLASTOMA; IDENTIFICATION; TARGET; CYCLE	Fenretinide is a synthetic retinoid characterized by anticancer activity in preclinical models and favorable toxicological profile, but also by a low bioavailability that hindered its clinical efficacy in former clinical trials. We developed a new formulation of fenretinide complexed with 2-hydroxypropyl-beta-cyclodextrin (nanofenretinide) characterized by an increased bioavailability and therapeutic efficacy. Nanofenretinide was active in cell lines derived from multiple solid tumors, in primary spheroid cultures and in xenografts of lung and colorectal cancer, where it inhibited tumor growth independently from the mutational status of tumor cells. A global profiling of pathways activated by nanofenretinide was performed by reverse-phase proteomic arrays and lipid analysis, revealing widespread repression of the mTOR pathway, activation of apoptotic, autophagic and DNA damage signals and massive production of dihydroceramide, a bioactive lipid with pleiotropic effects on several biological processes. In cells that survived nanofenretinide treatment there was a decrease of factors involved in cell cycle progression and an increase in the levels of p16 and phosphorylated p38 MAPK with consequent block in G0 and early G1. The capacity of nanofenretinide to induce cancer cell death and quiescence, together with its elevated bioavailability and broad antitumor activity indicate its potential use in cancer treatment and chemoprevention.	[Orienti, Isabella] Univ Bologna, Dept Pharm & Biotechnol, Via San Donato 19-2, I-40127 Bologna, Italy; [Francescangeli, Federica; De Angelis, Maria Laura; Bruselles, Alessandro; Costantino, Angelita; Eramo, Adriana; Salvati, Valentina; Sette, Giovanni; Contavalli, Paola; Baiocchi, Marta; Zeuner, Ann] Ist Super Sanita, Dept Oncol & Mol Med, Viale Regina Elena 299, I-00161 Rome, Italy; [Fecchi, Katia] Ist Super Sanita, Ctr Gender Specif Med, Viale Regina Elena 299, I-00161 Rome, Italy; [Bongiorno-Borbone, Lucilla; Peschiaroli, Angelo; Melino, Gerry] Univ Roma Tor Vergata, Dept Expt Med & Surg, Via Montpellier 1, I-00133 Rome, Italy; [Signore, Michele] Ist Super Sanita, RPPA Unit, Core Facil, Prote, Viale Regina Elena 299, I-00161 Rome, Italy; [Boe, Alessandra] Ist Super Sanita, Core Facil, Rome, Italy; [Costantino, Angelita] Univ Catania, Dept Biomed & Biotechnol Sci BIOMETEC, Via Santa Sofia 97, I-95123 Catania, Italy; [Zolla, Lello] Univ Tuscia, DAFNE Dept, Via S Camillo de Lellis, I-01100 Viterbo, Italy; [Oki, Toshihiko; Kitamura, Toshio] Univ Tokyo, Inst Med Sci, Div Cellular Therapy, Minato Ku, Tokyo 1088639, Japan; [Oki, Toshihiko; Kitamura, Toshio] Univ Tokyo, Inst Med Sci, Div Stem Cell Signaling, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan; [Spada, Massimo] Ist Super Sanita, Ctr Anim Res & Welf, Rome, Italy; [Giuliani, Alessandro] Ist Super Sanita, Environm & Hlth Dept, Rome, Italy; [La Torre, Filippo] Sapienza Univ, Div Emergency & Trauma Surg, Surg Sci & Emergency Dept, Emergency Dept,Policlin Umberto 1, Viale Policlin 155, I-00161 Rome, Italy; [Tartaglia, Marco] Osped Pediat Bambino Gesu, Genet & Rare Dis Res Div, Viale San Paolo 15, I-00146 Rome, Italy; [De Maria, Ruggero] Univ Cattolica Sacro Cuore, Inst Gen Pathol, Largo Francesco Vito 1, I-00168 Rome, Italy		Zeuner, A (corresponding author), Ist Super Sanita, Dept Oncol & Mol Med, Viale Regina Elena 299, I-00161 Rome, Italy.; De Maria, R (corresponding author), Univ Cattolica Sacro Cuore, Inst Gen Pathol, Largo Francesco Vito 1, I-00168 Rome, Italy.	ruggerodemaria@gmail.com; a.zeuner@gmail.com	Boe, Alessandra/AAA-2653-2019; Signore, Michele/J-8563-2016; De Angelis, Maria Laura/Y-4004-2019; Giuliani, Alessandro/K-7589-2016; Kitamura, Toshio/AAA-2071-2021; Spada, Massimo/Z-1345-2019; Zeuner, Ann/K-8607-2016; Francescangeli, Federica/K-6500-2016; Bruselles, Alessandro/M-7908-2017; Orienti, Isabella/X-2462-2019; Eramo, Adriana/K-6694-2016; La Torre, Filippo/AAI-7284-2020; Giuliani, Alessandro/AAF-1740-2020; Bruselles, Alessandro/M-6012-2019; Tartaglia, Marco/K-2955-2018; salvati, Valentina/J-1264-2018; Zeuner, Ann/A-8529-2010; Fecchi, Katia/N-1380-2017; Sette, Giovanni/K-6692-2016	Boe, Alessandra/0000-0002-8888-7501; Signore, Michele/0000-0002-0262-842X; De Angelis, Maria Laura/0000-0003-4220-8822; Giuliani, Alessandro/0000-0002-4640-804X; Spada, Massimo/0000-0003-0751-1893; Francescangeli, Federica/0000-0002-1086-5265; Bruselles, Alessandro/0000-0002-1556-4998; Eramo, Adriana/0000-0002-0814-6683; La Torre, Filippo/0000-0002-0787-8794; Giuliani, Alessandro/0000-0002-4640-804X; Bruselles, Alessandro/0000-0002-1556-4998; Tartaglia, Marco/0000-0001-7736-9672; salvati, Valentina/0000-0002-0322-3504; PESCHIAROLI, ANGELO/0000-0001-6311-2382; ORIENTI, ISABELLA/0000-0003-1972-2807; Zeuner, Ann/0000-0002-8295-3715; Costantino, Angelita/0000-0002-2519-6279; Fecchi, Katia/0000-0003-4397-5783; Sette, Giovanni/0000-0002-3378-2446; Baiocchi, Marta/0000-0003-0976-0690	AIRCFondazione AIRC per la ricerca sul cancro [15749, 20744]; ERA-NET TRANSCAN Ref TACTIC JTC 2014; Sapienza University of Rome [C26H15ZKWL]; AIRC 5 x 1000 Molecular Clinical Oncology Extension ProgramFondazione AIRC per la ricerca sul cancro [9979]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MC_U132670600, MC_UU_00025/2] Funding Source: UKRI	We thank Paola Di Matteo and Stefano Guida for excellent technical assistance, Antonio Di Virgilio and Daniele Macchia for their essential contribution for in vivo experiments. This work was supported by the following grants: AIRC IG 2017 Ref: 20744, AIRC IG 2014 Ref: 15749, ERA-NET TRANSCAN Ref TACTIC JTC 2014 to A.Z., by Awards 2015 Sapienza University of Rome C26H15ZKWL grant to F.L.T. and by AIRC 5 x 1000 Molecular Clinical Oncology Extension Program Ref 9979 grant to R.D.M., G.M. and M.T.	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JUL 23	2019	10								529	10.1038/s41419-019-1775-y			19	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	IM6JH	WOS:000478098700001	31332161	Green Published, gold			2022-04-25	
J	Xiao, M; Benoit, A; Hasmim, M; Duhem, C; Vogin, G; Berchem, G; Noman, MZ; Janji, B				Xiao, Malina; Benoit, Alice; Hasmim, Meriem; Duhem, Caroline; Vogin, Guillaume; Berchem, Guy; Noman, Muhammad Zaeem; Janji, Bassam			Targeting Cytoprotective Autophagy to Enhance Anticancer Therapies	FRONTIERS IN ONCOLOGY			English	Review						autophagy; cancer resistance; chemotherapy; radiotherapy; targeted therapy; immunotherapy	CANCER-CELLS; COLORECTAL-CANCER; INHIBITING AUTOPHAGY; CHLOROQUINE; RESISTANCE; PROMOTES; RADIOSENSITIVITY; ANGIOGENESIS; SIMVASTATIN; INDUCTION	Autophagy is a highly regulated multi-step process that occurs at the basal level in almost all cells. Although the deregulation of the autophagy process has been described in several pathologies, the role of autophagy in cancer as a cytoprotective mechanism is currently well established and supported by experimental and clinical evidence. Our understanding of the molecular mechanism of the autophagy process has largely contributed to defining how we can harness this process to improve the benefit of cancer therapies. While the role of autophagy in tumor resistance to chemotherapy is extensively documented, emerging data point toward autophagy as a mechanism of cancer resistance to radiotherapy, targeted therapy, and immunotherapy. Therefore, manipulating autophagy has emerged as a promising strategy to overcome tumor resistance to various anti-cancer therapies, and autophagy modulators are currently evaluated in combination therapies in several clinical trials. In this review, we will summarize our current knowledge of the impact of genetically and pharmacologically modulating autophagy genes and proteins, involved in the different steps of the autophagy process, on the therapeutic benefit of various cancer therapies. We will also briefly discuss the challenges and limitations to developing potent and selective autophagy inhibitors that could be used in ongoing clinical trials.	[Xiao, Malina; Benoit, Alice; Hasmim, Meriem; Berchem, Guy; Noman, Muhammad Zaeem; Janji, Bassam] Luxembourg Inst Hlth, Dept Oncol, Tumor Immunotherapy & Microenvironrnent TIME Grp, Luxembourg, Luxembourg; [Duhem, Caroline; Berchem, Guy] Ctr Hosp Luxembourg, Dept Hematooncol, Luxembourg, Luxembourg; [Vogin, Guillaume] Univ Lorraine, UMR 7365, Ingn Mol & Physiopathol Articulaire IMoPA, Vandoeuvre Les Nancy, France; [Vogin, Guillaume] Ctr Francois Baolesse, Esch Sur Alzette, Luxembourg		Janji, B (corresponding author), Luxembourg Inst Hlth, Dept Oncol, Tumor Immunotherapy & Microenvironrnent TIME Grp, Luxembourg, Luxembourg.	bassam.janji@lih.lu	Berchem, Guy/C-9364-2014; NOMAN, Muhammmad Zaeem/AAJ-1466-2021	Berchem, Guy/0000-0003-0157-2257; NOMAN, Muhammmad Zaeem/0000-0002-1837-3097	Luxembourg Institute of Health; Luxembourg National Research FundLuxembourg National Research Fund [PRIDE15/10675146/CANBIO, C18/BM/12670304/COMBATIC]; FNRS TelevieFonds de la Recherche Scientifique - FNRS [7.4606.18, 7.4579.20]; Fondation Cancer, Luxembourg [FC/2018/06]; Kriibskrank Kanner Foundation, Luxembourg; RCMS foundation; Action LIONS Vaincre le Cancer Luxembourg; Janssen Cilag Pharma; Roche Pharma	This work was supported by Luxembourg Institute of Health and grants from the Luxembourg National Research Fund (PRIDE15/10675146/CANBIO and C18/BM/12670304/COMBATIC); FNRS Televie (grants 7.4606.18 and 7.4579.20); Fondation Cancer, Luxembourg (FC/2018/06); Kriibskrank Kanner Foundation, Luxembourg (2019); RCMS foundation, and Action LIONS Vaincre le Cancer Luxembourg. The authors also declare that this study received funding from Janssen Cilag Pharma and Roche Pharma. These funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.	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Oncol.	FEB 25	2021	11								626309	10.3389/fonc.2021.626309			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	QU7IC	WOS:000627451800001	33718194	gold, Green Published			2022-04-25	
J	Chen, YL; Yan, MY; Chien, SY; Kuo, SJ; Chen, DR; Cheng, CY; Su, CC				Chen, Yao-Li; Yan, Meng-Yi; Chien, Su-Yu; Kuo, Shou-Jen; Chen, Dar-Ren; Cheng, Chun-Yuan; Su, Chin-Cheng			Sann-Joong-Kuey-Jian-Tang inhibits hepatocellular carcinoma Hep-G2 cell proliferation by increasing TNF-alpha, Caspase-8, Caspase-3 and Bax but by decreasing TCTP and Mcl-1 expression in vitro	MOLECULAR MEDICINE REPORTS			English	Article						Sann-Joong-Kuey-Jian-Tang; Hep-G2 cells; apoptosis; TCTP; TNF-alpha	PROTEIN EXPRESSION; FORTILIN	Hepatic cancer remains a challenging disease and there is a need to identify new treatments. Sann-Joong-Kuey-Jian-Tang (SJKJT), a traditional medicinal prescription, has been used to treat lymphadenopathy and exhibits cytotoxic activity in many types of human cancer cells. Our previous studies revealed that SJKJT is capable of inhibiting colon cancer colo 205 cells by inducing autophagy and apoptosis. However, the effects and molecular mechanisms of SJKJT in human hepatocellular carcinoma have not been clearly elucidated. In the present study we evaluated the effects of SJKJT in human hepatic cellular carcinoma Hep-G2 cells. The cytotoxicity of SJKJT in Hep-G2 cells was measured by MTT assay. The cell cycles were analyzed by fluorescence-activated cell sorting (FACS). The protein expression of translationally controlled tumor protein (TCTP), Mcl-1, Fas, TNF-alpha, Caspase-8, Caspase-3 and Bax in Hep-G2 cells treated with SJKJT was evaluated by western blotting. The protein expression of Caspase-3 was also detected by immunofluorescence staining. The results showed that SJKJT inhibits Hep-G2 cells in a time- and dose-dependent manner. During SJKJT treatment for 48 and 72 h, the half-maximum inhibitory concentration (IC50) was 1.48 and 0.94 mg/ml, respectively. The FACS results revealed that increased doses of SJKJT were capable of increasing the percentage of cells in the sub-G1 phase. Immunofluorescence staining showed that Hep-G2 treated with SJKJT had increased expression of Caspase-3. The western blot results showed that the protein expression of Fas, TNF-alpha, Caspase-8, Caspase-3 and Bax was upregulated, but that of TCTP and Mcl-1 was downregulated in Hep-G2 cells treated with SJKJT. In conclusion, these findings indicated that SJKJT inhibits Hep-G2 cells. One of the molecular mechanisms responsible for this may be the increased Fas, TNF-alpha, Caspase-8, Caspase-3 and Bax expression; another mechanism may be via decreasing TCTP and Mcl-1 expression in order to induce apoptosis.	[Chen, Yao-Li; Yan, Meng-Yi; Kuo, Shou-Jen; Chen, Dar-Ren; Cheng, Chun-Yuan; Su, Chin-Cheng] Changhua Christian Hosp, Dept Surg, Changhua 50006, Taiwan; [Su, Chin-Cheng] Changhua Christian Hosp, Tumor Res Ctr Integrat Med, Changhua 50006, Taiwan; [Kuo, Shou-Jen; Chen, Dar-Ren; Su, Chin-Cheng] Changhua Christian Hosp, Comprehens Breast Canc Ctr, Changhua 50006, Taiwan; [Chien, Su-Yu] Changhua Christian Hosp, Dept Pharm, Changhua 50006, Taiwan; [Su, Chin-Cheng] China Med Univ, Coll Chinese Med, Sch Chinese Med, Taichung 40402, Taiwan		Su, CC (corresponding author), Changhua Christian Hosp, Comprehens Breast Canc Ctr, Dept Surg, Tumor Res Ctr Integrat Med, 135 Nan Hsiao St, Changhua 50006, Changhua County, Taiwan.	succ.maeva@msa.hinet.net			Changhua Christian Hospital [100-CCH-ICO-06-3]	This study was supported by grant 100-CCH-ICO-06-3 from Changhua Christian Hospital.	[Anonymous], 2012, STAT CAUS DEATH 2010, P153; CARSWELL EA, 1975, P NATL ACAD SCI USA, V72, P3666, DOI 10.1073/pnas.72.9.3666; Cheng CY, 2010, MOL MED REP, V3, P63, DOI 10.3892/mmr_00000219; Cheng CY, 2009, MOL MED REP, V2, P707, DOI 10.3892/mmr_00000160; Cohen GM, 1997, BIOCHEM J, V326, P1, DOI 10.1042/bj3260001; Gaur U, 2003, BIOCHEM PHARMACOL, V66, P1403, DOI 10.1016/S0006-2952(03)00490-8; Graidist P, 2004, J BIOL CHEM, V279, P40868, DOI 10.1074/jbc.M401454200; Hsu YL, 2006, BIOL PHARM BULL, V29, P2388, DOI 10.1248/bpb.29.2388; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Leung TWT, 2001, SEMIN ONCOL, V28, P514, DOI 10.1053/sonc.2001.26954; Liu H, 2005, MOL CELL BIOL, V25, P3117, DOI 10.1128/MCB.25.8.3117-3126.2005; Lowe SW, 2004, NATURE, V432, P307, DOI 10.1038/nature03098; Susini L, 2008, CELL DEATH DIFFER, V15, P1211, DOI 10.1038/cdd.2008.18; Zhang D, 2002, J BIOL CHEM, V277, P37430, DOI 10.1074/jbc.M207413200	14	7	10	0	7	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1791-2997	1791-3004		MOL MED REP	Mol. Med. Rep.	MAY	2013	7	5					1487	1493		10.3892/mmr.2013.1381			7	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	136TF	WOS:000318385600021	23525225	Bronze			2022-04-25	
J	De Luise, M; Girolimetti, G; Okere, B; Porcelli, AM; Kurelac, I; Gasparre, G				De Luise, Monica; Girolimetti, Giulia; Okere, Bernard; Porcelli, Anna Maria; Kurelac, Ivana; Gasparre, Giuseppe			Molecular and metabolic features of oncocytomas: Seeking the blueprints of indolent cancers	BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS			English	Review						Oncocytic tumors; Mitochondrial DNA mutations; Mitochondrial biogenesis; Autophagy; Mitophagy; Respiratory complex I	MITOCHONDRIAL-DNA MUTATIONS; BIRT-HOGG-DUBE; HURTHLE CELL-CARCINOMA; RESPIRATORY COMPLEX I; OXIDATIVE-PHOSPHORYLATION; RENAL ONCOCYTOMA; RECTAL ADENOCARCINOMA; HUMAN-PAPILLOMAVIRUS; POINT MUTATIONS; MTDNA MUTATIONS	Oncocytic tumors are a peculiar subset of human neoplasms in which mitochondria have been proven to have a prominent role. A number of paradoxes render these clinical entities interesting from the translational research point of view. Most oncocytic tumors are generally metabolically constrained due to the impaired respiratory capacity and lack of the ability to respond to hypoxia, yet they maintain features that allow them to strive and persist in an indolent form. Their unique molecular and metabolic characteristics are an object of investigation that may reveal novel ways for therapeutic strategies based on metabolic targeting. With this aim in mind, we here examine the current knowledge on oncocytomas and delve into the molecular causes and consequences that revolve around the oncocytic phenotype, to understand whether we can learn to design therapies from the dissection of benign neoplasms. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. (C) 2017 Elsevier B.V. All rights reserved.	[De Luise, Monica; Girolimetti, Giulia; Okere, Bernard; Kurelac, Ivana; Gasparre, Giuseppe] Univ Hosp S Orsola Malpighi, Unit Med Genet, Dept Med & Surg Sci DIMEC, Via G Massarenti 9, I-40138 Bologna, BO, Italy; [Okere, Bernard; Porcelli, Anna Maria] Univ Bologna, Dept Pharm & Biotechnol FABIT, Via Selmi 3, Bologna, Italy; [Porcelli, Anna Maria] Univ Bologna, Interdept Ind Res Ctr Hlth Sci & Technol, Bologna, Italy; [Kurelac, Ivana] Francis Crick Inst, Tumour Host Interact Lab, 1 Midland Rd, London NW1 1AT, England		Kurelac, I (corresponding author), Univ Hosp S Orsola Malpighi, Unit Med Genet, Dept Med & Surg Sci DIMEC, Via G Massarenti 9, I-40138 Bologna, BO, Italy.	ivana_kurelac@yahoo.com	De Luise, Monica/AAC-5959-2022; Kurelac, Ivana/K-3070-2016; GIROLIMETTI, GIULIA/J-6648-2018; Gasparre, Giuseppe/K-3879-2016	De Luise, Monica/0000-0002-3486-3985; Kurelac, Ivana/0000-0002-8364-9985; Girolimetti, Giulia/0000-0001-8917-3634; Gasparre, Giuseppe/0000-0003-1229-9006	Italian Association for Cancer Research (AIRC) JANEUTICSFondazione AIRC per la ricerca sul cancro [IG14242 JANEUTICS, IG17387 TOUCHME]; Italian Ministry of HealthMinistry of Health, Italy [GR-2013-02356666 DISCO TRIP]; Worldwide Cancer Research [15-1144 DHoMOs]; European CommissionEuropean CommissionEuropean Commission Joint Research Centre [ITN -317433 MEET]; triennial AIRC fellowship "Livia Perotti"	This paper was supported by the Italian Association for Cancer Research (AIRC) grants IG14242 JANEUTICS to G. Gasparre and IG17387 TOUCHME to AMP. It was also supported by the Italian Ministry of Health project GR-2013-02356666 DISCO TRIP, Worldwide Cancer Research project 15-1144 DHoMOs and the European Commission FP7 Marie Curie ITN -317433 MEET to G. Gasparre. G. Girolimetti is supported by a triennial AIRC fellowship "Livia Perotti".	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Biophys. Acta-Bioenerg.	AUG	2017	1858	8			SI		591	601		10.1016/j.bbabio.2017.01.009			11	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	FA9KF	WOS:000405763800005	28115060	Bronze			2022-04-25	
J	Roussi, S; Gosse, F; Aoude-Werner, D; Zhang, X; Marchioni, E; Geoffroy, P; Miesch, M; Raul, F				Roussi, Stamatiki; Gosse, Francine; Aoude-Werner, Dalal; Zhang, Xin; Marchioni, Eric; Geoffroy, Philippe; Miesch, Michel; Raul, Francis			Mitochondrial perturbation, oxidative stress and lysosomal destabilization are involved in 7 beta-hydroxysitosterol and 7 beta-hydroxycholesterol triggered apoptosis in human colon cancer cells	APOPTOSIS			English	Article						apoptosis; Caco-2 cells; 7 beta-hydroxysitosterol; 7 beta-hydroxycholesterol; mitochondria; lysosomes	BCL-2 FAMILY PROTEINS; BETA-SITOSTEROL OXIDES; CYTOCHROME-C RELEASE; MEMBRANE PERMEABILIZATION; DNA-DAMAGE; DEATH; OXYSTEROLS; MECHANISMS; ACTIVATION; AUTOPHAGY	We reported previously that 7 beta-hydroxysitosterol and 7 beta-hydroxycholesterol induced apoptosis in Caco-2 cells. Apoptosis caused by 7 beta-hydroxysitosterol but not by 7 beta-hydroxycholesterol was related to a caspase-dependent process. In the present report, we compared the effects of both compounds on mitochondria integrity and on various modulators of apoptosis. When Caco-2 cells were exposed to both hydroxysterols, no changes in Bcl-2 and Bax expressions were detected indicating a Bcl-2/Bax-independent cell death pathway, whereas loss of mitochondrial membrane potential and cytochrome c release were observed. Endonuclease G expression and enhanced production of reactive oxygen species were detected in 7 beta-hydroxycholesterol treated cells, but not with 7 beta-hydroxysitosterol. Loss of mitochondrial membrane potential and cell death produced by both hydroxysterols were prevented by vitamin C. Lysosomal membrane integrity was altered with both hydroxysterols, but 7 beta-hydroxysitosterol was significantly more active on than 7 beta-hydroxycholesterol. Both hydroxysterols induced apoptosis by mitochondrial membrane permeabilization. However, 7 beta-hydroxycholesterol exhibited a specific enhancement of oxidative stress and of endonuclease G expression despite its closely related chemical structure with 7 beta-hydroxysitosterol. The two hydroxysterols exhibit different lipophilic properties which may explain their different biological effects.	IRCAD, Lab Nutr Canc Prevent, F-67091 Strasbourg, France; Univ Strasbourg, INSERM, U682, IRCAD, F-67091 Strasbourg, France; Aerial, F-67300 Schiltigheim, France; ULP, CNRS, UMR 7512, Fac Pharm,Lab Chim Analyt & Sci Aliment, F-67400 Illkirch Graffenstaden, France; ULP, CNRS, UMR 7123, Lab Chim Organ Synthet, F-67008 Strasbourg, France		Roussi, S (corresponding author), IRCAD, Lab Nutr Canc Prevent, 1,Pl Hop, F-67091 Strasbourg, France.	roussi@ulp.u-strasbg.fr	Akram, Muhammad Usman U/I-4917-2013	Akram, Muhammad Usman U/0000-0002-0999-6567; Aoude-Werner, Dalal/0000-0003-0262-3896			Antonsson B, 2004, MOL CELL BIOCHEM, V256, P141, DOI 10.1023/B:MCBI.0000009865.70898.36; Antunes F, 2001, BIOCHEM J, V356, P549, DOI 10.1042/0264-6021:3560549; Armstrong JS, 2006, BIOESSAYS, V28, P253, DOI 10.1002/bies.20370; Awad AB, 1996, ANTICANCER RES, V16, P2797; Benimetskaya L, 2004, CLIN CANCER RES, V10, P8371, DOI 10.1158/1078-0432.CCR-04-1294; BLOCH KE, 1983, CRC CR REV BIOCH MOL, V14, P47, DOI 10.3109/10409238309102790; Boudard D, 2002, AM J HEMATOL, V70, P115, DOI 10.1002/ajh.10108; Breckenridge DG, 2004, CURR OPIN CELL BIOL, V16, P647, DOI 10.1016/j.ceb.2004.09.009; Brown AJ, 1999, ATHEROSCLEROSIS, V142, P1, DOI 10.1016/S0021-9150(98)00196-8; Chen Q, 2003, CELL DEATH DIFFER, V10, P323, DOI 10.1038/sj.cdd.4401148; Chwieralski CE, 2006, APOPTOSIS, V11, P143, DOI 10.1007/s10495-006-3486-y; de Jong A, 2003, J NUTR BIOCHEM, V14, P362, DOI 10.1016/S0955-2863(03)00002-0; Egler RA, 2005, ONCOGENE, V24, P8038, DOI 10.1038/sj.onc.1208821; Enns GM, 2003, MOL GENET METAB, V80, P11, DOI 10.1016/j.ymgme.2003.08.009; Fleury C, 2002, BIOCHIMIE, V84, P131, DOI 10.1016/S0300-9084(02)01369-X; Garrido C, 2006, CELL DEATH DIFFER, V13, P1423, DOI 10.1038/sj.cdd.4401950; HATCH GM, 1993, J LIPID RES, V34, P1873; Henry-Mowatt J, 2004, ONCOGENE, V23, P2850, DOI 10.1038/sj.onc.1207534; KARCZEWSKI JM, 2000, ANN NY ACAD SCI, V15, P275; Kim R, 2006, CANCER CHEMOTH PHARM, V57, P545, DOI 10.1007/s00280-005-0111-7; Kim R, 2006, J PATHOL, V208, P319, DOI 10.1002/path.1885; KRAJEWSKI S, 1993, CANCER RES, V53, P4701; Kroemer G, 2005, NAT MED, V11, P725, DOI 10.1038/nm1263; Kroemer G, 2005, NAT REV CANCER, V5, P886, DOI 10.1038/nrc1738; Lea LJ, 2004, FOOD CHEM TOXICOL, V42, P771, DOI 10.1016/j.fct.2003.12.014; Lemaire-Ewing S, 2005, CELL BIOL TOXICOL, V21, P97, DOI 10.1007/s10565-005-0141-2; Lizard G, 1997, FEBS LETT, V419, P276, DOI 10.1016/S0014-5793(97)01473-7; Maguire L, 2003, BRIT J NUTR, V90, P767, DOI 10.1079/BJN2003956; Massey JB, 2006, CURR OPIN LIPIDOL, V17, P296, DOI 10.1097/01.mol.0000226123.17629.ab; Miguet-Alfonsi C, 2002, BIOCHEM PHARMACOL, V64, P527, DOI 10.1016/S0006-2952(02)01110-3; Miura Y, 2004, BIOSCI BIOTECH BIOCH, V68, P2415, DOI 10.1271/bbb.68.2415; Prunet C, 2005, J BIOCHEM MOL TOXIC, V19, P311, DOI 10.1002/jbt.20096; Roussi S, 2005, CELL DEATH DIFFER, V12, P128, DOI 10.1038/sj.cdd.4401530; Ryan E, 2005, BRIT J NUTR, V94, P443, DOI 10.1079/BJN20051500; Ryan L, 2005, BRIT J NUTR, V94, P519, DOI 10.1079/BJN20051524; Schroepfer GJ, 2000, PHYSIOL REV, V80, P361, DOI 10.1152/physrev.2000.80.1.361; Shimizu S, 2004, NAT CELL BIOL, V6, P1221, DOI 10.1038/ncb1192; Tapiero H, 2003, BIOMED PHARMACOTHER, V57, P321, DOI 10.1016/S0753-3322(03)00104-5; Touyz RM, 2004, J HYPERTENS, V22, P1141, DOI 10.1097/00004872-200406000-00015; Tsujimoto Y, 2003, J CELL PHYSIOL, V195, P158, DOI 10.1002/jcp.10254; Valko M, 2004, MOL CELL BIOCHEM, V266, P37, DOI 10.1023/B:MCBI.0000049134.69131.89; van Loo G, 2001, CELL DEATH DIFFER, V8, P1136, DOI 10.1038/sj.cdd.4400944; Wenzel U, 2004, CARCINOGENESIS, V25, P703, DOI 10.1093/carcin/bgh079; Yu J, 2005, BIOCHEM BIOPH RES CO, V331, P851, DOI 10.1016/j.bbrc.2005.03.189; Yuan XM, 2002, P NATL ACAD SCI USA, V99, P6286, DOI 10.1073/pnas.092135599; Yuan XM, 2000, FREE RADICAL BIO MED, V28, P208, DOI 10.1016/S0891-5849(99)00220-8; Zhang X, 2005, STEROIDS, V70, P896, DOI 10.1016/j.steroids.2005.06.004	47	55	57	0	12	SPRINGER	DORDRECHT	VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS	1360-8185	1573-675X		APOPTOSIS	Apoptosis	JAN	2007	12	1					87	96		10.1007/s10495-006-0485-y			10	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	118UO	WOS:000242968200007	17136497				2022-04-25	
J	Murphy, A; Costa, M				Murphy, Anthony; Costa, Max			Nuclear protein 1 imparts oncogenic potential and chemotherapeutic resistance in cancer	CANCER LETTERS			English	Review						NUPR1; Chemotherapeutic resistance; Breast cancer; Lung cancer; Colorectal cancer	HUMAN BREAST-CANCER; P8 MESSENGER-RNA; TRANSCRIPTION FACTORS; TUMOR PROGRESSION; CELL GROWTH; EXPRESSION; NUPR1; STRESS; METASTASIS; COM-1/P8	Nuclear protein 1 (NUPR1) also known as p8 and candidate of metastasis 1 (COM1) functions as a transcriptional regulator, and plays a role in cell cycle, DNA damage response, apoptosis, autophagy, and chromatin remodeling in response to various cellular stressors. Since it was first suggested to contribute to cancer development and progression in 1999, a number of studies have sought to reveal its function. However, NUPR1 and its biological relevance in cancer have proven difficult to pinpoint. Based on evidence of NUPR1 expression in cancers, its function extends from carcinogenesis and tumorigenesis to metastasis and chemotherapeutic resistance. A tumor suppressive function of NUPR1 has also been documented in multiple cancers. By and large, literature involving NUPR1 and cancer is confined to pancreatic and breast cancers, yet significant progress has been made with respect to NUPR1 expression and its function in lung, colorectal, blood, and prostate cancers, among others. Recent evidence strongly supports the notion that NUPR1 is key in chemotherapeutic resistance by mediating both anti-apoptotic activity and autophagy when challenged with anti-cancer compounds. Therefore, it is of significant importance to understand the broad range of molecular functions directed by NUPR1. In this review, NUPR1 expression and its role in breast, lung, and colorectal cancer development and progression will be addressed.	[Murphy, Anthony; Costa, Max] NYU, Sch Med, Dept Environm Med, New York, NY 10003 USA		Costa, M (corresponding author), 341 East 25th St, New York, NY 10016 USA.	Anthony.Murphy@nyumc.org; Max.Costa@nyumc.org		Murphy, Anthony/0000-0002-0967-2896	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [ES000260, ES022935, ES023174, ES026138]	This research was funded by the following NIH grants: ES000260, ES022935, ES023174, ES026138.	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DEC 1	2020	494						132	141		10.1016/j.canlet.2020.08.019			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	OF9NS	WOS:000581525200017	32835767	Green Accepted			2022-04-25	
J	Kim, CW; HA, YJ; Tak, KH; Roh, SA; Kim, SK; Kim, SY; Kim, YS; Cho, DH; Kim, JC				Kim, Chan Wook; HA, Ye Jin; Tak, Ka Hee; Roh, Seon Ae; Kim, Seon-Kyu; Kim, Seon-Young; Kim, Yong Sung; Cho, Dong-Hyung; Kim, Jin Cheon			Clinically Applicable Serum Biomarkers Among 14 Candidates Associated With Recurrence of Stage II and III Colorectal Cancer	ANTICANCER RESEARCH			English	Article						Colorectal cancer; biomarkers; recurrence; CEA; CKS2; OAS2; ATG5	CARCINOEMBRYONIC ANTIGEN; UP-REGULATION; EXPRESSION; PROGNOSIS; GENES; IDENTIFICATION; CLASSIFIER; AUTOPHAGY; PREDICTS; MARKERS	Background/Aim: We evaluated the predictive value of candidate serum biomarkers for recurrence in stage II and III colorectal cancer (CRC) after curative surgery. Patients and Methods: A total of 33 and 120 patients with CRC with or without recurrence at 5 years after curative surgery were included in the training set and the validation set, respectively. Possible serum biomarkers were examined for associations with CRC recurrence using receiver operating characteristics (ROC) curve analysis. Results: In the training set, the expression levels of the 14 biomarkers were compared according to recurrence. Among them, five biomarkers that had significantly different expression levels were validated in 60 patients with recurrence at 5 years after curative surgery and 60 patients without. Multivariate analysis showed that natural log-transformed values of carcinoembryonic antigen (CEA), cyclin-dependent kinase regulatory subunit 2 (CKS2), 2'-5'-oligoadenylate synthetase 2 (OAS2), and autophagy-related gene 5 (ATG5) in preoperative serum were significantly related to recurrence. ROC analysis showed that these biomarkers were able to discriminate patients with recurrence from those without (area under the curve=0.828, 95% confidence interval=0.755-0.990). Conclusion: Preoperative serum levels of CEA, CKS2, OAS2 and ATG5 were independent risk factors for recurrence. A combination of serum CEA, CKS2, OAS2 and ATG5 predicted tumor recurrence well in patients with stage II and III CRC.	[Kim, Chan Wook; Kim, Jin Cheon] Univ Ulsan, Dept Surg, Asan Med Ctr, Coll Med, 88 Olymp Ro 43-gil, Seoul 05505, South Korea; [HA, Ye Jin; Tak, Ka Hee; Roh, Seon Ae] Univ Ulsan, Asan Inst Life Sci, Asan Med Ctr, Coll Med, Seoul, South Korea; [Kim, Seon-Kyu; Kim, Seon-Young; Kim, Yong Sung] Korea Res Inst Biosci & Biotechnol, Personalized Genom Med Res Ctr, Daejeon, South Korea; [Cho, Dong-Hyung] Kyungpook Natl Univ, Sch Life Sci, Daegu, South Korea		Kim, JC (corresponding author), Univ Ulsan, Dept Surg, Asan Med Ctr, Coll Med, 88 Olymp Ro 43-gil, Seoul 05505, South Korea.	jckim@amc.seoul.kr		Kim, Seon-Kyu/0000-0002-4176-5187	National Research Foundation of Korea - Korea government (NSIT) [2020R1C11009345, 2017R1A2B1009062, 2016R1E1A1A02919844]	Statistical analyses were supervised by research associate Min Kyu Han at the Department of Clinical Epidemiology and Biostatistics. This study was cooperatively supported by grants (2020R1C11009345, 2017R1A2B1009062, and 2016R1E1A1A02919844) from the National Research Foundation of Korea funded by the Korea government (NSIT).	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SEP	2021	41	9					4651	4658		10.21873/anticanres.15279			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	WZ8RL	WOS:000720228900008	34475094				2022-04-25	
J	Lin, G; Hill, DK; Andrejeva, G; Boult, JKR; Troy, H; Fong, ACLFWT; Orton, MR; Panek, R; Parkes, HG; Jafar, M; Koh, DM; Robinson, SP; Judson, IR; Griffiths, JR; Leach, MO; Eykyn, TR; Chung, YL				Lin, G.; Hill, D. K.; Andrejeva, G.; Boult, J. K. R.; Troy, H.; Fong, A-C L. F. W. T.; Orton, M. R.; Panek, R.; Parkes, H. G.; Jafar, M.; Koh, D-M; Robinson, S. P.; Judson, I. R.; Griffiths, J. R.; Leach, M. O.; Eykyn, T. R.; Chung, Y-L			Dichloroacetate induces autophagy in colorectal cancer cells and tumours	BRITISH JOURNAL OF CANCER			English	Article						dichloroacetate; hyperpolarised C-13-MRS; H-1-MRS; autophagy; monocarboxylate transporter-1 inhibitor; [1-C-13]pyruvate; pyruvate to lactate exchange rate	IN-VITRO; APOPTOSIS; PYRUVATE; GLYCOLYSIS; METABOLISM; RESISTANCE; MITOCHONDRIA; INHIBITION; CYTOPLASM; LACTATE	Background: Dichloroacetate (DCA) has been found to have antitumour properties. Methods: We investigated the cellular and metabolic responses to DCA treatment and recovery in human colorectal (HT29, HCT116 WT and HCT116 Bax-ko), prostate carcinoma cells (PC3) and HT29 xenografts by flow cytometry, western blotting, electron microscopy, H-1 and hyperpolarised C-13-magnetic resonance spectroscopy. Results: Increased expression of the autophagy markers LC3B II was observed following DCA treatment both in vitro and in vivo. We observed increased production of reactive oxygen species (ROS) and mTOR inhibition (decreased pS6 ribosomal protein and p4E-BP1 expression) as well as increased expression of MCT1 following DCA treatment. Steady-state lactate excretion and the apparent hyperpolarised [1-C-13] pyruvate-to-lactate exchange rate (k(PL)) were decreased in DCA-treated cells, along with increased NAD(+)/NADH ratios and NAD(+). Steady-state lactate excretion and k(PL) returned to, or exceeded, control levels in cells recovered from DCA treatment, accompanied by increased NAD(+) and NADH. Reduced k(PL) with DCA treatment was found in HT29 tumour xenografts in vivo. Conclusions: DCA induces autophagy in cancer cells accompanied by ROS production and mTOR inhibition, reduced lactate excretion, reduced k(PL) and increased NAD(+)/NADH ratio. The observed cellular and metabolic changes recover on cessation of treatment.	[Lin, G.; Hill, D. K.; Andrejeva, G.; Boult, J. K. R.; Troy, H.; Fong, A-C L. F. W. T.; Orton, M. R.; Panek, R.; Parkes, H. G.; Jafar, M.; Koh, D-M; Robinson, S. P.; Leach, M. O.; Eykyn, T. R.; Chung, Y-L] Inst Canc Res London, Canc Res UK Canc Imaging Ctr, Div Radiotherapy & Imaging, Sutton SM2 5PT, Surrey, England; [Lin, G.; Hill, D. K.; Andrejeva, G.; Boult, J. K. R.; Troy, H.; Fong, A-C L. F. W. T.; Orton, M. R.; Panek, R.; Parkes, H. G.; Jafar, M.; Koh, D-M; Robinson, S. P.; Leach, M. O.; Eykyn, T. R.; Chung, Y-L] Royal Marsden Hosp, Sutton SM2 5PT, Surrey, England; [Lin, G.] Chang Gung Univ, Chang Gung Mem Hosp Linkou, Coll Med, Dept Med Imaging & Intervent, Taoyuan 333, Taiwan; [Judson, I. R.] Inst Canc Res London, Canc Res UK Canc Therapeut Unit, Sutton SM2 5NG, Surrey, England; [Griffiths, J. R.] CR UK Cambridge Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England; [Eykyn, T. R.] St Thomas Hosp, Kings Coll London, Rayne Inst, Div Imaging Sci & Biomed Engn, London SE1 7EH, England		Leach, MO (corresponding author), Inst Canc Res London, Canc Res UK Canc Imaging Ctr, Div Radiotherapy & Imaging, Sutton SM2 5PT, Surrey, England.	martin.leach@icr.ac.uk; ylichung@icr.ac.uk	leach, martin o/C-2248-2008; Parkes, Harold G/I-7412-2012; Chung, Yuen-Li/K-2269-2019; Eykyn, Thomas/J-3284-2016; Lin, Gigin/A-2676-2017	leach, martin o/0000-0002-0756-5368; Chung, Yuen-Li/0000-0003-0807-1658; Eykyn, Thomas/0000-0003-1768-3808; Lin, Gigin/0000-0001-7246-1058; Panek, Rafal/0000-0002-9432-6698; Koh, Dow-Mu/0000-0001-7654-8011; Robinson, Simon/0000-0003-4101-7274; Andrejeva, Gabriela/0000-0002-3508-7682; Parkes, Harold/0000-0003-4981-864X; Hill, Deborah/0000-0002-6441-5489	CRUKCancer Research UK; EPSRC Cancer Imaging CentreUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [C1060/A10334]; CRUKCancer Research UK [C1060/A16464]; NHS; Chang Gung Medical Foundation (Taiwan) [CMRPG370441]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MRC119X]; EPSRCUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [EP/H046526/1] Funding Source: UKRI; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [G0701533] Funding Source: UKRI; Cancer Research UKCancer Research UK [16464, 11562] Funding Source: researchfish; Engineering and Physical Sciences Research CouncilUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [EP/H046526/1, GR/S23612/01] Funding Source: researchfish; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [G0701533, 1100738] Funding Source: researchfish; National Institute for Health ResearchNational Institute for Health Research (NIHR) [NF-SI-0512-10162] Funding Source: researchfish	We acknowledge the support received from the CRUK and EPSRC Cancer Imaging Centre in association with the MRC and Department of Health (England) grant C1060/A10334, CRUK grant C1060/A16464, also NHS funding to the NIHR Biomedical Research Centre, Chang Gung Medical Foundation (Taiwan) grant CMRPG370441 and MRC-funded studentship (MRC119X). MOL is an NIHR Senior Investigator. We thank Alice Warley at the Kings College London Centre for Ultrastructural Imaging (CUI) for providing facilities for electron microscopy.	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J. Cancer	JUL 15	2014	111	2					375	385		10.1038/bjc.2014.281			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AL5LX	WOS:000339176300019	24892448	hybrid, Green Published			2022-04-25	
J	Chang, YT; Tseng, HC; Huang, CC; Chen, YP; Chiang, HC; Chou, FP				Chang, Ying-Tse; Tseng, Hsien-Chun; Huang, Chi-Chou; Chen, Ya-Pei; Chiang, Huei-Ching; Chou, Fen-Pi			Relative down-regulation of apoptosis and autophagy genes in colorectal cancer	EUROPEAN JOURNAL OF CLINICAL INVESTIGATION			English	Article						Gene expression; programmed cell death; RT-qPCR	EXPRESSION; YEAST; CELL; MACROAUTOPHAGY; INHIBITION; PATHWAYS; BECLIN-1; PROTEIN; GROWTH; DEATH	P>Background Cancer is often caused by disturbance in the regulation and/or execution of programmed cell death (PCD, including apoptosis and autophagy). Our aim was to investigate these two pathways simultaneously in the same samples to understand further the pathological roles of PCDs in colorectal cancer. Materials and methods Real time quantitative PCR (RT-qPCR) array was used to analyse the mRNA levels of 22 apoptosis and autophagy-related genes involved in pro- and anti-action of the pathways in 15 paired (tumour and non-cancerous part) colorectal samples using Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the reference gene. Results GAPDH mRNA content was significantly higher (approximately 4 center dot 01 fold) in tumour tissue than that of paired non-cancerous part. The absolute mRNA levels for most of the 22 genes were higher in the tumour tissue also. However, after normalization with GAPDH Ct, the expressions of all the analysed genes were decreased in the tumour tissues, except for damage-regulated autophagy modulator (DRAM). The expression of most of the genes involved in the same pathway was closely correlated to each other in both tumour and non-cancerous tissues, and the correlation of tumour necrosis factor receptor (TNFR) and Akt to other genes in the same pathway was increased in tumour tissues. Conclusions The high level expression of GAPDH might reflect the metabolic state of cancer cells, and PCDs were down-regulated in the tumour tissues when metabolic state was taken into consideration. This relative suppression of PCDs in tumour tissue is supposed to be in favour of cancer cell survival.	[Chang, Ying-Tse] Tungs Taichung Metro Harbor Hosp, Div Gastroenterol, Taichung Cty, Taiwan; [Tseng, Hsien-Chun; Chen, Ya-Pei; Chou, Fen-Pi] Chung Shan Med Univ Hosp, Coll Med, Inst Biochem & Biotechnol, Taichung, Taiwan; [Tseng, Hsien-Chun; Chou, Fen-Pi] Chung Shan Med Univ Hosp, Dept Radiat Oncol, Taichung, Taiwan; [Huang, Chi-Chou] Chung Shan Med Univ Hosp, Dept Colorectal Surg, Taichung, Taiwan; [Chiang, Huei-Ching] Chung Shan Med Univ Hosp, Dept Pathol, Taichung, Taiwan		Chou, FP (corresponding author), Chung Shan Med Univ, Inst Biochem & Biotechnol, 110,Sec 1,Jianguo N Rd, Taichung 402, Taiwan.	fpchou@csmu.edu.tw			Chung Shan Medical University, Taichung, Taiwan [CSMU-TTM-097-003]; Tungs' Taichung Metro Harbor Hospital, Taichung County, Taiwan	This work was supported by the grant (CSMU-TTM-097-003) funded by Chung Shan Medical University, Taichung, Taiwan, and Tungs' Taichung Metro Harbor Hospital, Taichung County, Taiwan. All authors have nothing to declare for interest conflict and financial disclosure.	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J. Clin. Invest.	JAN	2011	41	1					84	92		10.1111/j.1365-2362.2010.02383.x			9	Medicine, General & Internal; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine; Research & Experimental Medicine	691WA	WOS:000285110300012	20880300				2022-04-25	
J	Saporita, AJ; Maggi, LB; Apicelli, AJ; Weber, JD				Saporita, Anthony J.; Maggi, Leonard B., Jr.; Apicelli, Anthony J.; Weber, Jason D.			Therapeutic targets in the ARF tumor suppressor pathway	CURRENT MEDICINAL CHEMISTRY			English	Review						ARF; Mdm2; p53; nucleophosmin; nucleolus; ribosome biogenesis	SQUAMOUS-CELL CARCINOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN HEPATOCELLULAR-CARCINOMA; ABERRANT PROMOTER METHYLATION; ACUTE MYELOGENOUS LEUKEMIA; NERVOUS-SYSTEM LYMPHOMAS; CPG ISLAND METHYLATION; HUMAN BLADDER-CANCER; HUMAN COLON-CANCER; WILD-TYPE P53	One of the outstanding fundamental questions in cancer cell biology concerns how cells coordinate cellular growth (or macromolecular synthesis) with cell cycle progression and mitosis. Intuitively, rapidly dividing cells must have some control over these processes; otherwise cells would continue to shrink in volume with every passing cycle, similar to the cytoreductive divisions seen in the very early stagges of embryogenesis. The problem is easily solved in unicellular organisms, such as yeast, as their growth rates are entirely dependent on nutrient availability. Multicellular organisms Such as mammals, however, must have acquired additional levels of control, as nutrient availability is seldom an issue and the organism has a prodigious capacity to store necessary metabolites in the form of glycogen, lipids, and protein, Furthermore, the specific needs and specialized architecture of tissues must constrain growth for growth's sake; if not, the necessary function of the organ could be lost. While certainly a myriad of mechanisms for preventing this exist via initiating cell death (e.g. apoptosis, autophagy, necrosis), these all depend on some external cue; such as death signals, hypoxia, lack of nutrients or survival signals. However there must also be some cell autonomous method for surveying against inappropriate growth signals (such as oncogenic stress) that occur in a stochastic fashion, possibly as a result of random mutations. The ARF tumor suppressor seems to Fulfill that role, as its expression is near undetectable in normal tissues, yet is potently induced by oncogenic stress (such as overexpression of oncogenic Ras or myc). As a result of induced expression of ARF, the tumor suppressor protein p53 is stabilized and promotes cell cycle arrest. Mutations or epiggenetic alterations of the INK4a/Arflocus are second only to p53 mutations in cancer cells, and in some cancers, alterations in both Arf and p53 observed, suggesting that these two tumor suppressors act coordinately to prevent unwarranted cell growth and proliferation. The aim of this review is to characterize the current knowledge in the field about both p53-dependent and independent functions of ARF as well as to summarize the present models for how ARF might control rates of cell proliferation and/or macromolecular synthesis. We will discuss potential therapeutic targets in the ARF pathway, and some preliminary attempts at enhancing or restoring the activity of this important tumor suppressor.	Washington Univ, Sch Med, Siteman Canc Ctr, Dept Internal Med,Div Mol Oncol, St Louis, MO 63110 USA; Washington Univ, Sch Med, Siteman Canc Ctr, Dept Cell Biol,Div Mol Oncol, St Louis, MO 63110 USA		Weber, JD (corresponding author), Washington Univ, Sch Med, Dept Internal Med, Div Mol Oncol, St Louis, MO 63110 USA.	jweber@im.wustl.edu	Maggi, Leonard/L-5217-2019; Apicelli, Anthony/AAB-8879-2021	Maggi, Leonard/0000-0003-0138-0984; Apicelli, Anthony/0000-0001-6791-8113; Weber, Jason/0000-0002-1069-6983	NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [T32CA11327501] Funding Source: Medline; NIGMS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM066032, R01 GM066032-05, R01 GM066032] Funding Source: Medline; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM066032] Funding Source: NIH RePORTER		Alonso ME, 2003, CANCER GENET CYTOGEN, V144, P134, DOI 10.1016/S0165-4608(02)00928-7; 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Med. Chem.		2007	14	17					1815	1827					13	Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	186JE	WOS:000247774200002	17627519				2022-04-25	
J	Vigen, RA; Kodama, Y; Viset, T; Fossmark, R; Waldum, H; Kidd, M; Wang, TC; Modlin, IM; Chen, D; Zhao, CM				Vigen, Reidar Alexander; Kodama, Yosuke; Viset, Trond; Fossmark, Reidar; Waldum, Helge; Kidd, Mark; Wang, Timothy C.; Modlin, Irvin M.; Chen, Duan; Zhao, Chun-Mei			Immunohistochemical evidence for an impairment of autophagy in tumorigenesis of gastric carcinoids and adenocarcinomas in rodent models and patients	HISTOLOGY AND HISTOPATHOLOGY			English	Article						Cotton rats; Mastomys; INS-GAS mice; patients	DOUBLE-EDGED-SWORD; COTTON RATS; COLORECTAL CANCERS; CELL CARCINOMAS; BECLIN-1; ANTAGONIST; EXPRESSION; LOXTIDINE; APOPTOSIS; DEATH	Background/Aim: Autophagy has dual roles in tumorigenesis: tumor-promoting or tumor-suppressing. The aim of the present study was to examine autophagy-related markers by immunohistochemistry in gastric carcinoids and adenocarcinomas in rodent models and patients. Methods: Gastric carcinoids in Mastomys were induced by loxtidine treatment. Spontaneously developed gastric adenocarcinomas in Japanese cotton rats and INS-GAS transgenic mice were included. Patient tissue samples of gastric carcinoids or adenocarcinomas were collected. Immunohistochemistry was performed against autophagy-related gene protein-6 (ATG-6, also called beclin-1), ATG-5 and ATG-16. Results: In tumor-free Mastomys, ATG-5, ATG-16 and beclin-1 were immunepositive in the gastric mucosa. In tumor-bearing Mastomys, ATG-5 and ATG-16 were negative in the tumors, whereas beclin-1 was positive in four of five animals. In carcinoid patients, ATG-5 was negative in six of ten, ATG-16 negative in nine of ten, and beclin-1 negative in three of ten patients. In cotton rats, ATG-5 and ATG-16 were negative in all tumors. Beclin-1 was negative in three of five rats. In INS-GAS mice, ATG-5 and beclin-1 were positive in the tumor area, but the numbers of immunopositive cells per gland were reduced by about 50% in comparison with wildtype mice. In adenocarcinoma patients, ATG-5 and ATG-16 were negative in eight of ten, and beclin-1 positive in all ten patients. Conclusions: An impaired autophagy took place at the stage of formation of ATG-5-ATG-12-ATG-16 complex in both gastric carcinoids and adenocarcinoma of both rodent models and patients. ATG-5 and ATG-16 might be better markers than beclin-1 in assessing autophagy in these lesions.	[Vigen, Reidar Alexander; Kodama, Yosuke; Fossmark, Reidar; Waldum, Helge; Chen, Duan; Zhao, Chun-Mei] Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, NO-7006 Trondheim, Norway; [Viset, Trond] St Olavs Univ Hosp, Dept Pathol, Trondheim, Norway; [Fossmark, Reidar; Waldum, Helge] St Olavs Univ Hosp, Dept Med Genet & Gastroenterol & Hepatol, Trondheim, Norway; [Kidd, Mark; Modlin, Irvin M.] Yale Univ, Sch Med, Dept Gastrointestinal Surg Pathobiol, New Haven, CT USA; [Wang, Timothy C.] Columbia Univ, Med Ctr, Dept Med, New York, NY USA; [Wang, Timothy C.] Columbia Univ, Med Ctr, Irving Canc Res Ctr, New York, NY USA		Zhao, CM (corresponding author), Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Erling Skjalgssons Gate 1, NO-7006 Trondheim, Norway.	chun-mei.zhao@ntnu.no	Fossmark, Reidar/AAP-6442-2021	Fossmark, Reidar/0000-0002-5365-9357; Waldum, Helge/0000-0002-3137-0843; Wang, Timothy/0000-0001-5730-3019	Research Council of NorwayResearch Council of Norway; Medical Faculty and St. Olavs' University Hospital; Liaison Committee between the Central Norway Regional Health Authority (RHA); Faculty of Medicine of NTNU; Central Norway Regional FUGE programme	This study was supported by grants from the Research Council of Norway and the Joint Programme of the Medical Faculty and St. Olavs' University Hospital, and the Liaison Committee between the Central Norway Regional Health Authority (RHA). Dr. Vigen has received a fellowship from the Faculty of Medicine of NTNU, and Kodama received a fellowship from Central Norway Regional FUGE programme. The histology was performed partly at the Cellular and Molecular Imaging Core Facility, NTNU.	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Histopath.	APR	2013	28	4					531	542					12	Cell Biology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Pathology	107BP	WOS:000316190000013	23389729				2022-04-25	
J	Morales, PR; Dillehay, DL; Moody, SJ; Pallas, DC; Pruett, S; Allgood, JC; Symolon, H; Merrill, AH				Morales, Pablo R.; Dillehay, Dirck L.; Moody, Steven J.; Pallas, David C.; Pruett, Sarah; Allgood, Jeremy C.; Symolon, Holly; Merrill, Alfred H., Jr.			Safingol toxicology after oral administration to TRAMP mice: Demonstration of safingol uptake and metabolism by N-acylation and n-methylation	DRUG AND CHEMICAL TOXICOLOGY			English	Article						cancer; hepatotoxicity; mass spectrometry; safingol; safingol metabolites; sphingolipids; TRAMP mice	PROTEIN-KINASE-C; 1,2-DIMETHYLHYDRAZINE-TREATED CF1 MICE; TANDEM MASS-SPECTROMETRY; INHIBITOR SAFINGOL; IN-VITRO; COLON-CANCER; CRYPT FOCI; CELL LINES; SPHINGOLIPIDS; SPHINGOSINE	Safingol [(2S, 3S)-2-amino-1,3-octadecanediol] is an unnatural L-threo-stereoisomer of sphinganine that is cytotoxic for cancer cells in culture and is being tested in phase 1 human clinical trials. To determine if safingol can be absorbed orally and if it affects prostate cancer in a mouse strain used in prostate cancer studies, safingol was fed to TRAMP (transgenic adenocarcinoma of mouse prostate) mice for 2 weeks at 0.0125% to 0.1% w/w of the diet. Analysis of safingol and safingol metabolites in blood and tissues by liquid chromatography electrospray ionization tandem mass spectrometry revealed uptake in tissue and extensive conversion of safingol to N-acyl species (comparable to natural "ceramides") and mono-, di-, and tri-N-methyl metabolites that have not been observed previously. Safingol caused significant hepatotoxicity at all dosages, as reflected in elevated liver alanine aminotransferase, and at the highest dose (0.1 %) caused changes in liver histology (appearance of autophagosomal vacuoles) and renal toxicity (based on elevation of blood urea nitrogen) and decreases in packed blood cell volume and body weight. Safingol did not inhibit the prostate pre-neoplastic lesion (prostate intraepithelial neoplasia) in TRAMP mice; however, additional studies at lower dosages for longer time were not pursued due to host toxicity. Safingol and its N-methyl metabolites were cytotoxic to both a human prostate cell line (DU145) and mouse BALB 3T3 cells; therefore, the host and potential antitumor toxicity may be due to multiple molecular species of safingol.	Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA; Emory Univ, Sch Med, Div Anim Resources, Atlanta, GA 30322 USA; Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA; Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA; Emory Univ, Dept Chem, Atlanta, GA 30322 USA; Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA; Georgia Inst Technol, Sch Chem, Atlanta, GA 30332 USA; Georgia Inst Technol, Sch Biochem, Atlanta, GA 30332 USA; Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA		Dillehay, DL (corresponding author), Emory Univ, Sch Med, Dept Pathol & Lab Med, Whitehead Biomed Res Bldg,615 Michael St, Atlanta, GA 30322 USA.	ddilleh@dar.emory.edu	Pruett, Sarah/C-7433-2009	Merrill, Alfred/0000-0002-6673-968X	NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA057327, CA87525, CA57327, U19 CA087525] Funding Source: Medline; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA057327, U19CA087525] Funding Source: NIH RePORTER		BUEHRER BM, 1992, J BIOL CHEM, V267, P3154; Carfagna MA, 1996, TOXICOL APPL PHARM, V137, P173, DOI 10.1006/taap.1996.0070; Cuvillier O, 2002, BBA-MOL CELL BIOL L, V1585, P153, DOI 10.1016/S1388-1981(02)00336-0; DILLEHAY DL, 1994, J NUTR, V124, P615, DOI 10.1093/jn/124.5.615; Foster BA, 1997, CANCER RES, V57, P3325; GREENBERG NM, 1994, MOL ENDOCRINOL, V8, P230, DOI 10.1210/me.8.2.230; HANNUN YA, 1986, J BIOL CHEM, V261, P2604; Humpf HU, 1998, J BIOL CHEM, V273, P19060, DOI 10.1074/jbc.273.30.19060; IGARASHI Y, 1989, BIOCHEM BIOPH RES CO, V164, P1411, DOI 10.1016/0006-291X(89)91827-5; Inamine M, 2005, CANCER SCI, V96, P876, DOI 10.1111/j.1349-7006.2005.00127.x; Jarvis WD, 1998, MOL PHARMACOL, V54, P844, DOI 10.1124/mol.54.5.844; KEDDERIS LB, 1995, FUND APPL TOXICOL, V25, P201, DOI 10.1006/faat.1995.1056; Komatsu M, 2005, J CELL BIOL, V169, P425, DOI 10.1083/jcb.200412022; Lemonnier LA, 2003, ARCH BIOCHEM BIOPHYS, V419, P129, DOI 10.1016/j.abb.2003.08.023; Maurer BJ, 2000, JNCI-J NATL CANCER I, V92, P1897, DOI 10.1093/jnci/92.23.1897; Menaldino DS, 2003, PHARMACOL RES, V47, P373, DOI 10.1016/S1043-6618(03)00054-9; Merrill AH, 2005, METHODS, V36, P207, DOI 10.1016/j.ymeth.2005.01.009; Milstien S, 2006, CANCER CELL, V9, P148, DOI 10.1016/j.ccr.2006.02.025; Nardacci R, 2000, CELL MOL BIOL, V46, P1277; *NAT TOX PROGR, 2001, 4961352 NTP; *NRC RES COUNC GUI, 1985, PUBL, V88; Ogretmen B, 2004, NAT REV CANCER, V4, P604, DOI 10.1038/nrc1411; RILEY RT, 1994, J NUTR, V124, P594, DOI 10.1093/jn/124.4.594; RILEY RT, 2006, IN PRESS TOXICOL SCI; SACHS CW, 1995, J BIOL CHEM, V270, P26639, DOI 10.1074/jbc.270.44.26639; SALAS M, 1980, PATHOL RES PRACT, V167, P217, DOI 10.1016/S0344-0338(80)80052-5; Schmelz EM, 2004, FRONT BIOSCI, V9, P2632, DOI 10.2741/1422; Schmelz EM, 2000, J NUTR, V130, P522, DOI 10.1093/jn/130.3.522; SCHMELZ EM, 1994, J NUTR, V124, P702, DOI 10.1093/jn/124.5.702; Schmelz EM, 1996, CANCER RES, V56, P4936; Schmelz EM, 2001, CANCER RES, V61, P6723; Schwartz GK, 1997, CLIN CANCER RES, V3, P537; SCHWARTZ GK, 1995, J NATL CANCER I, V87, P1394, DOI 10.1093/jnci/87.18.1394; Silins I, 2003, CARCINOGENESIS, V24, P1077, DOI 10.1093/carcin/bgg055; Sosnowski J, 1997, J UROLOGY, V158, P269, DOI 10.1097/00005392-199707000-00084; Sullards MC, 2000, J MASS SPECTROM, V35, P347, DOI 10.1002/(SICI)1096-9888(200003)35:3<347::AID-JMS941>3.0.CO;2-3; Suzuki E, 2004, P NATL ACAD SCI USA, V101, P14788, DOI 10.1073/pnas.0406536101; Symolon H, 2004, J NUTR, V134, P1157, DOI 10.1093/jn/134.5.1157; Vesper H, 1999, J NUTR, V129, P1239, DOI 10.1093/jn/129.7.1239; Zheng W, 2006, BBA-BIOMEMBRANES, V1758, P1864, DOI 10.1016/j.bbamem.2006.08.009	40	14	14	0	1	TAYLOR & FRANCIS LTD	ABINGDON	2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND	0148-0545	1525-6014		DRUG CHEM TOXICOL	Drug Chem. Toxicol.		2007	30	3					197	216		10.1080/01480540701375018			20	Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy; Toxicology	183WG	WOS:000247602500004	17613006				2022-04-25	
J	Ogando, DG; Choi, M; Shyam, R; Li, SM; Bonanno, JA				Ogando, Diego G.; Choi, Moonjung; Shyam, Rajalekshmy; Li, Shimin; Bonanno, Joseph A.			Ammonia sensitive SLC4A11 mitochondrial uncoupling reduces glutamine induced oxidative stress	REDOX BIOLOGY			English	Article						Slc4a11; Glutamine; Ammonia; Reactive oxygen species; Mitochondrial uncoupling	ION-TRANSPORT; CANCER-CELLS; PROTEIN; AUTOPHAGY; METABOLISM; HYPERAMMONEMIA; MUTATIONS; CHED2; MICE	SLC4A11 is a NH3 sensitive membrane transporter with H+ channel-like properties that facilitates Glutamine catabolism in Human and Mouse corneal endothelium (CE). Loss of SLC4A11 activity induces oxidative stress and cell death, resulting in Congenital Hereditary Endothelial Dystrophy (CHED) with corneal edema and vision loss. However, the mechanism by which SLC4A11 prevents ROS production and protects CE is unknown. Here we demonstrate that SLC4A11 is localized to the inner mitochondrial membrane of CE and SLC4A11 transfected PS120 fibroblasts, where it acts as an NH3-sensitive mitochondrial uncoupler that enhances glutamine-dependent oxygen consumption, electron transport chain activity, and ATP levels by suppressing damaging Reactive Oxygen Species (ROS) production. In the presence of glutamine, Slc4a11(-/-) (KO) mouse CE generate significantly greater mitochondrial superoxide, a greater proportion of damaged depolarized mitochondria, and more apoptotic cells than WT. KO CE can be rescued by MitoQ, reducing NH3 production by GLS1 inhibition or dimethyl alpha Ketoglutarate supplementation, or by BAM15 mitochondrial uncoupling. Slc4a11 KO mouse corneal edema can be partially reversed by aKetoglutarate eye drops. Moreover, we demonstrate that this role for SLC4A11 is not specific to CE cells, as SLC4A11 knockdown in glutamine-addicted colon carcinoma cells reduced glutamine catabolism, increased ROS production, and inhibited cell proliferation. Overall, our studies reveal a unique metabolic mechanism that reduces mitochondrial oxidative stress while promoting glutamine catabolism.	[Ogando, Diego G.; Choi, Moonjung; Shyam, Rajalekshmy; Li, Shimin; Bonanno, Joseph A.] Indiana Univ, Sch Optometry, Bloomington, IN 47405 USA		Bonanno, JA (corresponding author), Indiana Univ, Sch Optometry, Bloomington, IN 47405 USA.	jbonanno@indiana.edu		Shyam, Rajalekshmy/0000-0003-2154-4173; Choi, Moonjung/0000-0002-7218-4924	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NEI/5R01EY008834]; Indiana University CTSI Postdoctoral Fellow NIH/NCATS CTSI [TL1 TR002531, UL1 TR002529.gs1]; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [TL1TR002531] Funding Source: NIH RePORTER; NATIONAL EYE INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [R01EY008834] Funding Source: NIH RePORTER	NIH NEI/5R01EY008834 (JAB). RS is an Indiana University CTSI Postdoctoral Fellow NIH/NCATS CTSI TL1 TR002531 and UL1 TR002529.gs1	Adlimoghaddam A, 2016, FRONT MOL NEUROSCI, V9, DOI 10.3389/fnmol.2016.00057; Alka K, 2018, INVEST OPHTH VIS SCI, V59, P4258, DOI 10.1167/iovs.18-24301; Altman BJ, 2016, NAT REV CANCER, V16, P619, DOI 10.1038/nrc.2016.71; Berry BJ, 2018, J MOL BIOL, V430, P3873, DOI 10.1016/j.jmb.2018.03.025; Cetinbas NM, 2016, SCI REP-UK, V6, DOI 10.1038/srep32606; Cheong H, 2011, P NATL ACAD SCI USA, V108, P11121, DOI 10.1073/pnas.1107969108; Dasarathy S, 2017, METAB BRAIN DIS, V32, P529, DOI 10.1007/s11011-016-9938-3; Davuluri G, 2016, J PHYSIOL-LONDON, V594, P7341, DOI 10.1113/JP272796; Eng CH, 2010, SCI SIGNAL, V3, DOI 10.1126/scisignal.2000911; Gottsch JD, 2003, INVEST OPHTH VIS SCI, V44, P594, DOI 10.1167/iovs.02-0300; Grivennikova VG, 2008, FEBS LETT, V582, P2719, DOI 10.1016/j.febslet.2008.06.054; Guha S, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-03654-4; Han SB, 2013, INVEST OPHTH VIS SCI, V54, P6179, DOI 10.1167/iovs.13-12089; Harder LM, 2014, AUTOPHAGY, V10, P339, DOI 10.4161/auto.26863; Hogan MJ, 1971, HISTOLOGY HUMAN EYE; Hurtaud C, 2007, CELL MOL LIFE SCI, V64, P1853, DOI 10.1007/s00018-007-7039-5; Jalimarada SS, 2014, MOL VIS, V20, P1668; Jayakumar AR, 2004, GLIA, V46, P296, DOI 10.1002/glia.20003; Jiao XD, 2007, J MED GENET, V44, P64, DOI 10.1136/jmg.2006.044644; Jurkunas UV, 2010, AM J PATHOL, V177, P2278, DOI 10.2353/ajpath.2010.100279; Kao LY, 2016, AM J PHYSIOL-CELL PH, V311, pC820, DOI 10.1152/ajpcell.00233.2016; Kao LY, 2015, AM J PHYSIOL-CELL PH, V308, pC176, DOI 10.1152/ajpcell.00271.2014; Kareyeva AV, 2011, FEBS LETT, V585, P385, DOI 10.1016/j.febslet.2010.12.019; Kenwood BM, 2014, MOL METAB, V3, P114, DOI 10.1016/j.molmet.2013.11.005; Kitajima S, 2017, ONCOTARGET, V8; Klionsky DJ, 2016, AUTOPHAGY, V12, P1, DOI 10.1080/15548627.2015.1100356; Ko YH, 2011, CANCER BIOL THER, V12, P1085, DOI 10.4161/cbt.12.12.18671; Langford MP, 2007, CLIN OPHTHALMOL, V1, P43; Li SM, 2016, AM J PHYSIOL-CELL PH, V311, pC116, DOI 10.1152/ajpcell.00095.2016; Li XY, 2013, J HEMATOL ONCOL, V6, DOI 10.1186/1756-8722-6-19; Litman Thomas, 2009, Handb Exp Pharmacol, P327, DOI 10.1007/978-3-540-79885-9_17; Loganathan SK, 2016, AM J PHYSIOL-CELL PH, V311, pC735, DOI 10.1152/ajpcell.00078.2016; Loganathan SK, 2016, AM J PHYSIOL-CELL PH, V310, pC161, DOI 10.1152/ajpcell.00246.2015; Mailloux RJ, 2011, FREE RADICAL BIO MED, V51, P1106, DOI 10.1016/j.freeradbiomed.2011.06.022; Malik AN, 2016, MITOCHONDRION, V29, P59, DOI 10.1016/j.mito.2016.05.003; Myers EJ, 2016, AM J PHYSIOL-CELL PH, V311, pC945, DOI 10.1152/ajpcell.00259.2016; Ogando DG, 2013, AM J PHYSIOL-CELL PH, V305, pC716, DOI 10.1152/ajpcell.00056.2013; Parker MD, 2001, BIOCHEM BIOPH RES CO, V282, P1103, DOI 10.1006/bbrc.2001.4692; Qin LZ, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0187385; Qureshi K, 1998, NEUROCHEM RES, V23, P855, DOI 10.1023/A:1022406911604; Schmedt T, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0051427; Siddiqui S, 2014, CORNEA, V33, P247, DOI 10.1097/ICO.0000000000000041; Skowronska M, 2013, NEUROCHEM INT, V62, P731, DOI 10.1016/j.neuint.2012.10.013; Valente AJ, 2017, ACTA HISTOCHEM, V119, P315, DOI 10.1016/j.acthis.2017.03.001; Verdin E, 2015, SCIENCE, V350, P1208, DOI 10.1126/science.aac4854; Vilas GL, 2012, HUM MUTAT, V33, P419, DOI 10.1002/humu.21655; Vozza A, 2014, P NATL ACAD SCI USA, V111, P960, DOI 10.1073/pnas.1317400111; Wang YQ, 2012, AUTOPHAGY, V8, P1462, DOI 10.4161/auto.21211; Zhang WL, 2017, INVEST OPHTH VIS SCI, V58, P3723, DOI 10.1167/iovs.17-21781; Zhang W, 2017, EBIOMEDICINE, V16, P292, DOI 10.1016/j.ebiom.2017.01.004; Zhang WL, 2015, J BIOL CHEM, V290, P16894, DOI 10.1074/jbc.M114.627455; Zhdanov AV, 2014, BBA-BIOENERGETICS, V1837, P51, DOI 10.1016/j.bbabio.2013.07.008	52	16	16	1	6	ELSEVIER	AMSTERDAM	RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS	2213-2317			REDOX BIOL	Redox Biol.	SEP	2019	26								101260	10.1016/j.redox.2019.101260			14	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	JI9ZE	WOS:000493821500004	31254733	gold, Green Published			2022-04-25	
J	Xu, ZB; Chi, P; Pan, J; Shen, SF; Sun, YW; Wang, XJ; Lu, XR				Xu, Zongbin; Chi, Pan; Pan, Jie; Shen, Songfei; Sun, Yanwu; Wang, Xiaojie; Lu, Xingrong			Knockdown of KLK11 inhibits cell proliferation and increases oxaliplatin sensitivity in human colorectal cancer	EXPERIMENTAL AND THERAPEUTIC MEDICINE			English	Article						colorectal cancer; kallikrein 11; oxaliplatin; drug resistance; apoptosis	EXPRESSION LEVELS; PLUS OXALIPLATIN; LIVER METASTASES; 1ST-LINE THERAPY; PHASE-III; CHEMOTHERAPY; APOPTOSIS; IDENTIFICATION; CARCINOMA; AUTOPHAGY	It has been reported that kallikrein 11 (KLK11) is crucially involved in the development and progression of various types of cancer. However, the molecular mechanisms that underlie the involvement of KLK11 in aberrant colorectal cancer (CRC) cell growth remain largely unclear. The aim of the present study was to investigate the role of KLK11 and the effects of KLK11 on oxaliplatin (L-OHP) chemosensitivity by knocking down KLK11 in LOVO and HCT-8 cells. Loss-of-function assays revealed KLK11 inhibition significantly inhibited growth and induced apoptosis of CRC cells in vitro. Notably, further experiments found that knockdown of KLK11 expression increased the L-OHP chemosensitivity of CRC cells. KLK11 inhibition of increased L-OHP-induced apoptosis may be associated with activation of caspase-3 cleavage and the apoptosis signaling pathway. The present results indicated that KLK11 may be an potential target of interest for future research into therapies for CRC.	[Xu, Zongbin; Chi, Pan; Sun, Yanwu; Wang, Xiaojie; Lu, Xingrong] Fujian Med Univ, Union Hosp, Dept Colorectal Surg, 29 Xinquan Rd, Fuzhou 350001, Fujian, Peoples R China; [Pan, Jie] Fujian Med Univ, Union Hosp, Dept Emergency Surg, Fuzhou 350001, Fujian, Peoples R China; [Shen, Songfei] Fujian Med Univ, Union Hosp, Dept Med Oncol, Fuzhou 350001, Fujian, Peoples R China		Lu, XR (corresponding author), Fujian Med Univ, Union Hosp, Dept Colorectal Surg, 29 Xinquan Rd, Fuzhou 350001, Fujian, Peoples R China.	luxingrong2015@163.com					Alexopoulou DK, 2014, BIOMARK MED, V8, P671, DOI [10.2217/bmm.13.151, 10.2217/BMM.13.151]; Cassidy J, 2008, J CLIN ONCOL, V26, P2006, DOI 10.1200/JCO.2007.14.9898; Cunningham D, 2010, LANCET, V375, P1030, DOI 10.1016/S0140-6736(10)60353-4; Diaz-Rubio E, 2007, J CLIN ONCOL, V25, P4224, DOI 10.1200/JCO.2006.09.8467; Gan L, 2000, GENE, V257, P119, DOI 10.1016/S0378-1119(00)00382-6; Gillet JP, 2010, METHODS MOL BIOL, V596, P47, DOI 10.1007/978-1-60761-416-6_4; Kim SY, 2015, INT J MED SCI, V12, P92, DOI 10.7150/ijms.10497; Kuo IM, 2015, WORLD J SURG ONCOL, V13, DOI 10.1186/s12957-015-0497-6; Li ST, 2013, FUTURE ONCOL, V9, P727, DOI [10.2217/FON.13.25, 10.2217/fon.13.25]; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Mavridis K, 2010, FUTURE ONCOL, V6, P269, DOI [10.2217/fon.09.149, 10.2217/FON.09.149]; Nakamura T, 2003, PROSTATE, V54, P299, DOI 10.1002/pros.10191; Niitsu H, 2015, WORLD J SURG ONCOL, V13, DOI 10.1186/s12957-015-0570-1; Nordlinger B, 2008, LANCET, V371, P1007, DOI 10.1016/S0140-6736(08)60455-9; Ouyang L, 2012, CELL PROLIFERAT, V45, P487, DOI 10.1111/j.1365-2184.2012.00845.x; Patsis C, 2012, CLIN BIOCHEM, V45, P623, DOI 10.1016/j.clinbiochem.2012.03.005; Pettersson F, 2002, BRIT J CANCER, V87, P555, DOI 10.1038/sj.bjc.6600496; Porter AG, 1999, CELL DEATH DIFFER, V6, P99, DOI 10.1038/sj.cdd.4400476; Seki K, 2014, INT J MED SCI, V11, P641, DOI 10.7150/ijms.7643; Siegel R, 2014, CA-CANCER J CLIN, V64, P104, DOI 10.3322/caac.21220; Talbot R, 2010, LANCET, V376, P330, DOI 10.1016/S0140-6736(10)61182-8; Tol J, 2009, NEW ENGL J MED, V360, P563, DOI 10.1056/NEJMoa0808268; Tu JH, 2015, EXP THER MED, V9, P17, DOI 10.3892/etm.2014.2063; Unal D, 2013, PATHOL RES PRACT, V209, P779, DOI 10.1016/j.prp.2013.09.004; Van Cutsem E, 2006, EUR J CANCER, V42, P2212, DOI 10.1016/j.ejca.2006.04.012; Wang QJ, 2015, EXP THER MED, V9, P1314, DOI 10.3892/etm.2015.2230; Wang Y, 2014, INT J MED SCI, V11, P691, DOI 10.7150/ijms.8880; Wen YG, 2011, J SURG ONCOL, V104, P516, DOI 10.1002/jso.21981; Zhou FF, 2011, FEBS J, V278, P403, DOI 10.1111/j.1742-4658.2010.07965.x; Zhu XC, 2012, INT J MOL MED, V30, P1321, DOI 10.3892/ijmm.2012.1140	30	9	9	0	1	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-0981	1792-1015		EXP THER MED	Exp. Ther. Med.	NOV	2016	12	5					2855	2860		10.3892/etm.2016.3723			6	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	ED4ME	WOS:000388822000009	27882085	Green Submitted, Green Published, gold			2022-04-25	
J	Liu, JL; Chen, FF; Chang, SF; Chen, CN; Lung, J; Lo, CH; Lee, FH; Lu, YC; Hung, CH				Liu, Jing-Lan; Chen, Fen-Fen; Chang, Shun-Fu; Chen, Cheng-Nan; Lung, Jrhau; Lo, Cheng-Hsing; Lee, Fang-Hui; Lu, Ying-Chou; Hung, Chien-Hui			Expression of Beclin Family Proteins Is Associated with Tumor Progression in Oral Cancer	PLOS ONE			English	Article							SQUAMOUS-CELL CARCINOMA; POOR-PROGNOSIS; COLORECTAL-CANCER; COUPLED RECEPTORS; AUTOPHAGY GENE; BREAST-CANCER; ADENOCARCINOMA; TUMORIGENESIS; BCL-2; HIF-1-ALPHA	Background Beclin 1 and Beclin 2 are autophagy-related proteins that show similar amino acid sequences and domain structures. Beclin 1 established the first connection between autophagy and cancer. However, the role of Beclin 2 in cancer is unclear. The aims of this study were to analyze Beclin 1 and Beclin 2 expressions in oral cancer tissues and in cell lines, and to evaluate their possible roles in cancer progression. Methods We investigated Beclin 1 and Beclin 2 expressions by immunohistochemistry in 195 cases of oral cancer. The prognostic roles of Beclin 1 and Beclin 2 were analyzed statistically. In vitro, overexpression and knockdown of Beclin proteins were performed on an oral cancer cell line, SAS. The immunofluorescence and autophagy flux assays confirmed that Beclin proteins were involved in autophagy. The impacts of Beclin 1 and Beclin 2 on autophagy and tumor growth were evaluated by conversion of LC3-I to LC3-II and by clonogenic assays, respectively. Results Oral cancer tissues exhibited aberrant expressions of Beclin 1 and Beclin 2. The cytoplasmic Beclin 1 and Beclin 2 expressions were unrelated in oral cancer tissues. In survival analyses, high cytoplasmic Beclin 1 expression was associated with low disease specific survival, and negative nuclear Beclin 1 expression was associated with high recurrent free survival. Patients with either high or low cytoplasmic Beclin 2 expression had significantly lower overall survival and disease specific survival rates than those with moderate expression. In oral cancer cells, overexpression of either Beclin 1 or Beclin 2 led to autophagy activation and increased clonogenic survival; knockdown of Beclin 2 impaired autophagy and increased clonogenic survival. Conclusions Our results indicated that distinct patterns of Beclin 1 and Beclin 2 were associated with aggressive clinical outcomes. Beclin 1 overexpression, as well as Beclin 2 overexpression and depletion, contributed to tumor growth. These findings suggest Beclin proteins are associated with tumorigenesis.	[Liu, Jing-Lan; Chen, Fen-Fen] Chang Gung Mem Hosp, Chiayi Branch, Dept Pathol, Chiayi, Taiwan; [Liu, Jing-Lan; Hung, Chien-Hui] Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Taoyuan, Taiwan; [Chang, Shun-Fu] Chang Gung Mem Hosp, Chiayi Branch, Dept Med Res & Dev, Chiayi, Taiwan; [Chen, Cheng-Nan] Natl Chiayi Univ, Dept Biochem Sci & Technol, Chiayi 60004, Taiwan; [Lung, Jrhau] Chang Gung Mem Hosp, Chiayi Branch, Dept Med, Div Pulm & Crit Care Med, Chiayi, Taiwan; [Lo, Cheng-Hsing; Lee, Fang-Hui] St Martin De Porres Hosp, Dept Oral & Maxillofacial Surg, Chiayi, Taiwan; [Lu, Ying-Chou] St Martin De Porres Hosp, Dept Otolaryngol, Chiayi, Taiwan		Hung, CH (corresponding author), Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Taoyuan, Taiwan.	hungc01@mail.cgu.edu.tw			Ministry of Science and Technology of TaiwanMinistry of Science and Technology, Taiwan [MOST 103-2320-B-182A-018-, NMRPG6D0071, MOST 104-2320-B-182A-012-, NMRPG6E0041]; Chang Gung Memorial Hospital Chiayi Branch [CMRPG6E0071]; Chang Gung Medical Research Center [CMRPD6C0013]	This work was supported by grants from the Ministry of Science and Technology of Taiwan (MOST 103-2320-B-182A-018-, NMRPG6D0071) (MOST 104-2320-B-182A-012-, NMRPG6E0041), Chang Gung Memorial Hospital Chiayi Branch (CMRPG6E0071), and Chang Gung Medical Research Center (CMRPD6C0013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Yang, LF; Xing, YJ; Xiao, JX; Xie, J; Gao, W; Xie, JQ; Wang, LT; Wang, JH; Liu, MY; Yi, ZF; Qiu, WW				Yang, Lian-Fang; Xing, Yajing; Xiao, Jie-Xin; Xie, Jia; Gao, Wei; Xie, Jiuqing; Wang, Li-Ting; Wang, Jinhua; Liu, Mingyao; Yi, Zhengfang; Qiu, Wen-Wei			Synthesis of Cyanoenone-Modified Diterpenoid Analogs as Novel Bmi-1-Mediated Antitumor Agents	ACS MEDICINAL CHEMISTRY LETTERS			English	Article						Diterpenoid; cyanoenone; antitumor; colorectal cancer; Bmi-1	MYELOID-LEUKEMIA CELLS; COLORECTAL-CANCER; BARDOXOLONE METHYL; DOWN-REGULATION; BMI-1; GROWTH; APOPTOSIS; AUTOPHAGY; SURVIVAL; PROLIFERATION	Bmi-1 is overexpressed in colorectal cancer (CRC) and served as a novel therapeutic target for the treatment of CRC. A series of novel cyanoenone-modified diterpenoid analogs was synthesized and investigated for their antiproliferative activity against CRC cells. The results showed that most of these compounds exhibited potent antiproliferative and Bmi-1 inhibitory activity. Among them, the most active compound 33 (SH498) showed more potent antiproliferative activity than the positive control compound PTC-209. These synthetic diterpenoid analogs were less toxic for normal human fibroblasts (HAF) than for CRC cells. Especially 33, its selectivity index (SI) between HAF and tumor cells was 7.3-13.1, which was much better than PTC-209. The polycomb repressive complex 1 (PRC1) complex, transwell migration, colony formation, cancer stem cell proliferation, and apoptosis assays of 33 were performed on CRC cell lines. The in vivo antitumor effect of 33 was also observed in HCT116 tumor-bearing mice.	[Yang, Lian-Fang; Xiao, Jie-Xin; Gao, Wei; Wang, Li-Ting; Qiu, Wen-Wei] East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China; [Xing, Yajing; Xie, Jia; Xie, Jiuqing; Wang, Jinhua; Liu, Mingyao; Yi, Zhengfang] East China Normal Univ, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200241, Peoples R China; [Xing, Yajing; Xie, Jia; Xie, Jiuqing; Wang, Jinhua; Liu, Mingyao; Yi, Zhengfang] East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China		Qiu, WW (corresponding author), East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China.; Yi, ZF (corresponding author), East China Normal Univ, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200241, Peoples R China.; Yi, ZF (corresponding author), East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China.	zfyi@bio.ecnu.edu.cn; wwqiu@chem.ecnu.edu.cn			Shanghai Science and Technology Council [18ZR1411200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472788, 81773204]; Major State Basic Research Development Program of ChinaNational Basic Research Program of China [2015CB910400]	Shanghai Science and Technology Council (Grant. 18ZR1411200), National Natural Science Foundation of China (81472788, 81773204), and Major State Basic Research Development Program of China (2015CB910400).	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Chem. Lett.	NOV	2018	9	11					1105	1110		10.1021/acsmedchemlett.8b00345			11	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Pharmacology & Pharmacy	HA0HK	WOS:000449888400008	30429953	Green Published			2022-04-25	
J	Cheng, CY; Wang, T; Song, ZQ; Peng, LJ; Gao, MQ; Hermine, O; Rousseaux, S; Khochbin, S; Mi, JQ; Wang, J				Cheng, Chunyan; Wang, Tao; Song, Zhiqun; Peng, Lijun; Gao, Mengqing; Hermine, Olivier; Rousseaux, Sophie; Khochbin, Saadi; Mi, Jian-Qing; Wang, Jin			Induction of autophagy and autophagy-dependent apoptosis in diffuse large B-cell lymphoma by a new antimalarial artemisinin derivative, SM1044	CANCER MEDICINE			English	Article						Apoptosis; artemisinin derivative; autophagy; DLBCL; Survivin	SURVIVIN SUPPRESSANT; IN-VIVO; HEPATOCELLULAR-CARCINOMA; COMBINATION THERAPY; COLORECTAL-CANCER; DEATH; EXPRESSION; RITUXIMAB; PROTEINS; GROWTH	Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. R-CHOP is currently the standard therapy for DLBCL, but the prognosis of refractory or recurrent patients remains poor. In this study, we synthesized a new water-soluble antimalarial drug artemisinin derivative, SM1044. The treatment of DLBCL cell lines with SM1044 induces autophagy-dependent apoptosis, which is directed by an accelerated degradation of the antiapoptosis protein Survivin, via its acetylation-dependent interaction with the autophagy-related protein LC3-II. Additionally, SM1044 also stimulates the de novo synthesis of ceramide, which in turn activates the CaMKK2-AMPK-ULK1 axis, leading to the initiation of autophagy. Our findings not only elucidate the mechanism of autophagy-dependent apoptosis in DLBCL cells, but also suggest that SM1044 is a promising therapeutic molecule for the treatment of DLBCL, along with R-CHOP regimen.	[Cheng, Chunyan; Wang, Tao; Peng, Lijun; Gao, Mengqing; Mi, Jian-Qing; Wang, Jin] Shanghai Jiao Tong Univ, Sch Med,State Key Lab Med Genom, Rui Jin Hosp,Dept Hematol,Shanghai Inst Hematol, Pole Sinofrancais Sci Vivant & Genom,Collaborat I, Shanghai, Peoples R China; [Song, Zhiqun] Nanjing Med Univ, Affiliated Hosp 1, Dept Blood Transfus, Nanjing, Jiangsu, Peoples R China; [Hermine, Olivier] Univ Paris 05, Hop Necker Enfants Malad, AP HP, Serv Hematol Adultes, Paris, France; [Rousseaux, Sophie; Khochbin, Saadi] Univ Grenoble Alpes, Inst Adv Biosci, INSERM U1209, CNRS UMR 5309, La Tronche, France		Mi, JQ; Wang, J (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp,Shanghai Inst Hematol,State Key Lab, Pole Sinofrancais Sci Vivant & Genom,Collaborat I, 197 Rui Jin Er Rd, Shanghai 200025, Peoples R China.; Mi, JQ; Wang, J (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp,Shanghai Inst Hematol,Dept Hematol, Pole Sinofrancais Sci Vivant & Genom,Collaborat I, 197 Rui Jin Er Rd, Shanghai 200025, Peoples R China.	jianqingmi@shsmu.edu.cn; jinwang@shsmu.edu.cn	Khochbin, Saadi/M-8090-2013; Rousseaux, Sophie/G-1697-2013; Hermine, Olivier/Q-7072-2018	Khochbin, Saadi/0000-0002-0455-0857; Rousseaux, Sophie/0000-0001-5246-5350; Wang, Tao/0000-0002-5178-6969	Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570178, 81670147]; Shanghai Leading Talent Projects [2015048]; Academic Leader Program of Shanghai Science and Technology CommitteeShanghai Science & Technology Committee [16XD1402000]; International Cooperation Projects of Shanghai Science and Technology Committee [15410710200]; INCaInstitut National du Cancer (INCA) France [RPT13001CCA]; plan cancer (ITMO Cancer) [CH7-INS15B66, ASC16012CSA]; Fondation ARC [RAC16042CLA]; Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale; ANRFrench National Research Agency (ANR)	This study was supported by the Natural Science Foundation of China (81570178 to J. Wang and 81670147 to J. Mi), the Shanghai Leading Talent Projects (2015048 to J. Mi), the Academic Leader Program of Shanghai Science and Technology Committee (16XD1402000 to J. Mi), and the International Cooperation Projects of Shanghai Science and Technology Committee (15410710200 to J. Mi). SK Laboratory is supported by INCa (RPT13001CCA), plan cancer (ITMO Cancer, CH7-INS15B66, ASC16012CSA), Fondation ARC (RAC16042CLA), Fondation pour la Recherche Medicale (FRM), and ANR EpiSperm4 (EpiSperm4) grants.	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FEB	2018	7	2					380	396		10.1002/cam4.1276			17	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FV6TE	WOS:000424713800011	29277967	Green Published, gold			2022-04-25	
J	Notaro, A; Sabella, S; Pellerito, O; Vento, R; Calvaruso, G; Giuliano, M				Notaro, Antonietta; Sabella, Selenia; Pellerito, Ornella; Vento, Renza; Calvaruso, Giuseppe; Giuliano, Michela			The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma cells	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						SPARC; cannabinoids; osteosarcoma; apoptosis; caspase-8 activation	COLORECTAL CANCERS; BREAST-CANCER; SPARC; MATRIX; APOPTOSIS; EXPRESSION; OSTEONECTIN; INHIBITION; ACTIVATION; PROMOTER	Secreted protein acidic and rich in cysteine (SPARC) is a multi-functional protein which modulates cell-cell and cell-matrix interactions. In cancer cells, SPARC behaves as a tumor promoter in a number of tumors, but it can also act as a tumor suppressor factor. Our previous results showed that the synthetic cannabinoid WIN55,212-2 (WIN), a potent cannabinoid receptor agonist, is able to sensitize osteosarcoma MG63 cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis which is accompanied with endoplasmic reticulum (ER)-stress induction and the increase in autophagic markers. In the present investigation, we studied the role of SPARC in WIN/TRAIL-induced apoptosis demonstrating that WIN increased the level of SPARC protein and mRNA in a time-dependent manner. This event was functional to WIN/TRAIL-dependent apoptosis as demonstrated by RNA interfering analysis which indicated that SPARC-silenced cells were less sensitive to cytotoxic effects induced by the combined treatment. Our experiments also demonstrate that SPARC interacts with caspase-8 thus probably favoring its translocation to plasma membrane and the activation of extrinsic apoptotic pathway. In conclusion, to the best of our knowledge, our results are the first to show that WIN-dependent increase in the level of SPARC plays a critical role in sensitizing osteosarcoma cells to TRAIL action.	[Notaro, Antonietta; Sabella, Selenia; Vento, Renza; Calvaruso, Giuseppe; Giuliano, Michela] Univ Palermo, Polyclin, Biochem Lab, Dept Biol Chem & Pharmaceut Sci & Technol, Via Vespro 129, I-90128 Palermo, Italy; [Pellerito, Ornella] Toronto Western Hosp, Dept Genet & Dev, Toronto, ON M5T 2S8, Canada		Giuliano, M (corresponding author), Univ Palermo, Polyclin, Biochem Lab, Dept Biol Chem & Pharmaceut Sci & Technol, Via Vespro 129, I-90128 Palermo, Italy.	michela.giuliano@unipa.it		Notaro, Antonietta/0000-0002-9822-0823			Alford AI, 2006, BONE, V38, P749, DOI 10.1016/j.bone.2005.11.017; BELLAHCENE A, 1995, AM J PATHOL, V146, P95; Bradshaw AD, 2001, J CLIN INVEST, V107, P1049, DOI 10.1172/JCI12939; Brekken RA, 2001, MED SCI MONITOR, V13, P25; Cheetham S, 2008, BRIT J CANCER, V98, P1810, DOI 10.1038/sj.bjc.6604377; Chen ZY, 2014, SCI REP-UK, V4, DOI 10.1038/srep07035; Delany AM, 2003, ENDOCRINOLOGY, V144, P2588, DOI 10.1210/en.2002-221044; Horie K, 2010, CANCER SCI, V101, P913, DOI 10.1111/j.1349-7006.2009.01476.x; Kunigal S, 2006, INT J ONCOL, V29, P1349; LANE TF, 1994, FASEB J, V8, P163, DOI 10.1096/fasebj.8.2.8119487; Letourneau PA, 2011, J PEDIATR SURG, V46, P1333, DOI 10.1016/j.jpedsurg.2010.12.013; Mateo F, 2014, MOL CANCER, V13, DOI 10.1186/1476-4598-13-237; Mok SC, 1996, ONCOGENE, V12, P1895; Motamed K, 2002, J CELL BIOCHEM, V84, P759, DOI 10.1002/jcb.10095; Notaro A, 2014, INT J BIOL SCI, V10, P466, DOI 10.7150/ijbs.8337; Ottaviani G, 2009, CANCER TREAT RES, V152, P3, DOI 10.1007/978-1-4419-0284-9_1; Pellerito O, 2014, APOPTOSIS, V19, P1029, DOI 10.1007/s10495-014-0985-0; Portanova P, 2013, INT J ONCOL, V43, P121, DOI 10.3892/ijo.2013.1945; Rentz TJ, 2007, J BIOL CHEM, V282, P22062, DOI 10.1074/jbc.M700167200; Sailaja GS, 2013, INT J ONCOL, V42, P188, DOI 10.3892/ijo.2012.1678; Shi Q, 2004, J BIOL CHEM, V279, P52200, DOI 10.1074/jbc.M409630200; Tai IT, 2008, DRUG RESIST UPDATE, V11, P231, DOI 10.1016/j.drup.2008.08.005; Tang MJ, 2007, J BIOL CHEM, V282, P34457, DOI 10.1074/jbc.M704459200; Yunker CK, 2008, INT J CANCER, V122, P2735, DOI 10.1002/ijc.23450; Zhang JL, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0044618	25	9	9	0	8	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1019-6439	1791-2423		INT J ONCOL	Int. J. Oncol.	MAR	2016	48	3					1039	1044		10.3892/ijo.2015.3307			6	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DC4IS	WOS:000369185000019	26698404	Bronze			2022-04-25	
J	Kaur, H; Moreau, R				Kaur, Harleen; Moreau, Regis			Curcumin represses mTORC1 signaling in Caco-2 cells by a two-sided mechanism involving the loss of IRS-1 and activation of AMPK	CELLULAR SIGNALLING			English	Article						Raptor; PRAS40; ERK; p38; Nutrient signaling; Turmeric	MAMMALIAN TARGET; TUBEROUS-SCLEROSIS; PROTEIN-KINASE; EVEROLIMUS INTERFERES; INSULIN-RESISTANCE; P38 MAPK; RAPAMYCIN; AUTOPHAGY; AKT; PHOSPHORYLATION	The mechanistic target of rapamycin complex 1 (mTORC1) is a central modulator of inflammation and tumorigenesis in the gastrointestinal tract. Growth factors upregulate mTORC1 via the PI3K/AKT and/or Ras/MAPK signal pathways. Curcumin (CUR), a polyphenol found in turmeric roots (Curcuma longa) can repress mTORC1 kinase activity in colon cancer cell lines; however, key aspects of CUR mechanism of action remain to be elucidated including its primary cellular target. We investigated the molecular effects of physiologically attainable concentration of CUR (20 mu M) in the intestinal lumen on mTORC1 signaling in Caco-2 cells. CUR markedly inhibited mTORC1 kinase activity as determined by the decreased phosphorylation of p70S6K (Thr389, -99%, P < 0.0001) and S6 (Ser235/236, -92%, P < 0.0001). Mechanistically, CUR decreased IRS-1 protein abundance (-80%, P < 0.0001) thereby downregulating AKT phosphorylation (Ser473, -94%, P < 0.0001) and in turn PRAS40 phosphorylation (Thr246, -99%, P < 0.0001) while total PRAS40 abundance was unchanged. The use of proteasome inhibitor MG132 showed that CUR-mediated loss of IRS-1 involved proteasomal degradation. CUR lowered Raptor protein abundance, which combined with PRAS40 hypophosphorylation, suggests CUR repressed mTORC1 activity by inducing compositional changes that hinder the complex assembly. In addition, CUR activated AMPK (Thr172 phosphorylation, P < 0.0001), a recognized repressor of mTORC1, and AMPK upstream regulator LKB1. Although cargo adapter protein p62 was decreased by CUR (-49%, P < 0.004), CUR did not significantly induce autophagy. Inhibition of AKT/mTORC1 signaling by CUR may have lifted the cross-inhibition onto MAPK signaling, which became induced; p-ERK1/2 (+670%, P < 0.0001), p-p38 (+1433%, P < 0.0001). By concomitantly targeting IRS-1 and AMPK, CUR's mechanism of mTORC1 inhibition is distinct from that of rapamycin.	[Kaur, Harleen; Moreau, Regis] Univ Nebraska, Dept Nutr & Hlth Sci, Lincoln, NE 68583 USA		Moreau, R (corresponding author), Univ Nebraska, Dept Nutr & Hlth Sci, Lincoln, NE 68583 USA.	rmoreau2@unl.edu		Moreau, Regis/0000-0003-0532-9887	Agriculture and Food Research Initiative from the USDA National Institute of Food and Agriculture (Program: Food Safety, Nutrition, and Health) [2016-67017-24431, A1341]; Nebraska Agricultural Experiment Station; USDA National Institute of Food and AgricultureUnited States Department of Agriculture (USDA) [230874]	This work was supported in part by the Agriculture and Food Research Initiative (Award Number 2016-67017-24431) to R.M. from the USDA National Institute of Food and Agriculture (Program: Food Safety, Nutrition, and Health -A1341); and the Nebraska Agricultural Experiment Station with funding from the Hatch Act (Accession Number 230874) through the USDA National Institute of Food and Agriculture.	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Signal.	FEB	2021	78								109842	10.1016/j.cellsig.2020.109842			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	PN8SQ	WOS:000604742800002	33234350	Bronze			2022-04-25	
J	Ahlam, AA; Shaniba, VS; Jayasree, PR; Kumar, PRM				Ahlam, Abdul Aziz; Shaniba, V. S.; Jayasree, P. R.; Kumar, P. R. Manish			Spondias pinnata(L.f.) Kurz Leaf Extract Derived Zinc Oxide Nanoparticles Induce Dual Modes of Apoptotic-Necrotic Death in HCT 116 and K562 Cells	BIOLOGICAL TRACE ELEMENT RESEARCH			English	Article						Spondias pinnata; Zinc oxide nanoparticles; HCT 116; K562; Apoptosis; Necrosis	SOL-GEL SYNTHESIS; METAL NANOPARTICLES; ANTICANCER ACTIVITY; SPONDIAS-PINNATA; GREEN SYNTHESIS; PLANT-EXTRACTS; CYTOTOXICITY; AUTOPHAGY; SIGNAL	This study evaluates the effects of phyto-derived zinc oxide nanoparticles (ZnONPs) on human cancer cells, colon carcinoma HCT 116, and chronic myelogenous leukemic K562, along with normal lymphocytes/erythrocytes. The commercial, chemically synthesized ZnONPs (cZnONPs) were also assessed in parallel. Using an eco-friendly approach devoid of harmful chemicals, biogenic nanoparticles were synthesized from aqueous leaf extract ofSpondias pinnata(SpLZnONPs) by a sol-gel method. Optical, structural, and elemental characterization of both particle types were carried out deploying UV-Vis/photoluminescence spectroscopy, FTIR, XRD, FESEM, HRTEM, and EDX. Both SpLZnONPs and cZnONPs displayed hexagonal wurtzite structure with particle sizes averaging 30 and 48.5 nm, respectively. SpLZnONPs were found to be cytotoxic to both cancer cell types while cZnONPs exhibited toxicity only against HCT 116 cells. Interestingly, the cytomorphological changes and analysis of DNA laddering pattern observed in these treated cells were indicative of simultaneous induction of dual modes of death involving apoptosis and necrosis. Flow cytometric analysis of cell-cycle distribution, clonogenic, wound healing, and comet assays provided evidences of the antiproliferative potential of the tested nanoparticles. Apoptosis induction via oxidative stress-mediated Ca(2+)release, ROS generation, loss of mitochondrial membrane potential, and externalization of phosphatidylserine was also determined biochemically. Relative expression of apoptotic genes was quantified using RT-qPCR and Western blot analysis. Mitotic index analysis, MTT, and hemolytic assays on lymphocytes and erythrocytes clearly revealed the absence of any deleterious effect(s) of SpLZnONPs in these cells compared with the toxicity of the chemically derived cZnONPs, thereby attesting to the biocompatibility and selective action of the biogenic nanoparticles.	[Ahlam, Abdul Aziz; Shaniba, V. S.; Kumar, P. R. Manish] Univ Calicut, Dept Biotechnol, Recombinant DNA Lab, Calicut 673635, Kerala, India; [Jayasree, P. R.] Univ Calicut, Sch Hlth Sci, Calicut 673635, Kerala, India		Kumar, PRM (corresponding author), Univ Calicut, Dept Biotechnol, Recombinant DNA Lab, Calicut 673635, Kerala, India.	ahlamabdulaziz@gmail.com; Shanibavsn@gmail.com; jayasreepr@uoc.ac.in; manishramakrishnan@rediffmail.com			INSPIRE fellowship - Department of Science and Technology (DST), Government of India [IF140004]	AAA acknowledges receipt of INSPIRE fellowship (IF140004) awarded by the Department of Science and Technology (DST), Government of India.	Ahamed M, 2011, TOXICOLOGY, V283, P101, DOI 10.1016/j.tox.2011.02.010; Ahmed S, 2017, J PHOTOCH PHOTOBIO B, V166, P272, DOI [10.1016/j.JPhotobiol.2016.12.011, 10.1016/j.jphotobiol.2016.12.011]; Akhtar MJ, 2012, INT J NANOMED, V7, P845, DOI 10.2147/IJN.S29129; Al-Shabib NA, 2016, SCI REP-UK, V6, DOI 10.1038/srep36761; Attanayake A. 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Trace Elem. Res.	MAY	2021	199	5					1778	1801		10.1007/s12011-020-02303-8		AUG 2020	24	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	RC0CV	WOS:000556650800002	32761516				2022-04-25	
J	Wang, Y; Xia, CH; Lun, ZQ; Lv, YX; Chen, W; Li, T				Wang, Yu; Xia, Chunhui; Lun, Zhiqiang; Lv, Yanxin; Chen, Wei; Li, Tao			Crosstalk between p38 MAPK and caspase-9 regulates mitochondria-mediated apoptosis induced by tetra-alpha-(4-carboxyphenoxy) phthalocyanine zinc photodynamic therapy in LoVo cells	ONCOLOGY REPORTS			English	Article						tetra-alpha-(4-carboxyphenoxy) phthalocyanine zinc; photodynamic therapy; p38 MAPK; caspase-9; signaling crosstalk; apoptosis; mitochondria	ACTIVATED PROTEIN-KINASE; IN-VITRO; OXIDATIVE STRESS; DEATH PATHWAYS; CANCER-THERAPY; BCL-2 FAMILY; PHOTOSENSITIZER; INDUCTION; AUTOPHAGY; AGENT	Photodynamic therapy (PDT) is considered to be an advancing antitumor technology. PDT using hydrophilic/lipophilic tetra-alpha-(4-carboxyphenoxy) phthalocyanine zinc (T alpha PcZn-PDT) has exhibited antitumor activity in Bel-7402 hepatocellular cancer cells. However, the manner in which p38 MAPK and caspase-9 are involved in the regulation of mitochondria-mediated apoptosis in the T alpha PcZn-PDT-treated LoVo human colon carcinoma cells remains unclear. Therefore, in the present study, a siRNA targeting p38 MAPK (siRNA-p38 MAPK) and the caspase-9 specific inhibitor z-LEHD-fmk were used to examine the crosstalk between p38 MAPK and caspase-9 during mitochondria-mediated apoptosis in the T alpha PcZn-PDT-treated LoVo cells. The findings revealed that the T alpha PcZn-PDT treatment of LoVo cells resulted in the induction of apoptosis, the formation of p38 MAPK/caspase-9 complexes, the activation of p38 MAPK, caspase-9, caspase-3 and Bid, the downregulation of Bcl-2, the reduction of mitochondrial membrane potential (Delta Psi m), the upregulation of Bax and the release of apoptosis-inducing factor (AIF) and cytochrome c (Cyto c). By contrast, siRNA-p38 MAPK or z-LEHD-fmk both attenuated the effects of T alpha PcZn-PDT in the LoVo cells. Furthermore, the results revealed that siRNA-p38 MAPK had more significant inhibitory effects on apoptosis and mitochondria compared with the effects of z-LEHD-fmk in T alpha PcZn-PDT-treated LoVo cells. These findings indicated that p38 MAPK plays the major regulatory role in the crosstalk between p38 MAPK and caspase-9 and that direct interaction between p38 MAPK and caspase-9 may regulate mitochondria-mediated apoptosis in the T alpha PcZn-PDT-treated LoVo cells.	[Wang, Yu; Xia, Chunhui; Lun, Zhiqiang; Lv, Yanxin; Li, Tao] Qiqihar Med Univ, Dept Basic Med, 333 Bukuibeier Rd, Qiqihar 161006, Heilongjiang, Peoples R China; [Chen, Wei] Qiqihar Univ, Coll Chem & Chem Engn, Qiqihar 161006, Heilongjiang, Peoples R China		Li, T (corresponding author), Qiqihar Med Univ, Dept Basic Med, 333 Bukuibeier Rd, Qiqihar 161006, Heilongjiang, Peoples R China.	litao888@qmu.edu.cn			Natural Science Foundation of Heilongjiang ProvinceNatural Science Foundation of Heilongjiang Province [ZD201318]	The project was supported by the Natural Science Foundation of Heilongjiang Province (no. ZD201318).	Acedo P, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.77; Ameeramja J, 2016, J HAZARD MATER, V301, P554, DOI 10.1016/j.jhazmat.2015.09.037; Bi M. 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Y., 2009, J LIAONING NORMAL U, V32, P94; Xia CH, 2011, MOLECULES, V16, P1389, DOI 10.3390/molecules16021389; Xue LY, 1999, CELL DEATH DIFFER, V6, P855, DOI 10.1038/sj.cdd.4400558; Yang JB, 2016, ACTA PHARMACOL SIN, V37, P950, DOI 10.1038/aps.2016.34; Yslas EI, 2007, BIOORGAN MED CHEM, V15, P4651, DOI 10.1016/j.bmc.2007.03.079; Zhao W, 2015, SCI REP-UK, V5, DOI 10.1038/srep17175; Zhao ZX, 2012, INORG CHEM, V51, P812, DOI 10.1021/ic201178e; Zheng YQ, 2016, J AGR FOOD CHEM, V64, P2541, DOI 10.1021/acs.jafc.5b05343; Zou SB, 2016, PHARMACOL REP, V68, P7, DOI 10.1016/j.pharep.2015.06.004	48	18	20	0	24	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1021-335X	1791-2431		ONCOL REP	Oncol. Rep.	JAN	2018	39	1					61	70		10.3892/or.2017.6071			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FQ4WD	WOS:000418358200007	29115534	Green Submitted, Green Published, hybrid			2022-04-25	
J	Qian, QY; Zhou, H; Chen, Y; Shen, CL; He, SB; Zhao, H; Wang, L; Wan, DW; Gu, W				Qian, Qinyi; Zhou, Hao; Chen, Yan; Shen, Chenglong; He, Songbing; Zhao, Hua; Wang, Liang; Wan, Daiwei; Gu, Wen			VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Autophagy; Apoptosis; Colorectal cancer; VMP1	MOLECULAR-MECHANISMS; MEDIATED CLEAVAGE; BECLIN-1; AMBRA1; PANCREATITIS; INHIBITION; EXPRESSION; SURVIVAL; THERAPY	Vacuole membrane protein 1 (VMP1) is an autophagy-related protein and identified as a key regulator of autophagy in recent years. In pancreatic cell lines, VMP1-dependent autophagy has been linked to positive regulation of apoptosis. However, there are no published reports on the role of VMP1 in autophagy and apoptosis in colorectal cancers. Therefore, to address this gap of knowledge, we decided to interrogate regulation of autophagy and apoptosis by VMP1. We have studied the induction of autophagy by starvation and rapamycin treatment in colorectal cell lines using electron microscopy, immunofluorescence, and immunoblotting. We found that starvation-induced autophagy correlated with an increase in VMP1 expression, that VMP1 interacted with BECLIN1, and that siRNA mediated down-regulation of VMP1-reduced autophagy. Next, we examined the relationship between VMP1-dependent autophagy and apoptosis and found that VMP1 down-regulation sensitizes cells to apoptosis and that agents that induce apoptosis down-regulate VMP1. In conclusion, similar to its reported role in other cell types, VMP1 is an important regulator of autophagy in colorectal cell lines. However, in contrast to its role in pancreatic cell lines, in colorectal cancer cells, VMP1-dependent autophagy appears to be pro-survival rather than pro-cell death. (C) 2013 Elsevier Inc. All rights reserved.	[Zhou, Hao; Chen, Yan; He, Songbing; Zhao, Hua; Wang, Liang; Gu, Wen] Soochow Univ, Dept Gen Surg, Affiliated Hosp 1, Suzhou 215006, Peoples R China; [Qian, Qinyi] Changshu 2 Peoples Hosp, Dept Ultrasonograph, Changshu, Peoples R China; [Wan, Daiwei] Sun Yat Sen Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China; [Shen, Chenglong] Changshu 2 Peoples Hosp, Dept Gen Surg, Changshu, Peoples R China		Wan, DW (corresponding author), Sun Yat Sen Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, 58 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China.	372710369@qq.com; 505339704@qq.com					Ahn CH, 2007, APMIS, V115, P1344, DOI 10.1111/j.1600-0463.2007.00858.x; Cui JZ, 2013, BBA-REV CANCER, V1836, P15, DOI 10.1016/j.bbcan.2013.02.003; Dusetti NJ, 2002, BIOCHEM BIOPH RES CO, V290, P641, DOI 10.1006/bbrc.2001.6244; Fan YJ, 2013, CHIN J CANCER, V32, P121, DOI 10.5732/cjc.012.10106; Fimia GM, 2013, ONCOGENE, V32, P3311, DOI 10.1038/onc.2012.455; Fimia GM, 2007, NATURE, V447, P1121, DOI 10.1038/nature05925; Grothey A, 2005, J CLIN ONCOL, V23, P9441, DOI 10.1200/JCO.2005.04.4792; Jaboin JJ, 2009, METHOD ENZYMOL, V453, P287, DOI 10.1016/S0076-6879(08)04014-7; Jain K, 2013, AM J CANCER RES, V3, P251; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Levine B, 2004, DEV CELL, V6, P463, DOI 10.1016/S1534-5807(04)00099-1; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Lotze MT, 2013, CANCER J, V19, P341, DOI 10.1097/PPO.0b013e31829da0d6; Maiuri MC, 2007, NAT REV MOL CELL BIO, V8, P741, DOI 10.1038/nrm2239; Mathew R, 2011, CURR OPIN GENET DEV, V21, P113, DOI 10.1016/j.gde.2010.12.008; Mizushima N, 2009, METHOD ENZYMOL, V452, P13, DOI 10.1016/S0076-6879(08)03602-1; Pagliarini V, 2012, CELL DEATH DIFFER, V19, P1495, DOI 10.1038/cdd.2012.27; Pandey S, 2012, ASIAN PAC J CANCER P, V13, P4867, DOI 10.7314/APJCP.2012.13.10.4867; Pardo R, 2010, PANCREATOLOGY, V10, P19, DOI 10.1159/000264680; Rohn TT, 2011, NEUROBIOL DIS, V43, P68, DOI 10.1016/j.nbd.2010.11.003; Ropolo A, 2007, J BIOL CHEM, V282, P37124, DOI 10.1074/jbc.M706956200; Sato K, 2007, CANCER RES, V67, P9677, DOI 10.1158/0008-5472.CAN-07-1462; Strappazzon F, 2011, EMBO J, V30, P1195, DOI 10.1038/emboj.2011.49; Troiani T., 2013, CURR MED CH IN PRESS; Wirawan E, 2010, CELL DEATH DIS, V1, DOI 10.1038/cddis.2009.16; Wu SB, 2013, BIOCHEM BIOPH RES CO, V434, P898, DOI 10.1016/j.bbrc.2013.04.053; Xu HD, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0063232; Yousefi S, 2006, NAT CELL BIOL, V8, P1124, DOI 10.1038/ncb1482; Zheng Hai-yang, 2012, Cancer Biology Medicine, V9, P105, DOI 10.3969/j.issn.2095-3941.2012.02.004	29	14	14	1	11	ACADEMIC PRESS INC ELSEVIER SCIENCE	SAN DIEGO	525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA	0006-291X	1090-2104		BIOCHEM BIOPH RES CO	Biochem. Biophys. Res. Commun.	JAN 17	2014	443	3					1041	1047		10.1016/j.bbrc.2013.12.090			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	AA9LM	WOS:000331415000043	24365149				2022-04-25	
J	Yao, DH; Jiang, YN; Gao, SY; Shang, L; Zhao, YQ; Huang, J; Wang, JH; Yang, SL; Chen, LX				Yao, Dahong; Jiang, Yingnan; Gao, Suyu; Shang, Lei; Zhao, Yuqian; Huang, Jian; Wang, Jinhui; Yang, Shilin; Chen, Lixia			Deconvoluting the complexity of microRNAs in autophagy to improve potential cancer therapy	CELL PROLIFERATION			English	Review							NEGATIVELY REGULATE AUTOPHAGY; CISPLATIN-INDUCED APOPTOSIS; DOWN-REGULATION; INHIBITS AUTOPHAGY; COLORECTAL-CANCER; LUNG-CANCER; CELL-DEATH; GASTRIC-CANCER; TUMOR-GROWTH; SENSITIVITY	MicroRNAs (miRNAs) (small, non-coding RNAs approximate to 22 nucleotides [nt] in length), have been estimated to regulate in the region of 30% of human gene expression at the post-transcriptional and translational levels. They are also involved in a series of important cellular processes, such as autophagy. Autophagy is well-known to be an evolutionarily conserved lysosomal degradation process in which a cell degrades long-lived proteins and damaged organelles. Recent evidence has shown that miRNAs can function as either oncogenes or tumour-suppressive genes in human cancers. Also, they are well-characterized to be crucial in tumourigenesis, as either oncogenes or tumour suppressors, by regulating autophagy. However, discovering the intricate mechanism of miRNA-modulated autophagy remains in its infancy. Thus, in this review, we focus on summarizing the dual function of oncogenic or tumour-suppressive miRNAs in regulation of autophagy and their roles in carcinogenesis, thereby revealing the regulatory mechanism of miRNA-modulated autophagy in cancer, to shed light on more novel RNA therapeutic strategies in the future.	[Yao, Dahong; Jiang, Yingnan; Gao, Suyu; Zhao, Yuqian; Huang, Jian; Wang, Jinhui; Yang, Shilin; Chen, Lixia] Shenyang Pharmaceut Univ, Sch Tradit Chinese Mat Med, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Peoples R China; [Shang, Lei] China Med Univ, Sch Pharm, Shenyang 110122, Peoples R China		Wang, JH; Yang, SL; Chen, LX (corresponding author), Shenyang Pharmaceut Univ, Sch Tradit Chinese Mat Med, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Peoples R China.	profwjh@126.com; yangshilin@suda.edu.cn; syzyclx@163.com	Chen, Lixia/ABH-1629-2021	Chen, Lixia/0000-0003-2196-1428	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81303270, U1303124, 81202403, 81573290]	This work was supported by grants from National Natural Science Foundation of China (Grant Nos. 81303270, U1303124, 81202403, 81573290).	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J	Daskalaki, I; Gkikas, I; Tavernarakis, N				Daskalaki, Ioanna; Gkikas, Ilias; Tavernarakis, Nektarios			Hypoxia and Selective Autophagy in Cancer Development and Therapy	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY			English	Review						autophagy; cancer; ERphagy; HIFs; hypoxia; mitophagy; mTOR; pexophagy	REGULATES MITOCHONDRIAL DYNAMICS; ENDOPLASMIC-RETICULUM TURNOVER; UNFOLDED PROTEIN RESPONSE; NF-KAPPA-B; CELL-DEATH; ER STRESS; COLORECTAL-CANCER; INDUCIBLE FACTORS; BNIP3 PROTEIN; TRANSCRIPTIONAL RESPONSE	Low oxygen availability, a condition known as hypoxia, is a common feature of various pathologies including stroke, ischemic heart disease, and cancer. Hypoxia adaptation requires coordination of intricate pathways and mechanisms such as hypoxia-inducible factors (HIFs), the unfolded protein response (UPR), mTOR, and autophagy. Recently, great effort has been invested toward elucidating the interplay between hypoxia-induced autophagy and cancer cell metabolism. Although novel types of selective autophagy have been identified, including mitophagy, pexophagy, lipophagy, ERphagy and nucleophagy among others, their potential interface with hypoxia response mechanisms remains poorly understood. Autophagy activation facilitates the removal of damaged cellular compartments and recycles components, thus promoting cell survival. Importantly, tumor cells rely on autophagy to support self-proliferation and metastasis; characteristics related to poor disease prognosis. Therefore, a deeper understanding of the molecular crosstalk between hypoxia response mechanisms and autophagy could provide important insights with relevance to cancer and hypoxia-related pathologies. Here, we survey recent findings implicating selective autophagy in hypoxic responses, and discuss emerging links between these pathways and cancer pathophysiology.	[Daskalaki, Ioanna; Gkikas, Ilias; Tavernarakis, Nektarios] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion, Greece; [Daskalaki, Ioanna; Gkikas, Ilias] Univ Crete, Dept Biol, Iraklion, Greece; [Tavernarakis, Nektarios] Univ Crete, Sch Med, Dept Basic Sci, Iraklion, Greece		Tavernarakis, N (corresponding author), Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion, Greece.; Tavernarakis, N (corresponding author), Univ Crete, Sch Med, Dept Basic Sci, Iraklion, Greece.	tavernarakis@imbb.forth.gr	Tavernarakis, Nektarios/B-9684-2013	Tavernarakis, Nektarios/0000-0002-5253-1466; Gkikas, Ilias/0000-0002-5899-551X	European Research CouncilEuropean Research Council (ERC)European Commission [ERC-GA695190-MANNA, ERC-GA737599-NeuronAgeScreen]; European Commission Framework Programmes; Greek Ministry of EducationGreek Ministry of Development-GSRT	We apologize to those colleagues whose work could not be referenced owing to space limitations. Work in the authors' laboratory is funded by grants from the European Research Council (ERC-GA695190-MANNA, ERC-GA737599-NeuronAgeScreen), the European Commission Framework Programmes, and the Greek Ministry of Education.	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Cell. Dev. Biol.	SEP 10	2018	6								104	10.3389/fcell.2018.00104			22	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	HG9NP	WOS:000455335700001	30250843	Green Published, gold			2022-04-25	
J	Qi, YL; Zhang, MF; Li, H; Frank, JA; Dai, L; Liu, HJ; Zhang, Z; Wang, C; Chen, G				Qi, Yuanlin; Zhang, Mingfang; Li, Hui; Frank, Jacqueline A.; Dai, Lu; Liu, Huijuan; Zhang, Zhuo; Wang, Chi; Chen, Gang			Autophagy Inhibition by Sustained Overproduction of IL6 Contributes to Arsenic Carcinogenesis	CANCER RESEARCH			English	Article							BCL-2 FAMILY-MEMBERS; BECLIN 1; EPITHELIAL-CELLS; COLORECTAL-CANCER; LUNG-CANCER; INFLAMMATION; PATHWAY; IL-6; TRANSFORMATION; APOPTOSIS	Chronic inflammation has been implicated as an etiologic factor in cancer, whereas autophagy may help preserve cancer cell survival but exert anti-inflammatory effects. How these phenomenas interact during carcinogenesis remains unclear. We explored this question in a human bronchial epithelial cell-based model of lung carcinogenesis that is mediated by subchronic exposure to arsenic. We found that sustained overexpression of the pro-inflammatory IL6 promoted arsenic-induced cell transformation by inhibiting autophagy. Conversely, strategies to enhance autophagy counteracted the effect of IL6 in the model. These findings were confirmed and extended in a mouse model of arsenic-induced lung cancer. Mechanistic investigations suggested that mTOR inhibition contributed to the activation of autophagy, whereas IL6 overexpression was sufficient to block autophagy by supporting Beclin-1/Mcl-1 interaction. Overall, our findings argued that chronic inflammatory states driven by IL6 could antagonize autophagic states that may help preserve cancer cell survival and promote malignant progression, suggesting a need to uncouple inflammation and autophagy controls to enable tumor progression.	[Qi, Yuanlin; Zhang, Mingfang; Li, Hui; Frank, Jacqueline A.; Liu, Huijuan; Chen, Gang] Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA; [Dai, Lu; Zhang, Zhuo] Univ Kentucky, Coll Med, Grad Ctr Toxicol, Lexington, KY 40536 USA; [Wang, Chi] Univ Kentucky, Coll Publ Hlth, Markey Canc Ctr, Biostat Shared Resource Facil, Lexington, KY USA; [Wang, Chi] Univ Kentucky, Coll Publ Hlth, Dept Biostat, Lexington, KY USA; [Qi, Yuanlin] Fujian Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Fuzhou, Fujian, Peoples R China; [Zhang, Mingfang] Fujian Med Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Fuzhou, Fujian, Peoples R China		Chen, G (corresponding author), Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, 125 Hlth Sci Res Bldg,800 Rose St, Lexington, KY 40536 USA.	gangchen6@uky.edu	Zhang, Zhuo/B-8601-2012	Qi, Yuanlin/0000-0002-5253-9732; Zhang, Mingfang/0000-0001-8061-5694	American Cancer SocietyAmerican Cancer Society [RSG-11-116-01-CNE]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA177558] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISMUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [R01AA020051] Funding Source: NIH RePORTER	This work was supported by the American Cancer Society (RSG-11-116-01-CNE; G. Chen).	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JUL 15	2014	74	14					3740	3752		10.1158/0008-5472.CAN-13-3182			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AL1GY	WOS:000338875000010	24830721	Green Accepted			2022-04-25	
J	Lin, R; Han, CQ; Ding, Z; Shi, HY; He, RH; Liu, J; Qian, W; Zhang, Q; Fu, XC; Deng, XH; Zhou, SC; Hou, XH				Lin, Rong; Han, Chaoqun; Ding, Zhen; Shi, Huiying; He, Ruohang; Liu, Jun; Qian, Wei; Zhang, Qin; Fu, Xiaochao; Deng, Xiaohua; Zhou, Shunchang; Hou, Xiaohua			Knock down of BMSC-derived Wnt3a or its antagonist analogs attenuate colorectal carcinogenesis induced by chronic Fusobacterium nucleatum infection	CANCER LETTERS			English	Article						Fusobacterium nucleatum; BMSC; Wnt3a; Apc(Min/+); Colorectal cancer	POTENTIATES INTESTINAL TUMORIGENESIS; TG-INTERACTING FACTOR; STEM-CELLS; GUT MICROBIOTA; CANCER; PROMOTES; OVEREXPRESSION; INFLAMMATION; SUPPRESSION; AUTOPHAGY	By establishing the Fusobacterium nucleatum (F. nucleatum) infected-bone mesenchymal stem cells (BMSCs) transplantation model in APC(Min/+) mice, we investigated the role of BMSCs in the development of intestinal tumors induced by F. nucleatum. Apc(Min/+)+F. nucleatum + BMSCs mice showed increased susceptibility to intestinal tumors and accelerated tumor growth. BMSCs could also enhance tumor-initiating capability, invasive traits after F. nucleatum infection in vitro, and tumorigenicity in a nude murine model. Mechanistically, BMSCs were recruited to the submucosa, migrated to the mucosal layer, and might activate the canonical Wnt/beta-catenin/TGIF axis signaling. Further mechanistic results illustrated increased production of the Wnt3a protein was found in Apc(Min/+)+F. nucleatum + BMSCs mice, and BMSCs were likely the major source of Wnt3a. Intriguingly, a deletion of Wnt3a via BMSC interference or antagonist analogs led to a significantly attenuated capacity of Apc(Min/+)+F. nucleatum mice to generate intestinal tumors. The findings suggest that BMSCs have the potential to migrate and accelerate F. nucleatum-induced colorectal tumorigenesis by modulating Wnt3a secretion; knockdown of BMSC-derived Wnt3a or antagonist analogs could attenuate carcinogenesis. Thus, Wnt3a might be a potential pharmaceutical target for the prevention and treatment of F. nucleatum-related colorectal cancer.	[Lin, Rong; Han, Chaoqun; Ding, Zhen; Shi, Huiying; He, Ruohang; Liu, Jun; Qian, Wei; Hou, Xiaohua] Huazhong Univ Sci & Technol, Union Hosp, Div Gastroenterol, Tongji Med Coll, Wuhan 430022, Hubei, Peoples R China; [Zhang, Qin] Huazhong Univ Sci & Technol, Union Hosp, Div Pathol, Tongji Med Coll, Wuhan 430022, Hubei, Peoples R China; [Fu, Xiaochao; Deng, Xiaohua] Hubei Ctr Ind Culture Collect & Res, Wuhan 430022, Hubei, Peoples R China; [Zhou, Shunchang] Huazhong Univ Sci & Technol, Div Expt Anim, Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China		Hou, XH (corresponding author), Huazhong Univ Sci & Technol, Union Hosp, Dept Gastroenterol, Tongji Med Coll, 1277 Jiefang Ave, Wuhan, Hubei, Peoples R China.	houxh@hust.edu.cn		lin, rong/0000-0001-9463-8942	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81720108006,81470039, 81330014, 81272656,81800467]	This study was supported in part by the National Natural Science Foundation of China (No. 81720108006,81470039, 81330014, 81272656,81800467).	Abed J, 2016, CELL HOST MICROBE, V20, P215, DOI 10.1016/j.chom.2016.07.006; Brennan CA, 2016, ANNU REV MICROBIOL, V70, P395, DOI 10.1146/annurev-micro-102215-095513; Bullman S, 2017, SCIENCE, V358, P1443, DOI 10.1126/science.aal5240; Chen ZX, 2014, BIOCHEM BIOPH RES CO, V450, P1402, DOI 10.1016/j.bbrc.2014.07.002; De Boeck A, 2013, GUT, V62, P550, DOI 10.1136/gutjnl-2011-301393; Dube C, 2017, AM J GASTROENTEROL, V112, P1790, DOI 10.1038/ajg.2017.360; Eklof V, 2017, INT J CANCER, V141, P2528, DOI 10.1002/ijc.31011; Fan HY, 2012, CELL MOL IMMUNOL, V9, P473, DOI 10.1038/cmi.2012.40; Fong WN, 2020, ONCOGENE, V39, P4925, DOI 10.1038/s41388-020-1341-1; Gong W, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2016.276; Han CQ, 2016, CELL PHYSIOL BIOCHEM, V38, P2464, DOI 10.1159/000445597; He S, 2015, CHIN J CANCER, V34, DOI 10.1186/s40880-015-0052-4; Houghton J, 2004, SCIENCE, V306, P1568, DOI 10.1126/science.1099513; Huang WH, 2013, ONCOGENE, V32, P4343, DOI 10.1038/onc.2012.458; Kaur N, 2013, MOL CELL NEUROSCI, V54, P44, DOI 10.1016/j.mcn.2013.01.001; Kostic AD, 2013, CELL HOST MICROBE, V14, P207, DOI 10.1016/j.chom.2013.07.007; Leung A, 2015, EXPERT REV GASTROENT, V9, P651, DOI 10.1586/17474124.2015.1001745; Ley RE, 2006, CELL, V124, P837, DOI 10.1016/j.cell.2006.02.017; Lin R, 2015, STEM CELLS, V33, P3545, DOI 10.1002/stem.2197; Lin R, 2013, STEM CELLS DEV, V22, P2836, DOI 10.1089/scd.2013.0166; Liu ZM, 2011, BIOCHEM J, V438, P349, DOI 10.1042/BJ20101653; Mima K, 2016, GUT, V65, P1973, DOI 10.1136/gutjnl-2015-310101; Mizutani S, 2020, CANCER SCI, V111, P766, DOI 10.1111/cas.14298; Nasuno M, 2014, STEM CELLS, V32, P913, DOI 10.1002/stem.1594; Neish AS, 2009, GASTROENTEROLOGY, V136, P65, DOI 10.1053/j.gastro.2008.10.080; Newman JV, 2001, J INFECT DIS, V184, P227, DOI 10.1086/321998; O'Keefe SJD, 2016, NAT REV GASTRO HEPAT, V13, P691, DOI 10.1038/nrgastro.2016.165; Parkin DM, 2005, CA-CANCER J CLIN, V55, P74, DOI 10.3322/canjclin.55.2.74; Pierre CC, 2015, BBA-MOL BASIS DIS, V1852, P1846, DOI 10.1016/j.bbadis.2015.06.011; Qi LS, 2015, INT J MOL SCI, V16, P18564, DOI 10.3390/ijms160818564; Quante M, 2011, CANCER CELL, V19, P257, DOI 10.1016/j.ccr.2011.01.020; Razzaque MS, 2016, BBA-REV CANCER, V1865, P101, DOI 10.1016/j.bbcan.2015.10.003; Rubinstein MR, 2013, CELL HOST MICROBE, V14, P195, DOI 10.1016/j.chom.2013.07.012; Sekiya I, 2002, STEM CELLS, V20, P530, DOI 10.1634/stemcells.20-6-530; Shi HY, 2017, CELL PHYSIOL BIOCHEM, V42, P2418, DOI 10.1159/000480184; Song J, 2015, TUMOR BIOL, V36, P2013, DOI 10.1007/s13277-014-2808-x; Sonnenberg GF, 2012, IMMUNITY, V37, P601, DOI 10.1016/j.immuni.2012.10.003; Tsai KS, 2011, GASTROENTEROLOGY, V141, P1046, DOI 10.1053/j.gastro.2011.05.045; Varon C, 2012, GASTROENTEROLOGY, V142, P281, DOI 10.1053/j.gastro.2011.10.036; Wei ZL, 2016, ONCOTARGET, V7, P46158, DOI 10.18632/oncotarget.10064; Yang Y., 2016, GASTROENTEROLOGY; Yeh BW, 2016, TOXICOL APPL PHARM, V290, P98, DOI 10.1016/j.taap.2015.11.007; Yeh BW, 2012, AM J PATHOL, V181, P1044, DOI 10.1016/j.ajpath.2012.05.024; Yu J, 2017, GUT, V66, P70, DOI 10.1136/gutjnl-2015-309800; Yu TC, 2017, CELL, V170, P548, DOI 10.1016/j.cell.2017.07.008; Zhang MZ, 2015, CANCER CELL, V27, P547, DOI 10.1016/j.ccell.2015.03.002; Zitvogel L, 2015, SCI TRANSL MED, V7, DOI 10.1126/scitranslmed.3010473	47	7	7	6	25	ELSEVIER IRELAND LTD	CLARE	ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND	0304-3835	1872-7980		CANCER LETT	Cancer Lett.	DEC 28	2020	495						165	179		10.1016/j.canlet.2020.08.032			15	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	OS5OM	WOS:000590213100001	32920199				2022-04-25	
J	Chen, YY; Chen, Y; Zhang, JX; Cao, P; Su, WH; Deng, YC; Zhan, N; Fu, XS; Huang, Y; Dong, WG				Chen, Yongyu; Chen, Yan; Zhang, Jixiang; Cao, Pan; Su, Wenhao; Deng, Yunchao; Zhan, Na; Fu, Xiangsheng; Huang, Yun; Dong, Weiguo			Fusobacterium nucleatum Promotes Metastasis in Colorectal Cancer by Activating Autophagy Signaling via the Upregulation of CARD3 Expression	THERANOSTICS			English	Article						microbe; gene regulation; gene targeting; colorectal cancer	CELLS; CARCINOGENESIS; BINDING	Aims: We aimed to measure the abundance of Fusobacterium nucleatum (F. nucleatum) in colorectal cancer (CRC) tissues from patients and to uncover the function of this bacterium in colorectal tumor metastasis. Methods: We collected metastatic and non-metastatic CRC tissues to analyze F. nucleatum abundance. Cells were incubated with F. nucleatum or chloroquine (CQ) or were transfected with CARD3-targeting siRNA; the expression of mRNAs and proteins was then measured. CRC cells stably transfected with shRNA-luc were mixed with F. nucleatum and intravenously injected into BALB/cJ mice. APC(Min/+), CARD3(-/-)and CARD3(wt) C57BL mice were given F. nucleatum; some mice were given azoxymethane (AOM) and dextran sodium sulfate (DSS). Results: F. nucleatum was abundant in CRC tissues from patients with metastasis. F. nucleatum infection increased CRC cell motility and upregulated the expression of CARD3, LC3-II, Beclin1 and Vimentin, and downregulated the expression of E-cadherin and P62 in CRC cells. These effects were attenuated by treatment with CQ, siCARD3 or both. APC(Min/+) mice gavaged with F. nucleatum developed more aggressive tumors than control mice. After AOM/DSS administration, the colorectums of CARD3(-/-) mice had fewer tumors than those of control mice. Tumors from CARD3(-/-) mice had lower levels of LC3-II and Beclin1 and higher levels of P62 than those from control mice. BALB/cJ mice injected with both CT26-luc cells and F. nucleatum formed more metastases than control mice. CQ treatment, CARD3 knockdown or both reduced the ability of CT26-luc cells to form metastases in vivo. Conclusions: F. nucleatum is enriched in CRC tissues from patients with metastasis. F. nucleatum orchestrates CARD3 and autophagy to control CRC metastasis. Measuring and targeting F. nucleatum and its associated pathways will yield approaches for the prevention and treatment of CRC metastasis.	[Chen, Yongyu; Chen, Yan; Zhang, Jixiang; Cao, Pan; Su, Wenhao; Deng, Yunchao; Zhan, Na; Dong, Weiguo] Wuhan Univ, Renmin Hosp, Dept Gastroenterol, Wuhan, Hubei, Peoples R China; [Chen, Yongyu; Chen, Yan; Zhang, Jixiang; Cao, Pan; Su, Wenhao; Deng, Yunchao; Zhan, Na; Dong, Weiguo] Key Lab Hubei Prov Digest Syst Dis, Wuhan, Hubei, Peoples R China; [Zhang, Jixiang; Su, Wenhao; Zhan, Na] Wuhan Univ, Renmin Hosp, Cent Lab, Wuhan, Hubei, Peoples R China; [Fu, Xiangsheng] North Sichuan Med Coll, Affiliated Hosp, Dept Gastroenterol, Rd Wenhua 63, Nanchong City 637000, Region Shunqing, Peoples R China; [Huang, Yun] Texas A&M Univ, Inst Biosci & Technol, Ctr Epigenet & Dis Prevent, Houston, TX 77030 USA		Dong, WG (corresponding author), Wuhan Univ, Renmin Hosp, Dept Gastroenterol, Key Lab Hubei Prov Digest Syst Dis, Jiefang Rd 238, Wuhan 430060, Hubei, Peoples R China.	dongweiguo@whu.edu.cn	Fu, Xiangsheng/H-9411-2019		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81870392, 81372551, 81572426]; Guiding Foundation of Renmin Hospital of Wuhan University [RMYD2018Z01]	This work was supported by grants from the National Natural Science Foundation of China (No. 81870392, No. 81372551, No. 81572426), and the Guiding Foundation of Renmin Hospital of Wuhan University (No. RMYD2018Z01).	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J	Kumari, M; Ray, L; Purohit, MP; Patnaik, S; Pant, AB; Shukla, Y; Kumar, P; Gupta, KC				Kumari, Manisha; Ray, L.; Purohit, M. P.; Patnaik, S.; Pant, A. B.; Shukla, Y.; Kumar, P.; Gupta, K. C.			Curcumin loading potentiates the chemotherapeutic efficacy of selenium nanoparticles in HCT116 cells and Ehrlich's ascites carcinoma bearing mice	EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS			English	Article						Cancer; Selenium nanoparticles; Curcumin; Autophagy; Apoptosis	NF-KAPPA-B; HUMAN PROSTATE-CANCER; INDUCED APOPTOSIS; CELLULAR UPTAKE; CYCLE ARREST; IN-VITRO; ELEMENTAL SELENIUM; DOWN-REGULATION; INDUCTION; EXPRESSION	The anticancer properties of selenium (Se) and curcumin nanoparticles in solo formulations as well as in combination with other therapeutic agents have been proved time and again. Exploiting this facet of the two, we clubbed their tumoricidal characteristics and designed curcumin loaded Se nanoparticles (SeCurNPs) to achieve an enhanced therapeutic effect. We evaluated their therapeutic effects on different cancer cell lines and Ehrlich's ascites carcinoma mouse model. In vitro results showed that Se-CurNPs were most effective on colorectal carcinoma cells (HCT116) compared to the other cancer cell lines used and possessed pleiotropic anticancer effects. The therapeutic effect on HCT116 was primarily attributed to an elevated level of autophagy and apoptosis as evident from significant up-regulation of autophagy associated (LOB-II) and pro-apoptotic (Bax) proteins, down-regulation of anti-apoptotic (Bcl-2) protein and Cytochrome c (cyt c) release from mitochondria along with reduced NPKB signaling and EMT based machineries marked by downregulation of inflammation (NFxB, phospho-NFKB) and epithelialmesenchymal transition (CD44, N-cadherin) associated proteins. In vivo studies on Ehrlich's ascites carcinoma (EAC) mice model indicated that Se-CurNPs significantly reduced the tumor load and enhanced the mean survival time (days) of tumor-bearing EAC mice. (C) 2017 Elsevier B.V. All rights reserved.	[Kumari, Manisha; Kumar, P.; Gupta, K. C.] CSIR Inst Genom & Integrat Biol, Delhi Univ Campus,Mall Rd, Delhi 110007, India; [Ray, L.; Purohit, M. P.; Patnaik, S.; Pant, A. B.; Shukla, Y.; Gupta, K. C.] CSIR Indian Inst Toxicol Res, MG Marg, Lucknow 226001, Uttar Pradesh, India; [Kumari, Manisha; Purohit, M. P.] Acad Sci & Innovat Res AcSIR, New Delhi, India; [Gupta, K. C.] Indian Inst Technol, Dept Biol Sci & Bioengn BSBE, Kanpur, Uttar Pradesh, India; [Gupta, K. C.] Indian Inst Technol, Ctr Environm Sci & Engn, Kanpur, Uttar Pradesh, India		Gupta, KC (corresponding author), CSIR Inst Genom & Integrat Biol, Delhi Univ Campus,Mall Rd, Delhi 110007, India.; Gupta, KC (corresponding author), Indian Inst Technol, Dept Biol Sci & Bioengn BSBE, Kanpur, Uttar Pradesh, India.; Gupta, KC (corresponding author), Indian Inst Technol, Ctr Environm Sci & Engn, Kanpur, Uttar Pradesh, India.	kcgupta9@gmail.com	Kumari, Manisha/AAX-5517-2021; Patnaik, Satyakam/O-3617-2019	Patnaik, Satyakam/0000-0003-4920-236X	CSIR network projectCouncil of Scientific & Industrial Research (CSIR) - India [BSC0112]; Indian Council of Medical Research (ICMR), New DelhiIndian Council of Medical Research (ICMR); CSIRCouncil of Scientific & Industrial Research (CSIR) - India	Financial support from CSIR network project BSC0112 is gratefully acknowledged. KCG thanks, Indian Council of Medical Research (ICMR), New Delhi for awarding Distinguished Scientist Chair at IGIB, Delhi. MK is thankful to CSIR for providing Senior Research Fellowship for carrying out this work. Ms. N. Arjaria and Mr. Jaishankar, CSIR-IITR are acknowledged for helping in TEM studies. Dr. P.N. Saxena, CSIR-IITR is acknowledged for helping in SEM studies. Mr. Puneet Khare, CSIR-IITR is acknowledged for helping in flow cytometry Mr. S.H.N. Naqvi, CSIR-IITR is acknowledged for helping in animal studies. CSIR-Central Drug Research Institute, Lucknow is acknowledged for use of sophisticated instrumentation facility for FTIR.	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J. Pharm. Biopharm.	AUG	2017	117						346	362		10.1016/j.ejpb.2017.05.003			17	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	FA0VJ	WOS:000405154400035	28499854				2022-04-25	
J	Takada, Y; Tayama, I; Sayama, T; Sasama, H; Saruta, M; Kikuchi, A; Ishimoto, M; Tsukamoto, C				Takada, Yoshitake; Tayama, Ippei; Sayama, Takashi; Sasama, Hiroko; Saruta, Masayasu; Kikuchi, Akio; Ishimoto, Masao; Tsukamoto, Chigen			Genetic analysis of variations in the sugar chain composition at the C-3 position of soybean seed saponins	BREEDING SCIENCE			English	Article						genetic analysis; Glycine max (L.) Merrill; Glycine soja Sieb. et Zucc.; DDMP saponin; group A saponin; sugar chain composition; mapping	GLYCINE-MAX MERRILL; COLON-CANCER CELLS; GROUP-A SAPONIN; SOYASAPOGENOL-A; STRUCTURAL ELUCIDATION; L. MERRILL; SOYASAPONINS; MACROAUTOPHAGY; BISDESMOSIDES; CONSTITUENTS	Saponins are sterols or triterpene glycosides that are widely distributed in plants. The biosynthesis of soybean saponins is thought to involve many kinds of glycosyltransferases, which is reflected in their structural diversity. Here, we performed linkage analyses of the Sg-3 and Sg-4 loci, which may control the sugar chain composition at the C-3 sugar moieties of the soybean saponin aglycones soyasapogenols A and B. The Sg-3 locus, which controls the production of group A saponin Af, was mapped to chromosome (Chr-) 10. The Sg-4 locus, which controls the production of DDMP saponin beta a, was mapped to Chr-1. To elucidate the preference of sugar chain formation at the C-3 and C-22 positions, we analyzed the F-2 population derived from a cross between a mutant variety, Kinusayaka (sg-1(0)), for the sugar chain structure at C-22 position, and Mikuriya-ao (sg-3), with respect to the segregation of the composition of the group A saponins, and found that the formation of these sugar chains was independently regulated. Furthermore, a novel saponin, predicted to be A0-gamma g, 3-O-[beta-D-galactopyranosyl (1 -> 2)-beta-D-glucuronopyranosyl]-22-O-alpha-L-arabinopyranosyl-soyasapogenol A, appeared in the hypocotyl of F-2 individuals with genotype sg-1(0)/sg-1(0) sg-3/sg-3.	[Takada, Yoshitake; Saruta, Masayasu] NARO Western Reg Agr Res Ctr, Zentsuuji, Kagawa 7658508, Japan; [Tayama, Ippei; Sasama, Hiroko; Tsukamoto, Chigen] Iwate Univ, Grad Sch Agr, Morioka, Iwate 0208550, Japan; [Sayama, Takashi; Sasama, Hiroko; Ishimoto, Masao] Natl Inst Agrobiol Sci, Tsukuba, Ibaraki 3058602, Japan; [Kikuchi, Akio] NARO Tohoku Agr Res Ctr, Akita 0192112, Japan		Takada, Y (corresponding author), NARO Western Reg Agr Res Ctr, 1-3-1 Senyuu, Zentsuuji, Kagawa 7658508, Japan.	yottake@affrc.go.jp			Ministry of Agriculture, Forestry and Fisheries of JapanMinistry of Agriculture Forestry & Fisheries - Japan [18063, DD-3260]	This work was supported by the Research Project for Utilizing Advanced Technologies in Agriculture, Forestry and Fisheries (18063) and in part by the Research Project for Genomics for Agricultural Innovation (DD-3260) of the Ministry of Agriculture, Forestry and Fisheries of Japan.	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Sci.	JAN	2011	61	5			SI		639	645		10.1270/jsbbs.61.639			7	Agronomy; Plant Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Agriculture; Plant Sciences	948NY	WOS:000304511100022	23136503	Green Published, Bronze, Green Submitted			2022-04-25	
J	Li, H; Tian, ML; Yu, G; Liu, YC; Wang, X; Zhang, J; Ji, SQ; Zhu, J; Wan, YL; Tang, JQ				Li, Hui; Tian, Mao-Lin; Yu, Ge; Liu, Yu-Cun; Wang, Xin; Zhang, Jing; Ji, Shi-Qi; Zhu, Jing; Wan, Yuan-Lian; Tang, Jian-Qiang			Hyperthermia synergizes with tissue factor knockdown to suppress the growth and hepatic metastasis of colorectal cancer in orthotopic tumor model	JOURNAL OF SURGICAL ONCOLOGY			English	Article						hyperthermia; tissue factor; colorectal cancer; apoptosis; matrix metalloproteinase; metastasis	FACTOR EXPRESSION; GASTRIC-CANCER; JNK; ANGIOGENESIS; CHEMOTHERAPY; COMBINATION; INHIBITION; THROMBOSIS; INDUCTION; AUTOPHAGY	Background Tissue factor (TF) is a significant risk factor for tumor growth and hepatic metastasis in patients with colorectal cancer (CRC). This study aimed to investigate whether hyperthermia has synergistic anti-tumor effects with TF knockdown in suppressing CRC progression and metastasis in vitro and in vivo. Methods Human colorectal cancer LOVO cells were treated by hyperthermia at 44 degrees C for 2?hr or/and TF siRNA. Then the cells were subjected to colony formation assay. Apoptosis was analyzed by flow cytometry, confocal microscopy, and transmission electron microscopy. The cell migration and invasion abilities were analyzed by wound healing and matrigel assay. In addition, orthotopic nude mice model of CRC was established. Results Hyperthermia synergized with TF knockdown to reduce colony formation ability, induce apoptosis, and suppress the migration and invasion of LOVO cells in vitro. Moreover, hyperthermia in combination with TF depletion inhibited the growth and hepatic metastasis of CRC in orthotopic nude mice model. Mechanistically, the synergistic effects were at least partly mediated by inducing JNK mediated apoptosis and suppressing matrix metalloproteinases (MMPs) mediated invasion. Conclusions Hyperthermia in combination with TF-targeted therapy could be a potential approach for CRC treatment. J. Surg. Oncol. 2012; 106:689695. (c) 2012 Wiley Periodicals, Inc.	[Wan, Yuan-Lian] Peking Univ, Hosp 1, Lab Colon Canc, Dept Gen Surg, Beijing 100034, Peoples R China; [Tian, Mao-Lin] Capital Med Univ, Beijing Chaoyang Hosp, Dept Hernia & Abdominal Wall Surg, Beijing, Peoples R China; [Zhang, Jing] Beijing Aerosp Cent Hosp, Dept Cardiovasc Med, Beijing, Peoples R China; [Ji, Shi-Qi] Peking Univ, Hosp 1, Dept Urol, Beijing 100034, Peoples R China		Wan, YL (corresponding author), Peking Univ, Hosp 1, Lab Colon Canc, Dept Gen Surg, 8 Xishiku St, Beijing 100034, Peoples R China.	wan@bjmu.edu.cn			National Natural Sciences Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30872469]; National Natural Sciences Youth Foundation of China [30801092]; "985" Project Foundation of Peking University	Grant sponsor: National Natural Sciences Foundation of China; Grant number: 30872469;; Grant sponsor: National Natural Sciences Youth Foundation of China; Grant number: 30801092; Grant sponsor: "985" Project Foundation of Peking University.	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Surg. Oncol.	NOV	2012	106	6					689	695		10.1002/jso.23136			7	Oncology; Surgery	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Surgery	026CJ	WOS:000310249900007	22532129				2022-04-25	
J	Long, YP; Gao, ZH; Hu, X; Xiang, F; Wu, ZZ; Zhang, JH; Han, X; Yin, LY; Qin, JF; Lan, L; Yin, FZ; Wang, Y				Long, Yaping; Gao, Zihe; Hu, Xiao; Xiang, Feng; Wu, Zhaozhen; Zhang, Jiahui; Han, Xiao; Yin, Liyong; Qin, Junfang; Lan, Lan; Yin, Fuzai; Wang, Yue			Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma	CANCER MEDICINE			English	Article						lactate; MCT4; NK cytotoxicity; NKG2D; NKG2DLs (H60)	MONOCARBOXYLATE TRANSPORTER 4; TUMOR METABOLISM; COLORECTAL-CANCER; POOR-PROGNOSIS; STROMAL CELLS; PH; EXPRESSION; LYMPHOMA; ACID; MICROENVIRONMENT	Monocarboxylate transporter-4 (MCT4), a monocarboxylic acid transporter, demonstrates significantly increased expression in the majority of malignancies. We performed an experiment using BALB/C mice, and our results showed that ShMCT4 transfection or the pharmaceutic inhibition of MCT4 with 7acc1 strengthens the activity of NK cells. The results of a calcein assay revealed that the cytotoxicity of NK cells was strengthened via inhibition of MCT4. In addition, ELISA testing showed that the content of perforin and CD107a was increased, and PCR amplification and immunoblotting revealed that the expression of NKG2D and H60 was upregulated after the inhibition of MCT4. Further, we observed an elevated pH value, decreased extracellular lactate flow, and attenuated tumor growth. Therefore, we concluded that the inhibition of MCT4 enhanced the cytotoxicity of NK cells by blocking lactate flux and reversing the acidified tumor microenvironment. In addition to these findings, we also discovered that MCT4 depletion may have a pronounced impact on autophagy, which was surmised by observing that the inhibition of autophagy (3MA) pulled the enhanced cytotoxicity of NK cells downwards. Together, these data suggest that the key effect of MCT4 depletion on NK cells probably utilizes inductive autophagy as a compensatory metabolic mechanism to minimize the acidic extracellular microenvironment associated with lactate export in tumors.	[Long, Yaping; Gao, Zihe; Hu, Xiao; Xiang, Feng; Wu, Zhaozhen; Zhang, Jiahui; Han, Xiao; Qin, Junfang; Wang, Yue] Nankai Univ, Sch Med, 94 Weijin Rd, Tianjin 300071, Peoples R China; [Yin, Liyong; Yin, Fuzai] First Hosp Qinhuangdao, Qinhuangdao 066000, Hebei, Peoples R China; [Lan, Lan] Tianjin Med Univ, Tianjin Canc Hosp, Tianjin, Peoples R China; [Wang, Yue] Nankai Univ, State Key Lab Med Chem Biol, Tianjin, Peoples R China		Wang, Y (corresponding author), Nankai Univ, Sch Med, 94 Weijin Rd, Tianjin 300071, Peoples R China.; Yin, FZ (corresponding author), First Hosp Qinhuangdao, Qinhuangdao 066000, Hebei, Peoples R China.	yfz2004747@sina.com; wangyue@nankai.edu.cn		Long, Yaping/0000-0002-2706-3656	Open Project Program of State Key Laboratory of Medicinal Chemical Biology; Open Project Program of Key Laboratory for Tumor Precision Medicine of Shaanxi Province; The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China;  [NSFC.81171975];  [NSFC.31770968];  [15JCYBJC26900];  [16JCQNJC11700]	We thank Dashuai Zhu (Nankai University, China) for mice IHC technical assistance, Yu Liu (Rutgers University, America) for a statistical consultant help and Professor Phillip Bryant (Nankai University) and Chang Liu (Tianjin University of Sport, China) for linguistic support. This work was supported by grants from the NSFC.81171975, NSFC.31770968, local 15JCYBJC26900, 16JCQNJC11700, the Open Project Program of State Key Laboratory of Medicinal Chemical Biology, and the Open Project Program of Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, People's Republic of China.	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J	Vara-Perez, M; Felipe-Abrio, B; Agostinis, P				Vara-Perez, Monica; Felipe-Abrio, Blanca; Agostinis, Patrizia			Mitophagy in Cancer: A Tale of Adaptation	CELLS			English	Review						mitophagy; mitochondria; autophagy; cancer; tumor microenvironment; anti-cancer therapy resistance; mitochondrial dynamics	HYPOXIA-INDUCED AUTOPHAGY; SQUAMOUS-CELL CARCINOMA; MITOCHONDRIAL QUALITY-CONTROL; PARKIN-MEDIATED MITOPHAGY; TUMOR-SUPPRESSOR GENES; RHOMBOID PROTEASE PARL; MARROW STROMAL CELLS; BREAST-CANCER; COLORECTAL-CANCER; DOWN-REGULATION	In the past years, we have learnt that tumors co-evolve with their microenvironment, and that the active interaction between cancer cells and stromal cells plays a pivotal role in cancer initiation, progression and treatment response. Among the players involved, the pathways regulating mitochondrial functions have been shown to be crucial for both cancer and stromal cells. This is perhaps not surprising, considering that mitochondria in both cancerous and non-cancerous cells are decisive for vital metabolic and bioenergetic functions and to elicit cell death. The central part played by mitochondria also implies the existence of stringent mitochondrial quality control mechanisms, where a specialized autophagy pathway (mitophagy) ensures the selective removal of damaged or dysfunctional mitochondria. Although the molecular underpinnings of mitophagy regulation in mammalian cells remain incomplete, it is becoming clear that mitophagy pathways are intricately linked to the metabolic rewiring of cancer cells to support the high bioenergetic demand of the tumor. In this review, after a brief introduction of the main mitophagy regulators operating in mammalian cells, we discuss emerging cell autonomous roles of mitochondria quality control in cancer onset and progression. We also discuss the relevance of mitophagy in the cellular crosstalk with the tumor microenvironment and in anti-cancer therapy responses.	[Vara-Perez, Monica; Felipe-Abrio, Blanca; Agostinis, Patrizia] Univ Leuven, Dept Cellular & Mol Med, Lab Cell Death Res & Therapy, KU Leuven, Campus Gasthuisberg,Herestr 49, B-3000 Leuven, Belgium; [Vara-Perez, Monica; Felipe-Abrio, Blanca; Agostinis, Patrizia] VIB KU Leuven, Lab Cell Death Res & Therapy, Ctr Canc Biol, B-3000 Leuven, Belgium		Agostinis, P (corresponding author), Univ Leuven, Dept Cellular & Mol Med, Lab Cell Death Res & Therapy, KU Leuven, Campus Gasthuisberg,Herestr 49, B-3000 Leuven, Belgium.; Agostinis, P (corresponding author), VIB KU Leuven, Lab Cell Death Res & Therapy, Ctr Canc Biol, B-3000 Leuven, Belgium.	monica.varaperez@kuleuven.vib.be; blanca.felipeabrio@kuleuven.vib.be; patrizia.agostinis@kuleuven.vib.be	Agostinis, Patrizia/AAO-2468-2020; Agostinis, Patrizia/ABI-1177-2020	Agostinis, Patrizia/0000-0003-1314-2115; Felipe-Abrio, Blanca/0000-0001-7025-3247; Vara-Perez, Monica/0000-0001-6196-4696	FWO Doctoral Fellowship from the Flemish Research Foundation (FWO-Vlaanderen), BelgiumFWO [1186017N]; EOS consortium [30837538]; Flemish Research Foundation (FWO-Vlaanderen)FWO [G076617N, G049817N, G070115N]; KU LeuvenKU Leuven [C16/15/073]; Stichting tegen Kanker [FAF-F/2018/1252]	M.V.P. is the recipient of a FWO Doctoral Fellowship from the Flemish Research Foundation (FWO-Vlaanderen, 1186017N), Belgium. B.F.A. is supported by the EOS consortium (30837538). P.A. is supported by grants from the Flemish Research Foundation (FWO-Vlaanderen; G076617N, G049817N, G070115N), the EOS consortium (30837538), KU Leuven (C16/15/073) and Stichting tegen Kanker (FAF-F/2018/1252).	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J	He, SJ; Cheng, J; Feng, X; Yu, Y; Tian, L; Huang, Q				He, Si-Jia; Cheng, Jin; Feng, Xiao; Yu, Yang; Tian, Ling; Huang, Qian			The dual role and therapeutic potential of high-mobility group box 1 in cancer	ONCOTARGET			English	Review						HMGB1; RAGE; TLRs; cancer; anticancer therapy	HMGB1 REGULATES AUTOPHAGY; SIGNALING PROTEIN HMGB1; SQUAMOUS-CELL CARCINOMA; GLYCATION END-PRODUCTS; DNA-BINDING; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; BREAST-CANCER; RECEPTOR 4; ISCHEMIA-REPERFUSION	High-mobility group box 1 (HMGB1) is an abundant protein in most eukaryocytes. It can bind to several receptors such as advanced glycation end products (RAGE) and Toll-like receptors (TLRs), in direct or indirect way. The biological effects of HMGB1 depend on its expression and subcellular location. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription, telomere maintenance, and genome stability. While outside the nucleus, it possesses more complicated functions, including regulating cell proliferation, autophagy, inflammation and immunity. During tumor development, HMGB1 has been characterized as both a pro-and anti-tumoral protein by either promoting or suppressing tumor growth, proliferation, angiogenesis, invasion and metastasis. However, the current knowledge concerning the positive and negative effects of HMGB1 on tumor development is not explicit. Here, we evaluate the role of HMGB1 in tumor development and attempt to reconcile the dual effects of HMGB1 in carcinogenesis. Furthermore, we would like to present current strategies targeting against HMGB1, its receptor or release, which have shown potentially therapeutic value in cancer intervention.	[He, Si-Jia; Cheng, Jin; Feng, Xiao; Tian, Ling; Huang, Qian] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Ctr Canc, Sch Med, Shanghai, Peoples R China; [He, Si-Jia; Cheng, Jin; Feng, Xiao; Tian, Ling; Huang, Qian] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Shanghai Key Lab Pancreat Dis, Sch Med, Shanghai, Peoples R China; [Yu, Yang] Henan Prov Peoples Hosp, Dept Oncol, Zhengzhou, Henan, Peoples R China; [Tian, Ling] Shanghai Jiao Tong Univ, Inst Translat Med, Shanghai Gen Hosp, Sch Med, Shanghai, Peoples R China		Huang, Q (corresponding author), Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Ctr Canc, Sch Med, Shanghai, Peoples R China.; Huang, Q (corresponding author), Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Shanghai Key Lab Pancreat Dis, Sch Med, Shanghai, Peoples R China.	Qhuang@sjtu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572951, 81502648]	This research is supported by grants from the National Natural Science Foundation of China (81572951) (Qian Huang) and (81502648) (Jin Cheng).	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J	Zhang, FQ; Cheong, JK				Zhang, Fuquan; Cheong, Jit Kong			The renewed battle against RAS-mutant cancers	CELLULAR AND MOLECULAR LIFE SCIENCES			English	Review						KRAS; NRAS; HRAS; Small GTPases; Kinases; Autophagy; Signaling; Cancer therapeutics	PANCREATIC DUCTAL ADENOCARCINOMA; ADVANCED SOLID TUMORS; CELL LUNG-CANCER; ISOPRENYLCYSTEINE CARBOXYL METHYLTRANSFERASE; FARNESYL-PROTEIN TRANSFERASE; METASTATIC COLORECTAL-CANCER; BLADDER-CARCINOMA ONCOGENE; PHASE-I TRIAL; K-RAS; N-RAS	The RAS genes encode for members of a large superfamily of guanosine-5'-triphosphate (GTP)-binding proteins that control diverse intracellular signaling pathways to promote cell proliferation. Somatic mutations in the RAS oncogenes are the most common activating lesions found in human cancers. These mutations invariably result in the gain-of-function of RAS by impairing GTP hydrolysis and are frequently associated with poor responses to standard cancer therapies. In this review, we summarize key findings of past and present landmark studies that have deepened our understanding of the RAS biology in the context of oncogenesis. We also discuss how emerging areas of research could further bolster a renewed global effort to target the largely undruggable oncogenic RAS and/or its activated downstream effector signaling cascades to achieve better treatment outcomes for RAS-mutant cancer patients.	[Zhang, Fuquan; Cheong, Jit Kong] Duke NUS Med Sch, Programme Canc & Stem Cell Biol, 8 Coll Rd, Singapore 169857, Singapore		Cheong, JK (corresponding author), Duke NUS Med Sch, Programme Canc & Stem Cell Biol, 8 Coll Rd, Singapore 169857, Singapore.	jitkong.cheong@duke-nus.edu.sg		Cheong, Jit Kong/0000-0002-2658-5436	NMRC-CBRG New Investigator Grant [NMRC/BNIG/1078/2012]; Duke-NUS-St. Baldrick's Foundation Pediatric Cancer Research Fund [Duke-NUS-SBF/2015/0004]	Space limitations preclude our manuscript from being a comprehensive review, and this unfortunately limits appropriate recognition of many of our colleagues worldwide, who have contributed immeasurably to the development of the RAS field. We thank David Virshup (Duke-NUS) for his critical review of our manuscript. This work was supported by an NMRC-CBRG New Investigator Grant (NMRC/BNIG/1078/2012) and a Duke-NUS-St. Baldrick's Foundation Pediatric Cancer Research Fund (Duke-NUS-SBF/2015/0004) to JKC.	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J	Frazzi, R				Frazzi, Raffaele			SIRT1 in Secretory Organ Cancer	FRONTIERS IN ENDOCRINOLOGY			English	Review						SIRT1; cancer; secretory organs; acetylation; epigenetic modulation	LONG NONCODING RNA; EPITHELIAL-MESENCHYMAL TRANSITION; PANCREATIC-CANCER; GASTRIC-CANCER; OVARIAN-CANCER; THYROID-CANCER; C-MYC; HEPATOCELLULAR-CARCINOMA; PROTECTIVE AUTOPHAGY; TUMOR-SUPPRESSOR	Mammalian silent information regulator 1 (SIRT1) is reported to play a role in cancers of the secretory organs, including thyroid, pancreatic endocrine, and ovarian tumors (1-4). A recentmeta-analysis conducted on 37 selected studies of human cancers analyzed the correlations of overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) with SIRT1 expression (5). This study reported that SIRT1 overexpression was associated with a worse OS in liver and lung cancers, while it was not correlated with OS in breast cancer, colorectal cancer, or gastric carcinoma. Collectively, the meta-analysis revealed that an unfavorable OS was associated with SIRT1 expression for solid malignancies. Given the growing importance of this class of lysine/histone deacetylases in human endocrine malignancies, a rational and focused literature assessment is desirable in light of future clinical translations.	[Frazzi, Raffaele] Azienda Unita Sanit Locale, IRCCS Reggio Emilia, Lab Translat Res, Reggio Emilia, Italy		Frazzi, R (corresponding author), Azienda Unita Sanit Locale, IRCCS Reggio Emilia, Lab Translat Res, Reggio Emilia, Italy.	raffaele.frazzi@ausl.re.it		Frazzi, Raffaele/0000-0003-1822-745X	Azienda Unita Sanitaria Locale - IRCCS Reggio Emilia, Italy	This work has been funded by Azienda Unita Sanitaria Locale - IRCCS Reggio Emilia, Italy.	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Endocrinol.	SEP 24	2018	9								569	10.3389/fendo.2018.00569			7	Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Endocrinology & Metabolism	GU5TF	WOS:000445353200001	30319549	Green Published, gold			2022-04-25	
J	Soliman, NA; Abd-Ellatif, RN; ELSaadany, AA; Shalaby, SM; Bedeer, AE				Soliman, Nema A.; Abd-Ellatif, Rania N.; ELSaadany, Amira A.; Shalaby, Shahinaz M.; Bedeer, Asmaa E.			Luteolin and 5-flurouracil act synergistically to induce cellular weapons in experimentally induced Solid Ehrlich Carcinoma: Realistic role of P53; a guardian fights in a cellular battle	CHEMICO-BIOLOGICAL INTERACTIONS			English	Article						Solid Ehrlich Carcinoma; Luteolin; 5-Fluorouracil; Apoptosis; Cell cycle arrest; Autophagy	CANCER-CELLS; LUNG-CANCER; SIGNALING PATHWAYS; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; INDUCED APOPTOSIS; CYCLE ARREST; TUMOR; 5-FLUOROURACIL; EXPRESSION	Background: Solid Ehrlich Carcinoma (SEC) is an undifferentiated tumor used in tumor studies and chemotherapy investigations. Aim: to assess the anti-tumor potential of luteolin when used either alone or combined to 5-fluorouracil (5-FU) against SEC. Method: SEC was induced in 40 female mice; they were categorized into 4 equal groups; group I (untreated SEC), group II (5-FU treated SEC), group III (luteolin treated SEC) and group IV (5-FU + luteolin treated SEC). Tumor volume and weight were calculated. P53, p21, caspase 3 and damage regulated autophagy modulator (DRAM) were assessed. Biomarkers of oxidant/antioxidant status in addition to immunohistochemistry for cylin D1 were evaluated. Results: combined administration of luteolin and 5-FU in SEC model increased levels of p53, p21, caspase 3, DRAM and survivability while, tumor volume, weight, thioredoxin reductase one (TR1) activity and cyclin D1 expression showed the reverse with restoration of oxidant/antioxidant indices. Conclusion: current results proved the antitumor therapeutic effects of luteolin alone or combined with 5-FU as a novel strategy for cancer therapy.	[Soliman, Nema A.; Abd-Ellatif, Rania N.] Tanta Univ, Fac Med, Dept Med Biochem, Tanta, Egypt; [ELSaadany, Amira A.; Shalaby, Shahinaz M.] Tanta Univ, Fac Med, Dept Pharmacol, Tanta, Egypt; [Bedeer, Asmaa E.] Tanta Univ, Fac Med, Dept Pathol, Tanta, Egypt		Soliman, NA (corresponding author), Tanta Univ, Fac Med, Med Biochem, Tanta, Egypt.	naema.ahmed@med.tanta.edu.eg; rania_drrania@yahoo.com; dra_elsaadany@yahoo.com; Shahinazmshams@med.tanta.edu.eg; Asmaa.bedeer@gmail.com	soliman, nema Ali/ABA-1044-2021; Shalaby, Shahinaz M/C-4756-2018; Soliman, Nema/AAB-5281-2022	soliman, nema Ali/0000-0003-0281-756X; Shalaby, Shahinaz M/0000-0002-9743-6470; 			Adamsen BL, 2007, INT J ONCOL, V31, P1491; Ambasta RK, 2019, BRIEF FUNCT GENOMICS, V18, P230, DOI 10.1093/bfgp/ely036; Amin ARMR, 2010, J BIOL CHEM, V285, P34557, DOI 10.1074/jbc.M110.141135; Awara WM, 2004, PHARMACOL RES, V50, P487, DOI 10.1016/j.phrs.2004.04.002; Barakat W, 2015, ADV PHARMACOL SCI, V2015, DOI 10.1155/2015/132873; Caputi M, 1999, AM J RESP CELL MOL, V20, P746, DOI 10.1165/ajrcmb.20.4.3366; Chen P, 2017, ONCOTARGET, V8, P27471, DOI 10.18632/oncotarget.15832; Chiang CT, 2007, MOL CANCER THER, V6, P2127, DOI 10.1158/1535-7163.MCT-07-0107; Chong DL, 2017, ANTI-CANCER DRUG, V28, P831, DOI 10.1097/CAD.0000000000000517; Chu Y, 2018, J BIOL REG HOMEOS AG, V32, P1185; Cui L, 2016, ONCOL REP, V35, P3639, DOI 10.3892/or.2016.4752; Dasgupta A, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18010023; EUHUS DM, 1986, J SURG ONCOL, V31, P229, DOI 10.1002/jso.2930310402; Handali S, 2018, BIOMED PHARMACOTHER, V108, P1259, DOI 10.1016/j.biopha.2018.09.128; HOLMGREN A, 1995, METHOD ENZYMOL, V252, P199; Ju W, 2007, MOL PHARMACOL, V71, P1381, DOI 10.1124/mol.106.032185; Kim HS, 2008, J BIOL CHEM, V283, P3731, DOI 10.1074/jbc.M704432200; Kim JK, 2009, J CELL PHYSIOL, V220, P292, DOI 10.1002/jcp.21791; Kouraklis Gregory, 2006, World J Surg Oncol, V4, P5, DOI 10.1186/1477-7819-4-5; Liao YX, 2018, J IMMUNOL RES, V2018, DOI 10.1155/2018/4623919; Lin CH, 2015, BMC CANCER, V15, DOI 10.1186/s12885-015-1965-7; Liu HC, 2006, CANCER J, V12, P482, DOI 10.1097/00130404-200611000-00008; LOWRY OH, 1951, J BIOL CHEM, V193, P265; Lum JJ, 2005, NAT REV MOL CELL BIO, V6, P439, DOI 10.1038/nrm1660; Manju V, 2007, CELL BIOCHEM FUNCT, V25, P189, DOI 10.1002/cbf.1305; Maruthanila VL, 2014, ADV PHARMACOL SCI, V2014, DOI 10.1155/2014/832161; MISRA HP, 1972, J BIOL CHEM, V247, P3170; Nazim UM, 2017, ONCOTARGET, V8, P18095, DOI 10.18632/oncotarget.14994; OSMAN AEM, 1993, TUMORI, V79, P268, DOI 10.1177/030089169307900408; Pandurangan AK, 2014, ASIAN PAC J CANCER P, V15, P5501, DOI 10.7314/APJCP.2014.15.14.5501; Pandya NB, 2013, INDIAN J PHARMACOL, V45, P464, DOI 10.4103/0253-7613.117754; Pappas K, 2017, MOL CANCER RES, V15, P1051, DOI 10.1158/1541-7786.MCR-17-0089; Park SH, 2014, J ENVIRON PATHOL TOX, V33, P219, DOI 10.1615/JEnvironPatholToxicolOncol.2014010923; Roy S, 2018, CELL BIOCHEM FUNCT, V36, P116, DOI 10.1002/cbf.3322; Russo A, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18030547; Russo A, 2016, ONCOTARGET, V7, P79656, DOI 10.18632/oncotarget.13216; Shi YY, 2018, J ZHEJIANG UNIV-SC B, V19, P750, DOI 10.1631/jzus.B1700456; SINHA AK, 1972, ANAL BIOCHEM, V47, P389, DOI 10.1016/0003-2697(72)90132-7; Srivastava S, 2018, J MAXILLOFAC ORAL SU, V17, P597, DOI 10.1007/s12663-018-1126-z; TOMAYKO MM, 1989, CANCER CHEMOTH PHARM, V24, P148, DOI 10.1007/BF00300234; Tuorkey MJ, 2016, EUR J CANCER PREV, V25, P65, DOI 10.1097/CEJ.0000000000000128; Wang H, 2017, ONCOTARGET, V8, P35728, DOI 10.18632/oncotarget.16113; Xia N, 2016, EXP THER MED, V12, P4049, DOI 10.3892/etm.2016.3854; Zhao YF, 2011, BIOMED PHARMACOTHER, V65, P151, DOI 10.1016/j.biopha.2011.02.009	44	7	7	1	3	ELSEVIER IRELAND LTD	CLARE	ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND	0009-2797	1872-7786		CHEM-BIOL INTERACT	Chem.-Biol. Interact.	SEP 1	2019	310								108740	10.1016/j.cbi.2019.108740			6	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	IS5GD	WOS:000482179600024	31288002				2022-04-25	
J	Livesey, KM; Kang, R; Vernon, P; Buchser, W; Loughran, P; Watkins, SC; Zhang, L; Manfredi, JJ; Zeh, HJ; Li, LY; Lotze, MT; Tang, DL				Livesey, Kristen M.; Kang, Rui; Vernon, Philip; Buchser, William; Loughran, Patricia; Watkins, Simon C.; Zhang, Lin; Manfredi, James J.; Zeh, Herbert J., III; Li, Luyuan; Lotze, Michael T.; Tang, Daolin			p53/HMGB1 Complexes Regulate Autophagy and Apoptosis	CANCER RESEARCH			English	Article							TUMOR-SUPPRESSOR P53; ENDOPLASMIC-RETICULUM STRESS; INDUCED CELL-DEATH; GROUP BOX 1; CANCER-CELLS; COLORECTAL-CANCER; DNA-DAMAGE; PROTEIN; HMGB1; P62	The balance between apoptosis ("programmed cell death") and autophagy ("programmed cell survival") is important in tumor development and response to therapy. Here, we show that high mobility group box 1 (HMGB1) and p53 form a complex that regulates the balance between tumor cell death and survival. We show that knockout of p53 in HCT116 cells increases expression of cytosolic HMGB1 and induces autophagy. Conversely, knockout of HMGB1 in mouse embryonic fibroblasts increases p53 cytosolic localization and decreases autophagy. p53 is thus a negative regulator of the HMGB1/Beclin 1 complex, and HMGB1 promotes autophagy in the setting of diminished p53. HMGB1-mediated autophagy promotes tumor cell survival in the setting of p53-dependent processes. The HMGB1/p53 complex affects the cytoplasmic localization of the reciprocal binding partner, thereby regulating subsequent levels of autophagy and apoptosis. These insights provide a novel link between HMGB1 and p53 in the cross-regulation of apoptosis and autophagy in the setting of cell stress, providing insights into their reciprocal roles in carcinogenesis. Cancer Res; 72(8); 1996-2005. (C) 2012 AACR.	[Watkins, Simon C.] Univ Pittsburgh, Inst Canc, Ctr Biol Imaging, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA; [Zhang, Lin] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA; [Li, Luyuan] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Dept Pathol, Pittsburgh, PA 15213 USA; [Manfredi, James J.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA; [Livesey, Kristen M.; Kang, Rui; Vernon, Philip; Buchser, William; Loughran, Patricia; Zeh, Herbert J., III; Lotze, Michael T.; Tang, Daolin] Univ Pittsburgh, Inst Canc, Ctr Biol Imaging, Dept Surg, Pittsburgh, PA 15213 USA		Tang, DL (corresponding author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Dept Surg, G-21,5117 Ctr Ave, Pittsburgh, PA 15213 USA.	lotzemt@upmc.edu; tangd2@upmc.edu	Zhang, Lin/A-7389-2009; Tang, Daolin/B-2905-2010; Li, Luyuan/E-8951-2012; Tang, Daolin/ABD-5062-2021; Watkins, Simon/ABG-2590-2021; Loughran, Patricia/AAB-1184-2021; Kang, Rui/ABD-5291-2021	Zhang, Lin/0000-0003-0018-3903; Tang, Daolin/0000-0002-1903-6180; Watkins, Simon/0000-0003-4092-1552; Kang, Rui/0000-0003-2725-1574; Buchser, William/0000-0002-6675-6359	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1 P01 CA 101944-04]; Department of Surgery, University of Pittsburgh;  [P30CA047904]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P01CA101944] Funding Source: NIH RePORTER; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000005] Funding Source: NIH RePORTER	The authors thank Megan Seippel for careful review of the manuscript. The authors also thank the Health Sciences Tissue Bank, especially Michelle Bisceglia, and the UPMC Network Cancer Registry, especially Sharon Winters, for their assistance with this project. This project used the UPCI Tissue and Research Pathology Services and Cancer Informatics Services Facilities and was supported in part by award P30CA047904.; This work was supported by a grant from the NIH 1 P01 CA 101944-04 (M. T. Lotze) and funding provided by the Department of Surgery, University of Pittsburgh (D. Tang and M. T. Lotze).	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APR 15	2012	72	8					1996	2005		10.1158/0008-5472.CAN-11-2291			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	927KH	WOS:000302905700011	22345153	Green Accepted			2022-04-25	
J	Xu, GL; Feng, DJ; Yao, Y; Li, PP; Sun, H; Yang, H; Li, CX; Jiang, RQ; Sun, BC; Chen, Y				Xu, Guolong; Feng, Dongju; Yao, Yao; Li, Peipei; Sun, Hua; Yang, Hong; Li, Changxian; Jiang, Runqiu; Sun, Beicheng; Chen, Yun			Listeria-based hepatocellular carcinoma vaccine facilitates anti-PD-1 therapy by regulating macrophage polarization	ONCOGENE			English	Article							PD-1/PD-L1 BLOCKADE; TUMOR MICROENVIRONMENT; COLORECTAL-CANCER; T-CELLS; AUTOPHAGY; ACTIVATION; IMMUNOTHERAPY; MECHANISMS; BGJ398; GROWTH	Recently, patients with advanced cancers have been benefited greatly from immune checkpoint blockade immunotherapy. However, immune checkpoint blockade is still suboptimal in HCC treatment and more immune modifications are needed to achieve an efficient therapeutic goal. Here, we investigated the combined administration of a Listeria-based HCC vaccine, Lmdd-MPFG, and the anti-PD-1 immune checkpoint blockade antibody. We found that Lmdd-MPFG promoted the expression of PD-L1 in HCC cells but resensitized the tumor local T cell to respond to the anti-PD-1 immunotherapy. Mechanistically, the Lmdd-MPFG vaccine activates the NF-kappa B pathway in the tumor-associated macrophages (TAMs) through the TLR2 and MyD88 pathway, and recruits p62 to activate the autophagy pathway. The overall effect is skewing the TAMs from M2-polarized TAMs into the M1-polarized TAMs. Most importantly, it skewed the cytokine profiles into antitumor one in the tumor microenvironment (TME). This change restores the T-cell reactivity to the anti-PD-1 blockade. Our results suggested that Lmdd-MPFG combined with PD-1 blockade exerted synergistic antitumor effects through modifying TAMs in the TME and removing T-cell inhibitory signals, thereby providing a new potential strategy for HCC treatment.	[Xu, Guolong; Feng, Dongju; Li, Peipei; Yang, Hong; Chen, Yun] Nanjing Med Univ, Dept Immunol, Key Lab Immune Microenvironm & Dis, Nanjing 211166, Jiangsu, Peoples R China; [Xu, Guolong; Li, Peipei; Chen, Yun] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing 211166, Jiangsu, Peoples R China; [Yao, Yao; Chen, Yun] Jiangsu Canc Hosp, Res Ctr Clin Oncol, Dept Head & Neck Surg, Nanjing 210018, Jiangsu, Peoples R China; [Yao, Yao; Chen, Yun] Jiangsu Inst Canc Res, Nanjing 210018, Jiangsu, Peoples R China; [Yao, Yao; Chen, Yun] Nanjing Med Univ, Canc Hosp, Nanjing 210018, Jiangsu, Peoples R China; [Sun, Hua] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Dept Immunol, Houston, TX 77030 USA; [Li, Changxian] Nanjing Med Univ, Liver Transplantat Ctr, Affiliated Hosp 1, Guangzhou Rd 300, Nanjing 210029, Jiangsu, Peoples R China; [Jiang, Runqiu; Sun, Beicheng] Nanjing Univ, Affiliated Drum Tower Hosp, Dept Hepatobiliary Surg, Med Sch, Nanjing 210093, Jiangsu, Peoples R China		Chen, Y (corresponding author), Nanjing Med Univ, Dept Immunol, Key Lab Immune Microenvironm & Dis, Nanjing 211166, Jiangsu, Peoples R China.; Chen, Y (corresponding author), Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing 211166, Jiangsu, Peoples R China.; Chen, Y (corresponding author), Jiangsu Canc Hosp, Res Ctr Clin Oncol, Dept Head & Neck Surg, Nanjing 210018, Jiangsu, Peoples R China.; Chen, Y (corresponding author), Jiangsu Inst Canc Res, Nanjing 210018, Jiangsu, Peoples R China.; Chen, Y (corresponding author), Nanjing Med Univ, Canc Hosp, Nanjing 210018, Jiangsu, Peoples R China.	chenyun@njmu.edu.cn		Xu, Guolong/0000-0002-0425-2040; Sun, Beicheng/0000-0002-8657-7024	National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81772602, 9174210027, 81902780]; Qing Lan ProjectJiangsu Polytech Institute; Six Talent Peaks Project [JY-018]; Jiangsu Provincial key research development program of China [BE2018750]; "333" projectNatural Science Foundation of Jiangsu Province	This work was supported by grants from the National Natural Science Foundation (Grant Number: 81772602, 9174210027 to YC, 81902780 to YY). The Qing Lan Project, the Six Talent Peaks Project (JY-018), the "333" project, Jiangsu Provincial key research development program of China (BE2018750 to YC).	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J	Sheng, JY; Zou, XH; Cheng, ZQ; Xiang, Y; Yang, W; Lin, Y; Cui, RJ				Sheng, Jiyao; Zou, Xiaohan; Cheng, Ziqian; Xiang, Yien; Yang, Wei; Lin, Yang; Cui, Ranji			Recent Advances in Herbal Medicines for Digestive System Malignancies	FRONTIERS IN PHARMACOLOGY			English	Review						herbal medicine; digestive system malignancies; comprehensive treatment; chemotherapy; side effect	TRADITIONAL CHINESE MEDICINE; GASTRIC-CANCER CELLS; HUMAN HEPATOCELLULAR-CARCINOMA; SHENQI FUZHENG INJECTION; HUAIER AQUEOUS EXTRACT; ENHANCES CISPLATIN CHEMOSENSITIVITY; RANDOMIZED CONTROLLED-TRIALS; ADVANCED COLORECTAL-CANCER; TUMOR-BEARING MICE; NF-KAPPA-B	Herbal medicines, as an important part of traditional Chinese medicine (TCM), have been used to treat digestive system malignancies (DSM) for many years, and have gradually gained recognition worldwide. The role of herbal medicines in the comprehensive treatment of DSM is being improved from adjuvant treatment of the autologous immune function in cancer patients, to the treatment of both the symptoms and disease, direct inhibition of tumor cell growth and proliferation, and induction of tumor cell autophagy and apoptosis. Their specific mechanisms in these treatments are also being explored. The paper reviews the current anti-tumor mechanisms of TCM, including single herbal medicines, Chinese herbal formulations, Chinese medicine preparations and TCM extract, and their application in the comprehensive treatment of digestive system tumors, providing a reference for clinical application of TCM.	[Sheng, Jiyao; Zou, Xiaohan; Cheng, Ziqian; Xiang, Yien; Yang, Wei; Lin, Yang; Cui, Ranji] Jilin Univ, Hosp 2, Jilin Prov Key Lab Mol & Chem Genet, Changchun, Jilin, Peoples R China		Lin, Y (corresponding author), Jilin Univ, Hosp 2, Jilin Prov Key Lab Mol & Chem Genet, Changchun, Jilin, Peoples R China.	linyang@jlu.edu.cn	cui, ranji/AAV-6234-2021		Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC: 81802613]; Jilin Science and Technology Agency [20180101114JC]; Finance Department of Jilin Province	This work was supported by grants from Natural Science Foundation of China (NSFC: 81802613), Jilin Science and Technology Agency funding (20180101114JC), and Finance Department of Jilin Province (2018).	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Pharmacol.	NOV 20	2018	9								1249	10.3389/fphar.2018.01249			14	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	HB0HY	WOS:000450695500001	30524272	Green Published, gold			2022-04-25	
J	Fernandez-Mateos, J; Seijas-Tamayo, R; Klain, JCA; Borgonon, MP; Perez-Ruiz, E; Mesia, R; del Barco, E; Coloma, CS; Dominguez, AR; Daroqui, JC; Ruiz, EF; Cruz-Hernandez, JJ; Gonzalez-Sarmiento, R				Fernandez-Mateos, Javier; Seijas-Tamayo, Raquel; Adansa Klain, Juan Carlos; Pastor Borgonon, Miguel; Perez-Ruiz, Elisabeth; Mesia, Ricard; del Barco, Elvira; Salvador Coloma, Carmen; Rueda Dominguez, Antonio; Caballero Daroqui, Javier; Fernandez Ruiz, Encarnacion; Jesus Cruz-Hernandez, Juan; Gonzalez-Sarmiento, Rogelio			Analysis of autophagy gene polymorphisms in Spanish patients with head and neck squamous cell carcinoma	SCIENTIFIC REPORTS			English	Article							RISK-FACTORS; MOLECULAR-BIOLOGY; COLORECTAL-CANCER; EPIDEMIOLOGY; ATG16L1; DISEASE	Head and neck squamous cell carcinoma (HNSCC) is the sixth cancer on incidence worldwide. Tobacco and alcohol consumption are the most classical risk factors associated with its development. Autophagy process has a dual effect both in tumourigenesis and tumour suppressing activity. To investigate the importance of this pathway in HNSCC susceptibility, a risk factor matched case-control association study was performed with four candidate polymorphisms in autophagy genes (ATG2B, ATG5, ATG10, ATG16L1). We found an association between the variant in ATG10 rs1864183 and a higher susceptibility to develop laryngeal cancer, ATG2B rs3759601 and pharyngeal cancer and ATG16L1 rs2241880 and oral carcinoma. ATG5 rs2245214 SNP was not associated with any location. Overall, our results indicate the importance of the autophagy pathway in the susceptibility of head and neck squamous cell carcinoma and demonstrate the heterogeneity between its locations encompassed under a single terminology.	[Fernandez-Mateos, Javier; Seijas-Tamayo, Raquel; Adansa Klain, Juan Carlos; del Barco, Elvira; Jesus Cruz-Hernandez, Juan] Univ Hosp Salamanca, IBSAL, Med Oncol Serv, Salamanca 37007, Spain; [Fernandez-Mateos, Javier; Seijas-Tamayo, Raquel; Adansa Klain, Juan Carlos; del Barco, Elvira; Jesus Cruz-Hernandez, Juan; Gonzalez-Sarmiento, Rogelio] Univ Salamanca, CSIC, SACYL, Biomed Res Inst Salamanca IBSAL, Salamanca 37007, Spain; [Fernandez-Mateos, Javier; Jesus Cruz-Hernandez, Juan; Gonzalez-Sarmiento, Rogelio] Univ Salamanca, Dept Med, IBSAL, Mol Med Unit, Salamanca 37007, Spain; [Fernandez-Mateos, Javier; Jesus Cruz-Hernandez, Juan; Gonzalez-Sarmiento, Rogelio] Univ Salamanca, CSIC, Inst Mol & Cellular Biol Canc IBMCC, Salamanca 37007, Spain; [Pastor Borgonon, Miguel; Salvador Coloma, Carmen; Caballero Daroqui, Javier] Hosp Univ Politecn La Fe, Med Oncol Serv, Valencia 46026, Spain; [Perez-Ruiz, Elisabeth; Rueda Dominguez, Antonio] Agencia Sanitaria Hosp Costa Sol Marbella, Oncol Dept, Div Med Oncol, Marbella 29603, Spain; [Mesia, Ricard] Univ Barcelona, IDIBELL, Inst Catala Oncol, Med Oncol Dept, Barcelona 08908, Spain; [Fernandez Ruiz, Encarnacion] Agencia Sanitaria Hosp Costa Sol Marbella, Otolaryngol Dept, Marbella 29603, Spain		Cruz-Hernandez, JJ (corresponding author), Univ Hosp Salamanca, IBSAL, Med Oncol Serv, Salamanca 37007, Spain.; Cruz-Hernandez, JJ; Gonzalez-Sarmiento, R (corresponding author), Univ Salamanca, CSIC, SACYL, Biomed Res Inst Salamanca IBSAL, Salamanca 37007, Spain.; Cruz-Hernandez, JJ; Gonzalez-Sarmiento, R (corresponding author), Univ Salamanca, Dept Med, IBSAL, Mol Med Unit, Salamanca 37007, Spain.; Cruz-Hernandez, JJ; Gonzalez-Sarmiento, R (corresponding author), Univ Salamanca, CSIC, Inst Mol & Cellular Biol Canc IBMCC, Salamanca 37007, Spain.	ttcc@seom.org; gonzalez@usal.es	Ruiz, Elísabeth Pérez/ABI-5900-2020; Fernandez-Mateos, Javier/ABH-4726-2020; Gonzalez-Sarmiento, Rogelio/V-5526-2019	Ruiz, Elísabeth Pérez/0000-0001-7204-0800; Gonzalez-Sarmiento, Rogelio/0000-0002-2726-6795; Salvador, Carmen/0000-0003-0715-4195; Cruz Hernandez, Juan Jesus/0000-0003-1980-2751; Fernandez-Mateos, Javier/0000-0002-4949-4131	Instituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Commission [PI11/00519, PI13/01741, PIE14/00066]; FEDER foundsEuropean Commission; Health Regional Management of the Junta de Castilla y LeonJunta de Castilla y Leon [GRS630/A11]; Consejeria de Educacion-Junta de Castilla y LeonJunta de Castilla y Leon; European Social FundEuropean Social Fund (ESF) [EDU/1084/2012]	This study was supported by the health research program of the "Instituto de Salud Carlos III" (PI11/00519, PI13/01741 and PIE14/00066) co financed with FEDER founds and for the Health Regional Management of the Junta de Castilla y Leon (GRS630/A11). J. Fernandez-Mateos was partially supported by a predoctoral research grant from the Consejeria de Educacion-Junta de Castilla y Leon and the European Social Fund to CC-B (EDU/1084/2012). Moreover the authors thank the 790 individuals who consented to participate in this study, and all their colleagues who have participated in this study and are not included in the list of authors, in alphabetical order: Daniel Almenar Cubells (H.U. Dr. Peset de Valencia), Ruth Alvarez Cabellos (H. Virgen de la Salud), Teresa Bonfill Abella (Corporacion Sanitaria Parc Tauli), Beatriz Castelo Fernandez (H.U. de La Paz), Jose Fuster Salva (H. Son Espases), Jose Angel Garcia Saenz (H. Clinico San Carlos), Maria Belen Gonzalez Gragera (H. Son Llatzer), Oscar Salvador Gallego Rubio (H. De la Santa Creu I Sant Pau), Alicia Hurtado Nuno (H.U. Alcarcon), Ana Lopez Alfonso (H. Infanta Leonor), Julio Lambea Sorrosal (H.C.U. Lozano Blesa), Javier Martinez Trufero (H.U. Miguel Servet), Isabel Ruiz Martin (Complejo Hospitalario de Palencia), Michalina Rusiecka (H. Clinic I Provincial) and Sergio Eloy Vazquez Estevez (H. U. Lucus Augusti). We also thank to the Spanish Head and Neck Cancer Cooperative Group (TTCC) and the Institute of Biomedical Research of Salamanca (IBSAL) for their efforts on behalf of the patients and protocol.	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J	Hoffmann, P; Lamerz, D; Hill, P; Kirchner, M; Gauss, A				Hoffmann, Peter; Lamerz, David; Hill, Petra; Kirchner, Marietta; Gauss, Annika			Gene Polymorphisms of NOD2, IL23R, PTPN2 and ATG16L1 in Patients with Crohn's Disease: On the Way to Personalized Medicine?	GENES			English	Article						inflammatory bowel disease; Crohn's disease; NOD2; PTPN2; rs7234029; IL23R; ustekinumab; anti-interleukin-12; 23	INFLAMMATORY-BOWEL-DISEASE; SUSCEPTIBILITY; ASSOCIATIONS; RISK; AUTOPHAGY; VARIANTS; CARD15; IMPACT	Genetic and environmental factors are involved in the pathogenesis of inflammatory bowel diseases (IBD). The study aimed at investigating the potential influence of single nucleotide polymorphisms (SNPs) NOD2 rs2066844, NOD2 rs2066845, NOD2 rs2066847, IL23R rs11209026, PTPN2 rs2542151, PTPN2 rs7234029, and ATG16L1 rs2241880 on the response to immunomodulatory therapies and disease course in Crohn's disease (CD). This is an uncontrolled retrospective monocentric study including patients from the IBD outpatient clinic of Heidelberg University Hospital. Therapy responses and disease courses were related to genetic findings. 379 patients with CD were included. The presence of at least one PTPN2 rs7234029 risk allele was associated with nonresponse to anti-interleukin-12/23 treatment (89.9% vs. 67.6%, p = 0.005). The NOD2 rs2066844 risk allele was associated with a first-degree family history of colon cancer (12.7% vs. 4.7%, p = 0.02), the ATG16L1 rs2241880 risk allele with ileal CD manifestation (p = 0.027), and the IL23R rs11209026 risk allele with a higher rate of CD-related surgeries per disease year (0.08 vs. 0.02, p = 0.025). The results of this study underline the relevance of genetic influences in CD. The association of the PTPN2 rs7234029 risk allele with nonresponse to anti-interleukin-12/23 treatment in CD patients is a novel finding and requires further investigation.	[Hoffmann, Peter; Lamerz, David; Hill, Petra; Gauss, Annika] Univ Hosp Heidelberg, Dept Gastroenterol & Hepatol, INF 410, D-69120 Heidelberg, Germany; [Kirchner, Marietta] Univ Hosp Heidelberg, Inst Med Biometry & Informat, Dept Med Biometry, INF 130-3, D-69120 Heidelberg, Germany		Gauss, A (corresponding author), Univ Hosp Heidelberg, Dept Gastroenterol & Hepatol, INF 410, D-69120 Heidelberg, Germany.	Peterhoffmann84@gmail.com; david.lamerz@web.de; petra.hill@med.uni-heidelberg.de; kirchner@imbi.uni-heidelberg.de; Annika.Gauss@med.uni-heidelberg.de		Kirchner, Marietta/0000-0003-0294-2483; Hoffmann, Peter/0000-0002-5736-445X			Anderson CA, 2011, NAT GENET, V43, P246, DOI 10.1038/ng.764; Boukercha A, 2015, WORLD J GASTROENTERO, V21, P7786, DOI 10.3748/wjg.v21.i25.7786; Burton PR, 2007, NATURE, V447, P661, DOI 10.1038/nature05911; Santos MPC, 2018, ANN GASTROENTEROL, V31, P14, DOI 10.20524/aog.2017.0208; Pena RD, 2015, REV ESP ENFERM DIG, V107, P560; Etienne-Mesmin Lucie, 2017, World J Gastrointest Pharmacol Ther, V8, P7, DOI 10.4292/wjgpt.v8.i1.7; Glas J, 2007, PLOS ONE, V2, DOI 10.1371/journal.pone.0000819; Glas J, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0033682; Iida T, 2017, WORLD J GASTROENTERO, V23, P1944, DOI 10.3748/wjg.v23.i11.1944; Juanola O, 2015, J GASTROENTEROL, V50, P758, DOI 10.1007/s00535-014-1020-5; Kaplan GG, 2015, NAT REV GASTRO HEPAT, V12, P720, DOI 10.1038/nrgastro.2015.150; Kennedy NA, 2018, INFLAMM BOWEL DIS, V24, P583, DOI 10.1093/ibd/izx061; Liu JW, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0089340; Maaser C, 2019, J CROHNS COLITIS, V13, P144, DOI 10.1093/ecco-jcc/jjy113; Moller FT, 2015, AM J GASTROENTEROL, V110, P564, DOI 10.1038/ajg.2015.50; Nuij VJAA, 2017, J TRANSL MED, V15, DOI 10.1186/s12967-017-1355-9; Nunez C, 2008, GENES IMMUN, V9, P289, DOI 10.1038/gene.2008.16; Pranculiene G, 2016, MEDICINA-LITHUANIA, V52, P325, DOI 10.1016/j.medici.2016.11.006; Prescott NJ, 2007, GASTROENTEROLOGY, V132, P1665, DOI 10.1053/j.gastro.2007.03.034; Salem M, 2015, AUTOPHAGY, V11, P585, DOI 10.1080/15548627.2015.1017187; Satsangi J, 2006, GUT, V55, P749, DOI 10.1136/gut.2005.082909; Schaffler H, 2018, J DIGEST DIS, V19, P678, DOI 10.1111/1751-2980.12677; Schnitzler F, 2020, PLOS ONE, V15, DOI 10.1371/journal.pone.0236421; Sidiq T, 2016, FRONT IMMUNOL, V7, DOI 10.3389/fimmu.2016.00367; Smyth DJ, 2008, NEW ENGL J MED, V359, P2767, DOI 10.1056/NEJMoa0807917; Todd JA, 2007, NAT GENET, V39, P857, DOI 10.1038/ng2068; Wang SL, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.00693; Zhu Y, 2020, INFLAMM RES, V69, P87, DOI 10.1007/s00011-019-01296-y	28	1	1	1	5	MDPI	BASEL	ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND		2073-4425		GENES-BASEL	Genes	JUN	2021	12	6							866	10.3390/genes12060866			10	Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Genetics & Heredity	SY5HC	WOS:000665917900001	34198814	gold, Green Published			2022-04-25	
J	Park, JM; Tougeron, D; Huang, SB; Okamoto, K; Sinicrope, FA				Park, Jae Myung; Tougeron, David; Huang, Shengbing; Okamoto, Koichi; Sinicrope, Frank A.			Beclin 1 and UVRAG Confer Protection from Radiation-Induced DNA Damage and Maintain Centrosome Stability in Colorectal Cancer Cells	PLOS ONE			English	Article							INDUCED APOPTOSIS; AUTOPHAGY; REPAIR; INHIBITION; RECOMBINATION; CYCLE; GENE; LC3; ATM	Beclin 1 interacts with UV-irradiation-resistance-associated gene (UVRAG) to form core complexes that induce autophagy. While cells with defective autophagy are prone to genomic instability that contributes to tumorigenesis, it is unknown whether Beclin1 or UVRAG can regulate the DNA damage/repair response to cancer treatment in established tumor cells. We found that siRNA knockdown of Beclin 1 or UVRAG can increase radiation-induced DNA double strand breaks (DSBs), shown by pATM and gamma H2Ax, and promote colorectal cancer cell death. Furthermore, knockdown of Beclin 1, UVRAG or ATG5 increased the percentage of irradiated cells with nuclear foci expressing 53BP1, a marker of nonhomologous end joining but not RAD51 (homologous recombination), compared to control siRNA. Beclin 1 siRNA was shown to attenuate UVRAG expression. Cells with a UVRAG deletion mutant defective in Beclin 1 binding showed increased radiation-induced DSBs and cell death compared to cells with ectopic wild-type UVRAG. Knockdown of Beclin 1 or UVRAG, but not ATG5, resulted in a significant increase in centrosome number (gamma-tubulin staining) in irradiated cells compared to control siRNA. Taken together, these data indicate that Beclin 1 and UVRAG confer protection against radiation-induced DNA DSBs and may maintain centrosome stability in established tumor cells.	[Sinicrope, Frank A.] Mayo Clin, Rochester, MN 55902 USA; Mayo Clin, Ctr Canc, Rochester, MN USA		Sinicrope, FA (corresponding author), Mayo Clin, Rochester, MN 55902 USA.	sinicrope.frank@mayo.edu	tougeron, david/ABF-3217-2020	tougeron, david/0000-0002-8065-9635	National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [5 K05 CA142885, CA113681]; Multi-Organizational Thematic Institute for Cancer; French National Cancer InstituteInstitut National du Cancer (INCA) France; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [K05CA142885, R01CA113681] Funding Source: NIH RePORTER	This work was supported by grants from the National Cancer Institute (5 K05 CA142885 and CA113681, both to FAS). DT is a recipient of financial support from the Multi-Organizational Thematic Institute for Cancer and the French National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Carbone, A; Parrino, B; Di Vita, G; Attanzio, A; Spano, V; Montalbano, A; Barraja, P; Tesoriere, L; Livrea, MA; Diana, P; Cirrincione, G				Carbone, Anna; Parrino, Barbara; Di Vita, Gloria; Attanzio, Alessandro; Spano, Virginia; Montalbano, Alessandra; Barraja, Paola; Tesoriere, Luisa; Livrea, Maria Antonia; Diana, Patrizia; Cirrincione, Girolamo			Synthesis and Antiproliferative Activity of Thiazolyl-bis-pyrrolo[2,3-b]pyridines and Indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, Nortopsentin Analogues	MARINE DRUGS			English	Article						marine alkaloids; bis-indolyl alkaloids; nortopsentins; thiazolyl-bis-pyrrolo[2,3-b]pyridines; indolyl-thiazolyl-pyrrolo[2,3-c]pyridines; apoptosis; autophagic death; antiproliferative activity	MARINE ALKALOID NORTOPSENTIN; BIS-INDOLE ALKALOIDS; ANTITUMOR-ACTIVITY; RING-SYSTEM; CYTOTOXICITY EVALUATION; BIS(INDOLE) ALKALOIDS; BISINDOLE ALKALOIDS; NATURAL-PRODUCTS; POTENT ANTITUMOR; SPONGOSORITES SP	Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contrast, a derivative of the latter series elicited distinct responses in accordance with the dose. Thus, low concentrations (GI(30)) induced morphological changes characteristic of autophagic death with massive formation of cytoplasmic acid vacuoles without apparent loss of nuclear material, and with arrest of cell cycle at the G1 phase, whereas higher concentrations (GI(70)) induced apoptosis with arrest of cell cycle at the G1 phase.	[Carbone, Anna; Parrino, Barbara; Di Vita, Gloria; Attanzio, Alessandro; Spano, Virginia; Montalbano, Alessandra; Barraja, Paola; Tesoriere, Luisa; Livrea, Maria Antonia; Diana, Patrizia; Cirrincione, Girolamo] Univ Palermo, STEBICEF, Biol Chem & Pharmaceut Sci & Technol Dept, I-90123 Palermo, Italy		Cirrincione, G (corresponding author), Univ Palermo, STEBICEF, Biol Chem & Pharmaceut Sci & Technol Dept, Via Archirafi 32, I-90123 Palermo, Italy.	anna.carbone@unipa.it; barbara.parrino@unipa.it; gloria.divita@unipa.it; alessandro.attanzio@unipa.it; virginia.spano@unipa.it; alessandra.montalbano@unipa.it; paola.barraja@unipa.it; luisa.tesoriere@unipa.it; maria.livrea@unipa.it; patrizia.diana@unipa.it; girolamo.cirrincione@unipa.it	PARRINO, Barbara/AAB-7594-2019	PARRINO, Barbara/0000-0003-0163-1579; BARRAJA, Paola/0000-0003-1415-6594	Ministero dell'Istruzione dell'Universita e della Ricerca (MIUR)Ministry of Education, Universities and Research (MIUR)	This work was financially supported by Ministero dell'Istruzione dell'Universita e della Ricerca (MIUR).	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Drugs	JAN	2015	13	1					460	492		10.3390/md13010460			33	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	AZ7MO	WOS:000348403200026	25603343	Green Published, Green Submitted, gold			2022-04-25	
J	Zhang, YH; Cui, SX; Wan, SB; Wu, SH; Qu, XJ				Zhang, Yu-hang; Cui, Shu-xiang; Wan, Sheng-biao; Wu, Shu-hua; Qu, Xian-jun			Increased S1P induces S1PR2 internalization to blunt the sensitivity of colorectal cancer to 5-fluorouracil via promoting intracellular uracil generation	ACTA PHARMACOLOGICA SINICA			English	Article						colorectal cancer; 5-FU resistance; sphingosine-1-phosphate (S1P); S1PR2 internalization; endoplasmic reticulum calcium ([Ca2+](ER)); uracil generation; JTE-013	THYMIDYLATE SYNTHASE; RESISTANCE; SPHINGOSINE-1-PHOSPHATE; CHEMORESISTANCE; INHIBITION; EXPRESSION; AUTOPHAGY; REVEAL; CELLS; MODEL	Sphingosine-1-phosphate (S1P), the backbone of most sphingolipids, activating S1P receptors (S1PRs) and the downstream G protein signaling has been implicated in chemoresistance. In this study we investigated the role of S1PR2 internalization in 5-fluorouracil (5-FU) resistance in human colorectal cancer (CRC). Clinical data of randomly selected 60 CRC specimens showed the correlation between S1PR2 internalization and increased intracellular uracil (P < 0.001). Then we explored the regulatory mechanisms in CRC model of villin-S1PR2(-/-)mice and CRC cell lines. We showed that co-administration of S1P promoted S1PR2 internalization from plasma membrane (PM) to endoplasmic reticulum (ER), thus blunted 5-FU efficacy against colorectal tumors in WT mice, compared to that inS1PR2(-/-)mice. In HCT116 and HT-29 cells, application of S1P (10 mu M) empowered S1PR2 to internalize from PM to ER, thus inducing 5-FU resistance, whereas the specific S1PR2 inhibitor JTE-013 (10 mu M) effectively inhibited S1P-induced S1PR2 internalization. Using Mag-Fluo-AM-labeling [Ca2+](ER)and LC-ESI-MS/MS, we revealed that internalized S1PR2 triggered elevating [Ca2+](ER)levels to activate PERK-eLF2 alpha-ATF4 signaling in HCT116 cells. The activated ATF4 upregulated RNASET2-mediated uracil generation, which impaired exogenous 5-FU uptake to blunt 5-FU therapy. Overall, this study reveals a previously unrecognized mechanism of 5-FU resistance resulted from S1PR2 internalization-upregulated uracil generation in colorectal cancer, and provides the novel insight into the significance of S1PR2 localization in predicting the benefit of CRC patients from 5-FU-based chemotherapy.	[Zhang, Yu-hang; Qu, Xian-jun] Capital Med Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100069, Peoples R China; [Cui, Shu-xiang] Capital Med Univ, Sch Publ Hlth, Dept Toxicol & Sanit Chem, Beijing 100069, Peoples R China; [Wan, Sheng-biao] Ocean Univ China, Lab Marine Drugs & Bioprod, Qingdao Natl Lab Marine Sci & Technol, Sch Med & Pharm,Key Lab Marine Drugs,Minist Educ, Qingdao 266100, Peoples R China; [Wu, Shu-hua] Hosp Binzhou Med Univ, Dept Pathol, Binzhou 264003, Peoples R China		Qu, XJ (corresponding author), Capital Med Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100069, Peoples R China.	qxj@sdu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [91629303, 81673449, 81872884, 81973350]; Beijing Natural Science FoundationBeijing Natural Science Foundation [KZ201710025020, KZ201810025033]; Scientific Research Program of Municipal Commission of Education [KZ201710025020, KZ201810025033]	This work was supported by the National Natural Science Foundation of China (91629303/81673449/81872884/81973350) and the Beijing Natural Science Foundation and Scientific Research Program of Municipal Commission of Education (KZ201710025020/KZ201810025033). In addition, YHZ wants to thank, in particular, the inimitable support and care from Wen-yu Wang. Hope to spend the rest of my life with you.	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Sin.	MAR	2021	42	3					460	469		10.1038/s41401-020-0460-0		JUL 2020	10	Chemistry, Multidisciplinary; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	QP8BK	WOS:000546883600001	32647340	Green Published			2022-04-25	
J	Qu, JY; Lin, ZH				Qu, Junyan; Lin, Zhenghong			Autophagy Regulation by Crosstalk between miRNAs and Ubiquitination System	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						microRNAs; E3 ubiquitin ligases; deubiquitinases; autophagy	GROWTH-FACTOR-BETA; E3 LIGASE MARCH7; HEPATOCELLULAR-CARCINOMA; DEUBIQUITINATING ENZYMES; CANCER PROGRESSION; CELL-PROLIFERATION; PROMOTES AUTOPHAGY; COLORECTAL-CANCER; MULIBREY NANISM; DOWN-REGULATION	MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes with ~22 nucleotides which are involved in the regulation of post-transcriptional gene expression. Ubiquitination and deubiquitination are common post-translational modifications in eukaryotic cells and important pathways in regulating protein degradation and signal transduction, in which E3 ubiquitin ligases and deubiquitinases (DUBs) play a decisive role. MiRNA and ubiquitination are involved in the regulation of most biological processes, including autophagy. Furthermore, in recent years, the direct interaction between miRNA and E3 ubiquitin ligases or deubiquitinases has attracted much attention, and the cross-talk between miRNA and ubiquitination system has been proved to play key regulatory roles in a variety of diseases. In this review, we summarized the advances in autophagy regulation by crosstalk between miRNA and E3 ubiquitin ligases or deubiquitinases.	[Qu, Junyan; Lin, Zhenghong] Chongqing Univ, Sch Life Sci, Chongqing 401331, Peoples R China		Lin, ZH (corresponding author), Chongqing Univ, Sch Life Sci, Chongqing 401331, Peoples R China.	qujunyan1229@yeah.net; zhenghonglin@cqu.edu.cn		Lin, Zhenghong/0000-0002-6354-0042	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82172888, 31571454]; Natural Science Foundation Project of CQ CSTCNatural Science Foundation Project of CQ CSTC [cstc2020jcyj-msxmX0154]	This work was supported by the National Natural Science Foundation of China (Grant No. 82172888 and 31571454) and Natural Science Foundation Project of CQ CSTC (Grant cstc2020jcyj-msxmX0154).	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J. Mol. Sci.	NOV	2021	22	21							11912	10.3390/ijms222111912			18	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	WY3SE	WOS:000719199500001	34769343	Green Published, gold			2022-04-25	
J	Li, YZ; Liu, Y; Shi, FY; Cheng, L; She, JJ				Li, Yazhou; Liu, Yang; Shi, Feiyu; Cheng, Liang; She, Junjun			Knockdown of Rap1b Enhances Apoptosis and Autophagy in Gastric Cancer Cells via the PI3K/Akt/mTOR Pathway	ONCOLOGY RESEARCH			English	Article						Gastric cancer (GC); Rap1b; Autophagy; Apoptosis; PI3K/Akt/mTOR pathway	COLORECTAL-CARCINOMA; PROLIFERATION; EXPRESSION; INDUCTION; INVASION	Gastric cancer (GC) is the fourth most common malignancy and the second leading cause of cancer mortality around the world. However, the regulatory mechanisms of GC tumorigenesis and cancer cell motility are completely unknown. We investigated the role of a RAS-related protein (Rap1b) in the progression of GC. Our results showed that the expression of Rap1b is aberrantly upregulated in GC tissue samples and human GC cell lines, and the high expression of Rap1b indicated a positive correlation with poor prognosis in patients with GC. Inhibition of endogenous Rap1b dramatically reduced the cell cycle progression but strongly enhanced the apoptosis capacity of human GC cell lines MKN-28 and SGC-7901 cells compared with the control group. Western blotting assay showed that Rap1b inhibition resulted in a significant increase in the ratio of LC3-II to LC3-I, and the levels of p62 protein were decreased in both MKN-28 and SGC-7901 cells. Furthermore, PI3K/Akt/mTOR activation was found to be maintained in a low level in the normal gastric mucosal epithelial cells, while it was significantly upregulated in GC cells, which could be decreased by Rap1b inhibition. The PI3K inhibitor LY294002 was enhanced but activator insulin-like growth factor 1 (IGF-1) blocked the Rap1b silencing-induced enhancement of apoptosis and autophagy in MKN-28 and SGC-7901 cells. In conclusion, we demonstrate that Rap1b expression is aberrantly increased in GC, resulting in the inhibition of autophagy and apoptosis of GC cells by the PI3K/Akt/mTOR pathway. This might provide a new understanding and represent a novel therapeutic target for human GC.	[Li, Yazhou] Hitech People Hosp, Dept Intervent Radiol, Baoji, Peoples R China; [Li, Yazhou; Shi, Feiyu; Cheng, Liang; She, Junjun] Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 1, Yanta Xi Rd 277, Xian 710061, Peoples R China; [Liu, Yang] Xi An Jiao Tong Univ, Honghui Hosp, Dept Orthopaed, Xian, Peoples R China		She, JJ (corresponding author), Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 1, Yanta Xi Rd 277, Xian 710061, Peoples R China.	junjunshe063@hotmail.com					Balcer-Kubiczek E. K., 2009, MOL TARGETS GASTRIC; Blankfield RP, 2002, NEW ENGL J MED, V346, P65; Caldas C, 1999, J MED GENET, V36, P873; de Martel C, 2013, GASTROENTEROL CLIN N, V42, P219, DOI 10.1016/j.gtc.2013.01.003; Dunlop EA, 2014, SEMIN CELL DEV BIOL, V36, P121, DOI 10.1016/j.semcdb.2014.08.006; Franke TF, 2003, ONCOGENE, V22, P8983, DOI 10.1038/sj.onc.1207115; Guo HY, 2012, INT J BIOCHEM CELL B, V44, P1465, DOI 10.1016/j.biocel.2012.05.015; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Kumar D, 2014, CANCER LETT, V343, P179, DOI 10.1016/j.canlet.2013.10.003; Lee HW, 2014, BMB REP, V47, P697, DOI 10.5483/BMBRep.2014.47.12.069; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Li B., 2016, MOL NEUROBIOL; Lin KT, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms6917; Liu M, 2014, INT J MOL MED, V33, P1451, DOI 10.3892/ijmm.2014.1713; Mitra RS, 2003, ONCOGENE, V22, P6243, DOI 10.1038/sj.onc.1206534; Park HS, 2011, J FOOD SCI, V76, pT77, DOI 10.1111/j.1750-3841.2011.02099.x; Peng H, 2014, ONCOL REP, V31, P2055, DOI 10.3892/or.2014.3075; Rasul A, 2012, ONCOL REP, V27, P1481, DOI 10.3892/or.2012.1694; Sun L, 2008, J AM SOC NEPHROL, V19, P2293, DOI 10.1681/ASN.2008030336; Tapia O, 2014, VIRCHOWS ARCH, V465, P25, DOI 10.1007/s00428-014-1588-4; Vigen RA, 2012, GASTROENTEROLOGY, V142, pS628; Wang D, 2012, J BIOSCIENCES, V37, P91, DOI 10.1007/s12038-011-9172-4; Won KY, 2015, PATHOL RES PRACT, V211, P308, DOI 10.1016/j.prp.2014.11.005; Xie B, 2013, CANCER CELL INT, V13, DOI 10.1186/1475-2867-13-18; Yang Y., 2015, IEEE T PARALL DISTR, P1, DOI DOI 10.18632/0NC0TARGET.3970; Ying JE, 2015, ONCOTARGETS THER, V8, P2427, DOI 10.2147/OTT.S88592; Yu L., 2007, J IMMUNOL, V179, P8322; Zhang L, 2014, TOXICOL LETT, V228, P248, DOI 10.1016/j.toxlet.2014.05.015; Zhang MX, 2012, FEBS LETT, V586, P3508, DOI 10.1016/j.febslet.2012.08.007	29	23	25	0	2	COGNIZANT COMMUNICATION CORP	PUTNAM VALLEY	18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA	0965-0407	1555-3906		ONCOL RES	Oncol. Res.		2016	24	5					287	293		10.3727/096504016X14648701447779			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DX5BQ	WOS:000384395200001	27712585	Green Published			2022-04-25	
J	Huang, KQ; Liu, DX				huang, Keqiang; liu, Dongxu			Targeting non-canonical autophagy overcomes erlotinib resistance in tongue cancer	TUMOR BIOLOGY			English	Article						Autophagy; Chemotherapeutic resistance; Erlotinib; ATG5	GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; COLORECTAL-CANCER; ENZALUTAMIDE RESISTANCE; PROSTATE-CANCER; NECK-CANCER; EGFR; GENE; PHOSPHORYLATION	Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) frequently occurs in many human cancers and hampers their therapeutic use. A large body of evidence has demonstrated the pro-survival role of autophagy in many human cancers. However, whether autophagy is involved in the induction of erlotinib resistance in tongue squamous cell carcinoma (TSCC) remains unknown. In this report, we found that autophagy prior to or induced by erlotinib treatment plays an important role in erlotinib resistance in tongue cancer cells. Using LC3 transfection, we observed that autophagy is upregulated and further induced when treated with erlotinib. Moreover, we found that autophagy plays a cytoprotective role by MTT analysis of the cell viability in TSCCs when treated with rapamycin or hydroxychloroquine (HCQ) in combination with erlotinib. However, 3-methyladenine (3-MA) did not influence the autophagy. Then, through siRNA technology and WB, we found that erlotinib-induced autophagy is mediated by ATG5 but not Beclin1. Also, knockdown of ATG5 significantly decreased the erlotinib resistance and knockdown of Beclin1 did not affect the sensitivity to erlotinib in TSCCs. Taken together, this indicates the critical role of non-canonical autophagy in erlotinib resistance in TSCCs.	[huang, Keqiang] Liaoning Med Univ, Sch Stomatol, 3-40 Songpo Rd, Jinzhou 121000, Liaoning, Peoples R China; [huang, Keqiang; liu, Dongxu] Shandong Univ, Shandong Prov Key Lab Oral Tissue Regenerat, Sch Stomatol, Jinan 250012, Peoples R China		Liu, DX (corresponding author), Shandong Univ, Shandong Prov Key Lab Oral Tissue Regenerat, Sch Stomatol, Jinan 250012, Peoples R China.	liudongxu@sdu.edu.cn					Atula S, 1996, ARCH OTOLARYNGOL, V122, P1313; Burtness B, 2013, LANCET ONCOL, V14, pE302, DOI 10.1016/S1470-2045(13)70085-8; Caiazza F, 2015, BIOMARK MED, V9, P363, DOI [10.2217/BMM.15.5, 10.2217/bmm.15.5]; Cappuzzo F, 2005, J CLIN ONCOL, V23, P5007, DOI 10.1200/JCO.2005.09.111; Chen G, 2012, BMC MED, V10, DOI 10.1186/1741-7015-10-28; Ciardiello F, 2001, CLIN CANCER RES, V7, P1459; Donev IS, 2011, CLIN CANCER RES, V17, P2260, DOI 10.1158/1078-0432.CCR-10-1993; Feaver CP, 1999, ORAL ONCOL, V35, P450; Gusenbauer S, 2013, ONCOGENE, V32, P3846, DOI 10.1038/onc.2012.396; Haddad RI, 2008, NEW ENGL J MED, V359, P1143, DOI 10.1056/NEJMra0707975; Ishiguro Y, 2013, ONCOTARGET, V4, P550, DOI 10.18632/oncotarget.939; Larsen AK, 2011, PHARMACOL THERAPEUT, V131, P80, DOI 10.1016/j.pharmthera.2011.03.012; Lindeman N, 2014, PATHOLOGY S2, V46, pS1; Lindzen M, 2012, ONCOGENE, V31, P3505, DOI 10.1038/onc.2011.518; Liu CF, 2014, CLIN CANCER RES, V20, P3198, DOI 10.1158/1078-0432.CCR-13-3296; Lu Z, 2008, J CLIN INVEST, V118, P3917, DOI 10.1172/JCI35512; Martin TD, 2014, MOL CELL, V53, P209, DOI 10.1016/j.molcel.2013.12.004; Messersmith WA, 2008, NEW ENGL J MED, V359, P1834, DOI 10.1056/NEJMe0806778; Metzger B, 2011, BMC MED GENET, V12, DOI 10.1186/1471-2350-12-144; Mlcochova J, 2013, J CANCER RES CLIN, V139, P1615, DOI 10.1007/s00432-013-1470-9; Mueller KL, 2012, TRANSL ONCOL, V5, P327, DOI 10.1593/tlo.12163; Nguyen HG, 2014, ONCOGENE, V33, P4521, DOI 10.1038/onc.2014.25; Sequist LV, 2008, J CLIN ONCOL, V26, P2442, DOI 10.1200/JCO.2007.14.8494; Shien K, 2014, ACTA MED OKAYAMA, V68, P191; Tan DSW, 2014, BMC CANCER, V14, DOI 10.1186/1471-2407-14-679; Tsai J, 2008, P NATL ACAD SCI USA, V105, P3041, DOI 10.1073/pnas.0711741105; Wang RC, 2012, SCIENCE, V338, P956, DOI 10.1126/science.1225967; Yoshida T, 2014, CLIN CANCER RES, V20, P4059, DOI 10.1158/1078-0432.CCR-13-1559; Zhang S, 2013, ONCOL REP, V29, P1819, DOI 10.3892/or.2013.2309	29	10	14	1	7	SPRINGER	DORDRECHT	VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS	1010-4283	1423-0380		TUMOR BIOL	Tumor Biol.	JUL	2016	37	7					9625	9633		10.1007/s13277-015-4689-z			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DU4HU	WOS:000382174500113	26797786				2022-04-25	
J	Zhang, W; Popovich, DG				Zhang, Wei; Popovich, David G.			Effect of soyasapogenol a and soyasapogenol B concentrated extracts on Hep-G2 cell proliferation and apoptosis	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY			English	Article						soyasaponins; soyasapogenol; apoptosis; Hep-G2	COLON-CANCER CELLS; LIQUID-CHROMATOGRAPHY; TRITERPENOID SAPONINS; HELA-CELLS; SOYASAPONINS; INDUCTION; MACROAUTOPHAGY; GINSENOSIDES; GINSENG	The growth inhibition and the induction of apoptosis brought about by soyasaponins extracted from soy flour (Glycine max (L.)) and concentrated for soyasapogenols A and B formed by hydrolysis were tested for cytoactivity in the human hepatocellular carcinoma cell line Hep-G2. Concentrated soyasapogenol A (SG-A) and soyasapogenol B (SG-B) extracts contained approximately 69.3% and 46.2% of their respective aglycones (soyasapogenols) assessed by HPLC and ESI-MS, while the soyasaponin extract (TS), derived from crude methanol extraction, did not contain any detectable amounts of SG-A or SG-B. An MTT viability assay showed that all three extracts had an effect on Hep-G2 proliferation in a dose-response manner with 72 h LC50 values of 0.594 +/- 0.021 mg/mL for TS, 0.052 +/- 0.011 mg/mL for SG-A, and 0.128 +/- 0.005 mg/mL for SG-B. Apoptotic cells were determined by flow cytometry cell cycle analysis and confocal laser scanning microscopy (CLSM). Cell cycle analysis indicated a significant (P < 0.05) greater sub-G1 buildup of apoptotic cells at 24 h (25.63 +/- 2.1%) and 72 h (47.1 +/- 3.5%) for the SG-A extract compared to SG-B, whereas the TS extract produced only a minor buildup of sub-G1 cells. CLSM confirmed a morphological change of all treatments after 24 h, at the respective LC50 concentrations. These results show that the samples that contained mainly soyasapogenols A and B showed a greater ability to inhibit proliferation of cultured Hep-G2 when compared to a total soyasaponin extract that did not contain any soyasapogenols.	[Zhang, Wei; Popovich, David G.] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore		Popovich, DG (corresponding author), Natl Univ Singapore, Dept Chem, 3 Sci Dr 3, Singapore 117543, Singapore.	chmpdg@nus.edu.sg	Zhang, Wei/G-8229-2016	Popovich, David/0000-0002-8630-320X; Zhang, Wei/0000-0003-2691-2721			Akao T, 1998, J PHARM PHARMACOL, V50, P1155, DOI 10.1111/j.2042-7158.1998.tb03327.x; Chang WW, 2006, BIOCHEM BIOPH RES CO, V341, P614, DOI 10.1016/j.bbrc.2005.12.216; Cheeke P.R., 2000, J ANIM SCI, V77, P1, DOI DOI 10.2527/JAS2000.00218812007700ES0009X; Darzynkiewicz Z, 1996, ANN NY ACAD SCI, V803, P93, DOI 10.1111/j.1749-6632.1996.tb26379.x; Ellington AA, 2006, CARCINOGENESIS, V27, P298, DOI 10.1093/carcin/bgi214; Ellington AA, 2005, CARCINOGENESIS, V26, P159, DOI 10.1093/carcin/bgh297; Guclu-Ustundag O, 2007, CRIT REV FOOD SCI, V47, P231, DOI 10.1080/10408390600698197; Gurfinkel DM, 2005, INT J FOOD SCI NUTR, V56, P501, DOI 10.1080/09637480500460601; Gurfinkel DM, 2003, NUTR CANCER, V47, P24, DOI 10.1207/s15327914nc4701_3; Jin MC, 2006, J CHROMATOGR A, V1108, P31, DOI 10.1016/j.chroma.2005.12.099; Kinjo J, 2003, BIOL PHARM BULL, V26, P1357, DOI 10.1248/bpb.26.1357; Miyao H, 1998, PLANTA MED, V64, P5, DOI 10.1055/s-2006-957355; MOSMANN T, 1983, J IMMUNOL METHODS, V65, P55, DOI 10.1016/0022-1759(83)90303-4; NOGUCH PD, 1991, CURRENT PROTOCOLS IM; Popovich DG, 2004, PHYTOCHEMISTRY, V65, P337, DOI 10.1016/j.phytochem.2003.11.020; Popovich DG, 2002, ARCH BIOCHEM BIOPHYS, V406, P1, DOI 10.1016/S0003-9861(02)00398-3; Rowlands JC, 2002, FOOD CHEM TOXICOL, V40, P1767, DOI 10.1016/S0278-6915(02)00181-3; Xiao JX, 2007, EXP TOXICOL PATHOL, V59, P35, DOI 10.1016/j.etp.2007.02.004; Xiao JX, 2007, TOXICOL IN VITRO, V21, P820, DOI 10.1016/j.tiv.2007.01.025; Yang YW, 2007, CHROMATOGRAPHIA, V65, P555, DOI 10.1365/s10337-007-0196-8; Yoshiki Y, 1998, BIOSCI BIOTECH BIOCH, V62, P2291, DOI 10.1271/bbb.62.2291; Zhang XW, 1999, ANTI-CANCER DRUG, V10, P569, DOI 10.1097/00001813-199907000-00009; [No title captured]	23	44	51	0	13	AMER CHEMICAL SOC	WASHINGTON	1155 16TH ST, NW, WASHINGTON, DC 20036 USA	0021-8561	1520-5118		J AGR FOOD CHEM	J. Agric. Food Chem.	APR 23	2008	56	8					2603	2608		10.1021/jf0731550			6	Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Agriculture; Chemistry; Food Science & Technology	290EQ	WOS:000255106500009	18361499				2022-04-25	
J	Jung, H; Seo, SB				Jung, Hyeonsoo; Seo, Sang-Beom			Histone lysine demethylase 3B (KDM3B) regulates the propagation of autophagy via transcriptional activation of autophagy-related genes	PLOS ONE			English	Article							TRANS-RETINOIC ACID; EPIGENETIC REGULATION; METHYLTRANSFERASE; INHIBITION; VCP/P97; CANCER; MTOR; MECHANISM; DISEASE; PROTEIN	Autophagy, a self-degradative physiological process, is critical for homeostasis maintenance and energy source balancing in response to various stresses, including nutrient deprivation. It is a highly conserved catabolic process in eukaryotes and is indispensable for cell survival as it involves degradation of unessential or excessive components and their subsequent recycling as building blocks for the synthesis of necessary molecules. Although the dysregulation of autophagy has been reported to broadly contribute to various diseases, including cancers and neurodegenerative diseases, the molecular mechanisms underlying the epigenetic regulation of autophagy are poorly elucidated. Here, we report that the level of lysine demethylase 3B (KDM3B) increases in nutrient-deprived HCT116 cells, a colorectal carcinoma cell line, resulting in transcriptional activation of the autophagy-inducing genes. KDM3B was found to enhance the transcription by demethylating H3K9me2 on the promoter of these genes. Furthermore, we observed that the depletion of KDM3B inhibited the autophagic flux in HCT116 cells. Collectively, these data suggested the critical role of KDM3B in the regulation of autophagy-related genes via H3K9me2 demethylation and induction of autophagy in nutrient-starved HCT116 cells.	[Jung, Hyeonsoo; Seo, Sang-Beom] Chung Ang Univ, Coll Nat Sci, Dept Life Sci, Seoul, South Korea		Seo, SB (corresponding author), Chung Ang Univ, Coll Nat Sci, Dept Life Sci, Seoul, South Korea.	sangbs@cau.ac.kr		Seo, Sang Beom/0000-0003-4709-6022	National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2019R1A4A2001609, NRF-2017R1A2B4004407]	This work was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (NRF-2019R1A4A2001609 and NRF-2017R1A2B4004407) to Sang Beom Seo. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Sun, J; Feng, DJ; Xi, HY; Luo, JJ; Zhou, ZW; Liu, QH; Chen, Y; Shao, Q				Sun, Jie; Feng, Dongju; Xi, Huiyu; Luo, Jiajing; Zhou, Zewei; Liu, Qinghuai; Chen, Yun; Shao, Qing			CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy	MOLECULAR ONCOLOGY			English	Article						autophagy; CD24; lipid raft; retinoblastoma; vincristine	TUMOR-SUPPRESSOR; DRUG-RESISTANCE; CANCER CELLS; LIPID RAFTS; DOXORUBICIN RESISTANCE; MULTIDRUG-RESISTANCE; TARGETING AUTOPHAGY; COLORECTAL-CANCER; SIGNALING PATHWAY; CERVICAL-CANCER	Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI-anchored protein, was overexpressed in human RB tissues and RB cell lines, and was associated with the sensitivity of RB cells in response to VCR therapy. We demonstrated that CD24 plays a critical role in impairing RB sensitivity to VCR via regulating autophagy. Mechanistically, CD24 recruits PTEN to the lipid raft domain and regulates the PTEN/AKT/mTORC1 pathway to activate autophagy. Lipid raft localization was essential for CD24 recruitment function. Collectively, our findings revealed a novel role of CD24 in regulating RB sensitivity to VCR and showed that CD24 is a potential target for improving chemotherapeutic sensitivity and RB patient outcomes.	[Sun, Jie; Xi, Huiyu; Liu, Qinghuai; Shao, Qing] Nanjing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Nanjing, Peoples R China; [Feng, Dongju; Luo, Jiajing; Zhou, Zewei; Chen, Yun] Nanjing Med Univ, Dept Immunol, Key Lab Immune Microenvironm & Dis, Nanjing 211166, Peoples R China; [Xi, Huiyu] Xuzhou Med Univ, Xuzhou Eye Res Inst, Dept Ophthalmol, Xuzhou Peoples Hosp 1, Xuzhou, Jiangsu, Peoples R China; [Chen, Yun] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Peoples R China		Liu, QH; Shao, Q (corresponding author), Nanjing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Nanjing, Peoples R China.; Chen, Y (corresponding author), Nanjing Med Univ, Dept Immunol, Key Lab Immune Microenvironm & Dis, Nanjing 211166, Peoples R China.	liuqh@njmu.edu.cn; chenyun@njmu.edu.cn; 13913862499@139.com		Liu, Qinghuai/0000-0003-1605-1964	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672673, 81772602, 9174210027]; Qing Lan Project, Jiangsu Provincial Key Research Development Program of China [BE2018750]	This work was supported by grants from the National Natural Science Foundation of China (Grant Number: 81672673 to QS, 81772602, 9174210027 to YC) and the Qing Lan Project, Jiangsu Provincial Key Research Development Program of China (BE2018750 to YC).	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Oncol.	AUG	2020	14	8					1740	1759		10.1002/1878-0261.12708		JUN 2020	20	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	MT6DN	WOS:000539822200001	32394616	gold, Green Published			2022-04-25	
J	Kang, MA; Kim, MS; Kim, W; Um, JH; Shin, YJ; Song, JY; Jeong, JH				Kang, Mi Ae; Kim, Mi-Sook; Kim, Wonwoo; Um, Jee-Hyun; Shin, Young-Joo; Song, Jie-Young; Jeong, Jae-Hoon			Lanatoside C suppressed colorectal cancer cell growth by inducing mitochondrial dysfunction and increased radiation sensitivity by impairing DNA damage repair	ONCOTARGET			English	Article						lanatoside C; autophagy; mitochondria; DNA damage repair; radiosensitivity	CARDIAC-GLYCOSIDES; ANTICANCER AGENT; NA+/K+-ATPASE; AUTOPHAGY; INHIBITION; APOPTOSIS; OUABAIN; DEATH; 53BP1; RNF8	Cardiac glycosides are clinically used for cardiac arrhythmias. In this study, we investigated the mechanism responsible for anti-cancer and radiosensitizing effects of lanatoside C in colorectal cancer cells. Lanatoside C-treated cells showed classic patterns of autophagy, which may have been caused by lanatoside C-induced mitochondrial aggregation or degeneration. This mitochondrial dysfunction was due to disruption of K+ homeostasis, possibly through inhibition of Na+/K+-ATPase activity. In addition, lanatoside C sensitized HCT116 cells (but not HT-29 cells) to radiation in vitro. gamma-H2AX, a representative marker of DNA damage, were sustained longer after combination of irradiation with lanatoside C, suggesting lanatoside C impaired DNA damage repair processes. Recruitment of 53BP1 to damaged DNA, a critical initiation step for DNA damage repair signaling, was significantly suppressed in lanatoside C-treated HCT116 cells. This may have been due to defects in the RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A that increases 53BP1 recruitment to DNA damage sites. Although lanatoside C alone reduced tumor growth in the mouse xenograft tumor model, combination of lanatoside C and radiation inhibited tumor growth more than single treatments. Thus, lanatoside C could be a potential molecule for anti-cancer drugs and radiosensitizing agents.	[Kang, Mi Ae; Kim, Mi-Sook; Kim, Wonwoo; Jeong, Jae-Hoon] Korea Inst Radiol & Med Sci, Res Ctr Radiotherapy, Seoul, South Korea; [Kim, Mi-Sook] Korea Inst Radiol & Med Sci, Dept Radiat, Seoul, South Korea; [Um, Jee-Hyun] Gachon Univ, Lee Gil Ya Canc & Diabet Inst, Korea Mouse Metab Phenotyping Ctr, Inchon, South Korea; [Shin, Young-Joo] Inje Univ, Sanggye Paik Hosp, Dept Radiat Oncol, Seoul, South Korea; [Song, Jie-Young] Korea Inst Radiol & Med Sci, Div Radiat Canc Res, Seoul, South Korea		Kim, MS; Jeong, JH (corresponding author), Korea Inst Radiol & Med Sci, Res Ctr Radiotherapy, Seoul, South Korea.	mskim@kcch.re.kr; jeongj@kirams.re.kr	Song, Jie-Young/AAG-6684-2019; Song, Jie-Young/AAH-1254-2019	Song, Jie-Young/0000-0002-5769-3886; 	National R&D Program through the Korea Institute of Radiological and Medical Sciences - Ministry of Science, ICT & Future Planning [711022056/50541-2015]	This research was supported by the National R&D Program through the Korea Institute of Radiological and Medical Sciences funded by the Ministry of Science, ICT & Future Planning (No. 711022056/50541-2015).	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J	Neitzel, C; Seiwert, N; Goder, A; Diehl, E; Weber, C; Nagel, G; Stroh, S; Rasenberger, B; Christmann, M; Fahrer, J				Neitzel, Carina; Seiwert, Nina; Goeder, Anja; Diehl, Erika; Weber, Carina; Nagel, Georg; Stroh, Svenja; Rasenberger, Birgit; Christmann, Markus; Fahrer, Joerg			Lipoic Acid Synergizes with Antineoplastic Drugs in Colorectal Cancer by Targeting p53 for Proteasomal Degradation	CELLS			English	Article						lipoic acid; p53; ubiquitin; proteasome; mitochondria; anticancer drugs	TRANSCRIPTION FACTOR NRF2; NF-KAPPA-B; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; SELECTIVE AUTOPHAGY; REDOX MODULATION; CELL-DEATH; APOPTOSIS; ACTIVATION; EXPRESSION; MECHANISMS	Lipoic acid (LA) is a redox-active disulphide compound, which functions as a pivotal co-factor for mitochondrial oxidative decarboxylation. LA and chemical derivatives were shown to target mitochondria in cancer cells with altered energy metabolism, thereby inducing cell death. In this study, the impact of LA on the tumor suppressor protein p53 was analyzed in various colorectal cancer (CRC) cell lines, with a focus on the mechanisms driving p53 degradation. First, LA was demonstrated to trigger the depletion of both wildtype and mutant p53 protein in all CRC cells tested without influencing its gene expression and preceded LA-triggered cytotoxicity. Depletion of p53 coincided with a moderate, LA-dependent ROS production, but was not rescued by antioxidant treatment. LA induced the autophagy receptor p62 and differentially modulated autophagosome formation in CRC cells. However, p53 degradation was not mediated via autophagy as shown by chemical inhibition and genetic abrogation of autophagy. LA treatment also stabilized and activated the transcription factor Nrf2 in CRC cells, which was however dispensable for p53 degradation. Mechanistically, p53 was found to be readily ubiquitinylated and degraded by the proteasomal machinery following LA treatment, which did not involve the E3 ubiquitin ligase MDM2. Intriguingly, the combination of LA and anticancer drugs (doxorubicin, 5-fluorouracil) attenuated p53-mediated stabilization of p21 and resulted in synergistic killing in CRC cells in a p53-dependant manner.	[Neitzel, Carina; Seiwert, Nina; Goeder, Anja; Diehl, Erika; Weber, Carina; Nagel, Georg; Stroh, Svenja; Rasenberger, Birgit; Christmann, Markus; Fahrer, Joerg] Univ Med Ctr Mainz, Inst Toxicol, D-55131 Mainz, Germany; [Neitzel, Carina; Seiwert, Nina; Fahrer, Joerg] Justus Liebig Univ Giessen, Rudolf Buchhe Inst Pharmacol, D-35392 Giessen, Germany; [Neitzel, Carina; Seiwert, Nina; Fahrer, Joerg] Tech Univ Kaiserslautern, Dept Chem, Div Food Chem & Toxicol, D-67663 Kaiserslautern, Germany		Fahrer, J (corresponding author), Univ Med Ctr Mainz, Inst Toxicol, D-55131 Mainz, Germany.; Fahrer, J (corresponding author), Justus Liebig Univ Giessen, Rudolf Buchhe Inst Pharmacol, D-35392 Giessen, Germany.; Fahrer, J (corresponding author), Tech Univ Kaiserslautern, Dept Chem, Div Food Chem & Toxicol, D-67663 Kaiserslautern, Germany.	fahrer@chemie.uni-kl.de	Seiwert, Nina/ABD-2627-2020	Seiwert, Nina/0000-0003-2169-3670; Goder, Anja/0000-0001-9743-1656	Wilhelm Sander Foundation [2016.039.1, 2016.039.2]; University of Mainz (Stufe I)	This research was funded by Wilhelm Sander Foundation (grant numbers 2016.039.1 and 2016.039.2 to J. F.), and University of Mainz (Stufe I, grant to J. F.).	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J	Anunobi, R; Boone, BA; Cheh, N; Tang, DL; Kang, R; Loux, T; Lotze, MT; Zeh, HJ				Anunobi, Reginald; Boone, Brian A.; Cheh, Nick; Tang, Daolin; Kang, Rui; Loux, Tara; Lotze, Michael T.; Zeh, Herbert J.			Extracellular DNA promotes colorectal tumor cell survival after cytotoxic chemotherapy	JOURNAL OF SURGICAL RESEARCH			English	Article						Autophagy; Apoptosis; TLR-9; DAMPs; Damage-associated molecular patterns receptors; Extracellular DNA	TOLL-LIKE RECEPTORS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; BREAST-CANCER PATIENTS; CIRCULATING DNA; HMGB1 RELEASE; DEOXYRIBONUCLEASE ACTIVITY; INFLAMMATORY RESPONSES; PANCREATIC-CANCER; BLOOD-PLASMA; IN-VITRO	Background: Inflammation promotes the growth and survival of malignant cells. Inflammation within the tumor microenvironment is a result of damage-associated molecular patterns released by dead or dying cells that provide survival signals to the surrounding cells. It has been proposed that extracellular DNA can act as a damage-associated molecular pattern given the association between circulating DNA and autoimmune diseases. Herein, we demonstrate a novel role for genomic extracellular DNA binding to the Toll-like receptor (TLR)-9 on tumor cells in response to cytotoxic insult. Materials and methods: The colorectal tumor cell line HCCT116 was used to study the role of DNA in tumor cell response to chemotherapy. Cell viability was assessed using CCK-8 assay. Cell death mechanisms were assessed by YOYO-1 and lactate dehydrogenase staining for necrosis and TUNEL staining for apoptosis. Autophagy was measured by LC3 punctate formation. TLR9-short hairpin RNA was used to knockdown TLR-9 and determine its role in tumor cell response to DNA. Results: DNAis released fromnecrotic tumor cells after chemotherapy. Survival after cytotoxic insult is enhanced by the presence of extracellular DNA as a result of inhibition of apoptosis and enhanced autophagy. Knockdown of TLR-9 enhanced apoptosis, diminished autophagy, and decreased survival after cytotoxic insult in the presence or absence of extracellular DNA. Conclusions: DNA in the tumor microenvironment promotes survival through induction of autophagy via TLR-9 signaling. This work has important implications for targeting extracellular DNA, TLR-9, and autophagy during treatment with chemotherapy and enhances our understanding of the role of extracellular DNA in the tumor microenvironment. (C) 2018 Elsevier Inc. All rights reserved.	[Anunobi, Reginald; Boone, Brian A.; Cheh, Nick; Tang, Daolin; Kang, Rui; Loux, Tara; Lotze, Michael T.; Zeh, Herbert J.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Dept Surg, UPMC Canc Pavil Suite 417 5150 Ctr Ave, Pittsburgh, PA 15232 USA		Zeh, HJ (corresponding author), Univ Pittsburgh, UPMC Canc Pavil Suite 417 5150 Ctr Ave, Pittsburgh, PA 15232 USA.	zehxhx@upmc.edu	Kang, Rui/ABD-5291-2021; Tang, Daolin/B-2905-2010; Tang, Daolin/ABD-5062-2021	Kang, Rui/0000-0003-2725-1574; Tang, Daolin/0000-0002-1903-6180; Boone, Brian/0000-0001-9006-059X	National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [T32CA113263]	This work was supported by grant number T32CA113263 from the National Cancer Institute.	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J	Yao, Z; Xie, FH; Li, M; Liang, ZR; Xu, WL; Yang, JH; Liu, C; Li, HWW; Zhou, H; Qu, LH				Yao, Zhuo; Xie, Fuhua; Li, Min; Liang, Zirui; Xu, Wenli; Yang, Jianhua; Liu, Chang; Li, Hongwangwang; Zhou, Hui; Qu, Liang-Hu			Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells	CELL DEATH & DISEASE			English	Article							IN-VITRO; MONOCARBOXYLATE TRANSPORTER; ANTITUMOR-ACTIVITY; INDUCED APOPTOSIS; GROWTH-INHIBITION; SMALL-MOLECULE; EXPRESSION; AMPK; GLUT1; VIVO	The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells. Then miRNA profiling of SW480 cells revealed those intracellular signaling related to energy supply was affected by oridonin, suggesting that glucose metabolism is a potential target for CRC therapy. Moreover, our results indicated that oridonin induced metabolic imbalances by significantly inhibiting glucose uptake and reducing lactate export through significantly downregulating the protein levels of GLUT1 and MCT1 in vitro and vivo. However, the ATP level in oridonin-treated CRC cells was not decreased when oridonin blocked the glucose supply, indicating that oridonin induced autophagy process, an important ATP source in cancer cells. The observation was then supported by the results of LC3-II detection and transmission electron microscopy analysis, which confirmed the presence of autophagy. Furthermore, p-AMPK was rapidly deactivated following oridonin treatment, resulting in downregulation of GLUT1 and induction of autophagy in the cancer cells. Thus our finding helped to clarify the anticancer mechanisms of oridonin and suggested it could be applied as a glucose metabolism-targeting agent for cancer treatment.	[Yao, Zhuo; Xie, Fuhua; Li, Min; Liang, Zirui; Xu, Wenli; Yang, Jianhua; Liu, Chang; Li, Hongwangwang; Zhou, Hui; Qu, Liang-Hu] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Key Lab Gene Engn,Minist Educ, Guangzhou 510275, Guangdong, Peoples R China; [Xie, Fuhua] Gannan Med Univ, Dept Biochem & Mol Biol, Ganzhou 341000, Peoples R China		Zhou, H (corresponding author), Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Key Lab Gene Engn,Minist Educ, Guangzhou 510275, Guangdong, Peoples R China.; Qu, LH (corresponding author), Sun Yat Sen Univ, Dept Biochem & Mol Biol, 135 XinGangXi Rd, Guangzhou 510275, Guangdong, Peoples R China.	lsszh@mail.sysu.edu.cn; lssqlh@mail.sysu.edu.cn		Liang, Zirui/0000-0002-1778-488X; Qu, Liang-Hu/0000-0003-3657-2863	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31230042, 31471223]; project of Science and Technology of Guangzhou [201504010022]	We would like to thank Qiao-Juan Huang, Yi-Ling Chen, and Xiao Hong Chen for their technical assistance. This work was supported by the National Natural Science Foundation of China (31230042, 31471223) and the project of Science and Technology of Guangzhou (201504010022).	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FEB	2017	8								e2633	10.1038/cddis.2017.35			10	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	GS5YC	WOS:000443751300014	28230866	Green Published, gold			2022-04-25	
J	Liang, J; Jia, XF; Wang, K; Zhao, NK				Liang, Jing; Jia, Xinfeng; Wang, Kun; Zhao, Niankun			High expression of TFEB is associated with aggressive clinical features in colorectal cancer	ONCOTARGETS AND THERAPY			English	Article						TFEB; colorectal cancer; clinicopathologic variables; prognostic factor; Beclin1	TRANSCRIPTIONAL ACTIVATION; FUTURE BIOMARKERS; AUTOPHAGY; IDENTIFICATION; EPIDEMIOLOGY; METABOLISM; GENES; RISK	Objectives: The transcription factor EB (TFEB), a member of the micropthalmia family, has been found to be associated with autophagy and upregulated in some kinds of tumors. However, very few studies focused on TFEB in colorectal cancer (CRC). TFEB expression status and its relevance to clinical features in CRC would be analyzed in this study. Materials and methods: Real-time PCR, Western blot, and immunohistological staining were used to evaluate TFEB expression in CRC tissues and adjacent normal tissues, and the role of TFEB in CRC cell lines was investigated in vitro and in vivo. Results: TFEB was expressed at lower level in CRC tissues than normal in both mRNA and protein level. However, there were significantly positive correlations between TFEB expression in cancer tissues and malignant progression of CRC. Cancers with TFEB overexpression always had deeper infiltration and higher lymphatic metastasis rate. Furthermore, patients with high TFEB levels always had poor survival, and higher TFEB expression could be a predictor of survival in multivariate analysis. Meanwhile, knockdown TFEB by shRNA or knockout TFEB by sgRNA in CRC cell lines could significantly inhibit cell proliferation and migration in amino acid-free medium. In addition, we found a positive relationship between TFEB and Beclinl expression, and silencing TFEB inhibited Beclin1 expression in CRC cells. Conclusion: TFEB expression correlated with aggressive clinical features in CRC, and higher TFEB expression could be a prognostic factor and potential treatment target of CRC.	[Liang, Jing] Tianjin Binhai New Area Dagang Hosp, Dept Oncol, Nanhuan Rd 1200, Tianjin 300270, Peoples R China; [Jia, Xinfeng] Tianjin Civil Affairs Bur Geriatr Hosp, Geriatr Dept, Tianjin 300111, Peoples R China; [Wang, Kun] Tianjin Med Univ, Dept Genitourinary Oncol, Canc Inst & Hosp, Natl Clin Res Ctr Canc,Key Lab Canc Prevent & The, Tianjin 300030, Peoples R China; [Zhao, Niankun] Tianjin Binhai New Area Dagang Hosp, Dept Internal Med, Tianjin 300270, Peoples R China		Liang, J (corresponding author), Tianjin Binhai New Area Dagang Hosp, Dept Oncol, Nanhuan Rd 1200, Tianjin 300270, Peoples R China.	liangjing_blue@163.com					Brody H, 2015, NATURE, V521, pS1, DOI 10.1038/521S1a; Cuyle PJ, 2017, ACTA CLIN BELG, V72, P103, DOI 10.1080/17843286.2016.1262996; Durinck S, 2015, NAT GENET, V47, P13, DOI 10.1038/ng.3146; Gayle S, 2017, BLOOD, V129, P1768, DOI 10.1182/blood-2016-09-736892; Giatromanolaki A, 2015, LUNG CANCER, V90, P98, DOI 10.1016/j.lungcan.2015.07.008; Hines RB, 2018, BMJ OPEN, V8, DOI 10.1136/bmjopen-2018-022393; Holch JW, 2017, VISC MED, V33, P70, DOI 10.1159/000454687; Hu JL, 2018, ONCOGENESIS, V7, DOI 10.1038/s41389-018-0028-8; Joung J, 2017, NAT PROTOC, V12, P828, DOI 10.1038/nprot.2017.016; Klein K, 2016, INT J ONCOL, V49, P164, DOI 10.3892/ijo.2016.3505; Li L, 2018, BIOCHEM PHARMACOL, V150, P265, DOI 10.1016/j.bcp.2018.02.026; Malouf GG, 2014, CLIN CANCER RES, V20, P4129, DOI 10.1158/1078-0432.CCR-13-3036; Marley AR, 2016, INT J MOL EPIDEMIOL, V7, P105; Medina DL, 2011, DEV CELL, V21, P421, DOI 10.1016/j.devcel.2011.07.016; Napolitano G, 2016, J CELL SCI, V129, P2475, DOI 10.1242/jcs.146365; Nezich CL, 2015, J CELL BIOL, V210, P435, DOI 10.1083/jcb.201501002; Perera R, 2015, NATURE, V524, P361, DOI 10.1038/nature14587; Ploper D, 2015, P NATL ACAD SCI USA, V112, pE420, DOI 10.1073/pnas.1424576112; Russo M, 2018, BIOCHEM PHARMACOL, V153, P51, DOI 10.1016/j.bcp.2018.02.007; Samawi HH, 2017, CURR ONCOL, V24, pE513, DOI 10.3747/co.24.3713; Settembre C, 2013, NAT CELL BIOL, V15, P647, DOI 10.1038/ncb2718; Wilde L, 2018, BIOCHEM J, V475, P1939, DOI 10.1042/BCJ20170847; Yu TC, 2017, CELL, V170, P548, DOI 10.1016/j.cell.2017.07.008; Zarkavelis G, 2017, ANN GASTROENTEROL, V30, P613, DOI 10.20524/aog.2017.0191; Zeng CJ, 2016, GASTROENTEROLOGY, V150, P1633, DOI 10.1053/j.gastro.2016.02.076; Zhang J, 2018, CELL MOL LIFE SCI, V75, P1803, DOI 10.1007/s00018-018-2759-2	26	15	16	1	11	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2018	11						8089	8098		10.2147/OTT.S180112			10	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	HA5ZW	WOS:000450359500002	30519051	Green Submitted, gold, Green Published			2022-04-25	
J	Law, BYK; Mok, SWF; Wu, AG; Lam, CWK; Yu, MXY; Wong, VKW				Law, Betty Yuen Kwan; Mok, Simon Wing Fai; Wu, An Guo; Lam, Christopher Wai Kei; Yu, Margaret Xin Yi; Wong, Vincent Kam Wai			New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy	MOLECULES			English	Review						autophagy; natural products; novel functions; Chinese herbal medicines	NF-KAPPA-B; APOPTOTIC CELL-DEATH; ACTIVATED PROTEIN-KINASE; ROTTLERIN INDUCES AUTOPHAGY; ENDOPLASMIC-RETICULUM STRESS; COLORECTAL-CARCINOMA HCT116; RESISTANT PROSTATE-CANCER; PLANT ALKALOID VOACAMINE; INDUCED OXIDATIVE STRESS; BLOOD-BRAIN-BARRIER	Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.	[Law, Betty Yuen Kwan; Mok, Simon Wing Fai; Wu, An Guo; Lam, Christopher Wai Kei; Yu, Margaret Xin Yi; Wong, Vincent Kam Wai] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China		Wong, VKW (corresponding author), Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.	yklaw@must.edu.mo; smok55@hotmail.com; wag1114@foxmail.com; wklam@must.edu.mo; yxyworld@aliyun.com; kawwong@must.edu.mo		Wong, Vincent Kam Wai/0000-0002-2951-8108	FDCT grant from Science and Technology Development Fund of Macao [084/2013/A3, 090/2013/A3]	This work was supported by FDCT grant from the Science and Technology Development Fund of Macao (Project code: 084/2013/A3 and 090/2013/A3).	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J	Mele, L; del Vecchio, V; Liccardo, D; Prisco, C; Schwerdtfeger, M; Robinson, N; Desiderio, V; Tirino, V; Papaccio, G; La Noce, M				Mele, Luigi; del Vecchio, Vitale; Liccardo, Davide; Prisco, Claudia; Schwerdtfeger, Melanie; Robinson, Nirmal; Desiderio, Vincenzo; Tirino, Virginia; Papaccio, Gianpaolo; La Noce, Marcella			The role of autophagy in resistance to targeted therapies	CANCER TREATMENT REVIEWS			English	Review						Autophagy; Drug resistance; Monoclonal antibodies; Targeted therapy; Tyrosine kinase inhibitors	ENDOPLASMIC-RETICULUM STRESS; SMALL-MOLECULE INHIBITORS; CHRONIC MYELOID-LEUKEMIA; PROSTATE-CANCER CELLS; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; ER STRESS	Autophagy is a self-degradative cellular process, involved in stress response such as starvation, hypoxia, and oxidative stress. This mechanism balances macro-molecule recycling to regulate cell homeostasis. In cancer, autophagy play a role in the development and progression, while several studies describe it as one of the key processes in drug resistance. In the last years, in addition to standard anti-cancer treatments such as chemotherapies and irradiation, targeted therapy became one of the most adopted strategies in clinical practices, mainly due to high specificity and reduced side effects. However, similar to standard treatments, drug resistance is the main challenge in most patients. Here, we summarize recent studies that investigated the role of autophagy in drug resistance after targeted therapy in different types of cancers. We highlight positive results and limitations of pre-clinical and clinical studies in which autophagy inhibitors are used in combination with targeted therapies.	[Mele, Luigi; del Vecchio, Vitale; Liccardo, Davide; Prisco, Claudia; Schwerdtfeger, Melanie; Desiderio, Vincenzo; Tirino, Virginia; Papaccio, Gianpaolo; La Noce, Marcella] Univ Campania L Vanvitelli Naples, Dept Expt Med, Naples, Italy; [Prisco, Claudia] Nottingham Trent Univ, Sch Sci & Technol, John van Geest Canc Res Ctr, Clifton Lane, Nottingham NG11 8NS, England; [Schwerdtfeger, Melanie] Univ Munich, Dept Med 4, Div Clin Pharmacol, Munich, Germany; [Robinson, Nirmal] SA Pathol, Ctr Canc Biol, GPO Box 2471, Adelaide, SA, Australia; [Robinson, Nirmal] Univ South Australia, GPO Box 2471, Adelaide, SA, Australia		Papaccio, G (corresponding author), Dept Expt Med, Via L Armanni 5, I-80128 Naples, Italy.	gianpaolo.papaccio@unicampania.it	Mele, Luigi/AAC-9887-2019; La Noce, Marcella/AAM-1750-2021; Papaccio, Gianpaolo/B-7150-2014	Mele, Luigi/0000-0002-6008-0802; La Noce, Marcella/0000-0002-8782-3821; Robinson, Nirmal/0000-0002-7361-9491; Papaccio, Gianpaolo/0000-0002-4014-5306; DEL VECCHIO, VITALE/0000-0002-7323-4444; Schwerdtfeger, Melanie/0000-0001-8193-3328	University of Campania "Luigi Vanvitelli" (Naples, Italy)	The costs of the open access publication were supported by the "Programma Valere 2020" of the University of Campania "Luigi Vanvitelli" (Naples, Italy).	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Rev.	AUG	2020	88								102043	10.1016/j.ctrv.2020.102043			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	MM6HO	WOS:000550255600007	32505806	hybrid, Green Accepted			2022-04-25	
J	Yang, SR; He, XL; Zhao, J; Wang, DL; Guo, SS; Gao, T; Wang, G; Jin, C; Yan, ZY; Wang, N; Wang, YX; Zhao, YL; Xing, JL; Huang, QC				Yang, Shirong; He, Xianli; Zhao, Jing; Wang, Dalin; Guo, Shanshan; Gao, Tian; Wang, Gang; Jin, Chao; Yan, Zeyu; Wang, Nan; Wang, Yongxing; Zhao, Yilin; Xing, Jinliang; Huang, Qichao			Mitochondrial transcription factor A plays opposite roles in the initiation and progression of colitis-associated cancer	CANCER COMMUNICATIONS			English	Article						colitis; colitis-associated cancer; colorectal cancer; energy metabolism; inflammatory bowel diseases; intestinal homeostasis; mitochondrial transcription factor A (TFAM)	HEPATOCELLULAR-CARCINOMA; ULCERATIVE-COLITIS; CELL-SURVIVAL; TFAM; DNA; TUMORIGENESIS; INFLAMMATION; ACTIVATION; AUTOPHAGY; MUTATION	Background Mitochondria are key regulators in cell proliferation and apoptosis. Alterations in mitochondrial function are closely associated with inflammation and tumorigenesis. This study aimed to investigate whether mitochondrial transcription factor A (TFAM), a key regulator of mitochondrial DNA transcription and replication, is involved in the initiation and progression of colitis-associated cancer (CAC). Methods TFAM expression was examined in tissue samples of inflammatory bowel diseases (IBD) and CAC by immunohistochemistry. Intestinal epithelial cell (IEC)-specific TFAM-knockout mice (TFAM(oIEC)) and colorectal cancer (CRC) cells with TFAM knockdown or overexpression were used to evaluate the role of TFAM in colitis and the initiation and progression of CAC. The underlying mechanisms of TFAM were also explored by analyzing mitochondrial respiration function and biogenesis. Results The expression of TFAM was downregulated in active IBD and negatively associated with the disease activity. The downregulation of TFAM in IECs was induced by interleukin-6 in a signal transducer and activator of transcription 3 (STAT3)/miR-23b-dependent manner. In addition, TFAM knockout impaired IEC turnover to promote dextran sulfate sodium (DSS)-induced colitis in mice. Of note, TFAM knockout increased the susceptibility of mice to azoxymethane/DSS-induced CAC and TFAM overexpression protected mice from intestinal inflammation and colitis-associated tumorigenesis. By contrast, TFAM expression was upregulated in CAC tissues and contributed to cell growth. Furthermore, it was demonstrated that beta-catenin induced the upregulation of TFAM through c-Myc in CRC cells. Mechanistically, TFAM promoted the proliferation of both IECs and CRC cells by increasing mitochondrial biogenesis and activity. Conclusions TFAM plays a dual role in the initiation and progression of CAC, providing a novel understanding of CAC pathogenesis.	[Yang, Shirong; Zhao, Jing; Guo, Shanshan; Wang, Gang; Zhao, Yilin; Xing, Jinliang; Huang, Qichao] Fourth Mil Med Univ, State Key Lab Canc Biol, Xian 710032, Shaanxi, Peoples R China; [Yang, Shirong; Zhao, Jing; Guo, Shanshan; Wang, Gang; Zhao, Yilin; Xing, Jinliang; Huang, Qichao] Fourth Mil Med Univ, Dept Physiol & Pathophysiol, Xian 710032, Shaanxi, Peoples R China; [Yang, Shirong; He, Xianli; Gao, Tian; Jin, Chao; Yan, Zeyu; Wang, Nan] Fourth Mil Med Univ, Tangdu Hosp, Dept Gen Surg, Xian 710032, Shaanxi, Peoples R China; [Wang, Dalin] Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China; [Wang, Yongxing] Fourth Mil Med Univ, Xijing Hosp, Dept Resp Med, Xian 710032, Shaanxi, Peoples R China		Xing, JL; Huang, QC (corresponding author), Fourth Mil Med Univ, State Key Lab Canc Biol, Xian 710032, Shaanxi, Peoples R China.; Xing, JL; Huang, QC (corresponding author), Fourth Mil Med Univ, Dept Physiol & Pathophysiol, Xian 710032, Shaanxi, Peoples R China.	xingjl@fmmu.edu.cn; 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Xing JL, 2008, JNCI-J NATL CANCER I, V100, P1104, DOI 10.1093/jnci/djn213; Zaki MH, 2010, IMMUNITY, V32, P379, DOI 10.1016/j.immuni.2010.03.003; Zheng J, 2012, ONCOL LETT, V4, P1151, DOI 10.3892/ol.2012.928	56	2	2	3	9	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA		2523-3548		CANCER COMMUN	Cancer Commun.	AUG	2021	41	8					695	714		10.1002/cac2.12184		JUN 2021	20	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	UA5CY	WOS:000664640600001	34160895	Green Published, gold			2022-04-25	
J	Zhao, CP; Dang, ZQ; Sun, JB; Yuan, SQ; Xie, L				Zhao, Changpu; Dang, Zhongqin; Sun, Junbo; Yuan, Shuaiqiang; Xie, Li			Up-regulation of microRNA-30b/30d cluster represses hepatocyte apoptosis in mice with fulminant hepatic failure by inhibiting CEACAM1	IUBMB LIFE			English	Article						apoptosis; carcinoembryonic antigen-related cell adhesion molecule 1; fulminant hepatic failure; MicroRNA-30b; MicroRNA-30d	COLON-CANCER CELLS; MIR-30B; MIGRATION; INVASION; AUTOPHAGY; GROWTH; INJURY	Recently, impacts of microRNAs have been unraveled in human diseases, and we aimed to confirm the role of miR-30b/30d in fulminant hepatic failure (FHF). Expression of miR-30b/30d and CEACAM1 in serum of FHF patients and healthy people was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Mice FHF models were established by injection of D-Galn and lipopolysaccharide, and were treated with miR-30b/30d mimics. Oxidative stress, liver injury, and inflammatory reaction in mouse liver tissues were measured using oxidative stress-related factor kits, hematoxylin-eosin staining and enzyme-linked immunosorbent assay, respectively. Moreover, cell cycle distribution and apoptosis of hepatocytes of mice were determined by flow cytometry, and the target relation between miR-30b/30d and CEACAM1 was confirmed by bioinformatic method and dual luciferase reporter gene assay. MiR-30b/30d expression was positively, and CEACAM1 expression was negatively related to prognosis of FHF patients. Up-regulation of miR-30b/30d attenuated oxidative stress, liver injury, and inflammatory reaction, and improved survival rate of FHF mice. Furthermore, elevated miR-30b/30d ameliorated apoptosis and cell cycle arrest of hepatocytes of FHF mice. CEACAM1 was a target gene of miR-30b/30d. This study highlights that up-regulated miR-30b/30d attenuates the progression of FHF by targeting CEACAM1, which may be helpful to FHF treatment.	[Zhao, Changpu] Henan Univ Chinese Med, Internal Med Dept, 6 Dongfeng Rd, Zhengzhou 450002, Henan, Peoples R China; [Dang, Zhongqin] Henan Univ Chinese Med, Hepatobiliary Spleen & Stomach Dept, Henan Hosp Chinese Med, Affiliated Hosp 2, Zhengzhou, Peoples R China; [Sun, Junbo] Henan Univ Chinese Med, Henan Hosp Chinese Med, Personnel Off, Affiliated Hosp 2, Zhengzhou, Peoples R China; [Yuan, Shuaiqiang] Henan Acad Chinese Med, Dept Digest, Affiliated Hosp, Zhengzhou, Peoples R China; [Xie, Li] Henan Elect Power Hosp, Internal Med Dept, Zhengzhou, Peoples R China		Zhao, CP (corresponding author), Henan Univ Chinese Med, Internal Med Dept, 6 Dongfeng Rd, Zhengzhou 450002, Henan, Peoples R China.	zhaochangpu2019@163.com					Caserta S, 2016, SCI REP-UK, V6, DOI 10.1038/srep28006; Chen Y, 2017, BRAZ J MED BIOL RES, V50, DOI [10.1590/1414-431X20176246, 10.1590/1414-431x20176246]; deLemos Andrew S, 2013, Clin Liver Dis (Hoboken), V2, P156, DOI 10.1002/cld.222; Ding H, 2018, INT J MOL MED, V42, P873, DOI 10.3892/ijmm.2018.3684; Ghaemi Z, 2019, FRONT ONCOL, V9, DOI 10.3389/fonc.2019.00653; Gu YF, 2013, CHINESE MED J-PEKING, V126, P4435, DOI 10.3760/cma.j.issn.0366-6999.20131112; Haque R, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0042542; Horst AK, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19103110; Jones DZ, 2018, BMC CANCER, V18, DOI 10.1186/s12885-018-4258-0; Kim TS, 2013, CLIN TRANSPLANT, V27, P297, DOI 10.1111/ctr.12055; Li Q, 2017, BIOCHEM BIOPH RES CO, V485, P506, DOI 10.1016/j.bbrc.2017.02.016; Li SP, 2016, WORLD J GASTROENTERO, V22, P4501, DOI 10.3748/wjg.v22.i18.4501; Li T, 2015, GENE, V561, P268, DOI 10.1016/j.gene.2015.02.051; Li XH, 2016, APOPTOSIS, V21, P708, DOI 10.1007/s10495-016-1238-1; Liang WC, 2017, J CELL BIOCHEM, V118, P530, DOI 10.1002/jcb.25722; Liu LL, 2018, EXP THER MED, V15, P2655, DOI 10.3892/etm.2017.5675; Liu YN, 2018, EBIOMEDICINE, V36, P140, DOI 10.1016/j.ebiom.2018.08.054; Melman YF, 2015, CIRCULATION, V131, P2202, DOI 10.1161/CIRCULATIONAHA.114.013220; Oliveira-Ferrer L, 2018, DIS MARKERS, V2018, DOI 10.1155/2018/6714287; Pavanello S, 2016, TOXICOL LETT, V259, P143, DOI 10.1016/j.toxlet.2016.08.002; Simonetti O, 2018, MED MOL MORPHOL, V51, P41, DOI 10.1007/s00795-017-0169-4; Suda T, 2018, HEPATOL COMMUN, V2, P1247, DOI 10.1002/hep4.1240; Tian SB, 2015, WORLD J GASTROENTERO, V21, P9337, DOI 10.3748/wjg.v21.i31.9337; Ueshima C, 2017, CANCER MED-US, V6, P845, DOI 10.1002/cam4.1050; Wallace K, 2008, BIOCHEM J, V411, P1, DOI 10.1042/BJ20071570; Wang HF, 2016, ONCOTARGET, V7, P82864, DOI 10.18632/oncotarget.12655; Wu P, 2019, ONCOL REP, V41, P1929, DOI 10.3892/or.2018.6947; Wu YB, 2017, BIOTECHNOL LETT, V39, P1827, DOI 10.1007/s10529-017-2428-9; Xiao JJ, 2017, CELL PHYSIOL BIOCHEM, V41, P865, DOI 10.1159/000459899; Xiong YC, 2018, J CANCER, V9, P2147, DOI 10.7150/jca.25006; Xu JG, 2018, CELL PHYSIOL BIOCHEM, V45, P1631, DOI 10.1159/000487730; Yu DS, 2012, INT J MOL MED, V29, P663, DOI 10.3892/ijmm.2012.888; Yu LX, 2019, ONCOL REP, V41, P257, DOI 10.3892/or.2018.6829; Zhang N, 2019, EXP THER MED, V17, P3233, DOI 10.3892/etm.2019.7280; Zhang R, 2017, TUMOR BIOL, V39, P1, DOI 10.1177/1010428317703984; Zou CX, 2016, ONCOL REP, V36, P2715, DOI 10.3892/or.2016.5056	36	0	0	3	4	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1521-6543	1521-6551		IUBMB LIFE	IUBMB Life	JUL	2020	72	7					1349	1363		10.1002/iub.2256		FEB 2020	15	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	ME8CH	WOS:000517270900001	32101367	Bronze			2022-04-25	
J	Petherick, KJ; Williams, AC; Lane, JD; Ordonez-Moran, P; Huelsken, J; Collard, TJ; Smartt, HJM; Batson, J; Malik, K; Paraskeva, C; Greenhough, A				Petherick, Katy J.; Williams, Ann C.; Lane, Jon D.; Ordonez-Moran, Paloma; Huelsken, Joerg; Collard, Tracey J.; Smartt, Helena J. M.; Batson, Jennifer; Malik, Karim; Paraskeva, Chris; Greenhough, Alexander			Autolysosomal beta-catenin degradation regulates Wnt-autophagy-p62 crosstalk	EMBO JOURNAL			English	Article						autophagy; cancer; LC3; p62; Wnt/beta-catenin	TRANSCRIPTION FACTOR NRF2; COLORECTAL-CANCER; WNT/BETA-CATENIN; CASPASE CLEAVAGE; STRUCTURAL BASIS; AUTOPHAGY; P62; P62/SQSTM1; INACTIVATION; INHIBITION	The Wnt/beta-catenin signalling and autophagy pathways each play important roles during development, adult tissue homeostasis and tumorigenesis. Here we identify the Wnt/beta-catenin signalling pathway as a negative regulator of both basal and stress-induced autophagy. Manipulation of beta-catenin expression levels in vitro and in vivo revealed that beta-catenin suppresses autophagosome formation and directly represses p62/SQSTM1 (encoding the autophagy adaptor p62) via TCF4. Furthermore, we show that during nutrient deprivation beta-catenin is selectively degraded via the formation of a beta-catenin-LC3 complex, attenuating beta-catenin/TCF-driven transcription and proliferation to favour adaptation during metabolic stress. Formation of the beta-catenin-LC3 complex is mediated by a W/YXXI/L motif and LC3-interacting region (LIR) in beta-catenin, which is required for interaction with LC3 and non-proteasomal degradation of beta-catenin. Thus, Wnt/beta-catenin represses autophagy and p62 expression, while beta-catenin is itself targeted for autophagic clearance in autolysosomes upon autophagy induction. These findings reveal a regulatory feedback mechanism that place beta-catenin at a key cellular integration point coordinating proliferation with autophagy, with implications for targeting these pathways for cancer therapy.	[Petherick, Katy J.; Williams, Ann C.; Collard, Tracey J.; Smartt, Helena J. M.; Paraskeva, Chris; Greenhough, Alexander] Univ Bristol, Sch Cellular & Mol Med, Canc Res UK Colorectal Tumour Biol Grp, Bristol BS8 1TD, Avon, England; [Lane, Jon D.] Univ Bristol, Sch Biochem, Cell Biol Labs, Bristol BS8 1TD, Avon, England; [Ordonez-Moran, Paloma; Huelsken, Joerg] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res, Canc Stem Cell Lab, Lausanne, Switzerland; [Batson, Jennifer] Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England; [Malik, Karim] Univ Bristol, Sch Cellular & Mol Med, Canc Epigenet Lab, Bristol BS8 1TD, Avon, England		Paraskeva, C (corresponding author), Univ Bristol, Sch Cellular & Mol Med, Canc Res UK Colorectal Tumour Biol Grp, Bristol BS8 1TD, Avon, England.	c.paraskeva@bristol.ac.uk; a.greenhough@bristol.ac.uk	Lane, Jon D/A-9320-2011; Greenhough, Alexander/J-9308-2012; Huelsken, Joerg/AAC-9581-2021; Greenhough, Alexander/Y-6728-2019; Ordonez-Moran, Paloma/B-6371-2016	Greenhough, Alexander/0000-0002-8306-811X; Huelsken, Joerg/0000-0003-3105-9606; Greenhough, Alexander/0000-0002-8306-811X; Williams, Ann/0000-0002-6009-7137; Malik, Karim/0000-0002-8965-200X; Lane, Jon/0000-0002-6828-5888; Ordonez-Moran, Paloma/0000-0001-7688-1252	Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission; Wolfson Foundation; Cancer Research UKCancer Research UK [C19/A11975]; Citrina Foundation; John James Bristol Foundation; Wellcome TrustWellcome TrustEuropean Commission; BBSRCUK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J002704/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research CouncilUK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J002704/1] Funding Source: researchfish; Cancer Research UKCancer Research UK [11975] Funding Source: researchfish	We thank all the members of our lab for their valuable support and discussion. In addition, we would like to thank Dr Nick Ktistakis for helpful discussion and the autophagy-inducing media recipe; Prof Terje Johansen for advice; Dr Benjamin Alman and Raymond Poon for providing the myc-tagged beta-catenin<SUP>AAAA</SUP> construct; Dr Eric Fearon for providing the beta-catenin<SUP>WT</SUP> and beta-catenin<SUP>S33Y</SUP> constructs; Dr Bert Vogelstein for providing the HCT116 CTNNB1 isogenic cell lines; Dr Ian McGough and Prof Pete Cullen for the HA-pcDNA3.1 plasmid; Dr Andrew Herman for cell sorting at the University of Bristol FMVS Flow Cytometry Facility; the Medical Research Council and Wolfson Foundation for supporting the Wolfson Bioimaging Facility at the University of Bristol; Dr Stefan Roberts for critical reading of the manuscript. This work was supported by a Cancer Research UK Programme Grant (C19/A11975), the Citrina Foundation, the John James Bristol Foundation and the Wellcome Trust.	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JUL 3	2013	32	13					1903	1916		10.1038/emboj.2013.123			14	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	176US	WOS:000321331900012	23736261	Green Published, Green Submitted			2022-04-25	
J	D'Apolito, O; Garofalo, D; Gelzo, M; Paris, D; Melck, D; Calemma, R; Izzo, F; Palmieri, G; Castello, G; Motta, A; Corso, G				D'Apolito, Oceania; Garofalo, Daniela; Gelzo, Monica; Paris, Debora; Melck, Dominique; Calemma, Rosa; Izzo, Francesco; Palmieri, Giuseppe; Castello, Giuseppe; Motta, Andrea; Corso, Gaetano			Basic amino acids and dimethylarginines targeted metabolomics discriminates primary hepatocarcinoma from hepatic colorectal metastases	METABOLOMICS			English	Article						Hepatic tumorigenesis; Metastases; Tissue metabolic profiling; Arginine; Dimethylarginines; Basic amino acids; Mass spectrometry	HUMAN HEPATOCELLULAR-CARCINOMA; ARGININOSUCCINATE SYNTHETASE; MAGNETIC-RESONANCE; CANCER METABOLISM; ARGININE; PROLIFERATION; SPECTROSCOPY; EXPRESSION; AUTOPHAGY; BIOMARKER	Hepatocellular carcinoma (HCC) is a very aggressive neoplasia requiring early and accurate diagnosis to improve patient outcomes with timely treatment. The liver is also very frequently colonized by metastases, and the most frequent differential diagnosis is HCC against intrahepatic cholangiocarcinoma or metastatic adenocarcinoma. Metabolomics is a powerful tool for identification of altered biomarkers in cancer, and to evaluate the efficacy of drug treatments. Here we analyzed by HILIC-MS/MS methylated arginines, basic amino acids (Arg, Cit, Orn), and their ratios in the extracts of primary HCC tissues, liver metastases from colorectal carcinoma (MET), cirrhotic related hepatitis-C-virus (CIR), and non-cirrhotic normal liver (NT) adjacent tissues. We found high levels of Arg (p < 0.0001) and Arg/Orn (p < 0.01) in MET compared to other tissues. In MET, compared to NT and CIR, Arg concentration was fivefold higher, while in HCC it was twofold higher. ADMA increased twofold compared to NT and CIR, while in HCC it was 50 % higher. Arg/Cit and ADMA/SDMA ratios were significantly higher in MET compared to NT and CIR (p < 0.005). Arg/Orn, Arg/Cit, and ADMA/SDMA ratios increased progressively from NT, CIR, HCC, to MET tissues. Arg/Cit correlated significantly with Arg/Orn ratios (r = 0.77; p < 0.0001), and discriminates tumor from non-tumor samples. In addition, the discriminant lactate/glucose ratio we previously found by NMR, also correlated significantly with the Arg levels (r = 0.64; p < 0.0001), and discriminated MET from all other tissues. The results indicated that Arg in MET is higher than other tissue classes, suggesting that, together with the lactate/glucose ratio, it can be considered a further biomarker for HCC-metastases differentiation.	[D'Apolito, Oceania; Garofalo, Daniela; Corso, Gaetano] Univ Foggia, Dipartimento Med Clin & Sperimentale, Foggia, Italy; [Gelzo, Monica] Univ Naples Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy; [Paris, Debora; Melck, Dominique; Motta, Andrea] CNR, Ist Chim Biomol, Pozzuoli, NA, Italy; [Calemma, Rosa; Izzo, Francesco; Castello, Giuseppe] Fdn G Pascale, Ist Nazl Studio & Cura Tumori, Naples, Italy; [Palmieri, Giuseppe] CNR, Ist Chim Biomol, Sassari, SS, Italy; [Castello, Giuseppe] Ctr Ric Oncol Mercogliano, Mercogliano, Italy		Corso, G (corresponding author), Univ Foggia, Dipartimento Med Clin & Sperimentale, Foggia, Italy.	andrea.motta@icb.cnr.it; gaetano.corso@unifg.it	Corso, Gaetano/H-9450-2013; Paris, Debora/ABI-2224-2020; Gelzo, Monica/K-6667-2016; Izzo, Francesco/P-3042-2019; Palmieri, Giuseppe/AAX-2627-2021; Paris, Debora/P-1624-2018; Palmieri, G/K-6095-2016	Corso, Gaetano/0000-0003-4720-1320; Paris, Debora/0000-0003-4526-8353; Gelzo, Monica/0000-0002-1500-0746; Izzo, Francesco/0000-0003-3093-5408; Paris, Debora/0000-0003-4526-8353; Palmieri, G/0000-0002-4350-2276; Motta, Andrea/0000-0002-8643-658X	University of Foggia (Premialita PRIN)	We are grateful to patients for their important contribution to this study. Financial support was received from the University of Foggia (Premialita PRIN 2008).	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J	Hagihara, T; Kondo, J; Endo, H; Ohue, M; Sakai, Y; Inoue, M				Hagihara, Takeshi; Kondo, Jumpei; Endo, Hiroko; Ohue, Masayuki; Sakai, Yoshiharu; Inoue, Masahiro			Hydrodynamic stress stimulates growth of cell clusters via the ANXA1/PI3K/AKT axis in colorectal cancer	SCIENTIFIC REPORTS			English	Article							CIRCULATING TUMOR-CELLS; FLUID SHEAR-STRESS; ANNEXIN A1; FREE SURVIVAL; SPHEROIDS; RECEPTOR; PROGRESSION; AUTOPHAGY; DYNAMICS; CULTURE	Cancer cells are exposed to various stresses in vivo, including hydrodynamic stress (HDS). HDS on cancer cells in the blood stream can influence the metastatic potential. Recent studies revealed that circulating tumor cell clusters are more responsible for metastasis than circulating single cells. Nevertheless, most studies on HDS are based on single cells prepared from established cancer cell lines. Here, we used cancer tissue-originated spheroids (CTOS) as a patient-derived, 3D organoid model to investigate the effect of HDS on cancer cell clusters. We found that HDS induced the growth of cancer cell clusters in a population of colorectal CTOSs. Microarray analyses revealed that the multifunctional protein, Annexin 1 (ANXA1), was upregulated upon HDS exposure. Chemically-induced membrane damage also triggered the expression of ANXA1. A knockdown of ANXA1 revealed that ANXA1 regulated HDS-stimulated growth in colorectal CTOSs. Mechanistically, activating the PI3K/AKT pathway downstream of ANXA1 contributed to the phenotype. These findings demonstrate that HDS induces the growth of cancer cell clusters via ANXA1/PI3K/AKT axis, which helps to elucidate the prometastatic feature of circulating cancer cell clusters.	[Hagihara, Takeshi; Kondo, Jumpei; Inoue, Masahiro] Kyoto Univ, Grad Sch Med, Dept Clin Bioresource Res & Dev, Sakyo Ku, Yoshida Honmachi, Kyoto 6068501, Japan; [Hagihara, Takeshi; Sakai, Yoshiharu] Kyoto Univ, Grad Sch Med, Dept Surg, Div Gastrointestinal Surg, Yoshida Honmachi, Kyoto 6068501, Japan; [Hagihara, Takeshi; Kondo, Jumpei; Endo, Hiroko; Ohue, Masayuki; Inoue, Masahiro] Osaka Int Canc Inst, Dept Biochem, Chuo Ku, 3-1-69 Otemae, Osaka 5418567, Japan		Kondo, J (corresponding author), Kyoto Univ, Grad Sch Med, Dept Clin Bioresource Res & Dev, Sakyo Ku, Yoshida Honmachi, Kyoto 6068501, Japan.; Kondo, J (corresponding author), Osaka Int Canc Inst, Dept Biochem, Chuo Ku, 3-1-69 Otemae, Osaka 5418567, Japan.	jumpeko@gmail.com	Kondo, Jumpei/AAC-4336-2020	Kondo, Jumpei/0000-0002-1350-0480	P-DIRECT, P-CREATE, Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) [JP18am0101084]; Research on Development of New Drugs grant from the Japan Agency for Medical Research and Development (AMED); Princess Takamatsu Cancer Research Fund	This article was supported by a Grants-in-Aid from the P-DIRECT, P-CREATE, Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) under Grant Number JP18am0101084, the Research on Development of New Drugs grant from the Japan Agency for Medical Research and Development (AMED), and by a Research Grant of the Princess Takamatsu Cancer Research Fund.	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J	Huang, YH; Sun, Y; Huang, FY; Li, YN; Wang, CC; Mei, WL; Dai, HF; Tan, GH; Huang, CH				Huang, Yong-Hao; Sun, Yan; Huang, Feng-Ying; Li, Yue-Nan; Wang, Cai-Chun; Mei, Wen-Li; Dai, Hao-Fu; Tan, Guang-Hong; Huang, Canhua			Toxicarioside O induces protective autophagy in a sirtuin-1-dependent manner in colorectal cancer cells	ONCOTARGET			English	Article						colorectal cancer; toxicarioside O (TCO); autophagy; apoptosis; sirtuin-1 (SIRT1)	ANTIARIS-TOXICARIA; CARDIAC-GLYCOSIDES; STRESS; APOPTOSIS; SIRT1; DEACETYLATION; GLIOBLASTOMA; INVOLVEMENT; STARVATION; HYPOXIA	Colorectal cancer is the most common cancer. It has high morbidity and mortality worldwide, and more effective treatment strategies need to be developed. Toxicarioside O (TCO), a natural product derived from Antiaris toxicaria, has been shown to be a potential anticancer agent. However, the molecular mechanisms involved remain poorly understood. In this study, our results demonstrated that TCO can induce both apoptosis and autophagy in colorectal cancer cells. Moreover, TCO-induced autophagy was due to the increase of the expression and activity of the enzyme sirtuin-1 (SIRT1), and subsequent inhibition of the Akt/mTOR pathway. Inhibition of SIRT1 activity by its inhibitor, EX-527, attenuated TCO-induced autophagy. Of interest, inhibition of autophagy by chloroguine, an autophagy inhibitor, enhanced TCO-induced apoptotic cell death, suggesting that autophagy plays a protective role in TCO-induced apoptosis. Together, these findings suggest that combination of TCO and autophagy inhibitor may be a novel strategy suitable for potentiating the anticancer activity of TCO for treatment of colorectal cancer.	[Huang, Yong-Hao; Sun, Yan; Huang, Feng-Ying; Li, Yue-Nan; Wang, Cai-Chun; Tan, Guang-Hong; Huang, Canhua] Hainan Med Coll, Minist Educ, Key Lab Trop Dis & Translat Med, Haikou 571199, Hainan, Peoples R China; [Huang, Yong-Hao; Sun, Yan; Huang, Feng-Ying; Li, Yue-Nan; Wang, Cai-Chun; Tan, Guang-Hong; Huang, Canhua] Hainan Med Coll, Hainan Prov Key Lab Trop Med, Haikou 571199, Hainan, Peoples R China; [Mei, Wen-Li; Dai, Hao-Fu] Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Haikou 571199, Hainan, Peoples R China; [Huang, Canhua] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Huang, Canhua] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China		Tan, GH; Huang, CH (corresponding author), Hainan Med Coll, Minist Educ, Key Lab Trop Dis & Translat Med, Haikou 571199, Hainan, Peoples R China.; Tan, GH; Huang, CH (corresponding author), Hainan Med Coll, Hainan Prov Key Lab Trop Med, Haikou 571199, Hainan, Peoples R China.; Dai, HF (corresponding author), Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Haikou 571199, Hainan, Peoples R China.; Huang, CH (corresponding author), Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China.; Huang, CH (corresponding author), Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China.	daihaofu@itbb.org.cn; tanhoho@163.com; hcanhua@hotmail.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81460557, 81560599, 81460020]	This work was funded by the National Natural Science Foundation of China (81460557, 81560599, 81460020). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.	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J	Chavez-Dominguez, R; Perez-Medina, M; Lopez-Gonzalez, JS; Galicia-Velasco, M; Aguilar-Cazares, D				Chavez-Dominguez, Rodolfo; Perez-Medina, Mario; Lopez-Gonzalez, Jose S.; Galicia-Velasco, Miriam; Aguilar-Cazares, Dolores			The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity	FRONTIERS IN ONCOLOGY			English	Review						autophagy; cell death; metabolic reprograming; metastasis; carcinogenesis; tumor microenvironment; immune evasion; chemotherapy and targeted therapy resistance	HYPOXIA-INDUCED AUTOPHAGY; CELL-DEATH; MOLECULAR-MECHANISMS; ANOIKIS RESISTANCE; MITOCHONDRIAL METABOLISM; GLUTAMINE-METABOLISM; GLUCOSE-METABOLISM; INHIBITS AUTOPHAGY; REGULATE AUTOPHAGY; COLORECTAL-CANCER	During tumorigenesis, cancer cells are exposed to a wide variety of intrinsic and extrinsic stresses that challenge homeostasis and growth. Cancer cells display activation of distinct mechanisms for adaptation and growth even in the presence of stress. Autophagy is a catabolic mechanism that aides in the degradation of damaged intracellular material and metabolite recycling. This activity helps meet metabolic needs during nutrient deprivation, genotoxic stress, growth factor withdrawal and hypoxia. However, autophagy plays a paradoxical role in tumorigenesis, depending on the stage of tumor development. Early in tumorigenesis, autophagy is a tumor suppressor via degradation of potentially oncogenic molecules. However, in advanced stages, autophagy promotes the survival of tumor cells by ameliorating stress in the microenvironment. These roles of autophagy are intricate due to their interconnection with other distinct cellular pathways. In this review, we present a broad view of the participation of autophagy in distinct phases of tumor development. Moreover, autophagy participation in important cellular processes such as cell death, metabolic reprogramming, metastasis, immune evasion and treatment resistance that all contribute to tumor development, is reviewed. Finally, the contribution of the hypoxic and nutrient deficient tumor microenvironment in regulation of autophagy and these hallmarks for the development of more aggressive tumors is discussed.	[Chavez-Dominguez, Rodolfo; Perez-Medina, Mario; Lopez-Gonzalez, Jose S.; Galicia-Velasco, Miriam; Aguilar-Cazares, Dolores] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Enfermedades Cronicodegenerat, Mexico City, DF, Mexico; [Chavez-Dominguez, Rodolfo] Univ Nacl Autonoma Mexico, Posgrad Ciencias Biol, Mexico City, DF, Mexico; [Perez-Medina, Mario] Inst Politecn Nacl, Dept Bioquim, Lab Quimioterapia Expt, Escuela Nacl Ciencias Biol, Mexico City, DF, Mexico		Aguilar-Cazares, D (corresponding author), Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Enfermedades Cronicodegenerat, Mexico City, DF, Mexico.	doloresaguilarcazares@yahoo.com.mx	Aguilar-Cazares, Dolores/AAA-4774-2021	Lopez-Gonzalez, Jose Sullivan/0000-0003-0746-2286			Alizadeh J, 2018, BBA-MOL CELL RES, V1865, P749, DOI 10.1016/j.bbamcr.2018.02.007; Amaravadi RK, 2019, CANCER DISCOV, V9, P1167, DOI 10.1158/2159-8290.CD-19-0292; Anderson CM, 2019, INT REV CEL MOL BIO, V347, P145, DOI 10.1016/bs.ircmb.2019.06.002; 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Oncol.	OCT 7	2020	10								578418	10.3389/fonc.2020.578418			19	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	OD4WU	WOS:000579853600001	33117715	gold, Green Published			2022-04-25	
J	Brest, P; Corcelle, EA; Cesaro, A; Chargui, A; Belaid, A; Klionsky, DJ; Vouret-Craviari, V; Hebuterne, X; Hofman, P; Mograbi, B				Brest, P.; Corcelle, E. A.; Cesaro, A.; Chargui, A.; Belaid, A.; Klionsky, D. J.; Vouret-Craviari, V.; Hebuterne, X.; Hofman, P.; Mograbi, B.			Autophagy and Crohn's Disease: At the Crossroads of Infection, Inflammation, Immunity, and Cancer	CURRENT MOLECULAR MEDICINE			English	Review						Autophagy; Crohn's disease; infection; inflammation; immunity; cancer	GENOME-WIDE ASSOCIATION; INDUCIBLY EXPRESSED GTPASE; BOWEL-DISEASE; SUSCEPTIBILITY LOCI; FRAMESHIFT MUTATION; RESISTANCE GTPASES; TOXOPLASMA-GONDII; CELLULAR-RESPONSE; GENETIC-VARIANTS; APOPTOTIC CELLS	Inflammatory bowel diseases (IBD) are common inflammatory disorders of the gastrointestinal tract that include ulcerative colitis (UC) and Crohn's disease (CD). The incidences of IBD are high in North America and Europe, affecting as many as one in 500 people. These diseases are associated with high morbidity and mortality. Colorectal cancer risk is also increased in IBD, correlating with inflammation severity and duration. IBD are now recognized as complex multigenetic disorders involving at least 32 different risk loci. In 2007, two different autophagy-related genes, ATG16L1 (autophagy-related gene 16-like 1) and IRGM (immunity-related GTPase M) were shown to be specifically involved in CD susceptibility by three independent genome-wide association studies. Soon afterwards, more than forty studies confirmed the involvement of ATG16L1 and IRGM variants in CD susceptibility and gave new information on the importance of macroautophagy (hereafter referred to as autophagy) in the control of infection, inflammation, immunity and cancer. In this review, we discuss how such findings have undoubtedly changed our understanding of CD pathogenesis. A unifying autophagy model then emerges that may help in understanding the development of CD from bacterial infection, to inflammation and finally cancer. The Pandora's box is now open, releasing a wave of hope for new therapeutic strategies in treating Crohn's disease.	[Brest, P.; Cesaro, A.; Chargui, A.; Belaid, A.; Vouret-Craviari, V.; Hebuterne, X.; Hofman, P.; Mograbi, B.] Univ Nice Sophia Antipolis, Fac Med, INSERM, ERI 21,EA 4319, Nice, France; [Corcelle, E. A.] Danish Canc Soc, Inst Canc Biol, Apoptosis Dept, Copenhagen, Denmark; [Corcelle, E. A.] Danish Canc Soc, Inst Canc Biol, Ctr Genotox Stress Res, Copenhagen, Denmark; [Klionsky, D. J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA; [Hebuterne, X.] Hop Archet II, Ctr Hosp Univ Nice, Nice, France; [Hofman, P.] Pasteur Hosp, Lab Clin & Expt Pathol, Nice, France		Mograbi, B (corresponding author), Univ Nice Sophia Antipolis, Fac Med, INSERM, ERI 21,EA 4319, Nice, France.	mograbi@unice.fr	brest, patrick/B-7311-2012; Cesaro, Annabelle/AAX-3177-2020; brest, patrick/K-6164-2019; Mograbi, Baharia/Q-7953-2019; Mograbi, Baharia/N-5531-2018; Hofman, Paul/P-7654-2018	brest, patrick/0000-0002-1252-4747; brest, patrick/0000-0002-1252-4747; Hofman, Paul/0000-0003-0431-9353; Corcelle-Termeau, Elisabeth/0000-0002-3706-3756; Mograbi, Baharia/0000-0002-1025-3429	INCAInstitut National du Cancer (INCA) France [07/3D1616/Pdoc-110-32/NG-NC]; Alfred Benzon Foundation; Infectiopole and Ademe [08 62 C 0044]; Institut National du Cancer, Paris, France (INCa)Institut National du Cancer (INCA) France [Vancol R0153AA, INCa Inflacol R07129AA]; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM053396] Funding Source: NIH RePORTER	The authors would like to thank Dr. R. Bocciardi and I. Ceccherini for their helpful comments on the manuscript. PB is funded by grants from INCA (07/3D1616/Pdoc-110-32/NG-NC), EAC is funded by the Alfred Benzon Foundation, AC and AB are funded by Infectiopole and Ademe (Convention n<SUP>o</SUP> 08 62 C 0044). This work was supported by grants from the Institut National du Cancer, Paris, France (INCa; Vancol R0153AA and INCa Inflacol R07129AA).	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Mol. Med.	JUL	2010	10	5					486	502		10.2174/156652410791608252			17	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	628OI	WOS:000280129400004	20540703	Green Accepted			2022-04-25	
J	Sugito, N; Taniguchi, K; Kuranaga, Y; Ohishi, M; Soga, T; Ito, Y; Miyachi, M; Kikuchi, K; Hosoi, H; Akao, Y				Sugito, Nobuhiko; Taniguchi, Kohei; Kuranaga, Yuki; Ohishi, Maki; Soga, Tomoyoshi; Ito, Yuko; Miyachi, Mitsuru; Kikuchi, Ken; Hosoi, Hajime; Akao, Yukihiro			Cancer-Specific Energy Metabolism in Rhabdomyosarcoma Cells Is Regulated by MicroRNA	NUCLEIC ACID THERAPEUTICS			English	Article						rhabdomyosarcoma; PTBP1; microRNA; PAX3-FOXO1	MUSCLE-SPECIFIC MICRORNA; KINASE MESSENGER-RNA; PYRUVATE-KINASE; ALVEOLAR RHABDOMYOSARCOMA; COLORECTAL TUMORS; C-MYC; GROWTH; EXPRESSION; FUSION; DIFFERENTIATION	Rhabdomyosarcoma (RMS) is a soft tissue sarcoma and is most frequently found in children. In RMS, there are two major subtypes, that is, embryonal RMS and alveolar RMS (ARMS). ARMS has exclusively the worse prognosis and is caused by formation of the chimeric PAX3-FOXO1 gene. Regarding cancer, the Warburg effect is known as a feature of cancer-specific metabolism. Polypyrimidine tract-binding protein 1 (PTBP1), a splicer of pyruvate kinase muscle (PKM) mRNA, is a positive regulator of cancer-specific energy metabolism. We investigated the expression and effects of muscle-specific miR-1 and miR-133b on RMS cells (RD, KYM-1, Rh30, and Rh41) from the view of energy metabolism and regulation of the chimeric gene. As a result, downregulated miR-1 and miR-133b/upregulated PTBP1 were found in RMS cell lines as well as in RMS clinical cases. Ectopic expression of either miR in both types of RMS cells induced autophagic cell death through silencing of PTBP1. Interestingly, we validated that miR-133b also knock downed PAX3-FOXO1. Moreover, we found that PAX3-FOXO1 positively regulated the PKM2-dominant expression through enhanced expression of PTBP1. These findings suggest that the miR-1 and miR-133b/PTBP1 axis and miR-133b/PAX3-FOXO1/PTBP1 axis contributed to the maintenance of cancer-specific energy metabolism.	[Sugito, Nobuhiko; Kuranaga, Yuki; Akao, Yukihiro] Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, 1-1 Yanagido, Gifu 5011193, Japan; [Taniguchi, Kohei] Osaka Med Coll, Dept Gen & Gastroenterol Surg, Takatsuki, Osaka, Japan; [Ohishi, Maki; Soga, Tomoyoshi] Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata, Japan; [Ito, Yuko] Osaka Med Coll, Dept Anat & Cell Biol, Div Life Sci, Takatsuki, Osaka, Japan; [Miyachi, Mitsuru; Kikuchi, Ken; Hosoi, Hajime] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Pediat, Kyoto, Japan		Akao, Y (corresponding author), Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, 1-1 Yanagido, Gifu 5011193, Japan.	yakao@gifu-u.ac.jp	Soga, Tomoyoshi/B-8105-2014; Kikuchi, Ken/ABG-8290-2020	Soga, Tomoyoshi/0000-0001-9502-2509; Kikuchi, Ken/0000-0003-3097-7480; Miyachi, Mitsuru/0000-0003-4522-2478; Taniguchi, Kohei/0000-0003-0648-1370	GSK Japan; Ministry of Education, Science, Sports, and Culture of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [YA-24659157]	This work was supported by a GSK Japan Research Grant and Grant-in-aid for scientific research from the Ministry of Education, Science, Sports, and Culture of Japan (YA-24659157).	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Acid Ther.	DEC	2017	27	6					365	377		10.1089/nat.2017.0673			13	Biochemistry & Molecular Biology; Chemistry, Medicinal; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Research & Experimental Medicine	FN8CJ	WOS:000416246300006	28981396				2022-04-25	
J	Sun, XD; Xu, HX; Dai, TY; Xie, LX; Zhao, Q; Hao, XC; Sun, Y; Wang, XB; Jiang, N; Sang, M				Sun, Xiaodong; Xu, Hongxia; Dai, Tianyu; Xie, Lixia; Zhao, Qiang; Hao, Xincai; Sun, Yan; Wang, Xuanbin; Jiang, Nan; Sang, Ming			Alantolactone inhibits cervical cancer progression by downregulating BMI1	SCIENTIFIC REPORTS			English	Article							EPITHELIAL-MESENCHYMAL TRANSITION; NF-KAPPA-B; INULA-HELENIUM; BREAST-CANCER; STEM-CELLS; SESQUITERPENE LACTONE; HUMAN-PAPILLOMAVIRUS; COLORECTAL-CANCER; ISOALANTOLACTONE; CARCINOMA	Cervical cancer is the second most common cancer in women. Despite advances in cervical cancer therapy, tumor recurrence and metastasis remain the leading causes of mortality. High expression of BMI1 is significantly associated with poor tumor differentiation, high clinical grade, and poor prognosis of cervical cancer, and is an independent prognostic factor in cervical carcinoma. Alantolactone (AL), a sesquiterpene lactone, exhibits potent anti-inflammatory and anticancer activities. In this paper, we investigated the mechanism of AL in reducing the proliferation, migration, and invasion of HeLa and SiHa cervical cancer cells as well as its promotion of mitochondrial damage and autophagy. BMI1 silencing decreased epithelial-mesenchymal transformation-associated proteins and increased autophagy-associated proteins in HeLa cells. These effects were reversed by overexpression of BMI1 in HeLa cells. Thus, BMI1 expression is positively correlated with invasion and negatively correlated with autophagy in HeLa cells. Importantly, AL decreased the weight, volume, and BMI1 expression in HeLa xenograft tumors. Furthermore, the structure of BMI1 and target interaction of AL were virtually screened using the molecular docking program Autodock Vina; AL decreased the expression of N-cadherin, vimentin, and P62 and increased the expression of LC3B and Beclin-1 in xenograft tumors. Finally, expression of BMI1 increased the phosphorylation of STAT3, which is important for cell proliferation, survival, migration, and invasion. Therefore, we suggest that AL plays a pivotal role in inhibiting BMI1 in the tumorigenesis of cervical cancer and is a potential therapeutic agent for cervical cancer.	[Sun, Xiaodong; Xu, Hongxia; Xie, Lixia; Zhao, Qiang; Hao, Xincai; Sun, Yan; Wang, Xuanbin; Sang, Ming] Hubei Univ Med, Hubei Key Lab Wudang Local Chinese Med Res, Xiangyang Peoples Hosp 1, Hubei Clin Res Ctr Parkinsons Dis, Shiyan 442000, Peoples R China; [Dai, Tianyu] Tongji Univ, Shanghai East Hosp, Sch Med, Dept Joint Surg, Shanghai 200092, Peoples R China; [Jiang, Nan] Hubei Prov Acad Tradit Chinese Med, Hubei Prov Hosp Tradit Chinese Med, Wuhan 430061, Peoples R China		Sang, M (corresponding author), Hubei Univ Med, Hubei Key Lab Wudang Local Chinese Med Res, Xiangyang Peoples Hosp 1, Hubei Clin Res Ctr Parkinsons Dis, Shiyan 442000, Peoples R China.	sangming@whu.edu.cn	Wang, Xuanbin/ABC-6550-2021; Sang, Ming/AAE-2187-2022	Wang, Xuanbin/0000-0003-0769-2874; 	National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81903005]; Hubei Province Innovation Project of Science and Technology Cooperation with Foreign countries [2019AHB068]; experimental animal resources development and utilization project of Hubei Province of China [2020DFE025]; Science and Technology Development Project of Xiangyang; Institute of Medicine and Nursing at Hubei University of Medicine [2017YHKT02]; Scientific Research Project of Hubei Province Health Committee [ZY2019F028]	This investigation was supported by the grants from the National Natural Science Foundation (81903005), the Hubei Province Innovation Project of Science and Technology Cooperation with Foreign countries (2019AHB068), the experimental animal resources development and utilization project of Hubei Province of China (2020DFE025), the Science and Technology Development Project of Xiangyang (Project Leader Sang Ming), the Innovative Team Project (2017YHKT02) from the Institute of Medicine and Nursing at Hubei University of Medicine, the Scientific Research Project of Hubei Province Health Committee (ZY2019F028). The funding bodies were not involved in the design of this study, in the collection, analysis, and interpretation of the data, or in writing of the manuscript.	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J	Janji, B; Hasmim, M; Parpal, S; De Milito, A; Berchem, G; Noman, MZ				Janji, Bassam; Hasmim, Meriem; Parpal, Santiago; De Milito, Angelo; Berchem, Guy; Noman, Muhammad Zaeem			Lighting up the fire in cold tumors to improve cancer immunotherapy by blocking the activity of the autophagy-related protein PIK3C3/VPS34	AUTOPHAGY			English	Article						Autophagy; cancer immunotherapy; cold; hot tumors; colorectal cancer; immune checkpoints; immune infiltration; melanoma; NK and T CD8 cells; proinflammatory cytokines; VPS34		Cancer immunotherapy based on Immune checkpoint blockade (ICB) is a promising strategy to treat patients with advanced highly aggressive therapy-resistant tumors. Unfortunately, the clinical reality is that only a small number of patients benefit from the remarkable clinical remissions achieved by ICB. Experimental and clinical evidence claimed that durable clinical benefit observed using ICB depends on the immune status of tumors, notably the presence of cytotoxic effector immune cells. In our paper, we revealed that genetically targeting the autophagy-related protein PIK3C3/VPS34 in melanoma and colorectal tumor cells, or treating tumor-bearing mice with selective inhibitors of the PIK3C3/VPS34 kinase activity, reprograms cold immune desert tumors into hot, inflamed immune infiltrated tumors. Such reprograming results from the establishment of a proinflammatory signature characterized by the release of CCL5 and CXCL10 in the tumor microenvironment, and the subsequent recruitment of natural killer (NK) and CD8(+)T cells into the tumor bed. Furthermore, we reported that combining pharmacological inhibitors of PIK3C3/VPS34 improves the therapeutic benefit of anti-PD-1/PD-L1 immunotherapy. Our results provided the proof-of-concept to set-up innovative clinical trials for cold ICB-unresponsive tumors by combining PIK3C3/VPS34 inhibitors with anti-PDCD1/PD-1 and anti-CD274/PD-L1.	[Janji, Bassam; Hasmim, Meriem; Berchem, Guy; Noman, Muhammad Zaeem] Luxembourg Inst Hlth LIH, Tumor Immunotherapy & Microenvironm TIME Grp, Dept Oncol, Luxembourg, Luxembourg; [Parpal, Santiago; De Milito, Angelo] Sprint Biosci, Stockholm, Sweden; [Parpal, Santiago; De Milito, Angelo] Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden; [Berchem, Guy] Ctr Hosp Luxembourg, Dept Hematooncol, Luxembourg, Luxembourg		Janji, B; Noman, MZ (corresponding author), Luxembourg Inst Hlth, Tumor Immunotherapy & MicroenvironmTIME Grp, Dept Oncol, 84 Val Fleuri, L-1526 Luxembourg, Luxembourg.	bassam.janji@lih.lu; muhammadzaeem.noman@lih.lu	NOMAN, Muhammmad Zaeem/AAJ-1465-2021; NOMAN, Muhammmad Zaeem/AAJ-1466-2021; Berchem, Guy/C-9364-2014	NOMAN, Muhammmad Zaeem/0000-0002-1837-3097; NOMAN, Muhammmad Zaeem/0000-0002-1837-3097; Berchem, Guy/0000-0003-0157-2257; Parpal, Santiago/0000-0003-2861-0516; JANJI, Bassam/0000-0002-9763-0943; De Milito, Angelo/0000-0003-2591-2914	Luxembourg National Research FundLuxembourg National Research Fund [C18/BM/12670304/COMBATIC]; FNRS TelevieFonds de la Recherche Scientifique - FNRS [7.4606.18]; Fondation Cancer Luxembourg [FC/2018/06]; Kriibskrank Kanner Foundation; Janssen Cilag Pharma; Roche pharma and Action LIONS Vaincre le Cancer Luxembourg	This work was supported by grants from Luxembourg National Research Fund C18/BM/12670304/COMBATIC; FNRS Televie (grants 7.4606.18); Fondation Cancer Luxembourg (FC/2018/06); Kriibskrank Kanner Foundation (2019); Janssen Cilag Pharma; Roche pharma and Action LIONS Vaincre le Cancer Luxembourg.	Noman MZ, 2020, SCI ADV, V6, DOI 10.1126/sciadv.aax7881	1	6	6	4	12	TAYLOR & FRANCIS INC	PHILADELPHIA	530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA	1554-8627	1554-8635		AUTOPHAGY	Autophagy	NOV 1	2020	16	11					2110	2111		10.1080/15548627.2020.1815439		SEP 2020	2	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	OI6MP	WOS:000567020700001	32892693	hybrid, Green Published			2022-04-25	
J	Varalda, M; Antona, A; Bettio, V; Roy, K; Vachamaram, A; Yellenki, V; Massarotti, A; Baldanzi, G; Capello, D				Varalda, Marco; Antona, Annamaria; Bettio, Valentina; Roy, Konkonika; Vachamaram, Ajay; Yellenki, Vaibhav; Massarotti, Alberto; Baldanzi, Gianluca; Capello, Daniela			Psychotropic Drugs Show Anticancer Activity by Disrupting Mitochondrial and Lysosomal Function	FRONTIERS IN ONCOLOGY			English	Article						lysosomotropism; cationic amphiphilic drugs (CADs); autophagy; psychotropic drug; cancer; repositioning	MEMBRANE PERMEABILIZATION; CELL-DEATH; METHYL-ESTER; CANCER; AUTOPHAGY; PHOSPHOLIPIDOSIS; IDENTIFICATION; INHIBITORS; RISK; ANTIHISTAMINES	Background and Purpose: Drug repositioning is a promising strategy for discovering new therapeutic strategies for cancer therapy. We investigated psychotropic drugs for their antitumor activity because of several epidemiological studies reporting lower cancer incidence in individuals receiving long term drug treatment. Experimental Approach: We investigated 27 psychotropic drugs for their cytotoxic activity in colorectal carcinoma, glioblastoma and breast cancer cell lines. Consistent with the cationic amphiphilic structure of the most cytotoxic compounds, we investigated their effect on mitochondrial and lysosomal compartments. Results: Penfluridol, ebastine, pimozide and fluoxetine, fluspirilene and nefazodone showed significant cytotoxicity, in the low micromolar range, in all cell lines tested. In MCF7 cells these drugs caused mitochondrial membrane depolarization, increased the acidic vesicular compartments and induced phospholipidosis. Both penfluridol and spiperone induced AMPK activation and autophagy. Neither caspase nor autophagy inhibitors rescued cells from death induced by ebastine, fluoxetine, fluspirilene and nefazodone. Treatment with 3-methyladenine partially rescued cell death induced by pimozide and spiperone, whereas enhanced the cytotoxic activity of penfluridol. Conversely, inhibition of lysosomal cathepsins significantly reduced cell death induced by ebastin, penfluridol, pimozide, spiperone and mildly in fluoxetine treated cells. Lastly, Spiperone cytotoxicity was restricted to colorectal cancer and breast cancer and caused apoptotic cell death in MCF7 cells. Conclusions: The cytotoxicity of psychotropic drugs with cationic amphiphilic structures relied on simultaneous mitochondrial and lysosomal disruption and induction of cell death that not necessarily requires apoptosis. Since dual targeting of lysosomes and mitochondria constitutes a new promising therapeutic approach for cancer, particularly those in which the apoptotic machinery is defective, these data further support their clinical development for cancer therapy.	[Varalda, Marco; Antona, Annamaria; Bettio, Valentina; Vachamaram, Ajay; Yellenki, Vaibhav; Baldanzi, Gianluca; Capello, Daniela] Univ Piemonte Orientale, Ctr Excellence Aging Sci, Dept Translat Med, Novara, Italy; [Varalda, Marco; Bettio, Valentina; Capello, Daniela] Univ Piemonte Orientale, UPO Biobank, Novara, Italy; [Roy, Konkonika; Vachamaram, Ajay; Baldanzi, Gianluca] Univ Piemonte Orientale, Ctr Translat Res Allerg & Autoimmune Dis CAAD, Novara, Italy; [Massarotti, Alberto] Univ Piemonte Orientale, Dept Pharmaceut Sci, Novara, Italy		Capello, D (corresponding author), Univ Piemonte Orientale, Ctr Excellence Aging Sci, Dept Translat Med, Novara, Italy.; Capello, D (corresponding author), Univ Piemonte Orientale, UPO Biobank, Novara, Italy.	daniela.capello@med.uniupo.it	Baldanzi, Gianluca/AAO-7673-2021; Bettio, Valentina/AFT-9834-2022	Baldanzi, Gianluca/0000-0002-1370-9903; Antona, Annamaria/0000-0002-8050-3462	Universita del Piemonte Orientale; Italian Ministry of Education, University and Research (MIUR) program Departments of Excellence 2018-2022, AGING Project-Department of Translational Medicine, Universita del Piemonte Orientale; Consorzio Interuniversitario di Biotecnologie (CIB) [PRIN 201799WCRH]	This study was (partially) funded by the Universita del Piemonte Orientale-FAR 2016 e FAR 2017 (DC), by the Italian Ministry of Education, University and Research (MIUR) program Departments of Excellence 2018-2022, AGING Project-Department of Translational Medicine, Universita del Piemonte Orientale (DC), by Consorzio Interuniversitario di Biotecnologie (CIB) call Network-CIB: Catalisi dell'Innovazione nelle Biotecnologie (PRIN 201799WCRH, GB).	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Oncol.	OCT 19	2020	10								562196	10.3389/fonc.2020.562196			19	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	OI5AL	WOS:000583291100001	33194631	Green Published, gold			2022-04-25	
J	Bai, C; Zhang, Z; Zhou, L; Zhang, HY; Chen, Y; Tang, Y				Bai, Can; Zhang, Zhe; Zhou, Li; Zhang, Huan-Yu; Chen, Yan; Tang, Yong			Repurposing Ziyuglycoside II Against Colorectal CancerviaOrchestrating Apoptosis and Autophagy	FRONTIERS IN PHARMACOLOGY			English	Article						Ziyuglycoside II; cancer therapy; autophagy; colorectal cancer; Akt	CELL-CYCLE ARREST; PROTECTIVE AUTOPHAGY; TARGETING AUTOPHAGY; CANCER CELLS; ACTIVATION; BLOCKING; AXIS	Effective chemotherapy drugs for colorectal cancer remain a challenge. In this research, Ziyuglycoside II (Ziyu II), exhibits considerable antitumor activity against CRC cells both in vitro and in vivo. The results showed that Ziyu II induced apoptosis through the accumulation of reactive oxygen species (ROS), which was necessary for Ziyu II to inhibit colorectal cancer cells. Intriguingly, The treatment of Ziyu II triggered complete autophagic flux in CRC cells. Inhibition of autophagy partially reversed Ziyu II-induced growth inhibition, demonstrating a cytotoxic role of autophagy in response to Ziyu II-treated. Mechanism indicated that Ziyu II-induced autophagy by inhibiting Akt/mTOR pathway. Akt reactivation partially reduced Ziyu II-induced LC3-II turnover and LC3 puncta accumulation. Especially, Ziyu II improves the sensitivity of 5-fluorouracil which is the first-line chemotherapy drug in colorectal cancer cells. This research provides novel insight into the molecular mechanism of Ziyu II's anti-proliferation, including apoptosis and autophagy, and lays a foundation for the potential application of Ziyu II in clinical CRC treatment.	[Bai, Can; Tang, Yong] Chengdu Univ Tradit Chinese Med, Acupuncture & Tuina Sch, Chengdu, Peoples R China; [Zhang, Zhe; Zhou, Li; Chen, Yan] Sichuan Univ, West China Hosp, State Key Lab Biotherapy & Canc Ctr, Chengdu, Peoples R China; [Zhang, Zhe; Zhou, Li; Chen, Yan] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu, Peoples R China; [Zhang, Zhe; Zhou, Li; Chen, Yan] Collaborat Innovat Ctr Biotherapy, Chengdu, Peoples R China; [Zhang, Huan-Yu] Hainan Med Coll, Minist Educ, Key Lab Trop Dis & Translat Med, Affiliated Hosp, Haikou, Hainan, Peoples R China; [Zhang, Huan-Yu] Hainan Med Coll, Affiliated Hosp, Dept Neurol, Haikou, Hainan, Peoples R China		Tang, Y (corresponding author), Chengdu Univ Tradit Chinese Med, Acupuncture & Tuina Sch, Chengdu, Peoples R China.	tangyong@cdutcm.edu.cn			Sino-German Center [GZ919]; Project First-Class Disciplines Development of Chengdu University of TCM [CZYHW1901]; Sichuan Science and Technology Program [2019YFH0108, 2018HH0123, 2018SZ0257]	This manuscript has been released as a pre-print at www.authorea.com (Bai et al., 2020). We sincerely thank L Zhang and Z Huang for useful discussions. We are grateful to the Sino-German Center (GZ919), The Project First-Class Disciplines Development (CZYHW1901) of Chengdu University of TCM, and Sichuan Science and Technology Program (2019YFH0108, 2018HH0123, 2018SZ0257) for financial support.	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Pharmacol.	SEP 18	2020	11								576547	10.3389/fphar.2020.576547			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	NY6IL	WOS:000576490500001	33071789	gold, Green Published			2022-04-25	
J	Zhang, N; Yang, YN; Wang, ZY; Yang, J; Chu, X; Liu, J; Zhao, YX				Zhang, Nan; Yang, Yanan; Wang, Ziyi; Yang, Jing; Chu, Xiao; Liu, Jin; Zhao, Yongxing			Polypeptide-engineered DNA tetrahedrons for targeting treatment of colorectal cancer via apoptosis and autophagy	JOURNAL OF CONTROLLED RELEASE			English	Article						Colorectal cancer; DNA tetrahedron; Cell apoptosis; Cell autophagy; Anti-cancer peptides	CD SPECTRA; NANOPARTICLES; DELIVERY	Smart delivery of therapeutic peptides that target cellular signaling pathways holds high specificity and great promise for cancer therapy. Here, DNA tetrahedrons (TDs) are designed to carry two therapeutic peptides-FAS peptide and FK-16 peptide. DNA TDs are designed with varied numbers and spatial placement of FAS peptides and FK-16 peptides, and tested for their anti-cancer efficacy. Trimerization of FAS receptors using TDs that are assembled with three FAS peptides enhances FAS-induced cell apoptosis. FK-16 peptides are conjugated to TDs via a peptide sequence sensitive to MMP-2/9 in tumor microenvironment. Therefore, FK-16 peptides are expected to detach from TDs once arrived the tumor microenvironment. A cell penetrating peptide (TAT) is also conjugated to the FK-16 peptide to facilitate its intracellular delivery, which increases the FK-16 peptide-induced cell apoptosis and autophagy. TD-3(TFM)3(FAS) (TFM: TAT+ FK-16+ MMP-2/9) exhibits the highest HT-29 inhibition in vitro and in vivo among all therapies. In addition to the high anti-cancer efficacy, TD-3(TFM)3(FAS) shows a high specificity to HT-29 cells in vitro and in vivo. Low cell inhibition rates and cellular uptake are observed in normal cells. In sum, the multifunctional TD-3(TFM)3(FAS) provides a new platform for the smart delivery of anti-cancer peptides to achieve enhanced efficacy and high specificity.	[Zhang, Nan; Yang, Yanan; Wang, Ziyi; Yang, Jing; Chu, Xiao; Zhao, Yongxing] Zhengzhou Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Zhengzhou 450001, Henan, Peoples R China; [Zhang, Nan; Zhao, Yongxing] Key Lab Targeting Therapy & Diag Crit Dis, Zhengzhou 450001, Henan, Peoples R China; [Zhang, Nan; Zhao, Yongxing] Minist Educ China, Key Lab Adv Pharmaceut Technol, Zhengzhou 450001, Henan, Peoples R China; [Liu, Jin] Fudan Univ, Inst Biomed Sci, Zhongshan Hosp, Shanghai, Peoples R China; [Liu, Jin] Fudan Univ, Shanghai Inst Cardiovasc Dis, Zhongshan Hosp, Shanghai, Peoples R China		Zhang, N; Zhao, YX (corresponding author), Zhengzhou Univ, Sch Pharmaceut Sci, 100 KeXue Ave,Room A315, Zhengzhou 450001, Henan, Peoples R China.	nanzhang@zzu.edu.cn; zhaoyx@zzu.edu.cn	Zhang, Nan/J-6823-2016; Zhang, Nan/AAK-2672-2021	Zhang, Nan/0000-0002-0941-482X; Zhang, Nan/0000-0002-0941-482X	National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81573011, 81861138004]; Key Project of Ministry of Education of HeNan Province for Higher Education Institutions [16A350012]	Financial support from the National Natural Science Foundation of China (NSFC No. 81573011 and 81861138004) and Key Project of Ministry of Education of HeNan Province for Higher Education Institutions (No. 16A350012) are gratefully acknowledged. We also thank the Center of Advanced Analysis & Computational Science, Zhengzhou University for the assistance of data acquirement.	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J	Liang, XY; Chavez, ARD; Schapiro, NE; Loughran, P; Thorne, SH; Amoscato, AA; Zeh, HJ; Beer-Stolz, D; Lotze, MT; de Vera, ME				Liang, Xiaoyan; Chavez, Antonio Romo de Vivar; Schapiro, Nicole E.; Loughran, Patricia; Thorne, Stephen H.; Amoscato, Andrew A.; Zeh, Herbert J.; Beer-Stolz, Donna; Lotze, Michael T.; de Vera, Michael E.			Ethyl pyruvate administration inhibits hepatic tumor growth	JOURNAL OF LEUKOCYTE BIOLOGY			English	Article						metabolism; cancer models; liver metastases; colorectal cancer; inflammation; HMGB1; apoptosis; autophagy	GLYCATION END-PRODUCTS; COLORECTAL-CANCER; LIVER METASTASIS; HMGB1 RELEASE; CELLS; EXPRESSION; INFLAMMATION; AUTOPHAGY; NECROSIS; APOPTOSIS	EP is a potent inhibitor of HMGB1 release that has significant anti-inflammatory activities and exerts a protective effect in animal models of inflammation. As inflammation is linked to cancer growth, we hypothesized that EP would have anti-tumor activity and explored its effects in a liver tumor model. Mice injected intraportally with MC38 colorectal cancer cells led to the growth of visible hepatic tumors within 2 weeks. Pretreatment with EP 30 min prior to infusion of tumor cells and continuing daily for 9 days inhibited tumor growth significantly in a dose-dependent manner, with 80 mg/kg EP achieving > 70% reduction in the number of tumor nodules when compared with untreated animals. Delayed treatment with EP also suppressed tumor growth significantly, although to a lesser extent. Tumors had early, marked leukocytic infiltrates, and EP administration decreased innate (NK cells, monocytes) and adaptive (T and B cell lymphocytic) immune cell infiltrates acutely and significantly in the liver. Serum IL-6 and HMGB1 levels, which were elevated following tumor injection, were decreased significantly in EP-treated animals. Tumors showed an increase in apoptosis in EP-treated mice, and tumor cells treated in vitro with EP had marked increases in LC3-II and cleaved PARP, consistent with enhanced autophagic flux and apoptosis. Thus, EP inhibition of tumor growth in the liver was mediated by tumor (induction of apoptosis) and host (decreased inflammation) effects. EP administration may have a therapeutic role in the treatment of cancer in conjunction with other therapeutic agents. J. Leukoc. Biol. 86: 599-607; 2009.	[de Vera, Michael E.] Univ Pittsburgh, UPMC Montefiore, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA; [Liang, Xiaoyan; Chavez, Antonio Romo de Vivar; Schapiro, Nicole E.; Loughran, Patricia; Thorne, Stephen H.; Amoscato, Andrew A.; Zeh, Herbert J.; Lotze, Michael T.; de Vera, Michael E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA; [Beer-Stolz, Donna] Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA 15213 USA		de Vera, ME (corresponding author), Univ Pittsburgh, UPMC Montefiore, Thomas E Starzl Transplantat Inst, 7 S 3459 5th Ave, Pittsburgh, PA 15213 USA.	deverame@upmc.edu	Loughran, Patricia/AAB-1184-2021; li, tao/B-2402-2008	Amoscato, Andrew/0000-0002-1340-9150			Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; Ashizawa T, 2006, ACTA MED OKAYAMA, V60, P325; Aychek T, 2008, INT J CANCER, V123, P1741, DOI 10.1002/ijc.23375; Bennett-Guerrero E, 2009, J CARDIOTHOR VASC AN, V23, P324, DOI 10.1053/j.jvca.2008.08.005; Chen GY, 2009, SCIENCE, V323, P1722, DOI 10.1126/science.1168988; Cheng BQ, 2007, PANCREAS, V35, P256, DOI 10.1097/MPA.0b013e318064678a; Chung YC, 2003, J SURG ONCOL, V83, P222, DOI 10.1002/jso.10269; Condeelis J, 2006, CELL, V124, P263, DOI 10.1016/j.cell.2006.01.007; Dagda RK, 2008, AUTOPHAGY, V4, P770, DOI 10.4161/auto.6458; de Visser KE, 2006, NAT REV CANCER, V6, P24, DOI 10.1038/nrc1782; DeNardo DG, 2008, CANCER METAST REV, V27, P11, DOI 10.1007/s10555-007-9100-0; Dong XD, 2007, J IMMUNOTHER, V30, P596, DOI 10.1097/CJI.0b013e31804efc76; Eisenberg-Lerner A, 2009, APOPTOSIS, V14, P376, DOI 10.1007/s10495-008-0307-5; Ellerman JE, 2007, CLIN CANCER RES, V13, P2836, DOI 10.1158/1078-0432.CCR-06-1953; FASHENA SJ, 1992, MOL CELL BIOL, V12, P894, DOI 10.1128/MCB.12.2.894; Gebhardt C, 2008, J EXP MED, V205, P275, DOI 10.1084/jem.20070679; Gupta S. 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Leukoc. Biol.	SEP	2009	86	3					599	607		10.1189/jlb.0908578			9	Cell Biology; Hematology; Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Hematology; Immunology	488VA	WOS:000269377200018	19584311	Bronze			2022-04-25	
J	Chu, CA; Wang, YW; Chen, YL; Chen, HW; Chuang, JJ; Chang, HY; Ho, CL; Chang, C; Chow, NH; Lee, CT				Chu, Chien-An; Wang, Yi-Wen; Chen, Yi-Lin; Chen, Hui-Wen; Chuang, Jing-Jing; Chang, Hong-Yi; Ho, Chung-Liang; Chang, Chen; Chow, Nan-Haw; Lee, Chung-Ta			The Role of Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 in the Pathogenesis of Human Cancer	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						PIK3C3; Vps34; autophagy; colorectal cancer; cancer	BECLIN 1; PHOSPHOINOSITIDE 3-KINASES; AUTOPHAGOSOME MATURATION; EMERGING MECHANISMS; POOR-PROGNOSIS; VPS34; PROTEIN; INHIBITION; EXPRESSION; DEGRADATION	Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), the mammalian ortholog of yeast vesicular protein sorting 34 (Vps34), belongs to the phosphoinositide 3-kinase (PI3K) family. PIK3C3 can phosphorylate phosphatidylinositol (PtdIns) to generate phosphatidylinositol 3-phosphate (PI3P), a phospholipid central to autophagy. Inhibition of PIK3C3 successfully inhibits autophagy. Autophagy maintains cell survival when modifications occur in the cellular environment and helps tumor cells resist metabolic stress and cancer treatment. In addition, PIK3C3 could induce oncogenic transformation and enhance tumor cell proliferation, growth, and invasion through mechanisms independent of autophagy. This review addresses the structural and functional features, tissue distribution, and expression pattern of PIK3C3 in a variety of human tumors and highlights the underlying mechanisms involved in carcinogenesis. The implications in cancer biology, patient prognosis prediction, and cancer therapy are discussed. Altogether, the discovery of pharmacological inhibitors of PIK3C3 could reveal novel strategies for improving treatment outcomes for PIK3C3-mediated human diseases.</p>	[Chu, Chien-An; Wang, Yi-Wen; Ho, Chung-Liang; Chang, Chen; Chow, Nan-Haw; Lee, Chung-Ta] Natl Cheng Kung Univ, Dept Pathol, Coll Med, Tainan 701401, Taiwan; [Chen, Yi-Lin; Chen, Hui-Wen; Ho, Chung-Liang; Chang, Chen; Chow, Nan-Haw; Lee, Chung-Ta] Natl Cheng Kung Univ Hosp, Dept Pathol, Tainan 704302, Taiwan; [Chuang, Jing-Jing] Natl Chiayi Univ, Dept Microbiol Immunol & Biopharmaceut, Chiayi 600355, Taiwan; [Chang, Hong-Yi] Southern Taiwan Univ Sci & Technol, Dept Biotechnol & Food Technol, Coll Engn, Tainan 710301, Taiwan; [Ho, Chung-Liang; Chow, Nan-Haw] Natl Cheng Kung Univ, Inst Mol Med, Coll Med, Tainan 701401, Taiwan; [Ho, Chung-Liang; Chow, Nan-Haw] Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med, Tainan 701401, Taiwan; [Lee, Chung-Ta] Natl Cheng Kung Univ Hosp, Dept Pathol, Dou Liou Branch, Tainan 640003, Taiwan		Chow, NH; Lee, CT (corresponding author), Natl Cheng Kung Univ, Dept Pathol, Coll Med, Tainan 701401, Taiwan.; Chow, NH; Lee, CT (corresponding author), Natl Cheng Kung Univ Hosp, Dept Pathol, Tainan 704302, Taiwan.; Chow, NH (corresponding author), Natl Cheng Kung Univ, Inst Mol Med, Coll Med, Tainan 701401, Taiwan.; Chow, NH (corresponding author), Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med, Tainan 701401, Taiwan.; Lee, CT (corresponding author), Natl Cheng Kung Univ Hosp, Dept Pathol, Dou Liou Branch, Tainan 640003, Taiwan.	yihyeh@mail.ncyu.edu.tw; czeus1974@gmail.com			Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [NSC108-2320-B-006-050-MY3, 110-2314-B-006-083, 110-2320-B-006-026]; National Cheng Kung University Hospital, Tainan, Taiwan [NCKUH-10704015, NCKUH-11008004]; Higher Education Sprout Project, Ministry of Education	This manuscript was supported by research grants NSC108-2320-B-006-050-MY3, 110-2314-B-006-083, and 110-2320-B-006-026 from the Ministry of Science and Technology, Taiwan; NCKUH-10704015, and NCKUH-11008004 from the National Cheng Kung University Hospital, Tainan, Taiwan. The research was also supported in part by the Higher Education Sprout Project, Ministry of Education to the Headquarters of University Advancement at National Cheng Kung University, Tainan, Taiwan.	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J. Mol. Sci.	OCT	2021	22	20							10964	10.3390/ijms222010964			20	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	WQ4ZU	WOS:000713827200001	34681622	Green Published			2022-04-25	
J	Wang, TX; Chen, ZX; Zhang, W				Wang, Tongxin; Chen, Zhixia; Zhang, Wei			Regulation of autophagy inhibition and inflammatory response in glioma by Wnt signaling pathway	ONCOLOGY LETTERS			English	Article						Wnt5a/beta-catenin signaling pathway; glioma cells; autophagy; inflammatory response	COLORECTAL-CANCER; EXPRESSION; CELLS; MTOR; PROLIFERATION; TRANSITION; STRESS; TARGET; TUMORS; BRAIN	The objective of this study was to investigate the mechanism of the function of Wnt signaling pathway in regulating autophagy and inflammatory response in glioma cells. Human brain glioma cells U118 were selected and divided into three groups: i) the Wnt signaling inhibitor IWR-1 group (the observation group); ii) the PBS negative control group (the PBS group) and iii) the blank control group. After 24 h culture, Wnt5a/beta-catenin protein, autophagy marker, microtubule- associated-proteins-1A1B-light-chain-3C (LC-3) II and Beclin I, and inflammatory factors IL-6 and TNF-alpha protein expression levels were evaluated using western blotting. Compared with both control groups, Wnt5a/beta-catenin, IL-6 and TNF-alpha protein expression levels were significantly lower, and LC-3II and Beclin I protein expression levels were significantly higher in the observation group. In conclusion, Wnt5a/beta-catenin signaling pathway regulates autophagy and inflammatory response of glioma cells.	[Wang, Tongxin; Chen, Zhixia; Zhang, Wei] Yidu Cent Hosp Weifang, Dept Neurosurg, 4138 Linglongshannan Rd, Qingzhou 262500, Shandong, Peoples R China		Wang, TX (corresponding author), Yidu Cent Hosp Weifang, Dept Neurosurg, 4138 Linglongshannan Rd, Qingzhou 262500, Shandong, Peoples R China.	drtongxinwang@163.com					Adachi K, 2007, STEM CELLS, V25, P2827, DOI 10.1634/stemcells.2007-0177; Al Dhaheri Y, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0109630; Banday MZ, 2016, META GENE, V9, P128, DOI 10.1016/j.mgene.2016.06.001; Bielen H, 2014, DEV NEUROBIOL, V74, P772, DOI 10.1002/dneu.22168; Boitard M, 2015, CELL REP, V10, P1349, DOI 10.1016/j.celrep.2015.01.061; Cerpa W, 2008, J BIOL CHEM, V283, P5918, DOI 10.1074/jbc.M705943200; Chen N, 2011, CANCER BIOL THER, V11, P157, DOI 10.4161/cbt.11.2.14622; Chen WL, 2016, ONCOTARGET, V7, P62425, DOI 10.18632/oncotarget.11515; Duchartre Y, 2016, CRIT REV ONCOL HEMAT, V99, P141, DOI 10.1016/j.critrevonc.2015.12.005; Hamed HA, 2010, CANCER BIOL THER, V9, P526, DOI 10.4161/cbt.9.7.11116; Kaza N, 2012, BRAIN PATHOL, V22, P89, DOI 10.1111/j.1750-3639.2011.00544.x; Kikuchi A, 2007, CELL SIGNAL, V19, P659, DOI 10.1016/j.cellsig.2006.11.001; Lee SC, 2015, ONCOTARGET, V6, P27146, DOI 10.18632/oncotarget.4354; Lerner UH, 2015, J INTERN MED, V277, P630, DOI 10.1111/joim.12368; Li SH, 2013, PLOS ONE, V8, DOI [10.1371/journal.pone.0057604, 10.1371/journal.pone.0067928, 10.1371/journal.pone.0083037]; Liu F, 2016, SCI REP-UK, V6, DOI 10.1038/srep21260; Liu WT, 2013, NEURO-ONCOLOGY, V15, P1127, DOI 10.1093/neuonc/not073; Maguschak KA, 2012, J NEUROIMMUNE PHARM, V7, P763, DOI 10.1007/s11481-012-9350-7; Nusse R, 2008, CELL RES, V18, P523, DOI 10.1038/cr.2008.47; Ostrom QT, 2015, NEURO-ONCOLOGY, V17, P1, DOI 10.1093/neuonc/nov189; Prakash Sharada, 2015, J Oral Maxillofac Pathol, V19, P230, DOI 10.4103/0973-029X.164537; Shan YZ, 2015, INT J CLIN EXP MED, V8, P9114; Suh Y, 2010, CARCINOGENESIS, V31, P1424, DOI 10.1093/carcin/bgq115; Van Camp J, 2014, STEM CELL REV REP, V10, P207, DOI 10.1007/s12015-013-9486-8; Wu SH, 2015, INT J CLIN EXP PATHO, V8, P3882; Xue H, 2016, AUTOPHAGY, V12, P1129, DOI 10.1080/15548627.2016.1178446; Zhao XY, 2011, J NEURO-ONCOL, V102, P367, DOI 10.1007/s11060-010-0346-y	27	5	7	1	1	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	DEC	2017	14	6					7197	7200		10.3892/ol.2017.7103			4	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FP0LV	WOS:000417293400118	29344152	Green Submitted, Green Published, gold			2022-04-25	
J	Xie, YC; Zhu, S; Zhong, MZ; Yang, MH; Sun, XF; Liu, JB; Kroemer, G; Lotze, M; Zeh, HJ; Kang, R; Tang, DL				Xie, Yangchun; Zhu, Shan; Zhong, Meizuo; Yang, Manhua; Sun, Xiaofan; Liu, Jinbao; Kroemer, Guido; Lotze, Michael; Zeh, Herbert J., III; Kang, Rui; Tang, Daolin			Inhibition of Aurora Kinase A Induces Necroptosis in Pancreatic Carcinoma	GASTROENTEROLOGY			English	Article						Regulated Cell Death; Antitumor Immunity; HMGB1; ATP	BREAST-CANCER CELLS; G2/M PHASE ARREST; DRUG-RESISTANCE; CYCLE ARREST; THERAPY; DISEASE; GENE; PHOSPHORYLATION; PROLIFERATION; INFLAMMATION	BACKGROUND & AIMS: Induction of nonapoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2.03, CFPAC1, MiaPaCa2, BxPc3, and PANC02) and the HEK293 cell line, measuring loss of plasma membrane integrity, gain in cell volume, swollen organelles, and cytoplasmic vacuoles. We tested the effects of CCT137690 in colon formation assays, and the effects of the necroptosis (necrostatin-1 and necrosulfonamide), apoptosis, autophagy, and ferroptosis inhibitors. We derived cells from tumors that developed in Pdx1-Cre; K-Ras(G12D/+); p53(R172H/+) (KPC) mice. Genes encoding proteins in cell death pathways were knocked out, knocked down, or expressed from transgenes in PDAC cell lines. Athymic nude or B6 mice were given subcutaneous injections of PDAC cells or tail-vein injections of KPC tumor cells. Mice were given CCT137690 (80 mg/kg) or vehicle and tumor growth was monitored; tumor tissues were collected and analyzed by immunohistochemistry. We compared gene expression levels between human pancreatic cancer tissues (n = 130) with patient survival times using the online R2 genomics analysis and visualization platform. RESULTS: CCT137690 induced necrosis-like death in PDAC cell lines and reduced colony formation; these effects required RIPK1, RIPK3, and MLKL, as well as inhibition of aurora kinase A (AURKA). AURKA interacted directly with RIPK1 and RIPK3 to reduce necrosome activation. AURKA-mediated phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) at serine 9 inhibited activation of the RIPK3 and MLKL necrosome. Mutations in AURKA (D274A) or GSK3 beta (S9A), or pharmacologic inhibitors of RIPK1 signaling via RIPK3 and MLKL, reduced the cytotoxic activity of CCT137690 in PDAC cells. Oral administration of CCT137690 induced necroptosis and immunogenic cell death in subcutaneous and orthotopic tumors in mice, and reduced tumor growth and tumor cell phosphorylation of AURKA and GSK3 beta. CCT137690 increased survival times of mice with orthotopic KPC PDACs and reduced tumor growth, stroma, and metastasis. Increased expression of AURKA and GSK3 beta mRNAs associated with shorter survival times of patients with pancreatic cancer. CONCLUSIONS: We identified the aurora kinase inhibitor CCT137690 as an agent that induces necrosis-like death in PDAC cells, via RIPK1, RIPK3, and MLKL. CCT137690 slowed growth of orthotopic tumors from PDAC cells in mice, and expression of AURKA and GSK3 beta associate with patient survival times. AURKA might be targeted for treatment of pancreatic cancer.	[Xie, Yangchun; Zhu, Shan; Sun, Xiaofan; Liu, Jinbao; Tang, Daolin] Guangzhou Med Univ, Affiliated Hosp 3, Ctr DAMP Biol,Prot Modificat & Degradat Lab, Key Lab Major Obstet Dis Guangdong Prov,Key Lab R, Guangzhou, Guangdong, Peoples R China; [Xie, Yangchun; Zhong, Meizuo] Cent S Univ, Xiangya Hosp, Dept Oncol, Changsha, Hunan, Peoples R China; [Yang, Manhua] Cent S Univ, Xiangya Hosp, Pediat, Changsha, Hunan, Peoples R China; [Xie, Yangchun; Yang, Manhua; Lotze, Michael; Zeh, Herbert J., III; Kang, Rui; Tang, Daolin] Univ Pittsburgh, Dept Surg, Hillman Canc Ctr, Pittsburgh, PA 15253 USA; [Kroemer, Guido] Univ Paris 05, Sorbonne Paris Cite, Paris, France; [Kroemer, Guido] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France; [Kroemer, Guido] INSERM, U1138, Paris, France; [Kroemer, Guido] Univ Paris 06, Paris, France; [Kroemer, Guido] Metabol & Cell Biol Platforms, Gustave Roussy Canc Campus, Villejuif, France; [Kroemer, Guido] Hop Europeeen Georges Pompidou, AP HP, Pole Biol, Paris, France; [Kroemer, Guido] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden		Tang, DL (corresponding author), Univ Pittsburgh, Hillman Canc Ctr, Room G27C,5117 Ctr Ave, Pittsburgh, PA 15253 USA.	tangd2@upmc.edu	Kroemer, Guido/AAY-9859-2020; Tang, Daolin/ABD-5062-2021; KROEMER, Guido/B-4263-2013; Tang, Daolin/B-2905-2010; Kang, Rui/ABD-5291-2021	Tang, Daolin/0000-0002-1903-6180; KROEMER, Guido/0000-0002-9334-4405; Kang, Rui/0000-0003-2725-1574; Xie, Yangchun/0000-0003-2571-4774	US National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01GM115366, R01CA160417, R01CA211070]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2016A030308011]; American Cancer SocietyAmerican Cancer Society [RSG-16-014-01-CDD]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31671435, 81400132, 81772508]; Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme; Ligue contre le Cancer (equipe labelisee)Ligue nationale contre le cancer; Agence National de la Recherche (ANR)-Projets blancsFrench National Research Agency (ANR); ANRFrench National Research Agency (ANR); ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC)Fondation ARC pour la Recherche sur le Cancer; Canceropole Ile-de-FranceRegion Ile-de-France; Institut National du Cancer (INCa)Institut National du Cancer (INCA) France; Institut Universitaire de France; Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale; European Commission (ArtForce)European CommissionEuropean Commission Joint Research Centre; European Research Council (ERC)European Research Council (ERC); LeDucq FoundationLeducq Foundation; LabEx Immuno-Oncology; RHU Torino Lumiere; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); Paris Alliance of Cancer Research Institutes (PACRI);  [P30CA047904]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA160417, R01CA211070, P30CA047904] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM115366] Funding Source: NIH RePORTER	This work was supported by grants from the US National Institutes of Health (R01GM115366, R01CA160417, and R01CA211070), the Natural Science Foundation of Guangdong Province (2016A030308011), the American Cancer Society (Research Scholar Grant RSG-16-014-01-CDD), the National Natural Science Foundation of China (31671435, 81400132, and 81772508), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2017). This project partly used University of Pittsburgh Cancer Institute shared resources supported by award P30CA047904. G.K. is supported by the Ligue contre le Cancer (equipe labelisee); Agence National de la Recherche (ANR)-Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Institut Universitaire de France; Fondation pour la Recherche Medicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LeDucq Foundation; the LabEx Immuno-Oncology; the RHU Torino Lumiere, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI).	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J	Nunez-Olvera, SI; Chavez-Munguia, B; Terrones-Gurrola, MCD; Marchat, LA; Puente-Rivera, J; Ruiz-Garcia, E; Campos-Parra, AD; Vazquez-Calzada, C; Lizarraga-Verdugo, ER; Ramos-Payan, R; Salinas-Vera, YM; Lopez-Camarillo, C				Nunez-Olvera, Stephanie, I; Chavez-Munguia, Bibiana; del Rocio Terrones-Gurrola, Maria Cruz; Marchat, Laurence A.; Puente-Rivera, Jonathan; Ruiz-Garcia, Erika; Campos-Parra, Alma D.; Vazquez-Calzada, Carlos; Lizarraga-Verdugo, Erik R.; Ramos-Payan, Rosalio; Salinas-Vera, Yarely M.; Lopez-Camarillo, Cesar			A novel protective role for microRNA-3135b in Golgi apparatus fragmentation induced by chemotherapy via GOLPH3/AKT1/mTOR axis in colorectal cancer cells	SCIENTIFIC REPORTS			English	Article							BREAST-CANCER; GOLPH3 LINKS; DNA-DAMAGE; PROLIFERATION; EXPRESSION; PROTEIN; PROGRESSION	Chemotherapy activates a novel cytoplasmic DNA damage response resulting in Golgi apparatus fragmentation and cancer cell survival. This mechanism is regulated by Golgi phosphoprotein-3 (GOLPH3)/Myo18A/F-actin axis. Analyzing the functions of miR-3135b, a small non-coding RNA with unknown functions, we found that its forced overexpression attenuates the Golgi apparatus fragmentation induced by chemotherapeutic drugs in colorectal cancer (CRC) cells. First, we found that miR-3135b is downregulated in CRC cell lines and clinical tumors. Bioinformatic predictions showed that miR-3135b could be regulating protein-encoding genes involved in cell survival, resistance to chemotherapy, and Golgi dynamics. In agreement, ectopic transfection of miR-3135b in HCT-15 cancer cells significantly inhibited cell proliferation, sensitized cells to 5-fluoruracil (5-FU), and promoted late apoptosis and necrosis. Also, miR-3135b overexpression impaired the cell cycle progression in HCT-15 and SW-480 cancer cells. Because GOLPH3, a gene involved in maintenance of Golgi structure, was predicted as a potential target of miR-3135b, we studied their functional relationships in response to DNA damage induced by chemotherapy. Immunofluorescence and cellular ultrastructure experiments using antibodies against TGN38 protein, a trans-Golgi network marker, showed that 5-FU and doxorubicin treatments result in an apoptosis-independent stacks dispersal of the Golgi ribbon structure in both HCT-15 and SW-480 cells. Remarkably, these cellular effects were dramatically hindered by transfection of miR-3135b mimics. In addition, our functional studies confirmed that miR-3135b binds to the 3 ' -UTR of GOLPH3 proto-oncogene, and also reduces the levels of p-AKT1 (Ser473) and p-mTOR (Ser2448) signaling transducers, which are key in cell survival and autophagy activation. Moreover, we found that after treatment with 5-FU, TGN38 factor coimmunolocalizes with beclin-1 autophagic protein in discrete structures associated with the fragmented Golgi, suggesting that the activation of pro-survival autophagy is linked to loss of Golgi integrity. These cellular effects in autophagy and Golgi dispersal were reversed by miR-3135b. In summary, we provided experimental evidence suggesting for the first time a novel role for miR-3135b in the protection of chemotherapy-induced Golgi fragmentation via GOLPH3/AKT1/mTOR axis and protective autophagy in colorectal cancer cells.	[Nunez-Olvera, Stephanie, I; Salinas-Vera, Yarely M.; Lopez-Camarillo, Cesar] Univ Autonoma Ciudad Mexico, Posgrad Ciencias Genom, San Lorenzo 290 Col Del Valle, Mexico City 03100, DF, Mexico; [Chavez-Munguia, Bibiana; Vazquez-Calzada, Carlos] CINVESTAV IPN, Dept Infectom & Patogenesis Mol, Mexico City, DF, Mexico; [del Rocio Terrones-Gurrola, Maria Cruz] Univ Autonoma San Luis Potosi, Coordinac Acad Reg Altiplano, San Luis Potosi, San Luis Potosi, Mexico; [Marchat, Laurence A.] Inst Politecn Nacl, Programa Biomed Mol & Red Biotecnol, Mexico City, DF, Mexico; [Puente-Rivera, Jonathan] Univ Nacl Autonoma Mexico, Inst Ecol, Dept Ecol Func, Mexico City, DF, Mexico; [Ruiz-Garcia, Erika] Inst Nacl Cancerol, Lab Med Translac, Mexico City, DF, Mexico; [Ruiz-Garcia, Erika] Inst Nacl Cancerol, Dept Tumores Gastrointestinales, Mexico City, DF, Mexico; [Campos-Parra, Alma D.] Inst Nacl Cancerol, Lab Genom, Mexico City, DF, Mexico; [Lizarraga-Verdugo, Erik R.; Ramos-Payan, Rosalio] Univ Autonoma Sinaloa, Fac Ciencias Quim Biol, Culiacan, Sinaloa, Mexico		Lopez-Camarillo, C (corresponding author), Univ Autonoma Ciudad Mexico, Posgrad Ciencias Genom, San Lorenzo 290 Col Del Valle, Mexico City 03100, DF, Mexico.	cesar.lopez@uacm.edu.mx	Lopez-Camarillo, Cesar/I-1946-2019; del Rocío Terrones Gurrola, María Cruz/AAS-1463-2021; Puente-Rivera, Jonathan/AAU-5545-2021; Marchat, Laurence A./S-8418-2018; Vera, Yarely/AFN-2618-2022	Lopez-Camarillo, Cesar/0000-0002-9417-2609; Puente-Rivera, Jonathan/0000-0001-6941-6248; Marchat, Laurence A./0000-0003-1615-8614; Vera, Yarely/0000-0003-2129-9980; Ruiz-Garcia, Erika/0000-0002-0446-123X; Ramos-Payan, Rosalio/0000-0001-7500-7571	Ciencia Basica SEP-CONACYT [2018-2019, A1-S-13656]	We thank to Universidad Autonoma de la Ciudad de Mexico for infrastructure and support. This investigation was partially funded by Ciencia Basica SEP-CONACYT 2018-2019 (Grant A1-S-13656).	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J	Wen, B; Wei, YT; Mu, LL; Wen, GR; Zhao, K				Wen, Bin; Wei, Ying-Ting; Mu, Lan-Lan; Wen, Guo-Rong; Zhao, Kui			The molecular mechanisms of celecoxib in tumor development	MEDICINE			English	Review						autophagy; cancer stem cells; celecoxib; cyclooxygenase-2; endoplasmic reticulum stress; prostaglandin E-2; reactive oxygen species; tumor	NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ENDOPLASMIC-RETICULUM STRESS; EPITHELIAL-MESENCHYMAL TRANSITION; HYPOXIA-INDUCIBLE FACTORS; CARCINOMA CELL-GROWTH; NF-KAPPA-B; COLORECTAL-CANCER; PROSTATE-CANCER; GASTRIC-CANCER; BREAST-CANCER	Background: Clinical studies have shown that celecoxib can significantly inhibit the development of tumors, and basic experiments and in vitro experiments also provide a certain basis, but it is not clear how celecoxib inhibits tumor development in detail. Methods: A literature search of all major academic databases was conducted (PubMed, China National Knowledge Internet (CNKI), Wan-fang, China Science and Technology Journal Database (VIP), including the main research on the mechanisms of celecoxib on tumors. Results: Celecoxib can intervene in tumor development and reduce the formation of drug resistance through multiple molecular mechanisms. Conclusion: Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis and thereby inhibiting the phosphorylation of nuclear factor-kappa-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. Meanwhile, it was found that celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy. Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.	[Wen, Bin; Wei, Ying-Ting; Mu, Lan-Lan; Wen, Guo-Rong; Zhao, Kui] Zunyi Med Univ, Affiliated Hosp, Dept Gastroenterol, Zunyi 563000, Guizhou, Peoples R China		Zhao, K (corresponding author), Zunyi Med Univ, Affiliated Hosp, Dept Gastroenterol, Zunyi 563000, Guizhou, Peoples R China.	Kuizhao95858@msn.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81560467]	This study was supported by research grants from the National Natural Science Foundation of China (No. 81560467 to KZ).	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J	Fels, DR; Ye, JB; Segan, AT; Kridel, SJ; Spiotto, M; Olson, M; Koong, AC; Koumenis, C				Fels, Diane R.; Ye, Jiangbin; Segan, Andrew T.; Kridel, Steven J.; Spiotto, Michael; Olson, Michael; Koong, Albert C.; Koumenis, Constantinos			Preferential Cytotoxicity of Bortezomib toward Hypoxic Tumor Cells via Overactivation of Endoplasmic Reticulum Stress Pathways	CANCER RESEARCH			English	Article							UNFOLDED PROTEIN RESPONSE; MULTIPLE-MYELOMA CELLS; ER STRESS; GENE-EXPRESSION; MESSENGER-RNA; PROTEASOME INHIBITION; TRANSLATIONAL CONTROL; TRANSCRIPTION-FACTOR; DRUG-RESISTANCE; CANCER-THERAPY	Hypoxia is a dynamic feature of the tumor microenvironment that contributes to drug resistance and cancer progression. We previously showed that components of the unfolded protein response (UPR), elicited by endoplasmic reticulum (ER) stress, are also activated by hypoxia in vitro and in vivo animal and human patient tumors. Here, we report that ER stressors, such as thapsigargin or the clinically used proteasome inhibitor bortezomib, exhibit significantly higher cytotoxicity toward hypoxic compared with normoxic tumor cells, which is accompanied by enhanced activation of UPR effectors in vitro and UPR reporter activity in vivo. Treatment of cells with the translation inhibitor cycloheximide, which relieves ER load, ameliorated this enhanced cytotoxicity, indicating that the increased cytotoxicity is ER stress-dependent. The mode of cell death was cell type-dependent, because DLD1 colorectal carcinoma cells exhibited enhanced apoptosis, whereas HeLa cervical carcinoma cells activated autophagy, blocked apoptosis, and eventually led to necrosis. Pharmacologic or genetic ablation of autophagy increased the levels of apoptosis. These results show that hypoxic tumor cells, which are generally more resistant to genotoxic agents, are hypersensitive to proteasome inhibitors and suggest that combining bortezomib with therapies that target the normoxic fraction of human tumors can lead to more effective tumor control. [Cancer Res 2008;68(22):9323-30]	[Fels, Diane R.; Ye, Jiangbin; Segan, Andrew T.; Koumenis, Constantinos] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA; [Fels, Diane R.; Kridel, Steven J.] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC USA; [Spiotto, Michael; Olson, Michael; Koong, Albert C.] Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA		Koumenis, C (corresponding author), Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA.	koumenis@xrt.upenn.edu	Ye, Jiangbin/A-1094-2007; Koumenis, Constantinos/B-2002-2008; Spiotto, Michael/AAC-8331-2021	Koumenis, Costas/0000-0001-5945-4726; Ye, Jiangbin/0000-0003-1117-4869; Koong, Albert/0000-0001-9824-1643	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA94214, CA112108]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA094214, R01CA112108] Funding Source: NIH RePORTER	Grant support: NIH grants CA94214 (D.R. Fels, J. Ye, A.T. Segan, S.S. Kridel, and C. Koumenis) and CA112108 (M. Spiotto, M. Olson, and A.C. Koong).	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NOV 15	2008	68	22					9323	9330		10.1158/0008-5472.CAN-08-2873			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	375TQ	WOS:000261136600029	19010906	Green Accepted			2022-04-25	
J	Lu, MZ; Zhang, XJ; Xu, Y; He, GZ; Liu, Q; Zhu, J; Zhang, CS				Lu, Mingzhu; Zhang, Xianjing; Xu, Yun; He, Guangzhao; Liu, Qian; Zhu, Jing; Zhang, Changsong			Elevated histone H3 citrullination is associated with increased Beclin1 expression in HBV-related hepatocellular carcinoma	JOURNAL OF MEDICAL VIROLOGY			English	Article						autophagy; Beclin1; citrullination; hepatocellular carcinoma; histone H3	COLORECTAL-CANCER; AUTOPHAGY; TARGET; GENE; TUMORIGENESIS; MARKER; HEALTH; CELLS	Citrullinated histone H3 (H3Cit) is the product of the conversion of peptidylarginine to citrulline in histone H3. We evaluated the H3Cit level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues and assessed its association with Beclin1 messenger RNA (mRNA) (a key autophagic regulator). The level of H3Cit was detected by a capture enzyme-linked immunosorbent assay, while Beclin1 mRNA was determined by real-time polymerase chain reaction in 80 HBV-related patients with HCC. We found that the mean level of H3Cit was 72.25 ng/mg in HCC and 44.02 ng/mg in nontumor tissues. The mean HCC/nontumor ratio of Beclin1 mRNA was higher (0.096) in tumor samples than in nontumor specimens (0.056). Specifically, Beclin1 mRNA was elevated in 51 HCC cases (63.75%) and decreased in 29 cases (36.25%). Moreover, the levels of H3Cit and Beclin1 mRNA were significantly associated with vascular invasion and serum AFP levels. A shorter survival (19 months) was associated with a high H3Cit level. We also found increased levels of Beclin1 mRNA in the H3Cit (high) group compared with the H3Cit (low) group. The results implied that elevated histone H3 citrullination is associated with increased Beclin1 expression during the development of HBV-related HCC.	[Lu, Mingzhu; He, Guangzhao; Liu, Qian] Soochow Univ, Changzhou Canc Hosp, Clin Oncol Lab, Changzhou, Peoples R China; [Zhang, Xianjing] Nanchang Univ, Clin Med Sch 2, Nanchang, Jiangxi, Peoples R China; [Xu, Yun] Nanyang Ctr Hosp, Dept Oncol, Nanyang, Peoples R China; [Zhu, Jing; Zhang, Changsong] Nanjing Med Univ, Affiliated Suzhou Sci & Technol Town Hosp, Dept Lab, Suzhou, Peoples R China		Zhang, CS (corresponding author), Nanjing Med Univ, Affiliated Suzhou Sci & Technol Town Hosp, 1 Lijiang Rd, Suzhou 215153, Jiangsu, Peoples R China.	changsong@suda.edu.cn		zhang, changsong/0000-0002-1425-7339	Changzhou Municipal Commission of Health and Family Planning [ZD201816]; Health Talents Project for Jiangsu [ZDRCC2016020]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BE2016656, BRA2018171]; Suzhou New District Science and Technology Plan [2019Z009]	Changzhou Municipal Commission of Health and Family Planning, Grant/Award Number: ZD201816; Health Talents Project for Jiangsu, Grant/Award Number: ZDRCC2016020; Natural Science Foundation of Jiangsu Province, Grant/Award Numbers: BE2016656, BRA2018171; Suzhou New District Science and Technology Plan, Grant/Award Number: 2019Z009	Al-Shenawy HA, 2016, APMIS, V124, P229, DOI 10.1111/apm.12498; Anzilotti C, 2010, AUTOIMMUN REV, V9, P158, DOI 10.1016/j.autrev.2009.06.002; Bortnik S, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18071496; Cao Y, 2007, CELL RES, V17, P839, DOI 10.1038/cr.2007.78; Cha YJ, 2014, INT J CLIN EXP PATHO, V7, P3389; Chang XT, 2009, BMC CANCER, V9, DOI 10.1186/1471-2407-9-40; Edge SB, 2010, ANN SURG ONCOL, V17, P1471, DOI 10.1245/s10434-010-0985-4; El-Khattouti Abdelouahid, 2013, J Cell Death, V6, P37, DOI 10.4137/JCD.S11034; Erstad DJ, 2018, CANCER-AM CANCER SOC, V124, P3084, DOI 10.1002/cncr.31257; Fan TT, 2014, CELL BIOSCI, V4, DOI 10.1186/2045-3701-4-49; Flavahan WA, 2017, SCIENCE, V357, DOI 10.1126/science.aal2380; Fu LL, 2013, INT J BIOCHEM CELL B, V45, P921, DOI 10.1016/j.biocel.2013.02.007; Guerrieri F, 2017, BMC GENOMICS, V18, DOI 10.1186/s12864-017-3561-5; Han Y, 2014, ASIAN PAC J CANCER P, V15, P4583, DOI 10.7314/APJCP.2014.15.11.4583; Jiang ZM, 2013, WORLD J SURG ONCOL, V11, DOI 10.1186/1477-7819-11-260; Kotsafti A, 2012, BMC GASTROENTEROL, V12, DOI 10.1186/1471-230X-12-118; Koukourakis MI, 2010, BRIT J CANCER, V103, P1209, DOI 10.1038/sj.bjc.6605904; Misztak P, 2018, PHARMACOL REP, V70, P398, DOI 10.1016/j.pharep.2017.08.001; Nakashima K, 2002, J BIOL CHEM, V277, P49562, DOI 10.1074/jbc.M208795200; Pfeifer GP, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19041166; Qiu DM, 2014, BMC CANCER, V14, DOI 10.1186/1471-2407-14-327; Sharma P, 2012, PLOS GENET, V8, DOI 10.1371/journal.pgen.1002934; Song JR, 2011, J CELL BIOCHEM, V112, P3406, DOI 10.1002/jcb.23274; Sun K, 2017, CANCER LETT, V388, P198, DOI 10.1016/j.canlet.2016.12.004; Sun K, 2013, CELL BIOSCI, V3, DOI 10.1186/2045-3701-3-35; Tanikawa C, 2012, NAT COMMUN, V3, DOI 10.1038/ncomms1676; Thalin C, 2018, PLOS ONE, V13, DOI 10.1371/journal.pone.0191231; Thalin C, 2017, IMMUNOL RES, V65, P706, DOI 10.1007/s12026-017-8905-3; Toton E, 2014, J PHYSIOL PHARMACOL, V65, P459; Wang S, 2013, BBA-GENE REGUL MECH, V1829, P1126, DOI 10.1016/j.bbagrm.2013.07.003; Xie DY, 2017, HEPATOBIL SURG NUTR, V6, P387, DOI 10.21037/hbsn.2017.11.01; Zhang XS, 2012, P NATL ACAD SCI USA, V109, P13331, DOI 10.1073/pnas.1203280109	32	2	2	0	4	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0146-6615	1096-9071		J MED VIROL	J. Med. Virol.	AUG	2020	92	8					1221	1230		10.1002/jmv.25663		JAN 2020	10	Virology	Science Citation Index Expanded (SCI-EXPANDED)	Virology	ML5GX	WOS:000507665100001	31900950				2022-04-25	
J	Brown, GT; Cash, B; Alnabulsi, A; Samuel, LM; Murray, GI				Brown, Gordon T.; Cash, Beatriz; Alnabulsi, Ayham; Samuel, Leslie M.; Murray, Graeme I.			The expression and prognostic significance of bcl-2-associated transcription factor 1 in rectal cancer following neoadjuvant therapy	HISTOPATHOLOGY			English	Article						bcl-2-associated transcription factor 1; biomarker; immunohistochemistry; monoclonal antibody; neoadjuvant therapy; prognosis; rectal cancer	COLORECTAL-CANCER; BCLAF1; DEATH; BTF; CHEMOTHERAPY; ROLES; ALDH1	Aimsbcl-2-associated transcription factor 1 (BCLAF1) is a nuclear protein that binds to bcl-related proteins and can induce apoptosis and autophagy. The aim of this study was to investigate the expression of BCLAF1 in a series of rectal cancers following neoadjuvant therapy. Methods and resultsImmunohistochemistry was performed on a post-neoadjuvant therapy rectal cancer tissue microarray. It contained rectal cancers (n = 248), lymph node metastases (n = 76), and non-neoplastic rectal mucosal samples (n = 73). A monoclonal antibody against BCLAF1 that we have developed was used. Non-neoplastic rectal epithelium showed nuclear localization of BCLAF1 in both crypt and surface epithelial cells, whereas rectal cancers showed both nuclear and cytoplasmic BCLAF1 expression. Most rectal cancers showed moderate or strong nuclear immunoreactivity, but showed weak cytoplasmic immunoreactivity. Cytoplasmic BCLAF1 expression was increased in primary rectal cancers as compared with non-neoplastic rectal mucosa (P = 0.008). Negative and weak nuclear BCLAF1 expression was associated with a poor prognosis [hazard ratio (HR) 0.502, 95% confidence interval (CI) 0.269-0.939, (2) = 4.876, P = 0.027]. Nuclear BCLAF1 expression was independently prognostic in a multivariate model (HR 0.431, 95% CI 0.221-0.840, P = 0.013). ConclusionsThis study has shown that both cytoplasmic BCLAF1 expression and nuclear BCLAF1 expression are increased in post-neoadjuvant therapy rectal cancer, and that negative and weak nuclear BCLAF1 expression are independently associated with a poor prognosis.	[Brown, Gordon T.; Murray, Graeme I.] Univ Aberdeen, Sch Med & Dent, Div Appl Med, Pathol, Foresterhill, Aberdeen AB25 2ZD, Scotland; [Cash, Beatriz; Alnabulsi, Ayham] Vertebrate Antibodies, Tillydrone Ave, Aberdeen, Scotland; [Samuel, Leslie M.] NHS Grampian, Aberdeen Royal Infirm, Dept Clin Oncol, Aberdeen, Scotland		Brown, GT (corresponding author), Univ Aberdeen, Sch Med & Dent, Div Appl Med, Pathol, Foresterhill, Aberdeen AB25 2ZD, Scotland.	g.i.murray@abdn.ac.uk		Samuel, Leslie/0000-0002-8402-8670	Encompass kick start and SMART: Scotland award schemes of Scottish Enterprise and Friends of Anchor	This study was supported by funding from the Encompass kick start and SMART: Scotland award schemes of Scottish Enterprise and Friends of Anchor. The Grampian Biorepository assisted with the immunohistochemical investigations.	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J	Gao, TY; Liu, XX; He, BS; Pan, YQ; Wang, SK				Gao, Tianyi; Liu, Xiangxiang; He, Bangshun; Pan, Yuqin; Wang, Shukui			IGF2 loss of imprinting enhances colorectal cancer stem cells pluripotency by promoting tumor autophagy	AGING-US			English	Article						IGF2 LOI; CRC; CSCs pluripotency; autophagy	RESISTANCE	Cancer stem cells (CSCs) are believed to be the driving force behind the tumor growth. We performed this study to further explore the role of IGF2 epigenetic on CRC stem cells pluripotency which showed that IGF2 LOI CRC cells usually had a higher CD133 expression and sphere forming efficiency than MOI cells. IGF2 LOI CSCs were also found to have a higher level of autophagy than MOI CSCs. Moreover, IGF2/IR-A signal was determined to play a more important role in CSCs formation than IGF2/IGF1R. At last, by using miRNA-195 mimics, we fortunately found the increased IR-A expression might be due to the degradation of miRNA-195 in CRC. In conclusion, our results might reveal that IGF2 LOI could promote CRC stem cells pluripotency by promoting CSCs autophagy. For the degradation of miRNA-195, IGF2 showed a higher ability in interacting with overexpressed IR-A rather than IGF1R which would further activate CSCs autophagy. All these findings might provide a novel mechanistic insight into CRC diagnosis and therapy.	[Gao, Tianyi; Wang, Shukui] Nanjing Med Univ, Nanjing Hosp 1, Dept Clin Lab, Nanjing 210006, Jiangsu, Peoples R China; [Liu, Xiangxiang; He, Bangshun; Pan, Yuqin; Wang, Shukui] Nanjing Med Univ, Nanjing Hosp 1, Cent Lab, Nanjing 210006, Jiangsu, Peoples R China; [Wang, Shukui] Nanjing Med Univ, Jiangsu Collaborat Innovat Ctr Canc Personalized, Nanjing 210006, Jiangsu, Peoples R China		Wang, SK (corresponding author), Nanjing Med Univ, Nanjing Hosp 1, Dept Clin Lab, Nanjing 210006, Jiangsu, Peoples R China.; Wang, SK (corresponding author), Nanjing Med Univ, Nanjing Hosp 1, Cent Lab, Nanjing 210006, Jiangsu, Peoples R China.; Wang, SK (corresponding author), Nanjing Med Univ, Jiangsu Collaborat Innovat Ctr Canc Personalized, Nanjing 210006, Jiangsu, Peoples R China.	sk_wang@njmu.edu.cn			National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972806, 81802093, 81903034]; Key Project of Science and Technology Development of Nanjing Medicine [ZDX16001]; development of Nanjing medical science and technology foundation [YKK17123]	This project was supported by grants from The National Nature Science Foundation of China (No. 81972806), Key Project of Science and Technology Development of Nanjing Medicine (ZDX16001) to SKW; The National Nature Science Foundation of China (No. 81802093) to HLS; The National Nature Science Foundation of China (No. 81903034) and the development of Nanjing medical science and technology foundation to Tianyi Gao (no. YKK17123).	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J	Avnet, S; Lemma, S; Cortini, M; Pellegrini, P; Perut, F; Zini, N; Kusuzaki, K; Chano, T; Grisendi, G; Dominici, M; De Milito, A; Baldini, N				Avnet, Sofia; Lemma, Silvia; Cortini, Margherita; Pellegrini, Paola; Perut, Francesca; Zini, Nicoletta; Kusuzaki, Katsuyuki; Chano, Tokuhiro; Grisendi, Giulia; Dominici, Massimo; De Milito, Angelo; Baldini, Nicola			Altered pH gradient at the plasma membrane of osteosarcoma cells is a key mechanism of drug resistance	ONCOTARGET			English	Article						osteosarcoma; doxorubicin; drug resistance; plasma membrane pH gradient; tumor microenvironment	COLON-CANCER CELLS; MULTIDRUG-RESISTANCE; THERAPEUTIC TARGET; IN-VITRO; METASTATIC NICHE; ACIDIC VESICLES; ACRIDINE-ORANGE; HUMAN-TUMORS; V-ATPASE; GLYCOPROTEIN	Current therapy of osteosarcoma (OS), the most common primary bone malignancy, is based on a combination of surgery and chemotherapy. Multidrug resistance mediated by P-glycoprotein (P-gp) overexpression has been previously associated with treatment failure and progression of OS, although other mechanisms may also play a role. We considered the typical acidic extracellular pH (pHe) of sarcomas, and found that doxorubicin (DXR) cytotoxicity is reduced in P-gp negative OS cells cultured at pHe 6.5 compared to standard 7.4. Short-time (24-48 hours) exposure to low pHe significantly increased the number and acidity of lysosomes, and the combination of DXR with omeprazole, a proton pump inhibitor targeting lysosomal acidity, significantly enhanced DXR cytotoxicity. In OS xenografts, the combination treatment of DXR and omeprazole significantly reduced tumor volume and body weight loss. The impaired toxicity of DXR at low pHe was not associated with increased autophagy or lysosomal acidification, but rather, as shown by SNARF staining, with a reversal of the pH gradient at the plasma membrane (Delta pH(cm)), eventually leading to a reduced DXR intracellular accumulation. Finally, the reversal of Delta pH(cm) in OS cells promoted resistance not only to DXR, but also to cisplatin and methotrexate, and, to a lesser extent, to vincristine. Altogether, our findings show that, in OS cells, short-term acidosis induces resistance to different chemotherapeutic drugs by a reversal of Delta pH(cm), suggesting that buffer therapies or regimens including proton pump inhibitors in combination to low concentrations of conventional anticancer agents may offer novel solutions to overcome drug resistance.	[Avnet, Sofia; Lemma, Silvia; Cortini, Margherita; Perut, Francesca; Baldini, Nicola] Ist Ortoped Rizzoli, Orthopaed Pathophysiol & Regenerat Med Unit, Bologna, Italy; [Pellegrini, Paola; De Milito, Angelo] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden; [Zini, Nicoletta] CNR, Inst Mol Genet, Natl Res Council Italy, Bologna, Italy; [Zini, Nicoletta] Ist Ortoped Rizzoli, Lab Musculoskeletal Cell Biol, Bologna, Italy; [Kusuzaki, Katsuyuki] Takai Hosp, Musculoskeletal Oncol Unit, Nara, Japan; [Chano, Tokuhiro] Shiga Univ Med Sci, Dept Clin Lab Med, Otsu, Shiga, Japan; [Grisendi, Giulia; Dominici, Massimo] Univ Hosp Modena & Reggio Emilia, Dept Med & Surg Sci Children & Adults, Modena, Italy; [Baldini, Nicola] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy		Baldini, N (corresponding author), Ist Ortoped Rizzoli, Orthopaed Pathophysiol & Regenerat Med Unit, Bologna, Italy.; Baldini, N (corresponding author), Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy.	nicola.baldini@ior.it	Lemma, Silvia/AAY-3835-2020; Perut, Francesca/J-4771-2016; Lemma, Silvia/O-1119-2017; Avnet, Sofia/B-3220-2018; Chano, Tokuhiro/F-5816-2018; Baldini, Nicola/J-4806-2016; Dominici, Massimo/K-8014-2016; Cortini, Margherita/J-7325-2018; Zini, Nicoletta/C-7544-2019; Grisendi, Giulia/J-6360-2016	Perut, Francesca/0000-0002-3783-7803; Lemma, Silvia/0000-0003-0714-3138; Avnet, Sofia/0000-0002-7843-0591; Chano, Tokuhiro/0000-0002-9959-1183; Baldini, Nicola/0000-0003-2228-3833; Zini, Nicoletta/0000-0002-4442-7079; Grisendi, Giulia/0000-0002-0120-6129; Cortini, Margherita/0000-0002-8151-8105; Dominici, Massimo/0000-0002-4007-1503; De Milito, Angelo/0000-0003-2591-2914	Italian Association for Cancer ResearchFondazione AIRC per la ricerca sul cancro [11426, 15608]; Swedish Cancer SocietySwedish Cancer Society [CAN 2012/415]	Italian Association for Cancer Research (grant No. 11426 and 15608 to N.B.), financial support for Scientific Research "5 per 1000 2012" (to N.B.), and Swedish Cancer Society (grant # CAN 2012/415 to A.D.).	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J	Knoll, G; Bittner, S; Kurz, M; Jantsch, J; Ehrenschwender, M				Knoll, Gertrud; Bittner, Sebastian; Kurz, Maria; Jantsch, Jonathan; Ehrenschwender, Martin			Hypoxia regulates TRAIL sensitivity of colorectal cancer cells through mitochondrial autophagy	ONCOTARGET			English	Article						TRAIL; SMAC mimetic; death receptor; hypoxia	ENDOPLASMIC-RETICULUM; INHIBITS APOPTOSIS; MEDIATED APOPTOSIS; CALCIUM-RELEASE; XIAP; NECROSIS; ACTIVATION; PROTEINS; BAX; MODULATION	The capacity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to selectively induce cell death in malignant cells triggered numerous attempts for therapeutic exploitation. In clinical trials, however, TRAIL did not live up to the expectations, as tumors exhibit high rates of TRAIL resistance in vivo. Response to anti-cancer therapy is determined not only by cancer cell intrinsic factors (e.g. oncogenic mutations), but also modulated by extrinsic factors such as the hypoxic tumor microenvironment. Here, we address the effect of hypoxia on pro-apoptotic TRAIL signaling in colorectal cancer cells. We show that oxygen levels modulate susceptibility to TRAIL-induced cell death, which is severely impaired under hypoxia (0.5% O-2). Mechanistically, this is attributable to hypoxia-induced mitochondrial autophagy. Loss of mitochondria under hypoxia restricts the availability of mitochondria-derived pro-apoptotic molecules such as second mitochondria-derived activator of caspase ( SMAC), thereby disrupting amplification of the apoptotic signal emanating from the TRAIL death receptors and efficiently blocking cell death in type-II cells. Moreover, we identify strategies to overcome TRAIL resistance in low oxygen environments. Counteracting hypoxia-induced loss of endogenous SMAC by exogenous substitution of SMAC mimetics fully restores TRAIL sensitivity in colorectal cancer cells. Alternatively, enforcing a mitochondria-independent type-I mode of cell death by targeting the type-II phenotype gatekeeper X-linked inhibitor of apoptosis protein ( XIAP) is equally effective. Together, our results indicate that tumor hypoxia impairs TRAIL efficacy but this limitation can be overcome by combining TRAIL with SMAC mimetics or XIAPtargeting drugs. Our findings may help to exploit the potential of TRAIL in cancer therapy.	[Knoll, Gertrud; Bittner, Sebastian; Kurz, Maria; Jantsch, Jonathan; Ehrenschwender, Martin] Univ Hosp Regensburg, Inst Clin Microbiol & Hyg, D-93053 Regensburg, Germany		Ehrenschwender, M (corresponding author), Univ Hosp Regensburg, Inst Clin Microbiol & Hyg, D-93053 Regensburg, Germany.	martin.ehrenschwender@ukr.de			Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [EH 465/2-1, JA1993/2-1]; Roggenbuck Stiftung; Walter-Schulz-Stiftung; Medical Faculty of the University of Regensburg (ReForM-B)	ME and JJ are supported by grants from Deutsche Forschungsgemeinschaft (EH 465/2-1 and JA1993/2-1). ME is supported by grants from the Roggenbuck Stiftung, the Walter-Schulz-Stiftung and the Medical Faculty of the University of Regensburg (ReForM-B).	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J	Jin, P; Jiang, JW; Xie, N; Zhou, L; Huang, Z; Zhang, L; Qin, SY; Fu, SY; Peng, LY; Gao, W; Li, BW; Lei, YL; Nice, EC; Li, CL; Shao, JC; Xie, K				Jin, Ping; Jiang, Jingwen; Xie, Na; Zhou, Li; Huang, Zhao; Zhang, Lu; Qin, Siyuan; Fu, Shuyue; Peng, Liyuan; Gao, Wei; Li, Bowen; Lei, Yunlong; Nice, Edouard C.; Li, Changlong; Shao, Jichun; Xie, Ke			MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling	CELL DEATH & DISEASE			English	Article							MONOCARBOXYLATE TRANSPORTER 1; TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; CANCER-CELLS; EGFR; AZD9291; APOPTOSIS; TUMOR; MECHANISMS; PATHWAY	Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Development of novel chemotherapeutics is still required to enable successful treatment and improve survival for CRC patients. Here, we found that osimertinib (OSI) exhibits potent anti-CRC effects by inducing apoptosis, independent of its selective inhibitory activity targeting the EGFR T790M mutation. Intriguingly, OSI treatment triggers autophagic flux in CRC cells. Inhibition of autophagy markedly augments OSI-induced apoptosis and growth inhibition in CRC cells, suggesting a protective role of autophagy in response to OSI treatment. Mechanistically, OSI upregulates the expression of monocarboxylate transporter 1 (MCT1) and subsequently activates LKB1/AMPK signaling, leading to autophagy induction in CRC cells. Notably, OSI significantly exaggerates the sensitivity of CRC cells to the first-line drugs 5-fluorouracil or oxaliplatin. Taken together, our study unravels a novel mechanism of OSI-mediated protective autophagy involving MCT1/LKB1/AMPK signaling, and suggests the use of OSI as a potential agent for clinical CRC treatment.	[Jin, Ping; Jiang, Jingwen; Xie, Na; Zhou, Li; Huang, Zhao; Zhang, Lu; Qin, Siyuan; Fu, Shuyue; Peng, Liyuan; Gao, Wei; Li, Bowen] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Jin, Ping; Jiang, Jingwen; Xie, Na; Zhou, Li; Huang, Zhao; Zhang, Lu; Qin, Siyuan; Fu, Shuyue; Peng, Liyuan; Gao, Wei; Li, Bowen] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China; [Jin, Ping; Jiang, Jingwen; Xie, Na; Zhou, Li; Huang, Zhao; Zhang, Lu; Qin, Siyuan; Fu, Shuyue; Peng, Liyuan; Gao, Wei; Li, Bowen; Li, Changlong] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Sichuan, Peoples R China; [Jin, Ping; Jiang, Jingwen; Xie, Na; Zhou, Li; Huang, Zhao; Zhang, Lu; Qin, Siyuan; Fu, Shuyue; Peng, Liyuan; Gao, Wei; Li, Bowen] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Lei, Yunlong] Chongqing Med Univ, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [Nice, Edouard C.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia; [Shao, Jichun] China Natl Nucl Corp 416 Hosp, Chengdu Med Coll, Affiliated Hosp 2, Dept Urol, Chengdu, Sichuan, Peoples R China; [Xie, Ke] Univ Elect Sci & Technol China, Sichuan Acad Med Sci, Dept Oncol, Chengdu 610054, Sichuan, Peoples R China; [Xie, Ke] Univ Elect Sci & Technol China, Sch Med, Sichuan Prov Peoples Hosp, Chengdu 610054, Sichuan, Peoples R China		Shao, JC (corresponding author), China Natl Nucl Corp 416 Hosp, Chengdu Med Coll, Affiliated Hosp 2, Dept Urol, Chengdu, Sichuan, Peoples R China.; Xie, K (corresponding author), Univ Elect Sci & Technol China, Sichuan Acad Med Sci, Dept Oncol, Chengdu 610054, Sichuan, Peoples R China.; Xie, K (corresponding author), Univ Elect Sci & Technol China, Sch Med, Sichuan Prov Peoples Hosp, Chengdu 610054, Sichuan, Peoples R China.	shaoji93@163.com; xieke@med.uestc.edu.cn	Jiang, Jing wen/AAP-5996-2021	Lei, Yunlong/0000-0002-7918-0221; Li, Bowen/0000-0001-8475-4800; Huang, Zhao/0000-0001-9994-2070; Zhang, Lu/0000-0002-8325-2793	Chinese NSFCNational Natural Science Foundation of China (NSFC) [81672867, 81430071, 81790251]; Sichuan Provincial Health and Family Planning [18PJ199]; Cadre Health Research Project of Sichuan Province [2019-235]; Science & Technology Department of Sichuan Province Applied Basic Research Program [2018JYKJ0368]; National 973 Basic Research Program of ChinaNational Basic Research Program of China [2013CB911300]; Sichuan Science and Technology Program [2018RZ0133]	This work was supported by the Chinese NSFC (81672867, 81430071, 81790251), Project from Sichuan Provincial Health and Family Planning (18PJ199), Cadre Health Research Project of Sichuan Province (2019-235), Science & Technology Department of Sichuan Province Applied Basic Research Program (2018JYKJ0368), National 973 Basic Research Program of China (2013CB911300), and Sichuan Science and Technology Program (2018RZ0133).	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AUG 13	2019	10								615	10.1038/s41419-019-1844-2			15	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	IS2DD	WOS:000481962300001	31409796	gold, Green Published			2022-04-25	
J	Li, CH; Li, JW; Li, Y; Li, L; Luo, YL; Li, JJ; Zhang, YM; Wang, YR; Liu, XZ; Zhou, XT; Gong, HX; Jin, XJ; Liu, YQ				Li, Chenghao; Li, Jiawei; Li, Yan; Li, Ling; Luo, Yali; Li, Junjie; Zhang, Yiming; Wang, Yanru; Liu, Xiuzhu; Zhou, Xiaotian; Gong, Hongxia; Jin, Xiaojie; Liu, Yongqi			Isorhamnetin Promotes MKN-45 Gastric Cancer Cell Apoptosis by Inhibiting PI3K-Mediated Adaptive Autophagy in a Hypoxic Environment	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY			English	Article						isorhamnetin; apoptosis; autophagy; PI3K; gastric cancer	COLORECTAL-CANCER; TUMOR; WORTMANNIN	A tumor-related hypoxic microenvironment can promote the proliferation of gastric cancer cells, and hypoxic-induced autophagy is the main mechanism of protection against hypoxia in gastric cancer cells. Isorhamnetin (ISO) is a chemical substance derived from plants, mainly from the sea buckthorn. Previous studies have shown that ISO has antitumor effects, but the effects of ISO against gastric cancer in a hypoxic environment are still unknown. In this study, we investigated the effects of ISO against gastric cancer in a hypoxic environment and the mechanisms underlying ISO-induced gastric cancer cell death. The results show that ISO targeted PI3K and blocked the PI3K-AKT-mTOR signaling pathway, significantly inhibiting gastric cancer cell autophagy in a hypoxic environment, inhibiting cell proliferation, decreasing mitochondrial membrane potential, and promoting mitochondria-mediated apoptosis. ISO, a functional food component, is a promising candidate for the treatment of gastric cancer.	[Li, Chenghao; Li, Jiawei; Li, Yan; Li, Ling; Luo, Yali; Li, Junjie; Zhang, Yiming; Wang, Yanru; Liu, Xiuzhu; Zhou, Xiaotian; Gong, Hongxia; Jin, Xiaojie; Liu, Yongqi] Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent, Lanzhou 730000, Gansu, Peoples R China; [Liu, Yongqi] Minist Educ, Key Lab Dun Huang Med & Transformat, Lanzhou 730000, Gansu, Peoples R China; [Jin, Xiaojie] Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China		Jin, XJ; Liu, YQ (corresponding author), Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent, Lanzhou 730000, Gansu, Peoples R China.; Liu, YQ (corresponding author), Minist Educ, Key Lab Dun Huang Med & Transformat, Lanzhou 730000, Gansu, Peoples R China.; Jin, XJ (corresponding author), Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China.	jinlovedream@163.com; liuyongqi73@163.com		Li, Chenghao/0000-0002-8680-1655	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81960869]; Provincial University Industry Support Project in Gansu [2020C-15]; Provincial Key Talent Project [GZT2020-9-1]; Basic Research Innovation Group in Gansu [20JR10RA332]	This study was supported by the National Natural Science Foundation of China (No.81960869), Provincial University Industry Support Project in Gansu (2020C-15), and Provincial Key Talent Project (GZT2020-9-1). Basic Research Innovation Group in Gansu (20JR10RA332).	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Agric. Food Chem.	JUL 28	2021	69	29					8130	8143		10.1021/acs.jafc.1c02620		JUL 2021	14	Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Agriculture; Chemistry; Food Science & Technology	TS8TG	WOS:000679919400007	34269571				2022-04-25	
J	Tsai, CY; Lin, TA; Huang, SC; Hsu, JT; Yeh, CN; Chen, TC; Chiu, CT; Chen, JS; Yeh, TS				Tsai, Chun-Yi; Lin, Tien-An; Huang, Shih-Chiang; Hsu, Jun-Te; Yeh, Chun-Nan; Chen, Tse-Ching; Chiu, Cheng-Tang; Chen, Jen-Shi; Yeh, Ta-Sen			Is Adjuvant Chemotherapy Necessary for Patients with Deficient Mismatch Repair Gastric Cancer?-Autophagy Inhibition Matches the Mismatched	ONCOLOGIST			English	Article						Microsatellite instability; Mismatch repair; Gastric cancer; Autophagy	TUMOR-INFILTRATING LYMPHOCYTES; MICROSATELLITE-INSTABILITY; STAGE-II; PROGNOSTIC IMPLICATIONS; T-CELLS; SURVIVAL; 5-FLUOROURACIL; EFFICACY; DENSITY; BENEFIT	Purpose The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for fluorouracil-based adjuvant chemotherapy in colorectal cancer has been a paradigm shift. However, whether this applies to gastric cancer is questionable. Furthermore, we herein investigated whether and how autophagy plays a role in MSI-relevant chemoresistance. Materials and Methods A total of 929 patients with deficient MMR (dMMR) and proficient MMR (pMMR) gastric cancers who underwent curative-intent gastrectomy were enrolled. We compared clinicopathological variables and survival among dMMR and pMMR cohorts and tested the responses of MSI-high and microsatellite stable (MSS) gastric cancer cell lines to 5-fluorouracil (5-FU) with or without chloroquine, an autophagy inhibitor. Results We identified an 8.9% prevalence of dMMR cases (83 out of 929) in our cohort. This was associated with old age, tumor site at the distal stomach, an intestinal phenotype, fewer nodal metastasis, and early pathological stages. MMR was an independent prognostic factor after multivariate adjustment. Overall survival (OS) of dMMR patients was better than that of the pMMR patients but was only applicable to stage III patients. There was no difference in OS between dMMR patients treated with or without adjuvant chemotherapy, although the latter showed more medical morbidities. The MSI-high gastric cancer cell lines, versus the MSS counterparts, displayed increased resistance to 5-FU and increased autophagy. Interestingly, autophagy inhibition abrogated the chemoresistance. Conclusion Our data show that fluorouracil-based adjuvant chemotherapy does not work for dMMR cases, if not worse. Autophagy inhibition and/or immune checkpoint inhibition might be promising alternative strategies for gastric cancer treatment. Implications for Practice The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for adjuvant chemotherapy in colorectal cancer has caused a paradigm shift in cancer therapy, although its implications in gastric cancer are still questionable. The data obtained in the current study indicate that MSI-MMR is an independent prognostic factor for gastric cancer. Standard fluorouracil-based adjuvant chemotherapy did not work for deficient MMR cases, and was likely worse. Instead, strategies like autophagy inhibition and/or immune checkpoint inhibition should be taken into consideration in the future.	[Tsai, Chun-Yi; Lin, Tien-An; Hsu, Jun-Te; Yeh, Chun-Nan; Yeh, Ta-Sen] Chang Gung Univ, Chang Gung Mem Hosp Linkou, Coll Med, Dept Surg, Taoyuan, Taiwan; [Huang, Shih-Chiang; Chen, Tse-Ching] Chang Gung Univ, Chang Gung Mem Hosp Linkou, Coll Med, Dept Pathol, Taoyuan, Taiwan; [Chiu, Cheng-Tang] Chang Gung Univ, Chang Gung Mem Hosp Linkou, Coll Med, Dept Gastroenterol, Taoyuan, Taiwan; [Chen, Jen-Shi] Chang Gung Univ, Chang Gung Mem Hosp Linkou, Coll Med, Dept Med Oncol, Taoyuan, Taiwan		Yeh, TS (corresponding author), Chang Gung Mem Hosp, Dept Surg, 5 Fu Hsing St, Taoyuan, Taiwan.	tsy471027@adm.cgmh.org.tw			Chang Gung Medical Research Program, Taiwan [CMRPG3D1121-3, CMRPG3D1131-3]	This work was supported by the Chang Gung Medical Research Program, Taiwan (CMRPG3D1121-3 and CMRPG3D1131-3).	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J	Liu, WJ; Zhang, ZY; Zhang, YX; Chen, XJ; Guo, SK; Lei, Y; Xu, Y; Ji, C; Bi, ZG; Wang, KH				Liu, Weijun; Zhang, Zhenyong; Zhang, Yongxue; Chen, Xinju; Guo, Shikui; Lei, Yi; Xu, Yu; Ji, Chao; Bi, Zhigang; Wang, Kunhua			HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway	CANCER BIOLOGY & THERAPY			English	Article						apoptosis; autophagy; colorectal cancer; HMGB1; MEK; ERK pathway; oxaliplatin	RESISTANCE; APOPTOSIS; CHEMOTHERAPY; MECHANISMS; CETUXIMAB	In the present study, we examined the mechanisms of oxaliplatin-induced drug resistance in human colorectal cancer cell lines HT29 and HCT116. Our results demonstrate a significant autophagy expression in CRC cells after an oxaliplatin treatment. Administration of oxaliplatin to human CRC cells significantly enhanced the expression of HMGB1, which regulated the autophagy response and negatively regulate the cell apoptosis. Moreover, a decreased oxaliplatin -induced autophagy response and an increased apoptosis level were detected in stable CRC cells harboring HMGB1 shRNA. Then we noted that HMGB1 significantly induced extracellular signal-regulated kinase (ERK)/Extracellular signal-regulated kinase kinase (MEK) phosphorylation. Taken together, these data suggest that HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway.	[Liu, Weijun; Zhang, Zhenyong; Wang, Kunhua] Kunming Univ Sci & Technol, Kunhua Hosp, Dept Anorectal Surg, Peoples Hosp Yunnan Prov 1, Kunming, Yunnan, Peoples R China; [Zhang, Yongxue; Guo, Shikui; Lei, Yi; Xu, Yu] Kunming Univ Sci & Technol, Kunhua Hosp, Dept Gen Surg, Peoples Hosp Yunnan Prov 1, Kunming, Yunnan, Peoples R China; [Chen, Xinju] Kunming Univ Sci & Technol, Kunhua Hosp, Dept Operating Room, Peoples Hosp Yunnan Prov 1, Kunming, Yunnan, Peoples R China; [Ji, Chao] Fujian Med Univ, Affiliated Hosp 1, Dept Dermatol, Fuzhou, Fujian, Peoples R China; [Bi, Zhigang] Nanjing Med Univ, Dept Dermatol, BenQ Med Ctr, Nanjing, Jiangsu, Peoples R China; [Wang, Kunhua] Kunming Med Univ, Affiliated Hosp 1, Dept Gen Surg, Kunming, Yunnan, Peoples R China		Wang, KH (corresponding author), Kunming Univ Sci & Technol, Kunhua Hosp, Dept Anorectal Surg, Peoples Hosp Yunnan Prov 1, Kunming, Yunnan, Peoples R China.	weijunliu.33@gmail.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30860257, 81101188, 810701297]; Yunnan Provincial Department of Education [ZD2011007]	This research was supported by grants from the National Natural Science Foundation of China (30860257, 81101188 and 810701297), and Yunnan Provincial Department of Education (Number: ZD2011007).	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Ther.	APR	2015	16	4					511	517		10.1080/15384047.2015.1017691			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CH3QO	WOS:000353945600003	25778491	Green Published, Bronze			2022-04-25	
J	Ser, J; Lee, JY; Kim, YH; Cho, H				Ser, Jinhui; Lee, Ji Yeon; Kim, Yong Ho; Cho, Hoonsung			Enhanced Efficacy of Photodynamic Therapy by Coupling a Cell-Penetrating Peptide with Methylene Blue	INTERNATIONAL JOURNAL OF NANOMEDICINE			English	Article						methylene blue; protamine; CPP; photodynamic therapy; bioconjugation; anticancer; fluorescent	PHOTOCHEMICAL PROPERTIES; MECHANISMS; APOPTOSIS; PHOTOSENSITIZERS; CHOLESTEROL; LYSOSOMES; AUTOPHAGY; DEATH	Introduction: Photodynamic therapy (PDT), which induces tissue damage by exposing tissue to a specific wavelength of light in the presence of a photosensitizer and oxygen, is a promising alternative treatment that could be used as an adjunct to chemotherapy and surgery in oncology. Cell-penetrating peptides (CPPs) with high arginine content, such as protamine, have membrane translocation and lysosome localization activities. They have been used in an extensive range of drug delivery applications. Methods: We conjugated cell-penetrating peptides (CPPs) with methylene blue (MB) and then purification by FPLC. Synthesis structure was characterized by the absorbance spectrum, FPLC, Maldi-TOF, and then evaluated cell viability by cytotoxicity assay after photodynamic therapy (PDT) assay. An uptake imaging assay was used to determine the sites of MB and MB-Pro in subcellular compartments. Results: In vitro assays showed that MB-Pro has more efficient photodynamic activities than MB alone for the colon cancer cells, owing to lysosome rupture causing the rapid necrotic cell death. In this study, we coupled protamine with MB for high efficacy PDT. The conjugates localized in the lysosomes and enhanced the efficiency of PDT by inducing necrotic cell death, whereas PDT with non-coupled MB resulted in only apoptotic processes. Discussion: Our research aimed to enhance PDT by engineering the photosensitizers using CPPs coupled with methylene blue (MB). MB alone permeates through the cell membrane and distributes into the cytoplasm, whereas coupling of MB dye with CPPs localizes the MB through an endocytic mechanism to a specific organelle where the localized conjugates enhance the generation of reactive oxygen species (ROS) and induce cell damage.	[Ser, Jinhui; Cho, Hoonsung] Chonnam Natl Univ, Sch Mat Sci & Engn, Gwangju 61186, South Korea; [Lee, Ji Yeon] Gachon Univ, Gil Med Ctr, Dept Anesthesiol & Pain Med, Incheon 21565, South Korea; [Kim, Yong Ho] Gachon Univ, Gachon Pain Ctr, Coll Med, Incheon 21999, South Korea; [Kim, Yong Ho] Gachon Univ, Dept Physiol, Coll Med, Incheon 21999, South Korea		Cho, H (corresponding author), Chonnam Natl Univ, Sch Mat Sci & Engn, Gwangju 61186, South Korea.; Kim, YH (corresponding author), Gachon Univ, Gachon Pain Ctr, Coll Med, Incheon 21999, South Korea.; Kim, YH (corresponding author), Gachon Univ, Dept Physiol, Coll Med, Incheon 21999, South Korea.	euro16@gachon.ac.kr; cho.hoonsung@jnu.ac.kr		Cho, Hoonsung/0000-0003-0778-5640; Ser, Jinhui/0000-0002-8673-7374	Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2018R1D1A1B07049867, 2018R1D1A1B07049089]	This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B07049867 and 2018R1D1A1B07049089).	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J. Nanomed.		2020	15						5803	5811		10.2147/IJN.S254881			9	Nanoscience & Nanotechnology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics; Pharmacology & Pharmacy	NZ5CV	WOS:000577115600008	32821102	Green Published, gold			2022-04-25	
J	Hu, X; Li, YQ; Li, QG; Ma, YL; Peng, JJ; Cai, SJ				Hu, Xiang; Li, Ya-Qi; Li, Qing-Guo; Ma, Yan-Lei; Peng, Jun-Jie; Cai, San-Jun			Osteoglycin-induced VEGF Inhibition Enhances T Lymphocytes Infiltrating in Colorectal Cancer	EBIOMEDICINE			English	Article						Osteoglycin; Tumor-infiltrating lymphocytes; Colorectal cancer; Immune response; Survival	SHOCK-PROTEIN GP96; CROSS-PRESENTATION; IMMUNE CELLS; EXPRESSION; PROGNOSIS; MIMECAN; INFLAMMATION; ACTIVATION; AUTOPHAGY; INNATE	Background: OGN could modify tissue inflammation and immune response via local and circulating innate immune cells, which was suggestive of a reciprocal relationship between OGN and T cell infiltration in cancer. Hence, we aim to measure the OGN expression patterns and immune cells response in colorectal cancer (CRC). Methods: This study enrolled three independent sets of patients from TCGA and the Fudan University Shanghai Cancer Center(FUSCC). The effect of OGN on T cell infiltration and the mechanism were examined in vitro and in vivo. Findings: Tumor OGN expression levels were positively associated with CD3, CD8, and PTPRC expressions in the training and testing sets from TCGA, respectively. In validation set from FUSCC, OGN expression level also paralleled positively with CD8+ cell density in colorectal cancer tissue (p<.001). For a unit decrease in outcome quartile categories, multivariable OR in the lowest (vs highest) OGN expression was 0.17 (95% CI 0.08-0.33). Consistently, immunofluorescence validated that OGN was preferentially expressed with CD8+ cells in both normal epithelium and cancer tissue. Xenograft tumors arising from MC38 cells with OGN-over-expression displayed a significant increase in CD8+ cells recruitment. Hence, high expression of OGN was associated with a profound longer survival (P=.009). In mechanism, elevated OGN expression inhibited the activation of the transcriptional genes HIF-1 alpha in CRC cells, then significantly impeded the expression of VEGF. As a result of this, T cell tumor infiltration was reduced. Interpretation: OGN expression is positively associated with CD8+ cell density in colorectal cancer tissue, suggesting a possible influence of OGN expression on tumor reactive T cells in the tumor niche. Fund: No (c) 2018 The Authors. Published by Elsevier B.V.	[Cai, San-Jun] Fudan Univ, Dept Colorectal Surg, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 20032, Peoples R China; Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China		Cai, SJ (corresponding author), Fudan Univ, Dept Colorectal Surg, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 20032, Peoples R China.	caisanjun_sh@163.com			China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2018M632024]	This work was supported by China Postdoctoral Science Foundation (2018M632024).	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J	Zheng, QY; Zhang, QY; Yu, X; He, YT; Guo, WZ				Zheng, Qingyuan; Zhang, Qiyao; Yu, Xiao; He, Yuting; Guo, Wenzhi			FENDRR: A pivotal, cancer-related, long non-coding RNA	BIOMEDICINE & PHARMACOTHERAPY			English	Review						LncRNA; FENDRR; Biomarker; Cancer; Therapeutic target	PREDICTS POOR-PROGNOSIS; STEM-CELLS; LUNG-CANCER; GASTRIC-CANCER; HEPATOCELLULAR-CARCINOMA; REGULATES AUTOPHAGY; COLORECTAL-CANCER; TUMOR-GROWTH; PROLIFERATION; INVASION	Long non-coding RNAs (lncRNAs) have more than 200 nucleotides and do not encode proteins. Based on numerous studies, lncRNAs have emerged as new and crucial regulators of biological function and have been implicated in the pathogenesis of a variety of diseases, especially cancers. Specific lncRNAs have been identified as novel molecular biomarkers for cancer diagnosis, prognosis, and treatment efficacy. Fetal-lethal non-coding developmental regulatory RNA (FENDRR, also known as FOXF1-AS1) is a novel lncRNA that is located at chr3q13.31 and has four exons and 3099 nucleotides, and its genomic site is located at chr3q13.31. FENDRR is abnormally expressed in a variety of cancers and is significantly associated with different clinical characteristics. In addition, FENDRR has shown potential as a biomarker for cancer diagnosis, prognosis, and treatment. In this review, we summarize the current understanding of FENDRR and its mechanistic role in cancer progression. We also discuss recent insights into the clinical significance of FENDRR for cancer diagnosis, prognosis, and treatment.	[Zheng, Qingyuan; Zhang, Qiyao; Yu, Xiao; He, Yuting; Guo, Wenzhi] Zhengzhou Univ, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Zhengzhou 450052, Peoples R China; [Zheng, Qingyuan; Zhang, Qiyao; Yu, Xiao; He, Yuting; Guo, Wenzhi] Zhengzhou Univ, Affiliated Hosp 1, Key Lab Hepatobiliary & Pancreat Surg & Digest Or, Zhengzhou 450052, Peoples R China; [Zheng, Qingyuan; Zhang, Qiyao; Yu, Xiao; He, Yuting; Guo, Wenzhi] Henan Univ, Open & Key Lab Hepatobiliary & Pancreat Surg & Di, Zhengzhou 450052, Peoples R China; [Zheng, Qingyuan; Zhang, Qiyao; Yu, Xiao; He, Yuting; Guo, Wenzhi] Henan Key Lab Digest Organ Transplantat, Zhengzhou 450052, Peoples R China		He, YT; Guo, WZ (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Zhengzhou 450052, Peoples R China.	fccheyt1@zzu.edu.cn; fccguowz@zzu.edu.cn			Youth Talent Lifting Project of Henan Province [2021HYTP059]; Key Scientific Research Project of Henan Higher Education Institutions of China [21A320026]	This work was supported by the Youth Talent Lifting Project of Henan Province (2021HYTP059) , and Key Scientific Research Project of Henan Higher Education Institutions of China (21A320026) .	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Pharmacother.	MAY	2021	137								111390	10.1016/j.biopha.2021.111390		FEB 2021	8	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	RF3PI	WOS:000634753200005	33761608	gold			2022-04-25	
J	Montero-Melendez, T; Llor, X; Garcia-Planella, E; Perretti, M; Suarez, A				Montero-Melendez, Trinidad; Llor, Xavier; Garcia-Planella, Esther; Perretti, Mauro; Suarez, Antonio			Identification of Novel Predictor Classifiers for Inflammatory Bowel Disease by Gene Expression Profiling	PLOS ONE			English	Article							MICROARRAY DATA; CROHNS-DISEASE; SIGNATURE; CLASSIFICATION; MANAGEMENT; PROGNOSIS; SURVIVAL; CANCER	Background: Improvement of patient quality of life is the ultimate goal of biomedical research, particularly when dealing with complex, chronic and debilitating conditions such as inflammatory bowel disease (IBD). This is largely dependent on receiving an accurate and rapid diagnose, an effective treatment and in the prediction and prevention of side effects and complications. The low sensitivity and specificity of current markers burden their general use in the clinical practice. New biomarkers with accurate predictive ability are needed to achieve a personalized approach that take the inter-individual differences into consideration. Methods: We performed a high throughput approach using microarray gene expression profiling of colon pinch biopsies from IBD patients to identify predictive transcriptional signatures associated with intestinal inflammation, differential diagnosis (Crohn's disease or ulcerative colitis), response to glucocorticoids (resistance and dependence) or prognosis (need for surgery). Class prediction was performed with self-validating Prophet software package. Results: Transcriptional profiling divided patients in two subgroups that associated with degree of inflammation. Class predictors were identified with predictive accuracy ranging from 67 to 100%. The expression accuracy was confirmed by real time-PCR quantification. Functional analysis of the predictor genes showed that they play a role in immune responses to bacteria (PTN, OLFM4 and LILRA2), autophagy and endocytocis processes (ATG16L1, DNAJC6, VPS26B, RABGEF1, ITSN1 and TMEM127) and glucocorticoid receptor degradation (STS and MMD2). Conclusions: We conclude that using analytical algorithms for class prediction discovery can be useful to uncover gene expression profiles and identify classifier genes with potential stratification utility of IBD patients, a major step towards personalized therapy.	[Montero-Melendez, Trinidad; Perretti, Mauro] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England; [Llor, Xavier] Univ Illinois, Dept Med, Digest Dis & Nutr Sect, Chicago, IL USA; [Llor, Xavier] Univ Illinois, Ctr Canc, Chicago, IL USA; [Garcia-Planella, Esther] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain; [Suarez, Antonio] Univ Granada, Ctr Invest Biomed, Armilla, Spain		Suarez, A (corresponding author), Univ Granada, Ctr Invest Biomed, Armilla, Spain.	asuarez@ugr.es	SUAREZ, ANTONIO/L-9221-2014; Montero-Melendez, Trinidad/AAF-6345-2020	SUAREZ, ANTONIO/0000-0002-1006-7490; Montero-Melendez, Trinidad/0000-0002-3563-376X	Fundacio la Marato de TV3 [031531]; Spanish Health Ministry - Carlos III Institute [PI61550]	This study was funded by Fundacio la Marato de TV3 (031531) and Spanish Health Ministry - Carlos III Institute (PI61550). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Hartman, KG; Bortner, JD; Falk, GW; Ginsberg, GG; Jhala, N; Yu, J; Martin, MG; Rustgi, AK; Lynch, JP				Hartman, Kira G.; Bortner, James D., Jr.; Falk, Gary W.; Ginsberg, Gregory G.; Jhala, Nirag; Yu, Jian; Martin, Martin G.; Rustgi, Anil K.; Lynch, John P.			Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems	EXPERIMENTAL BIOLOGY AND MEDICINE			English	Review						Inflammation; oxidative stress; autophagy; gastrointestinal disease; gastroesophageal reflux disease; Barrett's esophagus; esophageal adenocarcinoma; graft versus host disease; inflammatory bowel disease; human 3D organotypic model systems	VERSUS-HOST-DISEASE; HUMAN ESOPHAGEAL KERATINOCYTES; IN-VITRO MODEL; BOWEL-DISEASE; HUMAN-COLON; BARRETTS-ESOPHAGUS; EPITHELIAL-CELLS; CROHNS-DISEASE; CDX2 EXPRESSION; GENE-EXPRESSION	Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible.	[Hartman, Kira G.; Bortner, James D., Jr.; Falk, Gary W.; Ginsberg, Gregory G.; Rustgi, Anil K.; Lynch, John P.] Univ Penn, Dept Med, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA; [Jhala, Nirag] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA; [Yu, Jian] Univ Pittsburgh, Sch Med, Inst Canc, Dept Pathol, Pittsburgh, PA 15213 USA; [Yu, Jian] Univ Pittsburgh, Sch Med, Inst Canc, Dept Radiat Oncol, Pittsburgh, PA 15213 USA; [Martin, Martin G.] Univ Calif Los Angeles, Mattel Childrens Hosp, Div Gastroenterol & Nutr, Dept Pediat, Los Angeles, CA 90095 USA; [Martin, Martin G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA		Lynch, JP (corresponding author), Univ Penn, Dept Med, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA.	lynchj@mail.med.upenn.edu		Falk, Gary/0000-0002-7143-1436	National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI); Integrated Microphysiological Systems program; Intestinal Stem Cell Consortium; NCI Program Project [PO1 CA098101]; Morphology, Cell Culture, and Molecular Biology Core Facilities of the Center for Molecular Studies in Digestive and Liver Disease at the University of Pennsylvania [PO1 CA098101, P30-DK050306];  [TR 000536];  [OD 012097];  [DK 085551];  [DK085570];  [MGM DK 085535]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P01CA098101, U54CA163004] Funding Source: NIH RePORTER; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [U18TR000536] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [U01DK085535, P30DK050306, U01DK085570, U01DK085551] Funding Source: NIH RePORTER; OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K26OD012097] Funding Source: NIH RePORTER	The authors would like to thank the University of Pennsylvania Morphology and Pathology Imaging Core facility for their technical expertise and assistance. Tissue samples were kindly provided by the Cooperative Human Tissue Network, which is funded by the National Cancer Institute. This work is supported as part of the Integrated Microphysiological Systems program and the Intestinal Stem Cell Consortium with funding to JPL (TR 000536, OD 012097 and DK 085551), JY (DK085570), and MGM (DK 085535). This work was also supported by an NCI Program Project PO1 CA098101 (AKR) and the Morphology, Cell Culture, and Molecular Biology Core Facilities of the Center for Molecular Studies in Digestive and Liver Disease at the University of Pennsylvania (P30-DK050306 and PO1 CA098101) (AKR).	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Biol. Med.	SEP	2014	239	9					1108	1123		10.1177/1535370214529388			16	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	AQ4MV	WOS:000342773100006	24781339	Green Accepted			2022-04-25	
J	Okada, Y; Kato, S; Sakamoto, Y; Oishi, T; Ishioka, C				Okada, Yoshinari; Kato, Shunsuke; Sakamoto, Yasuhiro; Oishi, Takayuki; Ishioka, Chikashi			Synthetic lethal interaction of CDK inhibition and autophagy inhibition in human solid cancer cell lines	ONCOLOGY REPORTS			English	Article						synthetic lethality; cell cycle arrest; CKI; autophagy; apoptosis	BREAST-CANCER; APOPTOSIS; THERAPY; MODULATION	Cell cycle control is a promising target in cancer treatments, and some small-molecule cyclin-dependent kinase (CDK) inhibitors have exhibited clinical effectiveness. However, no biomarkers predictive of efficacy have been developed. Recent studies have revealed that CDK inhibitor (CKI) proteins, such as p27 and p16, also induced cytoprotective autophagy in cancer cells. However, it is unclear whether small-molecule CKIs also induce autophagy in solid tumors, as induced autophagy promotes cancer cell survival. In this study, we revealed that a CDK4 inhibitor and a CKI with a broad range of targets (flavopiridol) induced autophagy in some, but not all, solid cancer cell lines. Autophagy induction by CDK4 inhibitor was observed in BT474, MDA-MB435S, SKBr3 (derived from breast cancer), A431 (derived from epidermoid cancer), and SW480 (derived from colorectal cancer) cell lines. No such autophagy was observed in MCF7, MDA-MB231 (derived from breast cancer), NCI-N87 (derived from gastric cancer), and KMST-6 (derived from a fibroblast). In the cell lines showing autophagy, which was induced by CDK4 inhibitor, the combination of CDK4 inhibitor and autophagy inhibition by either chloroquine (CQ) or knockdown of ATG5 or BECN1 induced apoptosis. However, it did not induce apoptosis in the cell lines in which autophagy was not induced by CDK4 inhibitor. These findings indicate that the autophagy induced by CDK4 inhibitor mimics stress-induced autophagy in some solid cancer cell lines. The combination of a small-molecule CKI involved in G(1)/S arrest and an autophagy inhibitor leads to a synthetic lethal interaction and could become a new antitumor strategy for solid tumors showing cytoprotective autophagy induced by small-molecule CKIs.	[Okada, Yoshinari; Kato, Shunsuke; Sakamoto, Yasuhiro; Oishi, Takayuki; Ishioka, Chikashi] Tohoku Univ, Dept Clin Oncol, IDAC, Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan		Ishioka, C (corresponding author), Tohoku Univ, Dept Clin Oncol, IDAC, Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan.	chikashi@tohoku.ac.jp			Taiho Pharmaceutical; Tokyo Clinical Oncology Group; Chugai Pharmaceutical; Ono Pharmaceutical; Daiichi Sankyo PharmaceuticalDaiichi Sankyo Company Limited; Takeda PharmaceuticalTakeda Pharmaceutical Company Ltd; Yakult Pharmaceutical	We would like to thank Eri Yokota, Satoko Aoki, and Hiromi Nakano for their technical assistance. We would also like to thank Enago for the English language review. C.I. received lecture fees from Taiho Pharmaceutical and Tokyo Clinical Oncology Group and research funding from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo Pharmaceutical, Takeda Pharmaceutical, and Yakult Pharmaceutical.	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Rep.	JUL	2017	38	1					31	42		10.3892/or.2017.5684			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EY6JR	WOS:000404089500003	28560460	Green Published, hybrid, Green Submitted			2022-04-25	
J	Zhang, HL; Lu, BJ				Zhang, Huilin; Lu, Bingjian			The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis	CANCERS			English	Review						autophagy; ceRNA; lncRNA; circRNAs; miRNA; chemoresistance; metastasis; pre-metastasis niche	LONG NONCODING RNA; EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL-CANCER; HEPATOCELLULAR-CARCINOMA; PROMOTES CHEMORESISTANCE; REGULATE AUTOPHAGY; PANCREATIC-CANCER; DRUG-RESISTANCE; CELL-SURVIVAL; STEM-CELLS	Simple Summary Chemoresistance and metastasis are the main causes of treatment failure in cancers. Autophagy contribute to the survival and metastasis of cancer cells. Competing endogenous RNA (ceRNA), particularly long non-coding RNAs and circular RNA (circRNA), can bridge the interplay between autophagy and chemoresistance or metastasis in cancers via sponging miRNAs. This review aims to discuss on the function of ceRNA-mediated autophagy in the process of metastasis and chemoresistance in cancers. ceRNA network can sequester the targeted miRNA expression to indirectly upregulate the expression of autophagy-related genes, and thereof participate in autophagy-mediated chemoresistance and metastasis. Our clarification of the mechanism of autophagy regulation in metastasis and chemoresistance may greatly improve the efficacy of chemotherapy and survival in cancer patients. The combination of the tissue-specific miRNA delivery and selective autophagy inhibitors, such as hydroxychloroquine, is attractive to treat cancer patients in the future. Chemoresistance and metastasis are the main causes of treatment failure and unfavorable outcome in cancers. There is a pressing need to reveal their mechanisms and to discover novel therapy targets. Autophagy is composed of a cascade of steps controlled by different autophagy-related genes (ATGs). Accumulating evidence suggests that dysregulated autophagy contributes to chemoresistance and metastasis via competing endogenous RNA (ceRNA) networks including lncRNAs and circRNAs. ceRNAs sequester the targeted miRNA expression to indirectly upregulate ATGs expression, and thereof participate in autophagy-mediated chemoresistance and metastasis. Here, we attempt to summarize the roles of ceRNAs in cancer chemoresistance and metastasis through autophagy regulation.	[Zhang, Huilin; Lu, Bingjian] Zhejiang Univ, Sch Med, Womens Hosp, Dept Surg Pathol, Hangzhou 310002, Zhejiang, Peoples R China; [Lu, Bingjian] Zhejiang Univ, Sch Med, Womens Hosp, Ctr Uterine Canc Diag & Therapy Res Zhejiang Prov, Hangzhou 310002, Zhejiang, Peoples R China		Lu, BJ (corresponding author), Zhejiang Univ, Sch Med, Womens Hosp, Dept Surg Pathol, Hangzhou 310002, Zhejiang, Peoples R China.; Lu, BJ (corresponding author), Zhejiang Univ, Sch Med, Womens Hosp, Ctr Uterine Canc Diag & Therapy Res Zhejiang Prov, Hangzhou 310002, Zhejiang, Peoples R China.	huilinzhang@zju.edu.cn; lbj@zju.edu.cn			Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872112]; National Key Research and Development Program of China [2016YFC1302900]	This study is supported by grants from the Natural Science Foundation of China (no. 81872112) and National Key Research and Development Program of China (2016YFC1302900).	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J	Cui, Y; Bai, YB; Yang, JN; Yao, YF; Zhang, CH; Liu, C; Shi, JQ; Li, QW; Zhang, JC; Lu, XL; Zhang, YQ				Cui, Ying; Bai, Yibing; Yang, Jiani; Yao, Yuanfei; Zhang, Chunhui; Liu, Chao; Shi, Jiaqi; Li, QingWei; Zhang, Jingchun; Lu, Xiaolin; Zhang, Yanqiao			SIRT4 is the molecular switch mediating cellular proliferation in colorectal cancer through GLS mediated activation of AKT/GSK3 beta/CyclinD1 pathway	CARCINOGENESIS			English	Article							TUMOR-SUPPRESSIVE ACTIVITY; DNA-DAMAGE; GLUTAMINOLYSIS; AUTOPHAGY; NETWORK; CHINA; CELLS	Mitochondria-localized sirtuin 4 (SIRT4) is associated with malignant phenotypes in colorectal cancer (CRC). However, the molecular mechanisms that drive SIRT4-mediated carcinogenesis are unclear. Initially, we confirmed expression of SIRT4 in CRC through public database and in CRC patient tissues using quantitative real-time reverse transcription PCR. We established HCT116 colorectal cells that overexpressed SIRT4 and HT29 cells were transfected with plasmids bearing a small interfering RNA construct to silence SIRT4. Assays to determine the malignant phenotypes (proliferation, invasion and migration) were performed. Xenograft in vivo models were also constructed. A protein interactome network was built using differentially expressed proteins identified using the liquid chromatography/tandem mass spectrophotometry, the findings of which were confirmed using co-immunoprecipitation, western blotting and phenotype rescue experiments. Decreased SIRT4 expression was associated with malignant phenotypes in vitro and in vivo. The ribosomal biogenesis pathway was enriched in the interactome network. SIRT4 suppression activated glutaminase, thereby initiating AKT activation. Our research provided novel insights into the molecular mechanisms underlying CRC, and identified that SIRT4 exerts its antitumor activity in CRC possibly dependent on glutaminase to inhibit proliferation, migration and invasion via the AKT/GSK3 beta/CyclinD1 pathway.	[Cui, Ying] Harbin Med Univ, Dept Radiat Oncol, Canc Hosp, Harbin, Heilongjiang, Peoples R China; [Bai, Yibing; Yang, Jiani; Yao, Yuanfei; Zhang, Chunhui; Liu, Chao; Shi, Jiaqi; Li, QingWei; Zhang, Jingchun; Zhang, Yanqiao] Harbin Med Univ, Dept Gastrointestinal Med Oncol, Canc Hosp, Harbin 150001, Heilongjiang, Peoples R China; [Lu, Xiaolin] Harbin Med Univ, Dept Orthoped, Canc Hosp, Harbin 150001, Heilongjiang, Peoples R China; [Cui, Ying; Bai, Yibing; Yang, Jiani; Yao, Yuanfei; Zhang, Chunhui; Liu, Chao; Shi, Jiaqi; Li, QingWei; Zhang, Jingchun; Lu, Xiaolin; Zhang, Yanqiao] Heilongjiang Acad Med Sci, Translat Med Res & Cooperat Ctr Northern China, Harbin 150081, Heilongjiang, Peoples R China		Zhang, YQ (corresponding author), Harbin Med Univ, Dept Gastrointestinal Med Oncol, Canc Hosp, Harbin 150001, Heilongjiang, Peoples R China.; Zhang, YQ (corresponding author), Heilongjiang Acad Med Sci, Translat Med Res & Cooperat Ctr Northern China, Harbin 150081, Heilongjiang, Peoples R China.	yanqiaozhang@ems.hrbmu.edu.cn			National Natural and Science Foundation of China (NSFC) [81672428, 81872427, 81703000]; Applied Technology Research and Development Program of Heilongjiang Province [GA19C002]; Nn10 Excellent Discipline Construction Program (Hepatobiliary and Pancreatic Tumor 2017); Fundamental Research Funds for the Provincial Universities of Heilongjiang Province	This work was supported by the National Natural and Science Foundation of China (NSFC) (Grant No. 81672428, 81872427, 81703000); Applied Technology Research and Development Program of Heilongjiang Province (No. GA19C002); Nn10 Excellent Discipline Construction Program (No. Hepatobiliary and Pancreatic Tumor 2017) and Fundamental Research Funds for the Provincial Universities of Heilongjiang Province.	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J	Wang, CX; Peng, R; Zeng, M; Zhang, ZH; Liu, SP; Jiang, D; Lu, YY; Zou, FD				Wang, Caixia; Peng, Rui; Zeng, Min; Zhang, Zhenhua; Liu, Shengpeng; Jiang, Dan; Lu, Yuanyuan; Zou, Fangdong			An autoregulatory feedback loop of miR-21/VMP1 is responsible for the abnormal expression of miR-21 in colorectal cancer cells	CELL DEATH & DISEASE			English	Article							TUMOR-SUPPRESSOR GENE; MICRORNA-21 TARGETS; AUTOPHAGY; 5-FLUOROURACIL; METASTASIS; INVASION; PTEN; ACTIVATION; MECHANISMS; RESISTANCE	MircoRNA-21 (miR-21) was found to be highly expressed in various solid tumors, and its oncogenic properties have been extensively studied in recent years. However, the reason why miR-21 is highly expressed in various tumors remains elusive. Here, we found that the expression of miR-21 was negatively correlated with the expression of vacuole membrane protein-1 (VMP1) in colorectal cancer. Transcription of VMP1 activated either by small activating RNA (saRNA) or transcriptional activator GLI3 inhibited miR-21 expression through reducing its transcripts of VMP1-miR-21 and pri-miR-21, while no significant change in miR-21 expression after exogenous overexpression VMP1 in colorectal cancer cell HCT116. Considering the overlapping location of VMP1 and miR-21 gene in genome, the result suggested that the transcription of miR-21 was inhibited by the endogenous transcriptional activation of VMP1. Furthermore, we identified that miR-21 inhibited the activation and nuclear translocation of transcription factor EB (TFEB) through reducing the inhibitory of PTEN on AKT phosphorylation, which can directly activate the transcription of VMP1. Loss of miR-21 significantly increased VMP1 expression, which could be blocked by PTEN inhibitor (VO-Ohpic) or TFEB siRNA. These results showed that miR-21 negatively regulated VMP1 transcription through the PTEN/AKT/TFEB pathway, and TFEB-induced transcriptional activation of VMP1 could inhibit miR-21 expression, thus forming a feedback regulatory loop of miR-21/VMP1. We further found that disrupting the miR-21/VMP1 feedback loop will decrease the expression of miR-21, reduce the malignancy, and increase their sensitivity to 5-fluorouracil in colorectal cancer cells. Taken together, our results revealed a novel regulatory mechanism of miR-21 expression, and targeting the miR-21/VMP1 feedback loop may provide a new approach to inhibit miR-21 expression in colorectal cancer cells.	[Wang, Caixia; Peng, Rui; Zeng, Min; Zhang, Zhenhua; Liu, Shengpeng; Zou, Fangdong] Sichuan Univ, Coll Life Sci, Chengdu, Sichuan, Peoples R China; [Jiang, Dan] Sichuan Univ, West China Hosp Pathol, Chengdu, Sichuan, Peoples R China; [Lu, Yuanyuan] Fourth Mil Med Univ, Xijing Hosp Digest Dis, Xian, Shanxi, Peoples R China		Zou, FD (corresponding author), Sichuan Univ, Coll Life Sci, Chengdu, Sichuan, Peoples R China.	fundzou@scu.edu.cn	Zhang, Yonghui/AGY-9072-2022	Zou, Fangdong/0000-0002-2133-4320; Zou, Fangdong/0000-0003-4011-0856	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672942]	This work was supported by the National Natural Science Foundation of China (81672942), and we would like to thank Prof. Lin Zhang at University of Pittsburgh for the gift of RKO-miR-21-KO cell.	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J	Yang, YF; Yan, XB; Li, XX; Ma, YL; Goel, A				Yang, Yufei; Yan, Xuebing; Li, Xinxiang; Ma, Yanlei; Goel, Ajay			Long non-coding RNAs in colorectal cancer: Novel oncogenic mechanisms and promising clinical applications	CANCER LETTERS			English	Article						Colorectal cancer; Long non-coding RNAs; Signaling pathways; Biomarkers		Colorectal cancer (CRC) is the third most common malignancy and ranks as the second leading cause of cancer-related deaths worldwide. Despite the improvements in CRC diagnosis and treatment approaches, a considerable proportion of CRC patients still suffers from poor prognosis due to late disease detections and lack of personalized disease managements. Recent evidences have not only provided important molecular insights into their mechanistic behaviors but also indicated that identification of cancer-specific long non-coding RNAs (LncRNAs) could benefit earlier disease detections and improve treatment outcomes in patients suffering from CRC. LncRNAs have raised extensive attentions as they participate in various hallmarks of CRC. The mechanistic evidence gleaned in the recent decade clearly reveals that lncRNAs exert their oncogenic roles by regulating autophagy, epigenetic modifications, enhancing stem phenotype and modifying tumor microenvironment. In view of their pleiotropic functional roles in malignant progression, and their frequently dysregulated expression in CRC patients, they have great potential to be reliable diagnostic and prognostic biomarkers, as well as therapeutic targets for CRC. In the present review, we will focus on the oncogenic roles of lncRNAs and related mechanisms in CRC as well as discuss their clinical potential in the early diagnosis, prognostic prediction and therapeutic translation in patients with this malignancy.	[Yang, Yufei; Li, Xinxiang; Ma, Yanlei] Fudan Univ, Dept Colorectal Surg, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 200032, Peoples R China; [Yang, Yufei; Li, Xinxiang; Ma, Yanlei] Fudan Univ, Shanghai Med Coll, Dept Oncol, 270 Dongan Rd, Shanghai 200032, Peoples R China; [Yan, Xuebing] Yangzhou Univ, Dept Oncol, Affiliated Hosp, Yangzhou, Jiangsu, Peoples R China; [Goel, Ajay] City Hope Comprehens Canc Ctr, Beckman Res Inst, Dept Mol Diagnost & Expt Therapeut, Duarte, CA 91010 USA		Li, XX; Ma, YL (corresponding author), Fudan Univ, Dept Colorectal Surg, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 200032, Peoples R China.; Ma, YL (corresponding author), Fudan Univ, Shanghai Med Coll, Dept Oncol, 270 Dongan Rd, Shanghai 200032, Peoples R China.; Goel, A (corresponding author), City Hope Comprehens Canc Ctr, Beckman Res Inst, Dept Mol Diagnost & Expt Therapeut, Duarte, CA 91010 USA.	li_xinxiang@hotmail.com; yanleima@fadan.edu.cn; ajgoel@coh.org		Goel, Ajay/0000-0003-1396-6341	National Institute of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA72851, CA181572, CA184792, CA187956, CA202797]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81920108026, 81871964, 81902422]; National Ten Thousand Plan Young Top Talents; Shanghai Young Top Talents [QNBJ1701]; Shanghai Science and Technology Development Fund [19410713300, 20XD1421200]; CSCO-Roche Tumor Research Fund [Y-2019 Roche-079]; Fudan University Excellence 2025 Talent Cultivation Plan; Program of Jiangsu Commission of Health [M2020024]; Social Development Program of Yangzhou Science and Technology Bureau [YZ2020078]	The present work was supported by the grants CA72851, CA181572, CA184792, CA187956 and CA202797 from the National Institute of Health (NIH) to AG. This work was also supported by grants from the National Natural Science Foundation of China (Nos. 81920108026, 81871964), the National Ten Thousand Plan Young Top Talents (for Dr. Yanlei Ma), the Shanghai Young Top Talents (for Dr. Yanlei Ma. No. QNBJ1701), the Shanghai Science and Technology Development Fund (No.19410713300, No. 20XD1421200), the CSCO-Roche Tumor Research Fund (No. Y-2019 Roche-079), Fudan University Excellence 2025 Talent Cultivation Plan (for Dr. Yanlei Ma), the National Natural Science Foundation of China (for Xuebing Yan, No.81902422), Program of Jiangsu Commission of Health (for Xuebing Yan, No. M2020024); Social Development Program of Yangzhou Science and Technology Bureau (for Xuebing Yan, No. YZ2020078).	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APR 28	2021	504						67	80		10.1016/j.canlet.2021.01.009		FEB 2021	14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	QR7DW	WOS:000625376500007	33577977				2022-04-25	
J	Won, SJ; Yen, CH; Hsieh, HW; Chang, SW; Lin, CN; Huang, CYF; Su, CL				Won, Shen-Jeu; Yen, Cheng-Hsin; Hsieh, Hao-Wen; Chang, Shao-Wei; Lin, Chun-Nan; Huang, Chi-Ying F.; Su, Chun-Li			Using connectivity map to identify natural lignan justicidin A as a NF-kappa B suppressor	JOURNAL OF FUNCTIONAL FOODS			English	Article						Justicidin A; NF-kappa B; Caspase-independent apoptosis; L1000 gene expression profiling; Connectivity map; Human colorectal cancer	COLORECTAL-CANCER CELLS; CYTOTOXIC LIGNANS; LUNG-CANCER; APOPTOSIS; AUTOPHAGY; INFLAMMATION; PROCUMBENS; DRUG; DEGRADATION; RESISTANCE	Justicidin A (JA), a natural lignan, was isolated from the whole plant of Justicia procumbens, one of the most popular traditional Chinese medicines in China and Taiwan. Gene expression signatures of JA from human colorectal cancer HT-29 and hepatocellular carcinoma Hep 3B cells were used to query connectivity map. A NF-kappa B suppressor (15-delta prostaglandin J2) was predicted to display similar molecular action of JA. In JA-treated HT-29 cells, suppression of nuclear NF-kappa B expression and decrease of NF-kappa B DNA-binding activity were indeed observed. The classical pathway was involved in JA-induced inhibition of NF-kappa B, characterized by decreases in phosphorylation of ART, I kappa B kinase (IKK)-beta/IKK-alpha, and I kappa B-alpha. Furthermore, JA caused significant translocation of apoptosis-inducing factor and endonuclease G, caspase-independent apoptotic signaling molecules, from the mitochondrial to the nuclei. Our data suggest anti-inflammatory and cytotoxic mechanisms of JA, and using gene expression signatures to identify novel molecular actions of phytochemicals is an effective approach. (C) 2017 Elsevier Ltd. All rights reserved.	[Won, Shen-Jeu] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Coll Med, Tainan 701, Taiwan; [Yen, Cheng-Hsin; Su, Chun-Li] Natl Taiwan Normal Univ, Dept Human Dev & Family Studies, Taipei 106, Taiwan; [Hsieh, Hao-Wen; Huang, Chi-Ying F.] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan; [Chang, Shao-Wei; Huang, Chi-Ying F.] Natl Yang Ming Univ, Inst Biopharmaceut Sci, Taipei 112, Taiwan; [Lin, Chun-Nan] Kaohsiung Med Univ, Sch Pharm, Kaohsiung 807, Taiwan; [Huang, Chi-Ying F.] Kaohsiung Med Univ, Dept Biochem, Coll Med, Kaohsiung 807, Taiwan		Su, CL (corresponding author), Natl Taiwan Normal Univ, Dept Human Dev & Family Studies, Taipei 106, Taiwan.; Huang, CYF (corresponding author), Natl Yang Ming Univ, Inst Biopharmaceut Sci, Taipei 112, Taiwan.	cyhuang5@ym.edu.tw; chunlisu@ntnu.edu.tw	Huang, Chi-Ying/AAG-7672-2022; Huang, Chi-Ying/AFL-7729-2022	Huang, Chi-Ying/0000-0003-4898-4937; Huang, Chi-Ying/0000-0003-4898-4937	National Science Council, TaiwanMinistry of Science and Technology, Taiwan [NSC 98-2313-B-003-002-MY3, NSC 101-2313-B-003-002-MY3]; Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [MOST 105-3011-B010-001, MOST 104-2320-B-003-007]	This work was supported by grants from the National Science Council, Taiwan (NSC 98-2313-B-003-002-MY3 and NSC 101-2313-B-003-002-MY3) and the Ministry of Science and Technology, Taiwan (MOST 105-3011-B010-001 and MOST 104-2320-B-003-007).	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Funct. Food.	JUL	2017	34						68	76		10.1016/j.jff.2017.04.017			9	Food Science & Technology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Food Science & Technology; Nutrition & Dietetics	EX6WW	WOS:000403383800008					2022-04-25	
J	Ghafouri-Fard, S; Hussen, BM; Gharebaghi, A; Eghtedarian, R; Taheri, M				Ghafouri-Fard, Soudeh; Hussen, Bashdar Mahmud; Gharebaghi, Alireza; Eghtedarian, Reyhane; Taheri, Mohammad			LncRNA signature in colorectal cancer	PATHOLOGY RESEARCH AND PRACTICE			English	Review						lncRNA; Colorectal cancer; Biomarker	EPITHELIAL-MESENCHYMAL TRANSITION; ENDOPLASMIC-RETICULUM STRESS; PROMOTES CELL-PROLIFERATION; POOR-PROGNOSIS; SIGNALING PATHWAY; NONCODING RNAS; SNHG6 PROMOTES; UP-REGULATION; INVASION; MIGRATION	Colorectal cancer (CRC) is among the most frequent cancers and is associated with high mortality particularly when being diagnosed in advanced stages. Although several environmental and intrinsic risk factors have been identified, the underlying cause of CRC is not clear in the majority of cases. Several studies especially in the recent decade have pointed to the role of epigenetic factors in this kind of cancer. Long non-coding RNAs (lncRNAs) as important contributors in the epigenetic mechanisms are involved in the initiation, progression and metastasis of CRC. Tens of oncogenic lncRNAs and a lower number of tumor suppressor lncRNAs have been recently identified to be dysregulated in CRC cells and tissues. Notably, expressions of a number of these transcripts have been dysregulated in serum samples of CRC patients, providing a non-invasive route for detection of this kind of cancer. The involvement of lncRNAs in the regulation of autophagy has provided them the ability to modulate response of CRC cells to chemotherapeutic modalities. In the current manuscript, we review the studies which evaluated the role of lncRNAs in the pathogenesis and progression of CRC to appraise their application as diagnostic/ prognostic markers.	[Ghafouri-Fard, Soudeh; Eghtedarian, Reyhane] Shahid Beheshti Univ Med Sci, Dept Med Genet, Tehran, Iran; [Hussen, Bashdar Mahmud] Hawler Med Univ, Coll Pharm, Dept Pharmacognosy, Erbil, Iraq; [Gharebaghi, Alireza] Hamadan Univ Med Sci, Neurophysiol Res Ctr, Hamadan, Hamadan, Iran; [Taheri, Mohammad] Shahid Beheshti Univ Med Sci, Urol & Nephrol Res Ctr, Tehran, Iran		Taheri, M (corresponding author), Shahid Beheshti Univ Med Sci, Urol & Nephrol Res Ctr, Tehran, Iran.	mohammad_823@yahoo.com	Gharebaghi, Alireza/AAW-2565-2021	Eghtedarian, Reyhane/0000-0002-7603-0009; Hussen, Bashdar/0000-0003-1060-6527	Shahid Beheshti University of Medical Sciences	This study was financially supported by Shahid Beheshti University of Medical Sciences.	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Res. Pract.	JUN	2021	222								153432	10.1016/j.prp.2021.153432		APR 2021	11	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	SK5KB	WOS:000656253000002	33857856				2022-04-25	
J	Liu, LX; Pan, YJ; Ren, XL; Zeng, ZC; Sun, JB; Zhou, K; Liang, YS; Wang, FF; Yan, YR; Liao, WT; Ding, YQ; Liu, XL; Liang, L				Liu, Lixin; Pan, Yangjian; Ren, Xiaoli; Zeng, Zhicheng; Sun, Jingbo; Zhou, Kun; Liang, Yunshi; Wang, Feifei; Yan, Yongrong; Liao, Wenting; Ding, Yanqing; Liu, Xiaolong; Liang, Li			GFPT2 promotes metastasis and forms a positive feedback loop with p65 in colorectal cancer	AMERICAN JOURNAL OF CANCER RESEARCH			English	Article						GFPT2; NF-kappa B pathway; p-65 glycosylation; metastasis; colorectal cancer	HEXOSAMINE BIOSYNTHESIS; TRANSGENIC MICE; O-GLCNACYLATION; UP-REGULATION; GLUCOSE; TRANSFERASE; METABOLISM; AUTOPHAGY; GLUTAMINE; PATHWAY	As a rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which is responsible for glycosylation, Glutamine fructose-6-phosphate amidotransferase 2 (GFPT2) is involved in human breast and lung tumorigenesis. However, whether GFTP2 is associated with tumor metastasis remains unclear. Here, we found that GFPT2 promoted the proliferation, migration, invasion and metastasis of colorectal cancer (CRC) cells. Mechanically, p65 acted as an upstream transcription factor of GFPT2 and regulated its expression and function. In turn, GFPT2 enhanced the glycosylation of p65, which led to the nuclear translocation of p65 and then activated NF-kappa B pathway. Thus, GFTP2 and p65 formed a positive feedback loop to promote the progression of CRC. In addition, GFPT2 was up-regulated in CRC tissues and closely related with liver metastasis (P<0.0001) and tumor stage (P=0.0184). High expression of GFPT2 predicted poor prognosis for CRC patients. Moreover, GFTP2 expression was positively linked with O-linked N-acetylglucosamine transferase in CRC tissues. Our study reveals a new mechanism of GFPT2 in CRC metastasis and provides a new target therapeutic target to deter metastasis.	[Liu, Lixin; Pan, Yangjian; Sun, Jingbo; Zhou, Kun; Liu, Xiaolong] Southern Med Univ, Dept Gen Surg, Affiliated Hosp 3, Guangzhou 510515, Guangdong, Peoples R China; [Ren, Xiaoli; Zeng, Zhicheng; Liang, Yunshi; Wang, Feifei; Yan, Yongrong; Liao, Wenting; Ding, Yanqing; Liang, Li] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China; [Ren, Xiaoli; Zeng, Zhicheng; Liang, Yunshi; Wang, Feifei; Yan, Yongrong; Liao, Wenting; Ding, Yanqing; Liang, Li] Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou 510515, Guangdong, Peoples R China; [Ren, Xiaoli; Zeng, Zhicheng; Liang, Yunshi; Wang, Feifei; Yan, Yongrong; Liao, Wenting; Ding, Yanqing; Liang, Li] Southern Med Univ, Basic Med Coll, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China		Liu, XL (corresponding author), Southern Med Univ, Dept Gen Surg, Affiliated Hosp 3, 183 West Zhongshan Ave, Guangzhou 510630, Guangdong, Peoples R China.; Liang, L (corresponding author), Southern Med Univ, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China.	lxl1979@i.smu.edu.cn; lli@fimmu.com			National key R&D program of China [2017YFC1309002]; National Basic Research Program of China (973 Program)National Basic Research Program of China [2015CB554002]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672821, 81773101, 81802306]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2018M633081, 2018M633079]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2018A030310457]	This work was supported by the National key R&D program of China (2017YFC1309002), National Basic Research Program of China (973 Program, 2015CB554002), National Natural Science Foundation of China (81672821, 81773101, 81802306), Project funded by China Postdoctoral Science Foundation (2018M633081, 2018M633079), Natural Science Foundation of Guangdong Province (2018A030310457).	Ali A, 2017, MOL CELLS, V40, P476, DOI 10.14348/molcells.2017.2309; Alisson-Silva F, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0060471; Allison DF, 2012, P NATL ACAD SCI USA, V109, P16888, DOI 10.1073/pnas.1208468109; Apweiler R, 1999, BBA-GEN SUBJECTS, V1473, P4, DOI 10.1016/S0304-4165(99)00165-8; Baldwin AS, 2012, IMMUNOL REV, V246, P327, DOI 10.1111/j.1600-065X.2012.01095.x; Basak S, 2012, IMMUNOL REV, V246, P221, DOI 10.1111/j.1600-065X.2011.01092.x; Dennis JW, 2009, CELL, V139, P1229, DOI 10.1016/j.cell.2009.12.008; Fardini Y, 2013, FRONT ENDOCRINOL, V4, DOI 10.3389/fendo.2013.00099; Gao J, 2018, CARCINOGENESIS, V39, P1222, DOI 10.1093/carcin/bgy097; Gu MJ, 2018, BMC CANCER, V18, DOI 10.1186/s12885-017-3968-z; Guan F, 2009, P NATL ACAD SCI USA, V106, P7461, DOI 10.1073/pnas.0902368106; Hauselmann I, 2014, FRONT ONCOL, V4, DOI 10.3389/fonc.2014.00028; Itkonen HM, 2013, CANCER RES, V73, P5277, DOI 10.1158/0008-5472.CAN-13-0549; Lai JL, 2017, INFLAMMATION, V40, P1, DOI 10.1007/s10753-016-0447-7; Lynch TP, 2012, J BIOL CHEM, V287, P11070, DOI 10.1074/jbc.M111.302547; Ma ZY, 2013, J BIOL CHEM, V288, P15121, DOI 10.1074/jbc.M113.470047; MARSHALL S, 1991, J BIOL CHEM, V266, P4706; Mi WY, 2011, BBA-MOL BASIS DIS, V1812, P514, DOI 10.1016/j.bbadis.2011.01.009; Ramakrishnan P, 2013, SCI SIGNAL, V6, DOI 10.1126/scisignal.2004097; Ruan HB, 2013, TRENDS ENDOCRIN MET, V24, P301, DOI 10.1016/j.tem.2013.02.002; Rumberger JM, 2003, J BIOL CHEM, V278, P28547, DOI 10.1074/jbc.M302793200; Siegel RL, 2016, CA-CANCER J CLIN, V66, P7, DOI 10.3322/caac.21332; Simpson NE, 2012, BREAST CANCER RES TR, V133, P959, DOI 10.1007/s10549-011-1871-x; Slawson C, 2011, NAT REV CANCER, V11, P678, DOI 10.1038/nrc3114; Sun SC, 2017, NAT REV IMMUNOL, V17, P545, DOI 10.1038/nri.2017.52; Tang JP, 2000, DIABETES, V49, P1492, DOI 10.2337/diabetes.49.9.1492; Veerababu G, 2000, DIABETES, V49, P2070, DOI 10.2337/diabetes.49.12.2070; Wang LS, 2018, BMC CANCER, V18, DOI 10.1186/s12885-018-5033-y; Wise DR, 2010, TRENDS BIOCHEM SCI, V35, P427, DOI 10.1016/j.tibs.2010.05.003; Xing DQ, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0024021; Yde P, 2011, BMC SYST BIOL, V5, DOI 10.1186/1752-0509-5-115; YkiJarvinen H, 1996, DIABETES, V45, P302, DOI 10.2337/diabetes.45.3.302; Zhang HL, 2004, J CLIN ENDOCR METAB, V89, P748, DOI 10.1210/jc.2003-031286; Zhang WR, 2018, CANCER RES, V78, P3445, DOI 10.1158/0008-5472.CAN-17-2928; Zhou FX, 2018, THERANOSTICS, V8, P5200, DOI 10.7150/thno.27806	35	4	4	4	6	E-CENTURY PUBLISHING CORP	MADISON	40 WHITE OAKS LN, MADISON, WI 53711 USA	2156-6976			AM J CANCER RES	Am. J. Cancer Res.		2020	10	8					2510	+					15	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	OC8CX	WOS:000579385400020	32905539				2022-04-25	
J	Shi, Y; Tang, B; Yu, PW; Tang, B; Hao, YX; Lei, X; Luo, HX; Zeng, DZ				Shi, Yan; Tang, Bin; Yu, Pei-Wu; Tang, Bo; Hao, Ying-Xue; Lei, Xiao; Luo, Hua-Xing; Zeng, Dong-Zhu			Autophagy Protects against Oxaliplatin-Induced Cell Death via ER Stress and ROS in Caco-2 Cells	PLOS ONE			English	Article							COLORECTAL-CANCER; GENERATION; RESISTANCE; MECHANISMS; SURVIVAL; PATHWAYS; THERAPY	Oxaliplatin is included in a number of effective combination regimens used as first and subsequent lines of therapy for metastatic colorectal cancer. Accumulating evidence indicates that autophagy plays a significant role in response to cancer therapy. However, the role of autophagy in oxaliplatin-induced cell death remains to be clarified. In this study, we showed that oxaliplatin induced cell death and autophagy in Caco-2 colorectal cancer cells. The suppression of autophagy using either pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (ATG5 or Beclin1) enhanced the cell death and reactive oxygen species (ROS) production induced by oxaliplatin in Caco-2 cells. Blocking oxaliplatin-induced ROS production by using ROS scavengers (NAC or Tiron) decreased autophagy. Furthermore, numerous dilated endoplasmic reticula (ER) were present in oxaliplatin-treated Caco-2 cells, and blocking ER stress by RNA interference against candidate of metastasis-1 (P8) and C/EBP-homologous protein (CHOP) decreased autophagy and ROS production. Taken together, these data indicate that oxaliplatin activates autophagy as a cytoprotective response via ER stress and ROS in human colorectal cancer cells.	[Shi, Yan; Yu, Pei-Wu; Tang, Bo; Hao, Ying-Xue; Lei, Xiao; Luo, Hua-Xing; Zeng, Dong-Zhu] Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing, Peoples R China; [Shi, Yan; Yu, Pei-Wu; Tang, Bo; Hao, Ying-Xue; Lei, Xiao; Luo, Hua-Xing; Zeng, Dong-Zhu] Third Mil Med Univ, Southwest Hosp, Ctr Minimal Invas Gastrointestinal Surg, Chongqing, Peoples R China; [Tang, Bin] Third Mil Med Univ, Coll Med Lab Sci, Dept Clin Microbiol & Immunol, Chongqing, Peoples R China		Yu, PW (corresponding author), Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing, Peoples R China.	yupeiwu01@vip.sina.com; zdz1140@yahoo.com.cn		Multhoff, Gabriele/0000-0002-2616-3137			Arango D, 2004, BRIT J CANCER, V91, P1931, DOI 10.1038/sj.bjc.6602215; Azad MB, 2009, ANTIOXID REDOX SIGN, V11, P777, DOI 10.1089/ARS.2008.2270; Bae YS, 2011, MOL CELLS, V32, P491, DOI 10.1007/s10059-011-0276-3; Cabello CM, 2007, CURR OPIN INVEST DR, V8, P1022; Chen N, 2011, CANCER BIOL THER, V11, P157, DOI 10.4161/cbt.11.2.14622; Chen YQ, 2010, CAN J PHYSIOL PHARM, V88, P285, DOI 10.1139/Y10-010; Ding ZB, 2011, CLIN CANCER RES, V17, P6229, DOI 10.1158/1078-0432.CCR-11-0816; Grothey A, 2010, ONCOLOGY-BASEL, V79, P389, DOI 10.1159/000323491; He CC, 2009, ANNU REV GENET, V43, P67, DOI 10.1146/annurev-genet-102808-114910; Hersey P, 2008, PIGM CELL MELANOMA R, V21, P358, DOI 10.1111/j.1755-148X.2008.00467.x; Hisamuddin Irfan M, 2004, MedGenMed, V6, P13; Hu C, 2012, TOXICOL LETT, V210, P78, DOI 10.1016/j.toxlet.2012.01.019; Huang J, 2011, ANTIOXID REDOX SIGN, V14, P2215, DOI 10.1089/ars.2010.3554; Klionsky DJ, 2008, AUTOPHAGY, V4, P151, DOI 10.4161/auto.5338; Kroemer G, 2007, PHYSIOL REV, V87, P99, DOI 10.1152/physrev.00013.2006; Kung CP, 2011, CRIT REV EUKAR GENE, V21, P71, DOI 10.1615/CritRevEukarGeneExpr.v21.i1.50; Lee J, 2012, BIOCHEM J, V441, P523, DOI 10.1042/BJ20111451; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Li ZY, 2011, BIOCHEM BIOPH RES CO, V414, P5, DOI 10.1016/j.bbrc.2011.09.046; Mahoney E, 2012, BLOOD, V120, P1262, DOI 10.1182/blood-2011-12-400184; Marchetti P, 2004, ANTICANCER RES, V24, P219; Martins I, 2011, ONCOGENE, V30, P1147, DOI 10.1038/onc.2010.500; Mathew R, 2009, CELL, V137, P1062, DOI 10.1016/j.cell.2009.03.048; O'Connell JB, 2004, JNCI-J NATL CANCER I, V96, P1420, DOI 10.1093/jnci/djh275; Pardini B, 2012, MUTAGENESIS, V27, P161, DOI 10.1093/mutage/ger057; Santos CXC, 2009, ANTIOXID REDOX SIGN, V11, P2409, DOI [10.1089/ars.2009.2625, 10.1089/ARS.2009.2625]; Trachootham D, 2008, ANTIOXID REDOX SIGN, V10, P1343, DOI 10.1089/ars.2007.1957; White E, 2010, CURR OPIN CELL BIOL, V22, P212, DOI 10.1016/j.ceb.2009.12.008; Yokoyama T, 2008, GENE THER, V15, P1233, DOI 10.1038/gt.2008.98; Zhou S, 2012, CANC LETT	30	55	57	0	15	PUBLIC LIBRARY SCIENCE	SAN FRANCISCO	1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA	1932-6203			PLOS ONE	PLoS One	NOV 30	2012	7	11							e51076	10.1371/journal.pone.0051076			8	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	054WM	WOS:000312376100278	23226467	Green Submitted, Green Published, gold			2022-04-25	
J	Su, L; Zhang, HL; Yan, C; Chen, AP; Meng, G; Wei, JW; Yu, DC; Ding, YT				Su, Lei; Zhang, Hailin; Yan, Chen; Chen, Aiping; Meng, Gang; Wei, Jiwu; Yu, Decai; Ding, Yitao			Superior anti-tumor efficacy of diisopropylamine dichloroacetate compared with dichloroacetate in a subcutaneous transplantation breast tumor model	ONCOTARGET			English	Article						diisopropylamine dichloroacetate; dichloroacetate; subcutaneous transplantation breast tumor model; MDA-MB-231 cell line	COLORECTAL-CANCER CELLS; CROSS-TALK; IN-VITRO; AUTOPHAGY; METABOLISM; MITOCHONDRIA; APOPTOSIS; PREVENTION; THERAPY; KINASE	Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has antitumor properties in various carcinoma models. Diisopropylamine dichloroacetate (DADA), an over-the-counter drug for chronic liver disease, is a derivative of DCA. To date, few studies have evaluated the anticancer potential of DADA in breast cancer. In this study, MDA-MB-231 cells, a breast adenocarcinoma cell line, were used in in vitro and in vivo experiments to evaluate the anti-tumor efficacy of DADA and DCA. The half maximal inhibitory concentration (IC50) of DADA (7.1 +/- 1.1 mmol/L) against MDA-MB-231 cells was significantly lower than that of DCA (15.6 +/- 2.0 mmol/L); 100 mg/kg (0.0004 mol/kg) DADA was better than 100 mg/kg (0.0008 mol/kg) DCA at suppressing the growth of subcutaneous transplantation breast tumor at the same dose after 24 days intervention. Histological examination showed that both DCA and DADA interventions led to necrosis, inflammation, and fibrosis of tumor tissue in a mouse subcutaneous transplantation breast tumor model. DADA treatment inhibited Ki67 expression in tumor tissue. In vitro experiments showed that DADA could inhibit lactic acid production and glucose uptake in MDA-MB-231 cells at 10 mmol/L and these effects were stronger than DCA. DADA administration also induced complete autophagy during early treatment stages and incomplete autophagy and cell death at later treatment stages. In conclusion, DADA showed better anti-tumor efficacy than DCA in a breast cancer model.	[Su, Lei; Yan, Chen; Yu, Decai; Ding, Yitao] Nanjing Univ, Drum Tower Hosp, Sch Med, Dept Hepatobiliary Surg, Nanjing 210008, Jiangsu, Peoples R China; [Zhang, Hailin; Chen, Aiping; Meng, Gang; Wei, Jiwu] Nanjing Univ, Sch Med, Jiangsu Key Lab Mol Med, Nanjing 210008, Jiangsu, Peoples R China; [Zhang, Hailin; Chen, Aiping; Meng, Gang; Wei, Jiwu] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210008, Jiangsu, Peoples R China		Yu, DC; Ding, YT (corresponding author), Nanjing Univ, Drum Tower Hosp, Sch Med, Dept Hepatobiliary Surg, Nanjing 210008, Jiangsu, Peoples R China.	dryudecai@qq.com; yitao__ding@sina.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81372294, 81372455]	This work was supported by the National Natural Science Foundation of China (81372294,81372455).	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J	Zheng, TL; Li, DP; He, ZF; Feng, SB; Zhao, S				Zheng, Tianliang; Li, Deping; He, Zhanfeng; Feng, Shuaibing; Zhao, Song			Prognostic and clinicopathological significance of Beclin-1 in non-small-cell lung cancer: a meta-analysis	ONCOTARGETS AND THERAPY			English	Article						non-small-cell lung cancer; autophagy; Beclin-1; prognosis; meta-analysis	LYMPH-NODE METASTASIS; POOR-PROGNOSIS; COLORECTAL-CANCER; GASTRIC-CANCER; 1 EXPRESSION; GENE BECLIN1; AUTOPHAGY; CARCINOMA; ADENOCARCINOMA; APOPTOSIS	Background: Autophagy plays a key role in the development of non-small-cell lung cancer (NSCLC). Beclin-1 is essential for the initiation and regulation of autophagy. Accumulated studies have investigated the prognostic role of Beclin-1 in NSCLC, but conclusions remain controversial. Therefore, we conducted this meta-analysis to assess the potential significance of Beclin-1 in NSCLC. Materials and methods: PubMed and Fin base databases were searched for eligible studies published before December 31, 2017. Odds ratio (OR) was pooled to evaluate the clinico- pathological significance of Beclin-1 in NSCLC. Hazard ratio (HR) was adopted to assess the association of Beclin-1 with overall survival (OS). Results: Eight studies involving 1,159 patients were included in this meta-analysis. The pooled results showed that high Beclin-1 expression was significantly correlated with earlier tumor grade (OR=0.54, 95% CI: 0.36-0.81, P=0.003), less nodal involvement (OR=0.56, 95% CI: 0.37.-0.86, P=0.007), earlier TNM stage (OR=0.62, 95% CI: 0.43-0.89, P=0.010), smaller tumor size (OR=0.54, 95% CI: 0.36.-0.81, P=0.003), better differentiation (OR=0.48, 95% CI: 0.36-.0.64, P<0.001), and less recurrence (OR=0.24, 95% CI: 0.14-0.41, P<0.001). Moreover, high level of Beclin-1 was significantly associated with better OS in NSCLC (HR=0.41, 95% CI: 0.26-0.64, P<0.001). Conclusion: Our meta-analysis suggests that high Beclin-1 expression predicts a better clinicopathological status and a better prognosis in NSCLC. Beclin-1 might act as a promising prognostic biomarker for NSCLC.	[Zheng, Tianliang; He, Zhanfeng; Feng, Shuaibing; Zhao, Song] Zhengzhou Univ, Affiliated Hosp 1, Dept Thorac Surg, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China; [Li, Deping] Zhengzhou Hosp Tradit Chinese Med, Dept Pain Management, Zhengzhou, Henan, Peoples R China		Zhao, S (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Thorac Surg, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China.	zzuzhaosong@yahoo.com			Youth Innovation Fund Project of the First Affiliated Hospital of Zhengzhou University	This study was supported by the Youth Innovation Fund Project of the First Affiliated Hospital of Zhengzhou University.	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J	Wu, JF; Lie, W; Ning, JZ; Yu, WM; Rao, T; Cheng, F				Wu, Junfeng; Lie, Wei; Ning, Jinzhuo; Yu, Weimin; Rao, Ting; Cheng, Fan			Long noncoding RNA UCA1 targets miR-582-5p and contributes to the progression and drug resistance of bladder cancer cells through ATG7-mediated autophagy inhibition	ONCOTARGETS AND THERAPY			English	Article						IncRNA UCA1; miR-582-5p; bladder cancer; migration and invasion; resistance	CARCINOMA-ASSOCIATED 1; UROTHELIAL CARCINOMA; UP-REGULATION; COLORECTAL-CANCER; LUNG-CANCER; PROLIFERATION; APOPTOSIS; MIGRATION; PROMOTES; INVASION	Background: Rently, the incidence of bladder cancer has been on the rise. Accumulating researches have been conducted to clarify the molecular mechanisms and potential therapeutic targets of bladder cancer. The present study aims to explore the regulatory mechanism of the urothelial carcinoma-associated 1 (UCA1)-miR-582-5p-ATG7 axis in bladder cancer. Methods: Quantitative real-time polymerase chain reaction was used to detect mRNA level. Relative protein expression was detected by western blot, wound healing assay and transwell were used to determine migration and invasion of cells. in addtion, luciferase reporter assay and immunohistochemistry were performed. Results: UCA1 expression was upregulated in bladder cancer tissues and cells, while the depletion of UCA1 by shRNA resulted in the suppression of cell proliferation, invasion, migration, and drug resistance. Further studies demonstrated that UCA1 could directly interact with miR-582-5p, and that there was an inverse correlation between miR-582-5p and UCA1. In addition, we found that ATG7 is a target of miR-582-5p and can be downregulated by either miR-582-5p overexpression or UCA1 knockdown. In particular, the autophagy is reduced when UCA1 shRNA is introduced. Moreover, the in vivo experiment further demonstrated the contribution of UCA1 in bladder cancer including tumor growth, invasion, and migration, and UCA1 knockdown can inhibit the aforementioned activities. Conclusion: These results provided evidence for a novel UCA1 interaction regulatory network in bladder cancer, that is, UCA1-miR-582-5p-ATG7-autophagy axis. Our study provides a new insight into the treatment of bladder cancer.	[Wu, Junfeng; Ning, Jinzhuo; Yu, Weimin; Rao, Ting; Cheng, Fan] Wuhan Univ, Renmin Hosp, Dept Urol, Wuhan, Hubei, Peoples R China; [Lie, Wei] Wuhan Univ, Peoples Hosp, Dept Anesthesiol, Wuhan, Hubei, Peoples R China		Cheng, F (corresponding author), Wuhan Univ, Renmin Hosp, 238 Jiefang Rd, Wuhan 430060, Hubei, Peoples R China.	fanchengdoc@sohu.com					Antoni S, 2017, EUR UROL, V71, P96, DOI 10.1016/j.eururo.2016.06.010; Bao LL, 2014, EXP MOL PATHOL, V96, P149, DOI 10.1016/j.yexmp.2013.12.002; Bian ZH, 2016, SCI REP-UK, V6, DOI 10.1038/srep23892; Chandrasekar T, 2016, INVESTIG CLIN UROL, V57, pS89, DOI 10.4111/icu.2016.57.S1.S89; Fan Y, 2014, FEBS J, V281, P1750, DOI 10.1111/febs.12737; Ferlay J, 2015, INT J CANCER, V136, pE359, DOI 10.1002/ijc.29210; Geng JF, 2008, EMBO REP, V9, P859, DOI 10.1038/embor.2008.163; Homma I, 2009, CANCER SCI, V100, P2331, DOI 10.1111/j.1349-7006.2009.01329.x; Kang M, 2014, INT J MOL SCI, V15, P8106, DOI 10.3390/ijms15058106; Lai K, 2014, J CLIN PATHOL, V67, P854, DOI 10.1136/jclinpath-2014-202529; Li F, 2015, CRIT REV EUKAR GENE, V25, P191, DOI 10.1615/CritRevEukaryotGeneExpr.2015013770; Li LL, 2018, SAUDI J BIOL SCI, V25, P965, DOI 10.1016/j.sjbs.2018.03.007; Lin YC, 2016, J UROLOGY, V195, P1126, DOI 10.1016/j.juro.2015.10.128; Milowich D, 2015, SPRINGERPLUS, V4, DOI 10.1186/s40064-015-1092-6; Nie W, 2016, CANCER LETT, V371, P99, DOI 10.1016/j.canlet.2015.11.024; Pan JJ, 2016, CANCER LETT, V382, P64, DOI 10.1016/j.canlet.2016.08.015; Pilati P, 2012, CURR MED CHEM, V19, P3900, DOI 10.2174/092986712802002473; Sun SX, 2016, ONCOTARGETS THER, V9, P4975, DOI 10.2147/OTT.S107876; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; Tuo YL, 2015, EUR REV MED PHARMACO, V19, P3403; Uchino K, 2013, MOL THER, V21, P610, DOI 10.1038/mt.2012.269; Wang F, 2015, ONCOTARGET, V6, P1; Wang SS, 2017, MOL MED REP, V15, P1179, DOI 10.3892/mmr.2017.6111; Wang SS, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0157759; Wang WW, 2017, JPN J CLIN ONCOL, V47, P690, DOI 10.1093/jjco/hyx073; Wu SH, 2015, INT J CLIN EXP PATHO, V8, P3882; Xue M, 2016, CANCER SCI, V107, P18, DOI 10.1111/cas.12844; Xue M, 2014, TUMOR BIOL, V35, P6901, DOI 10.1007/s13277-014-1925-x; Xue M, 2014, ONCOL REP, V31, P1993, DOI 10.3892/or.2014.3092; Zeng XH, 2014, BIOMATERIALS, V35, P1227, DOI 10.1016/j.biomaterials.2013.10.042; Zhang X, 2015, CANCER GENE THER, V22, P475, DOI 10.1038/cgt.2015.44; Zhang Y, 2015, TUMOR BIOL, V36, P8309, DOI 10.1007/s13277-015-3582-0; Zhang Zheng, 2012, Zhonghua Yi Xue Za Zhi, V92, P384; Zhou J, 2018, EPIGENOMICS-UK, V10, P259, DOI 10.2217/epi-2017-0104; Zhu JL, 2017, MOL THER-NUCL ACIDS, V7, P299, DOI 10.1016/j.omtn.2017.04.012	35	49	51	0	8	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2019	12						495	508		10.2147/OTT.S183940			14	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	HH2AA	WOS:000455519800004	30666128	Green Published, gold, Green Submitted			2022-04-25	
J	Yoo, BH; Wu, X; Li, YL; Haniff, M; Sasazuki, T; Shirasawa, S; Eskelinen, EL; Rosen, KV				Yoo, Byong Hoon; Wu, Xue; Li, Yongling; Haniff, Mehnaaz; Sasazuki, Takehiko; Shirasawa, Senji; Eskelinen, Eeva-Liisa; Rosen, Kirill V.			Oncogenic ras-induced Down-regulation of Autophagy Mediator Beclin-1 Is Required for Malignant Transformation of Intestinal Epithelial Cells	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							TUMOR-SUPPRESSOR GENE; ANOIKIS RESISTANCE; COLORECTAL-CANCER; K-RAS; PANCREATIC ADENOCARCINOMA; FAMILY PROTEINS; ACTIVATED RAS; CYCLE ARREST; IN-VIVO; GROWTH	Detachment of non-malignant epithelial cells from the extracellular matrix causes their growth arrest and, ultimately, death. By contrast, cells composing carcinomas, cancers of epithelial origin, can survive and proliferate without being attached to the extracellular matrix. These properties of tumor cells represent hallmarks of malignant transformation and are critical for cancer progression. Previously we identified several mechanisms by which ras, a major oncogene, blocks detachment-induced apoptosis of intestinal epithelial cells, but mechanisms by which Ras promotes proliferation of those cells that remain viable following detachment are unknown. We show here that detachment of non-malignant intestinal epithelial cells promotes formation of autophagosomes, vacuole-like structures that mediate autophagy (a process of cellular self-cannibalization), and that oncogenic ras prevents this autophagosome formation. We also found that ras activates a GTPase RhoA, that RhoA promotes activation of a protease calpain, and that calpain triggers degradation of Beclin-1, a critical mediator of autophagy, in these cells. The reversal of the effect of ras on Beclin-1 (achieved by expression of exogenous Beclin-1) promoted autophagosome formation following cell detachment, significantly reduced the fraction of detached cells in the S phase of the cell cycle and their rate of proliferation without affecting their viability. Furthermore, RNA interference-induced Beclin-1 down-regulation in non-malignant intestinal epithelial cells prevented detachment-dependent reduction of the fraction of these cells in the S phase of the cell cycle. Thus, ras oncogene promotes proliferation of those malignant intestinal epithelial cells that remain viable following detachment via a distinct novel mechanism that involves Ras-induced down-regulation of Beclin-1.	[Rosen, Kirill V.] Dalhousie Univ, Atlantic Res Ctr, CRC, Dept Pediat & Biochem, Halifax, NS B3H 4H7, Canada; [Yoo, Byong Hoon; Wu, Xue; Li, Yongling; Haniff, Mehnaaz; Rosen, Kirill V.] Dalhousie Univ, Atlantic Res Ctr, Dept Mol Biol, Halifax, NS B3H 4H7, Canada; [Sasazuki, Takehiko] Int Med Ctr Japan, Dept Pathol, Res Inst, Tokyo 1628655, Japan; [Shirasawa, Senji] Fukuoka Univ, Sch Med, Dept Cell Biol, Fukuoka 8140180, Japan; [Eskelinen, Eeva-Liisa] Univ Helsinki, Div Biochem, Dept Biol & Environm Sci, FIN-00014 Helsinki, Finland		Rosen, KV (corresponding author), Dalhousie Univ, Atlantic Res Ctr, CRC, Dept Pediat & Biochem, Rm C-302,5849 Univ Ave, Halifax, NS B3H 4H7, Canada.	kirill.rosen@dal.ca	Eskelinen, Eeva-Liisa/AAF-3496-2019	Eskelinen, Eeva-Liisa/0000-0003-0006-7785; Rosen, Kirill/0000-0002-4317-9907	Canadian Cancer Society Research InstituteCanadian Cancer Society (CCS)	This work was supported by a grant from the Canadian Cancer Society Research Institute (formerly the National Cancer Institute of Canada).	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Biol. Chem.	FEB 19	2010	285	8					5438	5449		10.1074/jbc.M109.046789			12	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	565WQ	WOS:000275327200037	19778902	Green Published, hybrid			2022-04-25	
J	Wang, Y; Du, J; Wu, XM; Abdelrehem, A; Ren, Y; Liu, C; Zhou, X; Wang, SN				Wang, Yu; Du, Jiang; Wu, Xuemei; Abdelrehem, Ahmed; Ren, Yu; Liu, Chao; Zhou, Xuan; Wang, Sinan			Crosstalk between autophagy and microbiota in cancer progression	MOLECULAR CANCER			English	Review						Autophagy; Microbiota; Cancer progression; Target therapy	HELICOBACTER-PYLORI INFECTION; TUMOR-CELL SURVIVAL; FUSOBACTERIUM-NUCLEATUM; PORPHYROMONAS-GINGIVALIS; COLORECTAL-CANCER; CHEMOTHERAPY RESISTANCE; VACUOLATING CYTOTOXIN; INDUCED APOPTOSIS; HEDGEHOG PATHWAY; KAPPA-B	Autophagy is a highly conserved catabolic process seen in eukaryotes and is essentially a lysosome-dependent protein degradation pathway. The dysregulation of autophagy is often associated with the pathogenesis of numerous types of cancers, and can not only promote the survival of cancer but also trigger the tumor cell death. During cancer development, the microbial community might predispose cells to tumorigenesis by promoting mucosal inflammation, causing systemic disorders, and may also regulate the immune response to cancer. The complex relationship between autophagy and microorganisms can protect the body by activating the immune system. In addition, autophagy and microorganisms can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses involved in cancer progression. Various molecular mechanisms, correlating the microbiota disorders and autophagy activation, control the outcomes of protumor or antitumor responses, which depend on the cancer type, tumor microenvironment and disease stage. In this review, we mainly emphasize the leading role of autophagy during the interaction between pathogenic microorganisms and human cancers and investigate the various molecular mechanisms by which autophagy modulates such complicated biological processes. Moreover, we also highlight the possibility of curing cancers with multiple molecular agents targeting the microbiota/autophagy axis. Finally, we summarize the emerging clinical trials investigating the therapeutic potential of targeting either autophagy or microbiota as anticancer strategies, although the crosstalk between them has not been explored thoroughly.	[Wang, Yu; Du, Jiang; Liu, Chao; Zhou, Xuan] Tianjin Med Univ Canc Inst & Hosp, Dept Maxillofacial & Otorhinolaryngol Oncol, Tianjin 300060, Peoples R China; [Wang, Yu; Du, Jiang; Liu, Chao; Zhou, Xuan] Tianjin Canc Inst, Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China; [Wang, Yu; Du, Jiang; Liu, Chao; Zhou, Xuan] Natl Clin Res Ctr Canc, Tianjin 300060, Peoples R China; [Wu, Xuemei; Wang, Sinan] Tianjin Med Univ Gen Hosp, Dept Gastroenterol & Hepatol, Tianjin, Peoples R China; [Wu, Xuemei; Wang, Sinan] Tianjin Med Univ, Tianjin Gastroenterol & Hepatol Inst, Tianjin 300052, Peoples R China; [Wu, Xuemei; Wang, Sinan] Tianjin Med Univ, Key Lab Immune Microenvironm & Dis, Minist Educ, Tianjin 300070, Peoples R China; [Abdelrehem, Ahmed] Alexandria Univ, Fac Dent, Dept Craniomaxillofacial & Plast Surg, Alexandria, Egypt; [Ren, Yu] Tianjin Med Univ, Tianjin Res Ctr Basic Med Sci, Tianjin 300070, Peoples R China		Wang, Y; Zhou, X (corresponding author), Tianjin Med Univ Canc Inst & Hosp, Dept Maxillofacial & Otorhinolaryngol Oncol, Tianjin 300060, Peoples R China.; Wang, Y; Zhou, X (corresponding author), Tianjin Canc Inst, Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China.; Wang, Y; Zhou, X (corresponding author), Natl Clin Res Ctr Canc, Tianjin 300060, Peoples R China.; Wang, SN (corresponding author), Tianjin Med Univ Gen Hosp, Dept Gastroenterol & Hepatol, Tianjin, Peoples R China.; Wang, SN (corresponding author), Tianjin Med Univ, Tianjin Gastroenterol & Hepatol Inst, Tianjin 300052, Peoples R China.; Wang, SN (corresponding author), Tianjin Med Univ, Key Lab Immune Microenvironm & Dis, Minist Educ, Tianjin 300070, Peoples R China.	wangyu1991@tmu.edu.cn; xuanzhou@tmu.edu.cn; wangsinan@tmu.edu.cn			China National Natural Scientific FundNational Natural Science Foundation of China (NSFC) [82002892, 82073010, 82172764]; Tianjin Education Commission [2019KJ188]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [3332020079]	This work was supported by the China National Natural Scientific Fund No. 82002892 (to W.Y.), 82073010 (to Z.X.), 82172764 (to R.Y.); the Tianjin Education Commission Funded Projects No.2019KJ188 (to W.Y.); the Fundamental Research Funds for the Central Universities No.3332020079 (to W.SN.)	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Cancer	DEC 11	2021	20	1							163	10.1186/s12943-021-01461-0			19	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	XN0TR	WOS:000729227800001	34895252	gold, Green Published			2022-04-25	
J	Yoo, BH; Zagryazhskaya, A; Li, YL; Koomson, A; Khan, IA; Sasazuki, T; Shirasawa, S; V Rosen, K				Yoo, Byong Hoon; Zagryazhskaya, Anna; Li, Yongling; Koomson, Ananda; Khan, Iman Aftab; Sasazuki, Takehiko; Shirasawa, Senji; V Rosen, Kirill			Upregulation of ATG3 contributes to autophagy induced by the detachment of intestinal epithelial cells from the extracellular matrix, but promotes autophagy-independent apoptosis of the attached cells	AUTOPHAGY			English	Article						autophagy; apoptosis; anoikis; ATG3; ATG7; extracellular matrix	BCL-X-L; RAS-INDUCED TRANSFORMATION; BECLIN 1 PHOSPHORYLATION; DOWN-REGULATION; ANOIKIS RESISTANCE; TUMOR-SUPPRESSOR; IN-VIVO; PANCREATIC ADENOCARCINOMA; PHOTODYNAMIC THERAPY; APG3P/AUT1P HOMOLOG	Detachment of nonmalignant intestinal epithelial cells from the extracellular matrix (ECM) triggers their growth arrest and, ultimately, apoptosis. In contrast, colorectal cancer cells can grow without attachment to the ECM. This ability is critical for their malignant potential. We found previously that detachment-induced growth arrest of nonmalignant intestinal epithelial cells is driven by their detachment-triggered autophagy, and that RAS, a major oncogene, promotes growth of detached cells by blocking such autophagy. In an effort to identify the mechanisms of detachment-induced autophagy and growth arrest of nonmalignant cells we found here that detachment of these cells causes upregulation of ATG3 and that ATG3 upregulation contributes to autophagy and growth arrest of detached cells. We also observed that when ATG3 expression is artificially increased in the attached cells, ATG3 promotes neither autophagy nor growth arrest but triggers their apoptosis. ATG3 upregulation likely promotes autophagy of the detached but not that of the attached cells because detachment-dependent autophagy requires other detachment-induced events, such as the upregulation of ATG7. We further observed that those few adherent cells that do not die by apoptosis induced by ATG3 become resistant to apoptosis caused by cell detachment, a property that is critical for the ability of normal epithelial cells to become malignant. We conclude that cell-ECM adhesion can switch ATG3 functions: when upregulated in detached cells in the context of other autophagy-promoting events, ATG3 contributes to autophagy. However, when overexpressed in the adherent cells, in the circumstances not favoring autophagy, ATG3 triggers apoptosis.	[Yoo, Byong Hoon; Zagryazhskaya, Anna; Li, Yongling; Koomson, Ananda; Khan, Iman Aftab; V Rosen, Kirill] Dalhousie Univ, Dept Pediat, Halifax, NS, Canada; [Yoo, Byong Hoon; Zagryazhskaya, Anna; Li, Yongling; Koomson, Ananda; Khan, Iman Aftab; V Rosen, Kirill] Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada; [Sasazuki, Takehiko] Kyushu Univ, Inst Adv Study, Fukuoka 812, Japan; [Shirasawa, Senji] Fukuoka Univ, Fac Med, Dept Cell Biol, Fukuoka 81401, Japan; [Shirasawa, Senji] Fukuoka Univ, Ctr Adv Mol Med, Fukuoka 81401, Japan		V Rosen, K (corresponding author), Dalhousie Univ, Dept Pediat, Halifax, NS, Canada.	kirill.rosen@dal.ca		Rosen, Kirill/0000-0002-4317-9907	Canadian Institutes of Health Research Nova Scotia Regional Partnership Program (CIHR/NSRPP) [125109]; IWK Health Centre PosDoctoral Fellowship; CIHR/NS RPP New Investigator award	This study was supported by the Canadian Institutes of Health Research Nova Scotia Regional Partnership Program (CIHR/NSRPP) operating grant 125109 and the CIHR/NS RPP New Investigator award held by Kirill Rosen. Byong Yoo was a recipient of the IWK Health Centre Research Associateship. Yongling Li was a recipient of the IWK Health Centre PosDoctoral Fellowship.	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J	Roshani-Asl, E; Mansori, B; Mohammadi, A; Najafi, S; Danesh-Pouya, F; Rasmi, Y				Roshani-Asl, Elmira; Mansori, Behzad; Mohammadi, Ali; Najafi, Souzan; Danesh-Pouya, Fahima; Rasmi, Yousef			Interaction between DNA damage response and autophagy in colorectal cancer	GENE			English	Review						DNA damage; DNA repair; Autophagy; Colorectal cancer	BECLIN 1 EXPRESSION; FAVORABLE PROGNOSIS; MOLECULAR MACHINERY; DOWN-REGULATION; CELLS; INHIBITION; PATHWAY; MECHANISMS; BIOMARKERS; SURVIVAL	The subjection of DNA to numerous lethal damages is threatening for the stability and integrity of the whole body genome. DNA damage response (DDR) is a critical phosphorylation-based signaling pathway developed for the maintaining of the genome against these threatens. Recent studies showed that various targets of DDR are involved in the activation of autophagy, as one of the important effectors of this signaling. The interplay between DDR and autophagy may have a critical role in the pathogenesis of various malignancies such as colorectal cancer, which can be a basement for the designing novel therapeutic strategies for combating this cancer type. On the other hand, autophagy is also demonstrated to be contributed to the regulation of DDR components. Therefore, in this review article, we will discuss the crosstalk between DDR and autophagy and their exact function in the pathogenesis of various human cancer types, with special attention on colorectal cancer.	[Roshani-Asl, Elmira; Danesh-Pouya, Fahima; Rasmi, Yousef] Urmia Univ Med Sci, Sch Med, Dept Biochem, Orumiyeh, Iran; [Roshani-Asl, Elmira; Mansori, Behzad; Najafi, Souzan] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran; [Mansori, Behzad; Mohammadi, Ali] Univ Southern Denmark, Inst Mol Med, Dept Canc & Inflammat Res, Odense, Denmark; [Mansori, Behzad] Tabriz Univ Med Sci, Student Res Comm, Tabriz, Iran; [Rasmi, Yousef] Urmia Univ Med Sci, Cellular & Mol Res Ctr, Orumiyeh, Iran		Rasmi, Y (corresponding author), Urmia Univ Med Sci, Sch Med, Dept Biochem, Orumiyeh, Iran.	rasmiy@umsu.ac.ir	Rasmi, Yousef/H-1783-2017; Roshani Asl, Elmira/ABC-1868-2021; Pouya, Fahima Danesh/AAO-9209-2021; Mansoori, Behzad/T-2720-2017	Rasmi, Yousef/0000-0003-1506-1909; Pouya, Fahima Danesh/0000-0002-2636-9856; Mansoori, Behzad/0000-0001-9444-7134			An CH, 2011, PATHOL RES PRACT, V207, P433, DOI 10.1016/j.prp.2011.05.002; Beggs AD, 2008, CURR GENOMICS, V9, P1, DOI 10.2174/138920208783884865; Blackford AN, 2017, MOL CELL, V66, P801, DOI 10.1016/j.molcel.2017.05.015; 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J	Deng, YY; Song, PY; Chen, XH; Huang, Y; Hong, LJ; Jin, Q; Ji, J				Deng, Yongyan; Song, Pengyu; Chen, Xiaohui; Huang, Yue; Hong, Liangjie; Jin, Qiao; Ji, Jian			3-Bromopyruvate-Conjugated Nanoplatform-Induced Pro-Death Autophagy for Enhanced Photodynamic Therapy against Hypoxic Tumor	ACS NANO			English	Article						pro-death autophagy; hypoxia relief; 3-bromopyruvate; photodynamic therapy; respiration inhibition	COLORECTAL-CANCER; CELL-DEATH; NANOPARTICLES; APOPTOSIS; DEPLETION; RESISTANCE; SYNERGIZE; DELIVERY	Autophagy triggered by reactive oxygen species (ROS) in photodynamic therapy (PDT) generally exhibits an anti-apoptotic effect to promote cell survival. Herein, an innovative supramolecular nanoplatform was fabricated for enhanced PDT by converting the role of autophagy from pro-survival to pro-death. The respiration inhibitor 3-bromopyruvate (3BP), which can act as an autophagy promoter and hypoxia ameliorator, was integrated into photosensitizer chlorin e6 (Ce6)-encapsulated nanoparticles to combat hypoxic tumor. 3BP could inhibit respiration by down-regulating HK-II and GAPDH expression to significantly reduce intracellular oxygen consumption rate, which could relieve tumor hypoxia for enhanced photodynamic cancer therapy. More importantly, the autophagy level was significantly elevated by the combination of 3BP and PDT determined by Western blot, immunofluorescent imaging, and transmission electron microscopy. It was very surprising that excessively activated autophagy promoted cell apoptosis, leading to the changeover of autophagy from pro-survival to pro-death. Therefore, PDT combined with 3BP could achieve efficient cell proliferation inhibition and tumor regression. Furthermore, hypoxia-inducible factor-1 alpha (HIF-1 alpha) could be down-regulated after tumor hypoxia was relieved by 3BP. Tumor metastasis could then be effectively inhibited by eliminating primary tumors and down-regulating HIF-1 alpha expression. These results provide an inspiration for future innovative approaches of cancer therapy by triggering pro-death autophagy.	[Deng, Yongyan; Song, Pengyu; Chen, Xiaohui; Huang, Yue; Hong, Liangjie; Jin, Qiao; Ji, Jian] Zhejiang Univ, Dept Polymer Sci & Engn, MOE Key Lab Macromol Synth & Functionalizat, Minist Educ, Hangzhou 310027, Peoples R China		Jin, Q (corresponding author), Zhejiang Univ, Dept Polymer Sci & Engn, MOE Key Lab Macromol Synth & Functionalizat, Minist Educ, Hangzhou 310027, Peoples R China.	jinqiao@zju.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21774110]; Medical Science and Technology Project of Zhejiang Province [2019PY020]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [2019QNA4063]	This research was financially supported by the following programs: the National Natural Science Foundation of China (21774110), Medical Science and Technology Project of Zhejiang Province (2019PY020), and the Fundamental Research Funds for the Central Universities (2019QNA4063).	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J	Fu, Q; Yang, F; Zhao, J; Yang, XX; Xiang, TX; Huai, GL; Zhang, JS; Wei, L; Deng, SP; Yang, HJ				Fu, Qiang; Yang, Fan; Zhao, Ji; Yang, Xingxing; Xiang, Tengxiao; Huai, Guoli; Zhang, Jiashu; Wei, Liang; Deng, Shaoping; Yang, Hongji			Bioinformatical identification of key pathways and genes in human hepatocellular carcinoma after CSN5 depletion	CELLULAR SIGNALLING			English	Article						Bioinformatics analysis; Hepatocellular carcinoma; CSN5 depletion; Differentially expressed gene; SMAD5	GASTRIC-CANCER CELLS; COLORECTAL-CANCER; TUMOR-SUPPRESSOR; EXPRESSION; PROGRESSION; JAB1/CSN5; HEPATOCARCINOGENESIS; OVEREXPRESSION; CONTRIBUTE; GENOMICS	Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It has been previously reported that CSN5 depletion is an effective method in human HCC. In the current study, we aimed to uncover gene signatures and key pathways during HCC. Gene expression profiles of GSE26485 were downloaded from GEO database. Totally, 101 differentially expressed genes (DEGs) were up-regulated and 146 ones were downregulated. Biological processes (BP) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed that the DEGs were mainly enriched in regulation of cell growth, oxidation-reduction process, mitotic cytokinesis, negative regulation of macroautophagy, endosome organization, lysosome, biosynthesis of antibiotics, small cell lung cancer and glutathione metabolism and so on (P < 0.05). Protein-protein interaction (PPI) network, Kaplan-Meier, log-rank method, western blot, immunohistochemistry and encyclopedia of DNA elements (ENCODE) analysis showed that CSN5 depletion took effects through down-regulation of SMAD5-related pathways which include EXO1, CENPA and NCAPG, resulting in the inactivation of H3K4me3 and H3K36me3. Those genes represent the promising targets for therapeutic intervention in HCC patients.	[Fu, Qiang; Zhao, Ji; Yang, Xingxing; Huai, Guoli; Wei, Liang; Deng, Shaoping; Yang, Hongji] Univ Elect Sci & Technol China, Organ Transplantat Ctr, Sichuan Acad Med Sci, Chengdu 610072, Sichuan, Peoples R China; [Fu, Qiang; Zhao, Ji; Yang, Xingxing; Huai, Guoli; Wei, Liang; Deng, Shaoping; Yang, Hongji] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Sch Med, 1st Ring Rd West 2 Sect 32, Chengdu 610072, Sichuan, Peoples R China; [Fu, Qiang; Zhao, Ji; Yang, Xingxing; Huai, Guoli; Zhang, Jiashu; Wei, Liang; Deng, Shaoping; Yang, Hongji] Organ Transplantat Translat Med Key Lab Sichuan P, Chengdu 610072, Sichuan, Peoples R China; [Yang, Fan; Zhang, Jiashu] Women & Children Hlth Care Ctr Luoyang, Luoyang 471000, Henan, Peoples R China; [Xiang, Tengxiao] Peoples Hosp Changshou Chongqing, Chongqing 401220, Peoples R China; [Deng, Shaoping] North Sichuan Med Coll, Nanchong 637100, Sichuan, Peoples R China; [Deng, Shaoping] Harvard Med Sch, Massachusetts Gen Hosp, Human Islet Lab, Boston, MA 02114 USA		Deng, SP; Yang, HJ (corresponding author), Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Sch Med, 1st Ring Rd West 2 Sect 32, Chengdu 610072, Sichuan, Peoples R China.	sdeng10@163.com; hongji_yang65@126.com			Science and Technology Department of Sichuan Province [30504010361, 2014FZ0123]; Health and Family Planning Commission of Sichuan Province [2015SZ0241]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81571565]	Our gratitude goes to GEO and TCGA project which have generated comprehensive, multi-dimensional maps of the key genomic changes in HepG2, Huh7 cell lines and liver hepatocellular carcinoma. This work was supported by grants from the Science and Technology Department of Sichuan Province (funding number: No. 30504010361 and No. 2014FZ0123), grants from Health and Family Planning Commission of Sichuan Province (funding number: No. 2015SZ0241) and grants from the National Natural Science Foundation of China (funding number: No. 81571565).	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J	Wu, DD; Liu, SY; Gao, YR; Lu, D; Hong, Y; Chen, YG; Dong, PZ; Wang, DY; Li, T; Li, HM; Ren, ZG; Guo, JC; He, F; Ren, XQ; Sun, SY; Duan, SF; Ji, XY				Wu, Dong-Dong; Liu, Shi-Yu; Gao, Ying-Ran; Lu, Dan; Hong, Ya; Chen, Ya-Ge; Dong, Peng-Zhen; Wang, Da-Yong; Li, Tao; Li, Hui-Min; Ren, Zhi-Guang; Guo, Jian-Cheng; He, Fei; Ren, Xue-Qun; Sun, Shi-Yong; Duan, Shao-Feng; Ji, Xin-Ying			Tumour necrosis factor-alpha-induced protein 8-like 2 is a novel regulator of proliferation, migration, and invasion in human rectal adenocarcinoma cells	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						apoptosis; autophagy; rectal adenocarcinoma; signalling pathway; tumour necrosis factor-alpha-induced protein 8-like 2	CANCER CELLS; TIPE2; AUTOPHAGY; METASTASIS; SUPPRESSES; EXPRESSION; THERAPY; GROWTH; INHIBITION; TARGET	Tumour necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is a tumour suppressor in many types of cancer. However, the mechanism of action of TIPE2 on the growth of rectal adenocarcinoma is unknown. Our results showed that the expression levels of TIPE2 in human rectal adenocarcinoma tissues were higher than those in adjacent non-tumour tissues. Overexpression of TIPE2 reduced the proliferation, migration, and invasion of human rectal adenocarcinoma cells and down-regulation of TIPE2 showed reverse effects. TIPE2 overexpression increased apoptosis through down-regulating the expression levels of Wnt3a, phospho (p)-beta-Catenin, and p-glycogen synthase kinase-3 beta in rectal adenocarcinoma cells, however, TIPE2 knockdown exhibited reverse trends. TIPE2 overexpression decreased autophagy by reducing the expression levels of p-Smad2, p-Smad3, and transforming growth factor-beta (TGF-beta) in rectal adenocarcinoma cells, however, TIPE2 knockdown showed opposite effects. Furthermore, TIPE2 overexpression reduced the growth of xenografted human rectal adenocarcinoma, whereas TIPE2 knockdown promoted the growth of rectal adenocarcinoma tumours by modulating angiogenesis. In conclusion, TIPE2 could regulate the proliferation, migration, and invasion of human rectal adenocarcinoma cells through Wnt/beta-Catenin and TGF-beta/Smad2/3 signalling pathways. TIPE2 is a potential therapeutic target for the treatment of rectal adenocarcinoma.	[Wu, Dong-Dong; Liu, Shi-Yu; Gao, Ying-Ran; Lu, Dan; Hong, Ya; Chen, Ya-Ge; Dong, Peng-Zhen; Li, Tao; Li, Hui-Min; Ren, Zhi-Guang; Ji, Xin-Ying] Henan Univ, Coll Med, Sch Basic Med Sci, Kaifeng, Peoples R China; [Wu, Dong-Dong; Liu, Shi-Yu; Gao, Ying-Ran; Lu, Dan; Hong, Ya; Chen, Ya-Ge; Dong, Peng-Zhen; Wang, Da-Yong; Li, Tao; Li, Hui-Min; Ren, Zhi-Guang; Duan, Shao-Feng; Ji, Xin-Ying] Henan Univ, Henan Int Joint Lab Nucl Prot Regulat, Joint Natl Lab Antibody Drug Engn, Kaifeng, Peoples R China; [Wang, Da-Yong] Henan Univ, Affiliated Hosp 1, Kaifeng, Peoples R China; [Guo, Jian-Cheng] Zhengzhou Univ, Ctr Precis Med, Zhengzhou, Henan, Peoples R China; [He, Fei; Ren, Xue-Qun] Henan Univ, Huaihe Hosp, Kaifeng, Peoples R China; [Sun, Shi-Yong] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA USA; [Sun, Shi-Yong] Winship Canc Inst, Atlanta, GA USA; [Duan, Shao-Feng] Henan Univ, Sch Pharm, Inst Innovat Drug Design & Evaluat, Kaifeng, Peoples R China		Duan, SF; Ji, XY (corresponding author), Henan Univ, Henan Int Joint Lab Nucl Prot Regulat, Joint Natl Lab Antibody Drug Engn, Kaifeng, Peoples R China.	dsf_2007@163.com; 10190096@vip.henu.edu.cn	Wu, Dongdong/K-5194-2019; Wu, dongdong/F-6086-2012	Wu, Dongdong/0000-0001-6739-8437; 	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81670088, 81802718, U1504817]; Foundation of Science & Technology Department of Henan Province, China [162102410009, 172102410019, 182102310335]; Natural Science Foundation of Education Department of Henan Province, China [15A310017]; Science Foundation of Kaifeng City, China [1608004, 1703016]; Science Foundation of Henan University, China [yqpy20170044]	National Natural Science Foundation of China, Grant/Award Number: 81670088, 81802718, U1504817; Foundation of Science & Technology Department of Henan Province, China, Grant/Award Number: 162102410009, 172102410019, 182102310335; Natural Science Foundation of Education Department of Henan Province, China, Grant/Award Number: 15A310017; Science Foundation of Kaifeng City, China, Grant/Award Number: 1608004, 1703016; Science Foundation of Henan University, China, Grant/Award Number: yqpy20170044	Cao XL, 2013, MOL CANCER, V12, DOI 10.1186/1476-4598-12-149; 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Cell. Mol. Med.	MAR	2019	23	3					1698	1713		10.1111/jcmm.14065			16	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	HL7KN	WOS:000458920000007	30637920	Green Published, gold			2022-04-25	
J	Zhao, Z; Zhao, J; Xue, J; Zhao, XR; Liu, PS				Zhao, Zhe; Zhao, Jing; Xue, Jing; Zhao, Xinrui; Liu, Peishu			Autophagy inhibition promotes epithelial-mesenchymal transition through ROS/HO-1 pathway in ovarian cancer cells	AMERICAN JOURNAL OF CANCER RESEARCH			English	Article						Autophagy defect; EMT; HO-1; Zeb1; ovarian cancer	HEME OXYGENASE-1; COLORECTAL-CANCER; METASTASIS; EXPRESSION; CARCINOMA; INVASION; EMT; ROS; MIGRATION; ZEB1	Autophagy has been proved to be involved in metastasis of cancers. However, the detailed mechanisms are still unclear. In this work, we aim to provide the first study of the role that autophagy plays in migration and invasion in ovarian cancer cells. Transwell chamber was used to examine migration and invasion capacities. Western blotting and immunofluorescence were performed to investigate the expressions of mesenchymal markers (Vimentin, N-cadherin), epithelial marker (Keratin), transcript factor (Zeb1) and HO-1. Small interfering RNA (siRNA) was used to generate autophagy defect cells (A2780 Atg7 siRNA and Skov-3 Atg7 siRNA cells). Reactive oxygen species (ROS) were examined by flow cytometry. We found Skov-3 cells exhibited a fibroblastoid like phenotype and more invasive ability with lower level of autophagy than A2780. Transwell chamber showed that autophagy inhibition promoted migration and invasion capacities of autophagy defect cells. Western blotting showed that the expressions of mesenchymal markers and transcript factor were up-regulated, while, the expression of epithelial marker was down-regulated in autophagy defect cells. Conversely, autophagy induction could impair the migration and invasion through reversing epithelial-mesenchymal transition (EMT) in A2780 and Skov-3 cells. Besides, autophagy defect could increase the level of intracellular ROS and the expression of HO-1. NAC (ROS scavenging agent) could inhibit the migration and invasion through reversing EMT and decrease the expression of HO-1. What's more, Znpp (HO-1 inhibitor) impaired the migration and invasion through reversing EMT. In conclusion, our results suggest that autophagy inhibition may promote EMT through ROS/HO-1 pathway in ovarian cancer cells.	[Zhao, Zhe; Zhao, Jing; Xue, Jing; Zhao, Xinrui; Liu, Peishu] Shandong Univ, Dept Obstet & Gynecol, Qilu Hosp, 107 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China		Liu, PS (corresponding author), Shandong Univ, Dept Obstet & Gynecol, Qilu Hosp, 107 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.	peishuliu@126.com			Development and Reform commission Project of Shandong Province [26010104081103]	This work was supported by grants from Development and Reform commission Project of Shandong Province (26010104081103).	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J. Cancer Res.		2016	6	10					2162	2177					16	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EB8CJ	WOS:000387618300004	27822409				2022-04-25	
J	Perez-Plasencia, C; Lopez-Urrutia, E; Garcia-Castillo, V; Trujano-Camacho, S; Lopez-Camarillo, C; Campos-Parra, AD				Perez-Plasencia, Carlos; Lopez-Urrutia, Eduardo; Garcia-Castillo, Veronica; Trujano-Camacho, Samuel; Lopez-Camarillo, Cesar; Campos-Parra, Alma D.			Interplay Between Autophagy and Wnt/beta-Catenin Signaling in Cancer: Therapeutic Potential Through Drug Repositioning	FRONTIERS IN ONCOLOGY			English	Review						drug repositinging; autophagy; Wnt; b-catenin; cancer; signaling; signaling pathways	NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BETA-CATENIN; PATHWAY ACTIVATION; COLORECTAL-CANCER; EXPRESSION; RESISTANCE; APOPTOSIS; TARGET; CELLS; INHIBITION	The widespread dysregulation that characterizes cancer cells has been dissected and many regulation pathways common to multiple cancer types have been described in depth. Wnt/beta-catenin signaling and autophagy are among these principal pathways, which contribute to tumor growth and resistance to anticancer therapies. Currently, several therapeutic strategies that target either Wnt/beta-catenin signaling or autophagy are in various stages of development. Targeted therapies that block specific elements that participate in both pathways; are subject toin vitrostudies as well as pre-clinical and early clinical trials. Strikingly, drugs designed for other diseases also impact these pathways, which is relevant since they are already FDA-approved and sometimes even routinely used in the clinic. The main focus of this mini-review is to highlight the importance of drug repositioning to inhibit the Wnt/beta-catenin and autophagy pathways, with an emphasis on the interplay between them. The data we found strongly suggested that this field is worth further examination.	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Oncol.	AUG 18	2020	10								1037	10.3389/fonc.2020.01037			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NM1OI	WOS:000567873100001	33014767	gold, Green Published			2022-04-25	
J	Hung, KF; Yang, T; Kao, SY				Hung, Kai-Feng; Yang, Ting; Kao, Shou-Yen			Cancer stem cell theory: Are we moving past the mist?	JOURNAL OF THE CHINESE MEDICAL ASSOCIATION			English	Review						Autophagy; Cancer stem cells; Cellular stress; Epithelial-mesenchymal transition; Heterogenicity; Plasticity	EPITHELIAL-MESENCHYMAL TRANSITION; ENDOPLASMIC-RETICULUM; COLORECTAL-CANCER; INITIATING CELLS; DYNAMIC EQUILIBRIUM; DOWN-REGULATION; EXPRESSION; SNAIL; DIFFERENTIATION; HETEROGENEITY	Cancer stem cells (CSC) are a subpopulation of tumor cells that have superior capacities of self-renewal, metastatic dissemination, and chemoresistance. These characteristics resemble, to some extent, the outcome of certain biological processes, including epithelial-mesenchymal transition (EMT), autophagy, and cellular stress response. Indeed, it has been shown that the stimuli that induce these processes and CSC are overlapping, and CSC and tumor cells that underwent EMT or autophagy are much alike. However, as the cross talk between CSC, EMT, autophagy, and cellular stress is further explored, these processes are also found to have an opposing role in CSC, depending on the condition and status of cells. This contextual effect is likely due to overwhelming reliance on CSC markers for their identification, and/or discrepancies in recognition of CSC as a particular cell population or cellular state. In this review, we summarize how EMT, autophagy, and cellular stress response are tied or unwound with CSC. We also discuss the current view of CSC theory evolved from the emphasis of heterogenicity and plasticity of CSC.	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Chin. Med. Assoc.	NOV	2019	82	11					814	818		10.1097/JCMA.0000000000000186			5	Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine	KJ9NI	WOS:000512380700006	31469690	hybrid			2022-04-25	
J	Mei, HL; Xiang, Y; Mei, H; Fang, B; Wang, QG; Cao, DD; Hu, Y; Guo, T				Mei, Huiling; Xiang, Yu; Mei, Heng; Fang, Bin; Wang, Qiuguo; Cao, Dedong; Hu, Yu; Guo, Tao			Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK activation in multiple myeloma cells	INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE			English	Article						multiple myeloma; pterostilbene; AMPK-activated protein kinase; nutrient metabolism; apoptosis; autophagy	FATTY-ACID SYNTHASE; BREAST-CANCER CELLS; SIGNALING PATHWAY; PANCREATIC-CANCER; PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA; GLUCOSE-METABOLISM; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; ENERGY-METABOLISM	Multiple myeloma (MM) cells are characterized by an abnormal nutrient metabolism that is distinct from normal plasma cells. Pterostilbene (PTE), a bioactive component of blueberries, has been demonstrated to induce apoptosis in multiple types of cancer cell. The present study evaluated whether PTE treatment affected the survival of MM cells from a metabolic perspective, and the potential mechanisms of this. It was observed that the administration of PTE induced apoptosis, which was mediated by the increased activation of AMP-activated protein kinase (AMPK). Once activated, AMPK decreased the expression and/or activity of key lipo-genic enzymes, including fatty acid synthase and acetyl-CoA carboxylase. In addition, the activation of AMPK suppressed the downstream substrate, mechanistic target of rapamycin, which dephosphorylated eukaryotic initiation factor 4E-binding protein 1, leading to a general decrease in mRNA translation. Pre-treatment with the AMPK inhibitor compound C prior to PTE treatment compromised the anti-myeloma apoptosis effect, suggesting the critical role of AMPK in mediating PTE-induced cell toxicity. Consistent results were obtained in vivo. Finally, autophagy was adaptively upregulated subsequent to PTE treatment; the pro-apoptotic efficacy of PTE was potentiated once autophagic flux was inhibited by 3-methyladenine. Taken together, these data demonstrated that PTE exerts anti-tumor effects on MM cells via AMPK-induced nutrient suppression.	[Mei, Huiling; Xiang, Yu; Mei, Heng; Fang, Bin; Wang, Qiuguo; Hu, Yu; Guo, Tao] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Inst Hematol, 1,277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China; [Mei, Huiling; Mei, Heng; Hu, Yu; Guo, Tao] Huazhong Univ Sci & Technol, Collaborat Innovat Ctr Hematol, Wuhan 430022, Hubei, Peoples R China; [Cao, Dedong] Wuhan Univ, Renmin Hosp, Dept Oncol, Wuhan 430060, Hubei, Peoples R China		Hu, Y; Guo, T (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Inst Hematol, 1,277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China.	dr_huyu@126.com; guotao1968@163.com					Agnelli L, 2007, BRIT J HAEMATOL, V136, P565, DOI 10.1111/j.1365-2141.2006.06467.x; Besse A, 2018, LEUKEMIA, V32, P391, DOI 10.1038/leu.2017.212; Bjarnadottir O, 2013, BREAST CANCER RES TR, V138, P499, DOI 10.1007/s10549-013-2473-6; Cao DD, 2015, ONCOL REP, V33, P899, DOI 10.3892/or.2014.3635; Cao DD, 2014, ONCOL REP, V31, P1205, DOI 10.3892/or.2014.2974; 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J. Mol. Med.	NOV	2018	42	5					2676	2688		10.3892/ijmm.2018.3857			13	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	GX4LA	WOS:000447702700032	30226553	Green Published, hybrid, Green Submitted			2022-04-25	
J	Yang, PM; Liu, YL; Lin, YC; Shun, CT; Wu, MS; Chen, CC				Yang, Pei-Ming; Liu, Yuan-Ling; Lin, Yi-Chu; Shun, Chia-Tung; Wu, Ming-Shiang; Chen, Ching-Chow			Inhibition of Autophagy Enhances Anticancer Effects of Atorvastatin in Digestive Malignancies	CANCER RESEARCH			English	Article							CISPLATIN-INDUCED APOPTOSIS; ACID-INDUCED APOPTOSIS; HISTONE DEACETYLASE-1; COMPLEX-FORMATION; KINASE INHIBITOR; CELL INVASION; CANCER-RISK; PROTEIN; PHOSPHORYLATION; STATINS	Preclinical and clinical studies have shown that statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors with cholesterol-lowering properties, exhibited anticancer effects. However, the underlying mechanisms remain ill defined. In this study, we showed that atorvastatin could inhibit the growth of hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) cells via induction of apoptosis. Atorvastatin also induced autophagy that is a physiologic process involved in the turnover of intracellular organelles. Atorvastatin-induced autophagy was found to be inhibited by AMP-activated protein kinase (AMPK) small interfering RNA. Examination of HCC patients showed the positive correlation between AMPK activity and autophagic marker (beclin-1). Atorvastatin-induced AMPK activation could induce p21 expression, which was also positively correlated with beclin-1 expression in CRC patients. AMPK/p21 signaling caused endoplasmic reticulum (ER) stress response leading to the induction of autophagy. Inhibition of autophagy by an autophagic inhibitor bafilomycin A1 or genetic knockout of autophagy-related gene 5 enhanced atorvastatin-induced cytotoxicity and apoptosis. In summary, activation of AMPK by atorvastatin enhances p21 expression and ER stress response, leading to autophagy, which promotes survival of cancer cells. Combinations of atorvastatin with bafilomycin A1 provide a novel and promising strategy to improve the treatment of digestive malignancies. Cancer Res; 70(19); 7699-709. (C) 2010 AACR.	[Yang, Pei-Ming; Liu, Yuan-Ling; Lin, Yi-Chu; Chen, Ching-Chow] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10018, Taiwan; [Shun, Chia-Tung] Natl Taiwan Univ Hosp, Dept Forens Med & Pathol, Taipei, Taiwan; [Wu, Ming-Shiang] Natl Taiwan Univ Hosp, Dept Internal Med, Div Gastroenterol, Taipei 100, Taiwan		Chen, CC (corresponding author), Natl Taiwan Univ, Coll Med, Dept Pharmacol, 1 Jen Ai Rd,Sect 1, Taipei 10018, Taiwan.	chingchowchen@ntu.edu.tw	Shun, Chia-Tung/M-1400-2019; Yang, Pei-Ming/G-3763-2014	Yang, Pei-Ming/0000-0002-4004-2518; CHEN, CHING-CHOW/0000-0002-7810-0939; Wu, Ming-Shiang/0000-0002-1940-6428; SHUN, CHIA-TUNG/0000-0002-0468-4468	National Science Council of TaiwanMinistry of Science and Technology, Taiwan	National Science Council of Taiwan research grant.	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J	Elshaer, M; Chen, YR; Wang, XJ; Tang, XW				Elshaer, Mohamed; Chen, Yeru; Wang, Xiu Jun; Tang, Xiuwen			Resveratrol: An overview of its anti-cancer mechanisms	LIFE SCIENCES			English	Review						Resveratrol; Cancer metabolism; Nrf2; NLRP3; MAPK; NFkB; MKP-1; Autophagy	EPITHELIAL-MESENCHYMAL TRANSITION; CHEMOPREVENTIVE AGENT RESVERATROL; GROWTH-FACTOR EXPRESSION; SPINAL-CORD-INJURY; FACTOR-KAPPA-B; CANCER-CELLS; COLORECTAL-CANCER; INDUCED APOPTOSIS; TUMOR PROGRESSION; SIGNALING PATHWAY	Cancer is one of the leading causes of death worldwide. Chemotherapy and radiotherapy are the conventional primary treatments for cancer patients. However, most of cancer cells develop resistance to both chemotherapy and radiotherapy after a period of treatment, besides their lethal side-effects. This motivated investigators to seek more effective alternatives with fewer side-effects. In the last few years, resveratrol, a natural polyphenolic phytoalexin, has attracted much attention due to its wide biological effects. In this concise review, we highlight the role of resveratrol in the prevention and therapy of cancer with particular focus on colorectal and skin cancer. Also, we discuss the molecular mechanisms underlying its chemopreventive and therapeutic activity. Finally, we highlight the problems associated with the clinical application of resveratrol and how attempts have been made to overcome these drawbacks.	[Elshaer, Mohamed; Tang, Xiuwen] Zhejiang Univ, Sch Med, Dept Biochem & Genet, Hangzhou 310058, Zhejiang, Peoples R China; [Chen, Yeru; Wang, Xiu Jun] Zhejiang Univ, Sch Med, Dept Pharmacol, Hangzhou 310058, Zhejiang, Peoples R China		Tang, XW (corresponding author), Zhejiang Univ, Sch Med, Dept Biochem & Genet, Hangzhou 310058, Zhejiang, Peoples R China.	xiuwentang@zju.edu.cn		tang, xiuwen/0000-0002-6601-1234	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31571476, 91643110, 31470752]; Science Technology Department of Zhejiang Provence [2017C33082]	This work was supported by the National Natural Science Foundation of China (31571476, 91643110 and 31470752), Science Technology Department of Zhejiang Provence (2017C33082).	Afaq F, 2003, TOXICOL APPL PHARM, V186, P28, DOI 10.1016/S0041-008X(02)00014-5; Andrews CS, 2016, SCI REP-UK, V6, DOI 10.1038/srep34445; Aziz S. 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AUG 15	2018	207						340	349		10.1016/j.lfs.2018.06.028			10	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	GO3GG	WOS:000439876800039	29959028				2022-04-25	
J	Hu, J; Ding, XL; Tian, SB; Chu, YA; Liu, ZB; Li, YQ; Li, XQ; Wang, GB; Wang, L; Wang, Z				Hu, Jia; Ding, Xueliang; Tian, Shaobo; Chu, Yanan; Liu, Zhibo; Li, Yuqin; Li, Xiaoqiong; Wang, Guobin; Wang, Lin; Wang, Zheng			TRIM39 deficiency inhibits tumor progression and autophagic flux in colorectal cancer via suppressing the activity of Rab7	CELL DEATH & DISEASE			English	Article								The biological function of TRIM39, a member of TRIM family, remains largely unexplored in cancer, especially in colorectal cancer (CRC). In this study, we show that TRIM39 is upregulated in tumor tissues compared to adjacent normal tissues and associated with poor prognosis in CRC. Functional studies demonstrate that TRIM39 deficiency restrains CRC progression in vitro and in vivo. Our results further find that TRIM39 is a positive regulator of autophagosome-lysosome fusion. Mechanistically, TRIM39 interacts with Rab7 and promotes its activity via inhibiting its ubiquitination at lysine 191 residue. Depletion of TRIM39 inhibits CRC progression and autophagic flux in a Rab7 activity-dependent manner. Moreover, TRIM39 deficiency suppresses CRC progression through inhibiting autophagic degradation of p53. Thus, our findings uncover the roles as well as the relevant mechanisms of TRIM39 in CRC and establish a functional relationship between autophagy and CRC progression, which may provide promising approaches for the treatment of CRC.	[Hu, Jia; Ding, Xueliang; Tian, Shaobo; Chu, Yanan; Liu, Zhibo; Li, Yuqin; Li, Xiaoqiong; Wang, Lin; Wang, Zheng] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Res Ctr Tissue Engn & Regenerat Med, Wuhan 430022, Peoples R China; [Wang, Guobin; Wang, Zheng] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Gastrointestinal Surg, Wuhan 430022, Peoples R China; [Wang, Lin] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Clin Lab, Wuhan 430022, Peoples R China		Wang, L; Wang, Z (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Res Ctr Tissue Engn & Regenerat Med, Wuhan 430022, Peoples R China.; Wang, GB; Wang, Z (corresponding author), Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Gastrointestinal Surg, Wuhan 430022, Peoples R China.	wgb@hust.edu.cn; lin_wang@hust.edu.cn; zhengwang@hust.edu.cn			Natural Science Foundation Program of China Programs [81472740, 31701202, 81572866, 81773104]; Frontier Exploration Program of Huazhong University of Science and Technology [2015TS153]; Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College of HUST; Academic Medical Doctor Supporting Program of Tongji Medical College of HUST	This work was supported by the Natural Science Foundation Program of China Programs (81472740, 31701202, 81572866, and 81773104), the Frontier Exploration Program of Huazhong University of Science and Technology (2015TS153), the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College of HUST, and the Academic Medical Doctor Supporting Program of Tongji Medical College of HUST.	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APR 12	2021	12	4							391	10.1038/s41419-021-03670-3			18	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	RM9CZ	WOS:000639954300005	33846303	Green Published, gold			2022-04-25	
J	Sanchez-Martin, V; Schneider, DA; Ortiz-Gonzalez, M; Soriano-Lerma, A; Linde-Rodriguez, A; Perez-Carrasco, V; Gutierrez-Fernandez, J; Cuadros, M; Gonzalez, C; Soriano, M; Garcia-Salcedo, JA				Sanchez-Martin, Victoria; Schneider, David A.; Ortiz-Gonzalez, Matilde; Soriano-Lerma, Ana; Linde-Rodriguez, Angel; Perez-Carrasco, Virginia; Gutierrez-Fernandez, Jose; Cuadros, Marta; Gonzalez, Carlos; Soriano, Miguel; Garcia-Salcedo, Jose A.			Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment	CELL CHEMICAL BIOLOGY			English	Article							TRANSCRIPTION; BINDING; VISUALIZATION; TRANSPORTERS; VITRO	Guanine quadruplexes (G4s) are non-canonical nucleic acid structures commonly found in regulatory genomic regions. G4 targeting has emerged as a therapeutic approach in cancer. We have screened naphthalene-diimides (NDIs), a class of G4 ligands, in a cellular model of colorectal cancer (CRC). Here, we identify the leading compound T5 with a potent and selective inhibition of cell growth by high-affinity binding to G4s in ribosomal DNA, impairing RNA polymerase I (Pol I) elongation. Consequently, T5 induces a rapid inhibition of Pol I transcription, nucleolus disruption, proteasome-dependent Pol I catalytic subunit A degradation and autophagy. Moreover, we attribute the higher selectivity of carbohydrate-conjugated T5 for tumoral cells to its preferential uptake through the overexpressed glucose transporter 1. Finally, we succinctly demonstrate that T5 could be explored as a therapeutic agent in a patient cohort with CRC. Therefore, we report a mode of action for these NDIs involving ribosomal G4 targeting.	[Sanchez-Martin, Victoria; Ortiz-Gonzalez, Matilde; Soriano-Lerma, Ana; Linde-Rodriguez, Angel; Perez-Carrasco, Virginia; Cuadros, Marta; Soriano, Miguel; Garcia-Salcedo, Jose A.] Univ Granada, Pfizer, Andalusian Reg Govt, GENYO Ctr Genom & Oncol Res, Granada 18016, Spain; [Sanchez-Martin, Victoria; Linde-Rodriguez, Angel; Perez-Carrasco, Virginia; Gutierrez-Fernandez, Jose; Garcia-Salcedo, Jose A.] Univ Hosp Virgen de las Nieves, Biosanitary Res Inst IBS Granada, Microbiol Unit, Granada 18014, Spain; [Sanchez-Martin, Victoria; Cuadros, Marta] Univ Granada, Dept Biochem Mol Biol & Immunol 3, Granada 18016, Spain; [Schneider, David A.] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA; [Ortiz-Gonzalez, Matilde; Soriano, Miguel] Univ Almeria, Ctr Intens Mediterranean Agrosyst & Agrifood Biot, Almeria 04001, Spain; [Soriano-Lerma, Ana] Univ Granada, Dept Physiol, Granada 18011, Spain; [Gutierrez-Fernandez, Jose] Univ Granada, Dept Microbiol, Granada 18011, Spain; [Gonzalez, Carlos] CSIC, Inst Quim Fis Rocasolano, Madrid 28006, Spain		Garcia-Salcedo, JA (corresponding author), Univ Granada, Pfizer, Andalusian Reg Govt, GENYO Ctr Genom & Oncol Res, Granada 18016, Spain.; Garcia-Salcedo, JA (corresponding author), Univ Hosp Virgen de las Nieves, Biosanitary Res Inst IBS Granada, Microbiol Unit, Granada 18014, Spain.	jags@genyo.es	Soriano, Miguel/L-9532-2014; Gonzalez, Carlos/A-4734-2013	Soriano, Miguel/0000-0002-1838-3615; Gonzalez, Carlos/0000-0001-8796-1282; Schneider, David/0000-0003-0635-5091	European CommissionEuropean CommissionEuropean Commission Joint Research Centre; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM084946]; Government of SpainSpanish Government [FPU16/05822, FPU17/05413]; University of Almeria	We thank Juan Carlos Morales' laboratory (IPLN-CSIC, Granada, Spain) for kindly supplying GLUT inhibitors and NDI derivatives. We also thank Maria Jose Serrano's laboratory (Genyo, Granada, Spain) for supplying HCT116 and HT29 cell lines, and Pedro Real's group (Genyo, Granada, Spain) for providing us with MG132 reagent. We thank ``Manuel Rico'' NMR laboratory (LMR), a node of the Spanish Large-Scale National Facility (ICTS R-LRB) for performing NMR experiments. Finally, we gratefully acknowledge Javier Oliver (IPLN-CSIC, Granada, Spain) for supplying LC3 antibody and his valuable assistance. This work was supported by the European Commission (TARBRAINFECT to J.A.G.-S.) and the National Institutes of Health (GM084946 to D.A.S.). The Government of Spain granted with PhD fellowships FPU16/05822 to V.S.-M. and FPU17/05413 to A.S.-L. The University of Almeria granted with PhD fellowship to M.O.-G. Funding for open access charge: European Commission.	Ahmed AA, 2020, ACS MED CHEM LETT, V11, P1634, DOI 10.1021/acsmedchemlett.0c00317; Arevalo-Ruiz M, 2017, CHEM-EUR J, V23, P2157, DOI 10.1002/chem.201604886; Balasubramanian S, 2011, NAT REV DRUG DISCOV, V10, P261, DOI 10.1038/nrd3428; Bedwell GJ, 2012, GENE, V492, P94, DOI 10.1016/j.gene.2011.10.049; Biffi G, 2013, NAT CHEM, V5, P182, DOI [10.1038/NCHEM.1548, 10.1038/nchem.1548]; Boisvert FM, 2012, MOL CELL PROTEOMICS, V11, DOI 10.1074/mcp.M111.011429; Chambers VS, 2015, NAT BIOTECHNOL, V33, P877, DOI 10.1038/nbt.3295; Cuenca F, 2008, BIOORG MED CHEM LETT, V18, P1668, DOI 10.1016/j.bmcl.2008.01.050; de Wit M, 2014, J PROTEOMICS, V99, P26, DOI 10.1016/j.jprot.2014.01.001; Dekker E, 2019, LANCET, V394, P1467, DOI 10.1016/S0140-6736(19)32319-0; Drygin D, 2011, CANCER RES, V71, P1418, DOI 10.1158/0008-5472.CAN-10-1728; Drygin D, 2010, ANNU REV PHARMACOL, V50, P131, DOI 10.1146/annurev.pharmtox.010909.105844; Drygin D, 2009, CANCER RES, V69, P7653, DOI 10.1158/0008-5472.CAN-09-1304; Ganapathy V, 2009, PHARMACOL THERAPEUT, V121, P29, DOI 10.1016/j.pharmthera.2008.09.005; Gorski SA, 2008, MOL CELL, V30, P486, DOI 10.1016/j.molcel.2008.04.021; Nguyen HT, 2018, ONCOL LETT, V16, P9, DOI 10.3892/ol.2018.8679; Hansel-Hertsch R, 2018, NAT PROTOC, V13, P551, DOI 10.1038/nprot.2017.150; Hansel-Hertsch R, 2017, NAT REV MOL CELL BIO, V18, P279, DOI 10.1038/nrm.2017.3; Hansel-Hertsch R, 2016, NAT GENET, V48, P1267, DOI 10.1038/ng.3662; Hernandez-Verdun D, 2006, HISTOCHEM CELL BIOL, V125, P127, DOI 10.1007/s00418-005-0046-4; Hostettmann K., 1991, NEW PHYTOL, V474; Huppert JL, 2005, NUCLEIC ACIDS RES, V33, P2908, DOI 10.1093/nar/gki609; Katagiri N, 2015, SCI REP-UK, V5, DOI 10.1038/srep08903; Keener J, 1998, J BIOL CHEM, V273, P33795, DOI 10.1074/jbc.273.50.33795; Kuipers EJ, 2015, NAT REV DIS PRIMERS, V1, DOI 10.1038/nrdp.2015.65; Largy E, 2011, ANAL BIOANAL CHEM, V400, P3419, DOI 10.1007/s00216-011-5018-z; Lavrado J, 2015, SCI REP-UK, V5, DOI 10.1038/srep09696; Li Q, 2013, NUCLEIC ACIDS RES, V41, pD1115, DOI 10.1093/nar/gks1101; Liu Y, 2012, MOL CANCER THER, V11, P1672, DOI 10.1158/1535-7163.MCT-12-0131; Ma YX, 2015, J CANCER, V6, P658, DOI 10.7150/jca.11647; Marchetti C, 2018, J MED CHEM, V61, P2500, DOI 10.1021/acs.jmedchem.7b01781; MU JZ, 1994, BBA-MOL CELL RES, V1222, P483, DOI 10.1016/0167-4889(94)90058-2; Musso L, 2018, BBA-GEN SUBJECTS, V1862, P615, DOI 10.1016/j.bbagen.2017.12.002; Neidle S, 2017, NAT REV CHEM, V1, DOI 10.1038/s41570-017-0041; Ohnmacht SA, 2015, SCI REP-UK, V5, DOI 10.1038/srep11385; Palma P, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0112189; Pelletier J, 2018, NAT REV CANCER, V18, P51, DOI 10.1038/nrc.2017.104; Pirota V, 2019, MOLECULES, V24, DOI 10.3390/molecules24030426; Platella C, 2020, NUCLEIC ACIDS RES, V48, P12380, DOI 10.1093/nar/gkaa1001; Popov A, 2013, NUCLEUS-AUSTIN, V4, P134, DOI 10.4161/nucl.23985; Rasadean DM, 2017, CHEM-EUR J, V23, P8491, DOI 10.1002/chem.201700957; Siebeneicher H, 2016, CHEMMEDCHEM, V11, P2261, DOI 10.1002/cmdc.201600276; Tawani A, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-03906-3; Thorens B, 2010, AM J PHYSIOL-ENDOC M, V298, pE141, DOI 10.1152/ajpendo.00712.2009; Todd AK, 2005, NUCLEIC ACIDS RES, V33, P2901, DOI 10.1093/nar/gki553; Wei T, 2018, CELL REP, V23, P404, DOI 10.1016/j.celrep.2018.03.066; Xu H, 2017, NAT COMMUN, V8, DOI 10.1038/ncomms14432; Yang J, 2017, ONCOTARGET, V8, P11788, DOI 10.18632/oncotarget.14352; Zhang SG, 2018, BBA-GEN SUBJECTS, V1862, P1101, DOI 10.1016/j.bbagen.2018.01.022; Zuffo M, 2019, EUR J MED CHEM, V163, P54, DOI 10.1016/j.ejmech.2018.11.043	50	2	3	6	6	CELL PRESS	CAMBRIDGE	50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA	2451-9448			CELL CHEM BIOL	Cell Chem. Biol.	NOV 18	2021	28	11					1590	+		10.1016/j.chembiol.2021.05.021			17	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	XD3WB	WOS:000722642500006	34166611				2022-04-25	
J	Yin, J; Ren, WK; Huang, XG; Li, TJ; Yin, YL				Yin, Jie; Ren, Wenkai; Huang, Xingguo; Li, Tiejun; Yin, Yulong			Protein restriction and cancer	BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER			English	Review						Protein restriction; Cancer; Amino acid; IGF-1; mTOR; FGF21; Autophagy	AMINO-ACID PROFILES; CHEMICALLY-INDUCED HEPATOCARCINOGENESIS; CELL LUNG-CANCER; FACTOR-I SYSTEM; DIETARY-PROTEIN; BREAST-CANCER; PI3K/AKT/MTOR PATHWAY; GLUCOSE-HOMEOSTASIS; COLORECTAL-CANCER; SIGNALING PATHWAY	Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers.	[Yin, Jie; Li, Tiejun; Yin, Yulong] Chinese Acad Sci, Inst Subtrop Agr, Key Lab Agroecol Proc Subtrop Reg, Changsha, Hunan, Peoples R China; [Yin, Jie; Li, Tiejun; Yin, Yulong] Minist Agr, Sci Observing & Expt Stn Anim Nutr & Feed Sci Sou, Changsha, Hunan, Peoples R China; [Yin, Jie; Li, Tiejun; Yin, Yulong] Hunan Prov Engn Res Ctr Hlth Livestock & Poultry, Changsha, Hunan, Peoples R China; [Yin, Jie] Univ Chinese Acad Sci, Beijing, Peoples R China; [Ren, Wenkai; Yin, Yulong] South China Agr Univ, Inst Subtrop Anim Nutr & Feed, Coll Anim Sci, Guangdong Prov Key Lab Anim Nutr Control, Guangzhou, Guangdong, Peoples R China; [Ren, Wenkai] Yangzhou Univ, Coll Vet Med, Jiangsu Coinnovat Ctr Important Anim Infect Dis, Joint Int Res Lab Agr & Agriprod Safety,Minist Ed, Yangzhou, Jiangsu, Peoples R China; [Huang, Xingguo] Hunan Agr Univ, Dept Anim Sci, Changsha, Hunan, Peoples R China; [Huang, Xingguo; Li, Tiejun] Hunan Coinnovat Ctr Anim Prod Safety, Changsha, Hunan, Peoples R China		Li, TJ; Yin, YL (corresponding author), Chinese Acad Sci, Inst Subtrop Agr, Changsha 410125, Hunan, Peoples R China.	tjli@isa.ac.cn; yinyulong@isa.ac.cn	YIN, Jie/H-3578-2019	YIN, Jie/0000-0003-1852-1042	National Key R&D Program of China [2016YFD0501201]; National Basic Research Program of China (973)National Basic Research Program of China [2013CB127301]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31472106, 31772617]; Hunan Key Research Program [2017NK2321]; China Agriculture Research System [CARS-35]	This study was supported by the National Key R&D Program of China (2016YFD0501201), National Basic Research Program of China (973) (2013CB127301), National Natural Science Foundation of China (No. 31472106 and 31772617), Hunan Key Research Program (2017NK2321), and China Agriculture Research System (CARS-35).	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Biophys. Acta-Rev. Cancer	APR	2018	1869	2					256	262		10.1016/j.bbcan.2018.03.004			7	Biochemistry & Molecular Biology; Biophysics; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics; Oncology	GH7PG	WOS:000433645300015	29596961				2022-04-25	
J	Shukla, S; Patric, IRP; Patil, V; Shwetha, SD; Hegde, AS; Chandramouli, BA; Arivazhagan, A; Santosh, V; Somasundaram, K				Shukla, Sudhanshu; Patric, Irene Rosita Pia; Patil, Vikas; Shwetha, Shivayogi D.; Hegde, Alangar S.; Chandramouli, Bangalore A.; Arivazhagan, Arimappamagan; Santosh, Vani; Somasundaram, Kumaravel			Methylation Silencing of ULK2, an Autophagy Gene, Is Essential for Astrocyte Transformation and Tumor Growth	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							DNA METHYLATION; CELL-DEATH; MICROSATELLITE INSTABILITY; MAMMARY TUMORIGENESIS; COLORECTAL-CANCER; MALIGNANT GLIOMA; POOR-PROGNOSIS; GLIOBLASTOMA; PHENOTYPE; SURVIVAL	Glioblastoma (GBM) is the most aggressive type of brain tumor and shows very poor prognosis. Here, using genome-wide methylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct classes of biological processes. One of the hypermethylated genes in GBM, ULK2, an upstream autophagy inducer, was found to be down-regulated in GBM. Promoter hypermethylation of ULK2 was confirmed by bisulfite sequencing. GBM and glioma cell lines had low levels of ULK2 transcripts, which could be reversed upon methylation inhibitor treatment. ULK2 promoter methylation and transcript levels showed significant negative correlation. Ectopic overexpression of ULK2-induced autophagy, which further enhanced upon nutrient starvation or temozolomide chemotherapy. ULK2 also inhibited the growth of glioma cells, which required autophagy induction as kinase mutant of ULK2 failed to induce autophagy and inhibit growth. Furthermore, ULK2 induced autophagy and inhibited growth in Ras-transformed immortalized Baby Mouse Kidney (iBMK) ATG5(+/+) but not in autophagy-deficient ATG5(-/-) cells. Growth inhibition due to ULK2 induced high levels of autophagy under starvation or chemotherapy utilized apoptotic cell death but not at low levels of autophagy. Growth inhibition by ULK2 also appears to involve catalase degradation and reactive oxygen species generation. ULK2 overexpression inhibited anchorage independent growth, inhibited astrocyte transformation in vitro and tumor growth in vivo. Of all autophagy genes, we found ULK2 and its homologue ULK1 were only down-regulated in all grades of glioma. Thus these results altogether suggest that inhibition of autophagy by ULK1/2 down-regulation is essential for glioma development.	[Shukla, Sudhanshu; Patric, Irene Rosita Pia; Patil, Vikas; Somasundaram, Kumaravel] Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India; [Hegde, Alangar S.] Sri Satya Sai Inst Higher Med Sci, Bangalore 560066, Karnataka, India; [Chandramouli, Bangalore A.; Arivazhagan, Arimappamagan] Natl Inst Mental Hlth & Neurosci, Dept Neurosurg, Bangalore 560029, Karnataka, India; [Shwetha, Shivayogi D.; Santosh, Vani] Natl Inst Mental Hlth & Neurosci, Dept Neuropathol, Bangalore 560029, Karnataka, India		Somasundaram, K (corresponding author), Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India.	skumar@mcbl.iisc.ernet.in	Shukla, Sudhanshu/K-7830-2017; Shukla, Sudhanshu/AAC-8650-2020; Shukla, Sudhanshu/L-3530-2016	Shukla, Sudhanshu/0000-0002-5069-9708; Shukla, Sudhanshu/0000-0002-5069-9708; Shukla, Sudhanshu/0000-0002-5069-9708	Indian Council of Medical ResearchIndian Council of Medical Research (ICMR); Department of Biotechnology; Department of Science; University Grants CommissionUniversity Grants Commission, India	The results published here are in whole or part based upon data generated by The Cancer Genome Atlas pilot project established by the NCI and NHGRI. The use of datasets from Institute NC, 2005 and Phillips et al., 2006 is acknowledged. Infrastructural support by funding from Indian Council of Medical Research, Department of Biotechnology, Department of Science, and University Grants Commission to the Department of Microbiology and Cell Biology is acknowledged. The Central Animal Facility of the Indian Institute of Science is acknowledged for animal experiments. We thank Professors M. R. S. Rao and P. Kondaiah for valuable suggestions. We thank Dr. H. Noushmehr for help in acquiring TCGA data. We also thank B. Thota, Shruti Bhargava, K. Chandrashekar, K. Prem, and B. C. Shailaja for the help rendered.	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Biol. Chem.	AUG 8	2014	289	32					22306	22318		10.1074/jbc.M114.567032			13	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	AN4XQ	WOS:000340593500042	24923441	Green Published, hybrid			2022-04-25	
J	Wu, W; Hou, B; Tang, CL; Liu, FC; Yang, J; Pan, T; Si, K; Lu, DY; Wang, XX; Wang, J; Xiong, X; Liu, J; Xie, CG				Wu, Wei; Hou, Bing; Tang, Changli; Liu, Fucheng; Yang, Jie; Pan, Tao; Si, Ke; Lu, Deyun; Wang, Xiaoxiang; Wang, Jing; Xiong, Xing; Liu, Ji; Xie, Chunguang			(+)-Usnic Acid Inhibits Migration of c-KIT Positive Cells in Human Colorectal Cancer	EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE			English	Article							USNIC ACID; TYROSINE KINASE; ENZYME UBC9; PROLIFERATION; AUTOPHAGY; INVASION; TOXICITY; MOTILITY; RECEPTOR; GROWTH	Inhibition of tumor cell migration is a treatment strategy for patients with colorectal cancer (CRC). SCF-dependent activation of c-KIT is responsible for migration of c-KIT positive [c-KIT(+)] cells of CRC. Drug resistance to Imatinib Mesylate (c-KIT inhibitor) has emerged. Inhibition of mTOR can induce autophagic degradation of c-KIT. (+)-usnic acid [(+)-UA], isolated from lichens, has two major functions including induction of proton shuttle and targeting inhibition of mTOR. To reduce hepatotoxicity, the treatment concentration of (+)-UA should be lower than 10 mu M. HCT116 cells and LS174 cells were employed to investigate the inhibiting effect of (+)-UA (< 10 mu M) on SCF-mediated migration of c-KIT(+) CRC cells. HCT116 cells were employed to investigate the molecular mechanisms. The results indicated that firstly, 8 mu M (+)-UA decreased ATP content via uncoupling; secondly, 8 mu M (+)-UA induced mTOR inhibition, thereby mediated activation suppression of PKC-A, and induced the autophagy of the completed autophagic flux that resulted in the autophagic degradation and transcriptional inhibition of c-KIT and the increase in LDH release; ultimately, 8 mu M (+)-UA inhibited SCF-mediated migration of CRC c-KIT(+) cells. Taken together, 8 mu M could be determined as the effective concentration for (+)-UA to inhibit SCF-mediated migration of CRC c-KIT(+) cells.	[Wu, Wei; Hou, Bing; Liu, Fucheng; Yang, Jie; Pan, Tao; Si, Ke; Lu, Deyun; Wang, Xiaoxiang; Wang, Jing; Xiong, Xing; Liu, Ji] Chengdu Univ Tradit Chinese Med, Chengdu Peoples Hosp 1, Integrated Tradit Chinese Med & Western Med Hosp, Dept Gastroenterol, Chengdu 610041, Sichuan, Peoples R China; [Wu, Wei; Xie, Chunguang] Chengdu Univ Tradit Chinese Med, Sch Clin Med, Chengdu 610075, Sichuan, Peoples R China; [Wu, Wei; Tang, Changli; Liu, Ji] Chengdu Easton Biopharmaceut Ltd, Chengdu 611731, Sichuan, Peoples R China; [Wu, Wei; Liu, Ji] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, Chengdu 610041, Sichuan, Peoples R China; [Wu, Wei] Remeadjohn Technol Co Ltd, Chengdu 610044, Sichuan, Peoples R China; [Tang, Changli] Xichang Peoples Hosp, Pharm Dept, Xichang 615000, Peoples R China		Liu, J (corresponding author), Chengdu Univ Tradit Chinese Med, Chengdu Peoples Hosp 1, Integrated Tradit Chinese Med & Western Med Hosp, Dept Gastroenterol, Chengdu 610041, Sichuan, Peoples R China.; Xie, CG (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Clin Med, Chengdu 610075, Sichuan, Peoples R China.; Liu, J (corresponding author), Chengdu Easton Biopharmaceut Ltd, Chengdu 611731, Sichuan, Peoples R China.; Liu, J (corresponding author), Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, Chengdu 610041, Sichuan, Peoples R China.	rongsi8888@sina.com; xiecg88888@sina.com			National Natural Science FundNational Natural Science Foundation of China (NSFC) [81774302]; Science and Technology Project in Sichuan Province [2018JY0662]; Remeadjohn Technology Co., Ltd., Chengdu, China	This project was supported by the National Natural Science Fund [Grant Number: 81774302]; the Science and Technology Project in Sichuan Province [Grant Number: 2018JY0662]; and Remeadjohn Technology Co., Ltd., Chengdu 610044, China. These following researchers, including Dr. Hongmei Rang (Department of Gastroenterology, Chengdu First People's Hospital, Chengdu 610041, China), Dr. Yanzhi Wang, Prof. Wen Xie and Prof. Minshuang Zhu (College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China), and Prof. Qing Xia (Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre, West China Hospital, Sichuan University, Chengdu, China), have made their contributions to this study. We express our deep gratitude to the above researchers.	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Med.		2018	2018								5149436	10.1155/2018/5149436			13	Integrative & Complementary Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine	GU7QE	WOS:000445519100001	30298093	gold, Green Published, Green Submitted			2022-04-25	
J	Tang, J; Wang, DY; Shen, YG; Xue, F				Tang, Jian; Wang, Dongyang; Shen, Yuguang; Xue, Feng			ATG16L2 overexpression is associated with a good prognosis in colorectal cancer	JOURNAL OF GASTROINTESTINAL ONCOLOGY			English	Article						Colorectal cancer (CRC); prognosis; autophagy; biomarker	AUTOPHAGY-RELATED GENES; CROHNS-DISEASE; STATISTICS	Background: Colorectal cancer (CRC) is a highly aggressive, high-incidence malignancy. Several biomarkers associated with the prognosis and metastasis of CRC have been identified. Our study aimed to evaluate the value of ATG16L2 protein as a new biomarker to predict the prognosis of patients with CRC. Methods: One hundred and fifty-two pairs of paraffin-embedded tissue samples and 19 fresh tissue samples were collected from the Department of Pathology of Renji Hospital, Shanghai Jiao Tong University School of Medicine. All the patients had undergone surgery in the hospital's Department of Gastrointestinal Surgery between 2013 and 2014. The samples were arranged on two tissue microarrays of normal (n=152) and tumor (n=152) tissue. The tissues were immunostained and graded as low (<50%) or high (>= 50%) according to the proportion of ATG16L2-positive cells. An overexpression plasmid was constructed and transfected into RKO cells, and the cell proliferation and migration ability were detected. Finally, Flag-ATG16L2 RKO cells subcutaneous injection into the skin of BALB/c nude mice to determine the effects of ATG16L2 on the growth of subcutaneously transplanted tumors. Results: ATG16L2 expression was negatively correlated with lymph node metastasis (P<0.05) and tumor node-metastasis stage (P<0.05). High ATG16L2 expression in tumor tissues was related to a good prognosis, with patients with a high expression of ATG16L2 displaying longer overall survival. In vitro, overexpression of ATG16L2 in a CRC cell line RKO cell led to a decrease in cell proliferation but had no obvious influence on cell migration. In vivo, the mice in the Flag-NC (as control) group exhibited faster tumor growth than those in the experiment group. Conclusions: ATG16L2 expression is positively associated with patient prognosis in CRC. Further, ATG16L2 can negatively affect CRC cell proliferation in vitro and in vivo.	[Tang, Jian; Wang, Dongyang; Shen, Yuguang] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gastrointestinal Surg, Shanghai, Peoples R China; [Xue, Feng] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Liver Surg & Liver Transplantat, Shanghai, Peoples R China		Xue, F (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Liver Surg & Liver Transplantat, Shanghai, Peoples R China.	liversurgery6108_rj@sjtu.edu.cn			Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [19140903002]; Shanghai Municipal Population and Family Planning Commission [201840374]	Science and Technology Commission of Shanghai Municipality, 19140903002; Shanghai Municipal Population and Family Planning Commission, 201840374.	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Gastrointest. Oncol.	OCT	2021	12	5					2192	2202		10.21037/jgo-21-495		SEP 2021	11	Oncology; Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Gastroenterology & Hepatology	WR6KF	WOS:000706453900001	34790384	gold, Green Published			2022-04-25	
J	Arun, RP; Sivanesan, D; Vidyasekar, P; Verma, RS				Arun, Raj Pranap; Sivanesan, Divya; Vidyasekar, Prasanna; Verma, Rama Shanker			PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity	SCIENTIFIC REPORTS			English	Article							TUMOR-SUPPRESSOR; E-CADHERIN; PTEN; MIGRATION; P15(INK4B); INDUCTION; AUTOPHAGY; STRESS; STEM; AKT	Gravity is a major physical factor determining the stress and strain around cells. Both in space experiments and ground simulation, change in gravity impacts the viability and function of various types of cells as well as in vivo conditions. Cancer cells have been shown to die under microgravity. This can be exploited for better understanding of the biology and identification of novel avenues for therapeutic intervention. Here, we described the effect of microgravity simulated using Rotational Cell Culture System-High Aspect Ratio Vessel (RCCS-HARV) on the viability and morphological changes of colorectal cancer cells. We observed DLD1, HCT116 and SW620 cells die through apoptosis under simulated microgravity (SM). Gene expression analysis on DLD1 cells showed upregulation of tumor suppressors PTEN and FOXO3; leading to AKT downregulation and further induction of apoptosis, through upregulation of CDK inhibitors CDKN2B, CDKN2D. SM induced cell clumps had elevated hypoxia and mitochondrial membrane potential that led to adaptive responses like morphogenetic changes, migration and deregulated autophagy, when shifted to normal culture conditions. This can be exploited to understand the three-dimensional (3D) biology of cancer in the aspect of stress response. This study highlights the regulation of cell function and viability under microgravity through PTEN/FOXO3/AKT pathway.	[Arun, Raj Pranap; Sivanesan, Divya; Verma, Rama Shanker] Indian Inst Technol Madras, Dept Biotechnol, Bhupat & Jyoti Mehta Sch Biosci, Stem Cell & Mol Biol Lab, Madras 600036, Tamil Nadu, India; [Vidyasekar, Prasanna] CSI NUS, Singapore, Singapore		Verma, RS (corresponding author), Indian Inst Technol Madras, Dept Biotechnol, Bhupat & Jyoti Mehta Sch Biosci, Stem Cell & Mol Biol Lab, Madras 600036, Tamil Nadu, India.	vermars@iitm.ac.in		Arun, Raj Pranap/0000-0001-5746-4728; Verma, Rama/0000-0001-7287-7803	Defense Research Development organizationDefence Research & Development Organisation (DRDO) [DLS/81/48222/LSRB-273/SHDD/2013]; Indian Institute of Technology Madras, India; Ministry of Human Resource Department, India	We wish to thank the Defense Research Development organization for supporting this work (DLS/81/48222/LSRB-273/SH&DD/2013). Raj Pranap Arun and Divya Sivanesan wish to thank Indian Institute of Technology Madras, and Ministry of Human Resource Department, India for their fellowship. We thank all the previous researchers and their findings which has led us to this output.	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J	Ko, YH; Cho, YS; Won, HS; An, HJ; Sun, DS; Hong, SU; Park, JH; Lee, MA				Ko, Yoon Ho; Cho, Young-Seok; Won, Hye Sung; An, Ho Jung; Sun, Der Sheng; Hong, Soon Uk; Park, Jin Hee; Lee, Myung Ah			Stage-Stratified Analysis of Prognostic Significance of Bax-Interacting Factor-1 Expression in Resected Colorectal Cancer	BIOMED RESEARCH INTERNATIONAL			English	Article							DECREASED EXPRESSION; BIF-1; AUTOPHAGY; PROTEIN; TUMOR	Background/Aim. Bax-interacting factor-1 (Bif-1) plays a crucial role in apoptosis and autophagy. The aim of this study was to evaluate Bif-1 protein expression and its prognostic significance in colorectal cancer (CRC). Methods. We analyzed Bif-1 protein expression in 251 resected specimens from patients with CRC by immunohistochemistry using tissue microarray. Results. Low Bif-1 expression was observed in 131 patients (52.2%) and high Bif-1 expression in 120 patients (47.8%). No significant differences were observed in clinicopathological parameters between patients with high and low Bif-1 expression. Kaplan-Meier survival analysis showed no difference in survival between patients with high and low Bif-1 expression. Stratified analysis of Bif-1 according to TNM stage demonstrated that low Bif-1 expression was significantly associated with a poor outcome in patients with stages I and II (P = 0.034). Stratified multivariate analysis demonstrated that low Bif-1 expression was an independent indicator of poor prognosis (hazard ratio, 0.459; 95% confidence interval, 0.285-0.739;P = 0.001). Conclusion. Patients with low levels of Bif-1 expression have shortened survival rates in CRC of stages I and II. This suggests that Bif-1 protein expression may be a useful prognostic marker in early-stage CRC.	[Ko, Yoon Ho; Cho, Young-Seok; Won, Hye Sung; An, Ho Jung; Sun, Der Sheng] Catholic Univ Korea, Coll Med, Uijeongbu St Marys Hosp, Dept Internal Med, Uijongbu 480717, South Korea; [Hong, Soon Uk] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea; [Park, Jin Hee] Catholic Univ Korea, Coll Med, Dept Biomed Sci, Seoul 137701, South Korea; [Lee, Myung Ah] Catholic Univ Korea, Coll Med, Seoul St Marys Hosp, Dept Internal Med, Seoul 137701, South Korea		Cho, YS (corresponding author), Catholic Univ Korea, Coll Med, Uijeongbu St Marys Hosp, Dept Internal Med, Uijongbu 480717, South Korea.	yscho@catholic.ac.kr			Institute of Clinical Medicine Research, Uijeongbu St. Mary's Hospital; Catholic University of Korea; National Research Foundation of Korea (NRF)National Research Foundation of Korea; Ministry of Education, Science and TechnologyMinistry of Education, Science and Technology, Republic of Korea [2010-0023295]; Sanofi-Aventis Korea RD Project	This study was supported by a grant of the Institute of Clinical Medicine Research, Uijeongbu St. Mary's Hospital, The Catholic University of Korea (Young-Seok Cho and Yoon Ho Ko), grant of Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0023295) (Young-Seok Cho), and grant of Sanofi-Aventis Korea R&D Project made in the program year of 2011 (Young-Seok Cho).	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Int.		2013	2013								329839	10.1155/2013/329839			8	Biotechnology & Applied Microbiology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Research & Experimental Medicine	231HN	WOS:000325407100001	24175288	gold, Green Published, Green Submitted			2022-04-25	
J	Bretin, L; Pinon, A; Bouramtane, S; Ouk, C; Richard, L; Perrin, ML; Chaunavel, A; Carrion, C; Bregier, F; Sol, V; Chaleix, V; Leger, DY; Liagre, B				Bretin, Ludovic; Pinon, Aline; Bouramtane, Soukaina; Ouk, Catherine; Richard, Laurence; Perrin, Marie-Laure; Chaunavel, Alain; Carrion, Claire; Bregier, Frederique; Sol, Vincent; Chaleix, Vincent; Leger, David Yannick; Liagre, Bertrand			Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer	CANCERS			English	Article						anticancer drug; porphyrin; silica nanoparticles; drug delivery; photodynamic therapy	DRUG-CARRIER; IN-VITRO; AUTOPHAGY; APOPTOSIS; PHOTOSENSITIZERS; BIODISTRIBUTION; MECHANISMS; EFFICIENCY; INHIBITION; EFFICACY	Photodynamic therapy (PDT) using porphyrins has been approved for treatment of several solid tumors due to the generation of cytotoxic reactive oxygen species (ROS). However, low physiological solubility and lack of selectivity towards tumor sites are the main limitations of their clinical use. Nanoparticles are able to spontaneously accumulate in solid tumors through an enhanced permeability and retention (EPR) effect due to leaky vasculature, poor lymphatic drainage, and increased vessel permeability. Herein, we proved the added value of nanoparticle vectorization on anticancer efficacy and tumor-targeting by 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (TPPOH). Using 80 nm silica nanoparticles (SNPs) coated with xylan-TPPOH conjugate (TPPOH-X), we first showed very significant phototoxic effects of TPPOH-X SNPs mediated by post-PDT ROS generation and stronger cell uptake in human colorectal cancer cell lines compared to free TPPOH. Additionally, we demonstrated apoptotic cell death induced by TPPOH-X SNPs-PDT and the interest of autophagy inhibition to increase anticancer efficacy. Finally, we highlighted in vivo, without toxicity, elevated anticancer efficacy of TPPOH-X SNPs through improvement of tumor-targeting compared to a free TPPOH protocol. Our work demonstrated for the first time the strong anticancer efficacy of TPPOH in vitro and in vivo and the merit of SNPs vectorization.	[Bretin, Ludovic; Pinon, Aline; Leger, David Yannick; Liagre, Bertrand] Univ Limoges, Fac Pharm, Lab PEIRENE EA 7500, 2 Rue Docteur Raymond Marcland, F-87025 Limoges, France; [Bouramtane, Soukaina; Bregier, Frederique; Sol, Vincent; Chaleix, Vincent] Univ Limoges, Fac Sci & Tech, Lab PEIRENE EA 7500, 123 Ave Albert Thomas, F-87060 Limoges, France; [Ouk, Catherine; Carrion, Claire] Univ Limoges, BISCEm Pole Cytometrie Flux Microscop, 2 Rue Docteur Raymond Marcland, F-87025 Limoges, France; [Richard, Laurence; Chaunavel, Alain] CHU Limoges, Serv Anat Pathol, 2 Ave Martin Luther King, F-87042 Limoges, France; [Perrin, Marie-Laure] Univ Limoges, Fac Med, Lab Bio XLIM UMR CNRS 7252, 2 Rue Docteur Raymond Marcland, F-87025 Limoges, France		Liagre, B (corresponding author), Univ Limoges, Fac Pharm, Lab PEIRENE EA 7500, 2 Rue Docteur Raymond Marcland, F-87025 Limoges, France.	ludovic.bretin@unilim.fr; aline.pinon@unilim.fr; soukaina.bouramtane@unilim.fr; catherine.ouk@unilim.fr; laurence.richard@unilim.fr; marie-laure.perrin@unilim.fr; alain.chaunavel@chu-limoges.fr; claire.carrion@unilim.fr; frederique.bregier@unilim.fr; vincent.sol@unilim.fr; vincent.chaleix@unilim.fr; david.leger@unilim.fr; bertrand.liagre@unilim.fr	BREGIER, Frederique/AAX-5993-2020	BREGIER, Frederique/0000-0002-9880-7616; Pinon, Aline/0000-0002-3123-7495; carrion, claire/0000-0003-3221-6319; Liagre, Bertrand/0000-0003-4148-2598; BRETIN, Ludovic/0000-0002-2949-0512; chaleix, vincent/0000-0002-5324-3095; bouramtane, soukaina/0000-0002-7972-5148; sol, vincent/0000-0003-0175-0156; CHAUNAVEL, Alain/0000-0003-2419-8974	Ministere de l'Enseignement Superieur, de la Recherche et de l'Innovation through the European Fund of Regional Development FEDER; Conseil Regional Nouvelle Aquitaine	The expenses of this work were defrayed in part by the Ministere de l'Enseignement Superieur, de la Recherche et de l'Innovation through the European Fund of Regional Development FEDER 2014-2020 and by the Conseil Regional Nouvelle Aquitaine.	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J	Zhao, WH; Shi, FQ; Guo, ZK; Zhao, JJ; Song, XY; Yang, H				Zhao, Wenhua; Shi, Fengqiang; Guo, Zhikun; Zhao, Jiaojie; Song, Xueying; Yang, Hua			Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells	MOLECULAR CARCINOGENESIS			English	Article						autophagy; colorectal cancer; matrix metallo proteinases; metastasis; urolithin A	TEA POLYPHENOLS; ELLAGIC ACID; IN-VITRO; POMEGRANATE ELLAGITANNINS; DIETARY POLYPHENOLS; APOPTOSIS; MIGRATION; INVASION; INVOLVEMENT; EXPRESSION	Autophagy is an evolutionarily conserved pathway in which cytoplasmic contents are degraded and recycled. This study found that submicromolar concentrations of urolithin A, a major polyphenol metabolite, induced autophagy in SW620 colorectal cancer (CRC) cells. Exposure to urolithin A also dose-dependently decreased cell proliferation, delayed cell migration, and decreased matrix metalloproteinas-9 (MMP-9) activity. In addition, inhibition of autophagy by Atg5-siRNA, caspases by Z-VAD-FMK suppressed urolithin A-stimulated cell death and anti-metastatic effects. Micromolar urolithin A concentrations induced both autophagy and apoptosis. Urolithin A suppressed cell cycle progression and inhibited DNA synthesis. These results suggest that dietary consumption of urolithin A could induce autophagy and inhibit human CRC cell metastasis. Urolithins may thus contribute to CRC treatment and offer an alternative or adjunct chemotherapeutic agent to combat this disease.	[Zhao, Wenhua; Shi, Fengqiang; Guo, Zhikun; Zhao, Jiaojie; Song, Xueying; Yang, Hua] Capital Med Univ, Sch Pharmaceut Sci, Beijing 100069, Peoples R China		Zhao, WH (corresponding author), Capital Med Univ, Sch Pharmaceut Sci, Beijing 100069, Peoples R China.	zwhua@ccmu.edu.cn			National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21201124]; Beijing Municipal Institutions [CITTCD201304176]; Chinese Government [Z141100002114049, KM201310025007]	National Science Foundation of China, Grant number: 21201124; Beijing Municipal Institutions, Grant number: CIT&TCD201304176; Chinese Government, Grant number: Z141100002114049; Chinese Government, Grant number: KM201310025007	Adams LS, 2010, CANCER PREV RES, V3, P108, DOI 10.1158/1940-6207.CAPR-08-0225; agata RT, 2015, ONCOTARGET, V27, P1; Aichinger G, 2017, MOL NUTR FOOD RES, V61, DOI 10.1002/mnfr.201600462; Babykutty S, 2012, MOL CARCINOGEN, V51, P475, DOI 10.1002/mc.20812; Bendardaf R, 2010, CANCER INVEST, V28, P38, DOI 10.3109/07357900802672761; Bialonska D, 2009, J AGR FOOD CHEM, V57, P10181, DOI 10.1021/jf9025794; Cho H, 2015, FOOD FUNCT, V6, P1675, DOI 10.1039/c5fo00274e; Deryugina EI, 2006, CANCER METAST REV, V25, P9, DOI 10.1007/s10555-006-7886-9; Dong YH, 2014, AUTOPHAGY, V10, P296, DOI 10.4161/auto.27210; Fantini M, 2015, INT J MOL SCI, V16, P9236, DOI 10.3390/ijms16059236; Ferraresi A, 2017, MOL CARCINOGEN, V56, P1164, DOI 10.1002/mc.22582; Filomeni G, 2010, AUTOPHAGY, V6, P202, DOI 10.4161/auto.6.2.10971; Furlanetto V, 2012, J AGR FOOD CHEM, V60, P9162, DOI 10.1021/jf302600q; Gewirtz DA, 2013, AUTOPHAGY, V9, P1263, DOI 10.4161/auto.25233; Gimenez-Bastida JA, 2012, FOOD CHEM, V132, P1465, DOI 10.1016/j.foodchem.2011.12.003; Gonzalez-Sarrias A, 2016, MOL NUTR FOOD RES, V60, P701, DOI 10.1002/mnfr.201500780; Gonzalez-Sarrias A, 2015, FOOD FUNCT, V6, P1460, DOI [10.1039/C5FO00120J, 10.1039/c5fo00120j]; Gonzalez-Sarrias A, 2009, MOL NUTR FOOD RES, V53, P686, DOI 10.1002/mnfr.200800150; Halder B, 2008, CARCINOGENESIS, V29, P129, DOI 10.1093/carcin/bgm233; Haraguchi T, 2014, J AGR FOOD CHEM, V62, P5589, DOI 10.1021/jf501142k; Ito S, 2007, INT J ONCOL, V31, P261; Jane EP, 2017, MOL CARCINOGEN, V56, P1251, DOI 10.1002/mc.22587; Kang I, 2016, MOL NUTR FOOD RES, V60, P1129, DOI 10.1002/mnfr.201500796; Kasimsetty SG, 2010, J AGR FOOD CHEM, V58, P2180, DOI 10.1021/jf903762h; Kasimsetty SG, 2009, J AGR FOOD CHEM, V57, P10636, DOI 10.1021/jf902716r; Khan N, 2015, CANCER LETT, V359, P155, DOI 10.1016/j.canlet.2015.01.038; Lall RK, 2015, INT J MOL SCI, V16, P3350, DOI 10.3390/ijms16023350; Landete JM, 2011, FOOD RES INT, V44, P1150, DOI 10.1016/j.foodres.2011.04.027; Larrosa M, 2010, J NUTR BIOCHEM, V21, P717, DOI 10.1016/j.jnutbio.2009.04.012; Lee Won Sup, 2014, J Cancer Prev, V19, P14; Liao CC, 2013, AUTOPHAGY, V9, P5, DOI 10.4161/auto.22379; Trung LQ, 2015, MOL NUTR FOOD RES, V59, P2143, DOI 10.1002/mnfr.201500166; Martinez-Perez C, 2016, BRIT J CANCER, V114, P905, DOI 10.1038/bjc.2016.6; Mukherjee S, 2013, J NUTR BIOCHEM, V24, P2040, DOI 10.1016/j.jnutbio.2013.07.005; Nitta T, 2014, INT J CLIN EXP PATHO, V7, P4913; O'Connell JB, 2004, JNCI-J NATL CANCER I, V96, P1420, DOI 10.1093/jnci/djh275; Olennikov DN, 2015, NUTRIENTS, V7, P8456, DOI 10.3390/nu7105406; Piwowarski JP, 2015, MOL NUTR FOOD RES, V59, P2168, DOI 10.1002/mnfr.201500264; Qiu ZP, 2013, FOOD CHEM TOXICOL, V59, P428, DOI 10.1016/j.fct.2013.06.025; Rodriguez J, 2017, MOL NUTR FOOD RES, V61, DOI 10.1002/mnfr.201600169; Sancho M, 2015, NUTR HOSP, V31, P535, DOI 10.3305/nh.2015.31.2.8091; Su ZY, 2015, MOL CANCER, V14, DOI 10.1186/s12943-015-0321-5; Thakur VS, 2012, CARCINOGENESIS, V33, P377, DOI 10.1093/carcin/bgr277; Thorburn A, 2014, MOL PHARMACOL, V85, P830, DOI 10.1124/mol.114.091850; Tian LL, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2016.455; Tomas-Barberan FA, 2017, MOL NUTR FOOD RES, V61, DOI 10.1002/mnfr.201500901; Tyagi N, 2010, J RECEPT SIG TRANSD, V30, P78, DOI 10.3109/10799891003614808; Yang MP, 2015, ONCOTARGET, V6, P7084, DOI 10.18632/oncotarget.3054; Yu XF, 2017, SCI REP-UK, V7, DOI 10.1038/srep42226; Zakraoui O, 2017, MOL CARCINOGEN, V56, P18, DOI 10.1002/mc.22470; Zhao WH, 2015, J CHROMATOGR B, V990, P111, DOI 10.1016/j.jchromb.2015.03.024; Zhao WH, 2014, BIOCHEM BIOPH RES CO, V445, P346, DOI 10.1016/j.bbrc.2014.01.191; Zhao X, 2014, NUTRIENTS, V6, P3084, DOI 10.3390/nu6083084	53	34	35	2	24	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0899-1987	1098-2744		MOL CARCINOGEN	Mol. Carcinog.	FEB	2018	57	2					193	200		10.1002/mc.22746			8	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	FR9PI	WOS:000419405200005	28976622	hybrid, Green Published			2022-04-25	
J	Jing, Z; Fei, WQ; Zhou, JC; Zhang, LM; Chen, LX; Zhang, XM; Liang, X; Xie, JS; Fang, Y; Sui, XB; Han, WD; Pan, HM				Jing, Zhao; Fei, Weiqiang; Zhou, Jichun; Zhang, Lumin; Chen, Liuxi; Zhang, Xiaomin; Liang, Xiao; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming			Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells	ONCOTARGET			English	Article						salvianolic acid B; natural compound; autophagy; cell death; colorectal cancer	CERVICAL-CANCER; APOPTOSIS; PATHWAY; ACTIVATION; EXPRESSION; RESISTANCE; INHIBITOR; MECHANISM; P38	Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway.	[Jing, Zhao; Chen, Liuxi; Zhang, Xiaomin; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Med Oncol, Coll Med, Hangzhou, Zhejiang, Peoples R China; [Jing, Zhao; Fei, Weiqiang; Zhang, Lumin; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming] Zhejiang Univ, Coll Med, Biomed Res Ctr, Hangzhou, Zhejiang, Peoples R China; [Jing, Zhao; Fei, Weiqiang; Zhang, Lumin; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming] Zhejiang Univ, Coll Med, Key Lab Biotherapy Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China; [Zhou, Jichun] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Surg Oncol, Coll Med, Hangzhou, Zhejiang, Peoples R China; [Liang, Xiao] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gen Surg, Coll Med, Hangzhou, Zhejiang, Peoples R China		Sui, XB; Han, WD; Pan, HM (corresponding author), Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Med Oncol, Coll Med, Hangzhou, Zhejiang, Peoples R China.; Sui, XB; Han, WD; Pan, HM (corresponding author), Zhejiang Univ, Coll Med, Biomed Res Ctr, Hangzhou, Zhejiang, Peoples R China.; Sui, XB; Han, WD; Pan, HM (corresponding author), Zhejiang Univ, Coll Med, Key Lab Biotherapy Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China.	hzzju@aliyun.com; hanwd@126.com; drpanhm@aliyun.com	Zhou, Jichun/Q-8646-2019	Zhou, Jichun/0000-0002-0727-4034	Zhejiang province science and technology project of TCM [2015ZB033]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81301891, 81572361, 81572592]; Zhengshu Medical Elite Scholarship Fund	This study is supported by grants from Zhejiang province science and technology project of TCM (grant No. 2015ZB033), National Natural Science Foundation of China (grant No. 81301891, 81572361 and 81572592) and Zhengshu Medical Elite Scholarship Fund.	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J	Al-Harbi, SA; Abdulrahman, AO; Zamzami, MA; Khan, MI				Al-Harbi, Sami A.; Abdulrahman, Abdulrasheed O.; Zamzami, Mazin A.; Khan, Mohammad Imran			Urolithins: The Gut Based Polyphenol Metabolites of Ellagitannins in Cancer Prevention, a Review	FRONTIERS IN NUTRITION			English	Review						anticancer; ellagitannins; metabolites; polyphenols; urolithins	ELLAGIC ACID; CELL-CYCLE; COLONIC METABOLITE; COLORECTAL-CANCER; IN-VITRO; ANTIPROLIFERATIVE ACTIVITY; POMEGRANATE ELLAGITANNINS; MICROBIOTA METABOLITE; NATURAL POLYPHENOLS; DIETARY POLYPHENOLS	Cancer as a disease continues to ravage the world population without regard to sex, age, and race. Due to the growing number of cases worldwide, cancer exerts a significant negative impact on global health and the economy. Interestingly, chemotherapy has been used over the years as a therapeutic intervention against cancer. However, high cost, resistance, and toxic by-effects to treatment have overshadowed some of its benefits. In recent times, efforts have been ongoing in searching for anticancer therapeutics of plant origin, focusing on polyphenols. Urolithins are secondary polyphenol metabolites derived from the gut microbial action on ellagitannins and ellagic acid-rich foods such as pomegranate, berries, and nuts. Urolithins are emerging as a new class of anticancer compounds that can mediate their cancer-preventive activities through cell cycle arrest, aromatase inhibition, induction of apoptosis, tumor suppression, promotion of autophagy, and senescence, transcriptional regulation of oncogenes, and growth factor receptors. In this review, we discussed the growing shreds of evidence supporting these secondary phenolic metabolites' anticancer properties. Furthermore, we have pointed out some of the future directions needed to establish urolithins as anticancer agents.	[Al-Harbi, Sami A.] Umm Al Qura Univ, Univ Coll Al Jamoum, Dept Chem, Mecca, Saudi Arabia; [Abdulrahman, Abdulrasheed O.; Zamzami, Mazin A.; Khan, Mohammad Imran] King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah, Saudi Arabia; [Zamzami, Mazin A.; Khan, Mohammad Imran] King Abdulaziz Univ, Fac Sci, Canc Metab & Epigenet Unit, Jeddah, Saudi Arabia		Khan, MI (corresponding author), King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah, Saudi Arabia.; Khan, MI (corresponding author), King Abdulaziz Univ, Fac Sci, Canc Metab & Epigenet Unit, Jeddah, Saudi Arabia.	mikhan@kau.edu.sa	Abdulrahman, Abdulrasheed O./AAT-6410-2021	Al-Harbi, Sami A. Al-Harbi/0000-0002-8263-0641	Deanship of Scientific Research at Umm Al-Qura University [19-SCI-1-01-0031]	The authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant Code: 19-SCI-1-01-0031.	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Nutr.	JUN 7	2021	8								647582	10.3389/fnut.2021.647582			15	Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Nutrition & Dietetics	SV3OS	WOS:000663732400001	34164422	Green Published, gold			2022-04-25	
J	Li, X; Xia, L; Ouyang, XH; Suyila, Q; Su, LY; Su, XL				Li, Xian; Xia, Long; Ouyang, Xiaohui; Suyila, Qimuge; Su, Liya; Su, Xiulan			Bioactive Peptides Sensitize Cells to Anticancer Effects of Oxaliplatin in Human Colorectal Cancer Xenografts in Nude Mice	PROTEIN AND PEPTIDE LETTERS			English	Article						Anticancer peptide activity; oxaliplatin; colorectal cancer; nude mouse xenograft; bioactive peptides apoptosis; tumors	CHEMOTHERAPY; APOPTOSIS; AUTOPHAGY; GROWTH; DEATH	Background: Despite new agent development and short-term benefits in patients with Colorectal Cancer (CRC), metastatic CRC cure rates have not improved due to high rates of oxaliplatin resistance and toxicity. There is an urgent need for effective tools to prevent and treat CRC and reduce morbidity and mortality of CRC patients. Exploring the effects of bioactive peptides on the antitumor to CRC was of vital importance to the clinical application. Objective: This study aimed to investigate the therapeutic impact of Anticancer Bioactive Peptides (ACBP) on anticancer effect of oxaliplatin (LOHP) in human colorectal cancer xenografts models in nude mice. Methods: HCT-116 cells were cultured in vitro via CCK-8 assays and the absorbance was measured at 450 nm. Apoptosis and cell cycle were assessed by Flow Cytometry (FCM) in vitro. HCT-1 16 human colorectal cancer cells inoculated subcutaneously in nude mice of treatment with PBS (GG), ACBP, LOHP, ACBP+LOHP (A+L) in vivo. The quality of life was assessed by dietary amount of nude mice, the weight of nude mice, inhibition rates, tumor weight and tumor volume. Immunohistochemistry and RT-qPCR method was conducted to determine the levels of apoptosis regulating proteins/genes in transplanted tumors. Results: ACBP induced substantial reductions in viable cell numbers and apoptosis of HCT116 cells in combined with LOHP in vitro. Compared with the control GG group, ACBP combined low dose oxaliplatin (U) group demonstrated significantly different tumor volume, the rate of apoptosis, the expression levels of Cyt-C, caspase-3,8,9 proteins and corresponding RNAs (P<0.05). The expression of pro-apoptotic proteins in the cytoplasm around the nucleus was significantly enhanced by ACBP. Short term intermittent use of ACBP alone indicted a certain inhibitory effect on tumor growth, and improve the quality of life of tumor bearing nude mice. Conclusion: ACBP significantly increased the anti-cancer responses of low dose oxaliplatin (L-LOHP), thus, significantly improving the quality of life of tumor-bearing nude mice.	[Li, Xian; Xia, Long; Ouyang, Xiaohui; Suyila, Qimuge; Su, Liya; Su, Xiulan] Inner Mongolia Med Univ, Affiliated Hosp, Clin Med Res Ctr, Hohhot 010050, Inner Mongolia, Peoples R China		Su, XL (corresponding author), Inner Mongolia Med Univ, Affiliated Hosp, Clin Med Res Ctr, Hohhot 010050, Inner Mongolia, Peoples R China.	xlsu@hotmail.com	苏, 丽/AAM-5834-2021		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81660468, 81860541]; Natural Science Foundation of Inner Mongolia Autonomous region [2017BS0812]; General project of Clinical Medical Research Center, Affiliated Hospital of Inner Mongolia Medical University, China [NYFY YB044]	This study was financed by the National Natural Science Foundation of China (81660468 and 81860541), Natural Science Foundation of Inner Mongolia Autonomous region (2017BS0812) and General project of Clinical Medical Research Center, Affiliated Hospital of Inner Mongolia Medical University, China (NYFY YB044).	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J	Lai, K; Killingsworth, MC; Lee, CS				Lai, K.; Killingsworth, M. C.; Lee, C. S.			Gene of the month: PIK3CA	JOURNAL OF CLINICAL PATHOLOGY			English	Article							COLORECTAL-CANCER; ONCOGENIC MUTATIONS; HIGH-FREQUENCY; PTEN LOSS; HEAD; NECK; INHIBITOR; CORRELATE; NVP-BYL719; CARCINOMA	PIK3CA encodes the p110 alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K) which through its role in the PI3K/Akt pathway is important for the regulation of important cellular functions such as proliferation, metabolism and protein synthesis, angiogenesis and apoptosis. Mutations in PIK3CA are known to be involved in a wide range of human cancers and mutant PIK3CA is thought to act as an oncogene. The specific PIK3CA inhibitor, NVP-BYL719, has displayed promising results in cancer therapy and is currently under clinical trials. Furthermore, PI3K regulates autophagy, a cellular process that recycles proteins and organelles through lysosomal degradation and has recently been recognised as an attractive therapeutic target due to its pro-and anti-cancer properties. Several studies have attempted to investigate the effects of combining the inhibition of both PI3K and autophagy in cancer therapy, and an in vivo model has demonstrated that the combined use of a concomitant PI3K and autophagy inhibitor induced apoptosis in glioma cells.	[Lai, K.; Lee, C. S.] Ingham Inst Appl Med Res, Sydney, NSW, Australia; [Lai, K.; Killingsworth, M. C.; Lee, C. S.] Univ Western Sydney, Sch Med, Discipline Pathol & Mol Med, Liverpool, NSW 2170, Australia; [Lai, K.; Killingsworth, M. C.; Lee, C. S.] Univ Western Sydney, Sch Med, Res Grp, Liverpool, NSW 2170, Australia; [Lai, K.] Univ Sydney, Dept Pathol, Sydney, NSW 2006, Australia; [Lai, K.; Killingsworth, M. C.] Liverpool Hosp, Electron Microscopy Lab, Sydney, NSW, Australia; [Lai, K.; Killingsworth, M. C.; Lee, C. S.] Liverpool Hosp, Dept Anat Pathol, Sydney, NSW, Australia; [Lee, C. S.] Univ Sydney, Bosch Inst, Canc Pathol, Sydney, NSW 2006, Australia		Lai, K (corresponding author), Univ Western Sydney, Sch Med, Discipline Pathol & Mol Med, Liverpool, NSW 2170, Australia.	ken.lai@uws.edu.au	ravegnini, gloria/K-1330-2016; Killingsworth, Murray/O-3736-2019; Killingsworth, Murray C/G-5908-2015	ravegnini, gloria/0000-0002-7774-402X; Killingsworth, Murray/0000-0002-6125-1183; Lee, C. 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Clin. Pathol.	APR	2015	68	4					253	257		10.1136/jclinpath-2015-202885			5	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	CD6XG	WOS:000351233100001	25688137				2022-04-25	
J	O'Connell, CE; Vassilev, A				O'Connell, Constandina E.; Vassilev, Alex			Combined Inhibition of p38MAPK and PIKfyve Synergistically Disrupts Autophagy to Selectively Target Cancer Cells	CANCER RESEARCH			English	Article							P38 MAP KINASE; ACTIVATION; THERAPY; DRUG; COMBINATION; P38-ALPHA; PATHWAYS; STRESS	In nutrient-poor conditions, autophagy buffers metabolic stress and counteracts the effects of chemotherapy and radiation on cancer cells, which depend on autophagy for survival. However, clinical trials targeting autophagy have failed to produce successful anticancer treatments using currently available inhibitors. Recent studies have shown that PIKfyve kinase inhibitors disrupt lysosome function in autophagy and can selectively kill certain cancer cells. Analysis of biochemical changes caused by PIKfyve inhibition revealed that resistant cells contain significantly higher levels of cellular p38MAPK protein and phosphorylation. Expression of the lysosomal protein, lysosomal-associated membrane protein 2, carrying phosphomimetic mutations of the p38MAPK phosphorylation sites prevented all effects caused by PIKfyve inhibition-induced lysosome dysfunction. Thus, the activation of p38MAPK in response to PIKfyve inhibition revealed a novel compensatory role in maintaining lysosome function in autophagy. The functional cooperation between the cellular PIKfyve and p38MAPK pathways in regulating lysosome homeostasis was especially important in cancer cells. Combined inhibition of PIKfyve and p38MAPK activities synergistically blocked autophagy-mediated protein degradation, prevented cathepsin maturation, and markedly reduced the viability of multiple cancer cell types without affecting the viability of normal cells. Furthermore, combined PIKfyve and p38MAPK inhibitors synergistically reduced tumor growth in mice bearing xenografts of human colorectal adenocarcinoma, suggesting a novel way to target cancer cells by prolonged inhibition of autophagy using lower drug concentrations. Significance: This study demonstrates that PIKfyve and p38MAPK cooperate to regulate lysosome homeostasis and their combined inhibition synergistically blocks autophagy to reduce cancer cell viability in vitro and in vivo.	[O'Connell, Constandina E.; Vassilev, Alex] NICHHD, NIH, Bethesda, MD 20892 USA		Vassilev, A (corresponding author), NICHHD, NIH, Bethesda, MD 20892 USA.	vassilev@nih.gov			Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural research program [ZIA HD000506, ZIA HD000507]	The authors thank Dr. Elaine Jordan for providing training and expertise with the xenograft studies. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural research program (ZIA HD000506 and ZIA HD000507).	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JUN 1	2021	81	11					2903	2917		10.1158/0008-5472.CAN-20-3371			15	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	SO9ML	WOS:000659297500012	33685990	Bronze, Green Accepted			2022-04-25	
J	Bader, S; Wilmers, J; Ontikatze, T; Ritter, V; Jendrossek, V; Rudner, J				Bader, Sina; Wilmers, Julia; Ontikatze, Teona; Ritter, Violetta; Jendrossek, Verena; Rudner, Justine			Loss of pro-apoptotic Bax and Bak increases resistance to dihydroartemisinin-mediated cytotoxicity in normoxia but not in hypoxia in HCT116 colorectal cancer cells	FREE RADICAL BIOLOGY AND MEDICINE			English	Article						Hypoxia; Therapy resistance; Dihydroartemisinin; Reactive oxygen species; Lipid peroxidation; Apoptosis; Glutathione	MECHANISMS; ACTIVATION; ARTESUNATE; AUTOPHAGY; ARTEMISININ; EXPRESSION; OXIDATION; EXPOSURE; THERAPY; STRESS	Tumor hypoxia is a major biological factor that drives resistance to chemotherapy and radiotherapy. We previously demonstrated that the pro-oxidative drug dihydroartemisinin (DHA) efficiently targeted normoxic and hypoxic cancer cells. Although well studied in normoxia, the mechanism behind DHA-mediated cytotoxicity in hypoxia is insufficiently explored. Here, we analyzed the effect of DHA in HCT116 wild type (wt) cells and in HCT116 Bax-/-Baksh cells with a defective intrinsic apoptosis pathway. Normoxic HCT116 wt cells underwent apoptosis shortly after treatment with DHA. Autophagy-associated cell death contributes to short-term cytotoxicity of DHA in normoxia. These cells switched to an apoptosis- and autophagy-independent cell death after treatment with DHA in hypoxia and displayed similar long-term survival in response to DHA in normoxia and hypoxia. In HCT116 Bax- /-Baksh cells, DHA induced cell cycle arrest shortly after treatment irrespective of oxygen levels. Later, HCT116 Bax-/-Baksh cells induced a delayed cell death after treatment with DHA in hypoxia followed by return to normoxia, while treatment with DHA in normoxia was hardly toxic. We identified lower glutathione levels in hypoxic HCT116 cells which correlated with higher lipid peroxidation after treatment with DHA. Moreover, insufficient expression of Bax/Bak counteracted hypoxiamediated downregulation of mitochondrial function, thereby adding to DHA-induced ROS production and lipid peroxidation in hypoxia. In summary, DHA-mediated cytotoxicity in normoxia depended on Bax/Bak expression, while cytotoxicity after treatment with DHA in hypoxia was regulated independently of Bax/Bak in HCT116 colorectal cancer cells.	[Bader, Sina; Wilmers, Julia; Ontikatze, Teona; Ritter, Violetta; Jendrossek, Verena; Rudner, Justine] Univ Duisburg Essen, Univ Hosp Essen, Inst Cell Biol Canc Res, Essen, Germany		Rudner, J (corresponding author), Univ Hosp Essen, Dept Mol Cell Biol, Inst Cell Biol Tumor Res, Virchowstr 173, D-45122 Essen, Germany.	justine.rudner@uk-essen.de	Rudner, Justine/ABD-1397-2021; Jendrossek, Verena/ABD-2190-2021	Rudner, Justine/0000-0002-5067-755X	Deutsche Krebshilfe/Mil-dred Scheel StiftungDeutsche Krebshilfe [110344, 70112711]; DFG Research Training GroupGerman Research Foundation (DFG) [GRK1739/2]	This work was supported by grants of the Deutsche Krebshilfe/Mil-dred Scheel Stiftung (No.110344 to VJ and No. 70112711 to JR and VJ) as well as the DFG Research Training Group (GRK1739/2 to VJ) .	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Biol. Med.	OCT	2021	174						157	170		10.1016/j.freeradbiomed.2021.08.012		AUG 2021	14	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	UL2WO	WOS:000692517600004	34403740				2022-04-25	
J	Silva-Pavez, E; Villar, P; Trigo, C; Caamano, E; Niechi, I; Perez, P; Munoz, JP; Aguayo, F; Burzio, VA; Varas-Godoy, M; Castro, AF; Colombo, MI; Tapia, JC				Silva-Pavez, Eduardo; Villar, Paulina; Trigo, Cesar; Caamano, Esteban; Niechi, Ignacio; Perez, Pablo; Munoz, Juan P.; Aguayo, Francisco; Burzio, Veronica A.; Varas-Godoy, Manuel; Castro, Ariel F.; Colombo, Maria, I; Tapia, Julio C.			CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells	CELL DEATH & DISEASE			English	Article							PROTEIN-KINASE CK2; MTOR-SIGNALING PATHWAY; MAMMALIAN TARGET; DOWN-REGULATION; INDUCED APOPTOSIS; AUTOPHAGY; EXPRESSION; RAPAMYCIN; GROWTH; VIABILITY	Protein kinase CK2 is a highly conserved and constitutively active Ser/Thr-kinase that phosphorylates a large number of substrates, resulting in increased cell proliferation and survival. A known target of CK2 is Akt, a player in the PI3K/Akt/ mTORC1 signaling pathway, which is aberrantly activated in 32% of colorectal cancer (CRC) patients. On the other hand, mTORC1 plays an important role in the regulation of protein synthesis, cell growth, and autophagy. Some studies suggest that CK2 regulates mTORC1 in several cancers. The most recently developed CK2 inhibitor, silmitasertib (formerly CX-4945), has been tested in phase I/II trials for cholangiocarcinoma and multiple myeloma. This drug has been shown to induce autophagy and enhance apoptosis in pancreatic cancer cells and to promote apoptosis in nonsmall cell lung cancer cells. Nevertheless, it has not been tested in studies for CRC patients. We show in this work that inhibition of CK2 with silmitasertib decreases in vitro tumorigenesis of CRC cells in response to G2/M arrest, which correlates with mTORC1 inhibition and formation of large cytoplasmic vacuoles. Notably, molecular markers indicate that these vacuoles derive from massive macropinocytosis. Altogether, these findings suggest that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers.	[Silva-Pavez, Eduardo; Villar, Paulina; Trigo, Cesar; Caamano, Esteban; Niechi, Ignacio; Perez, Pablo; Munoz, Juan P.; Aguayo, Francisco; Tapia, Julio C.] Univ Chile, Fac Med, Dept Oncol Basico Clin, Santiago, Chile; [Burzio, Veronica A.] Univ Andres Bello, Fdn Ciencia & Vida, Andes Biotechnol SpA, Fac Ciencias Vida, Santiago, Chile; [Varas-Godoy, Manuel] Univ Los Andes, Fac Med, Ctr Invest Biomed, Santiago, Chile; [Castro, Ariel F.] Univ Concepcion, Dept Bioquim & Biol Mol, Fac Ciencias Biol, Lab Transducc Senales & Canc, Concepcion, Chile; [Colombo, Maria, I] Univ Nacl Cuyo, CONICET, Fac Ciencias Med, Inst Histol & Embriol,Lab Biol Celular & Mol, Mendoza, Argentina; [Niechi, Ignacio] Univ Austral Chile, Fac Ciencias, Lab Patol Mol, Inst Bioquim & Microbiol, Valdivia, Chile		Tapia, JC (corresponding author), Univ Chile, Fac Med, Dept Oncol Basico Clin, Santiago, Chile.	jtapia@med.uchile.cl	Pineda, Julio Tapia/AAW-8949-2020	Pineda, Julio Tapia/0000-0003-1678-2708; Niechi, Ignacio/0000-0003-1857-8698; Varas-Godoy, Manuel/0000-0001-5857-4793	CONICYT-FONDECYT-ChileComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)CONICYT FONDECYT [1140345, 1161219, 11150624, 1160731, 1160889]; Universidad Nacional de Cuyo [SeCTyP 06/J432]; Agencia Nacional de Investigacion Cientifica y Tecnologica, Argentina [PICT2013-0305]; CONICYT-FONDAP-Chile grant [15130011]	We thank Felix Urra, Hernan Huerta, and Barbara Pesce (Universidad de Chile), Diego A. Rodriguez (St. Jude Children's Research Hospital), as well as Milagros Lopez de Armentia (Universidad Nacional de Cuyo) for their valuable technical support in some cytometry, soft-agar, necroptosis and microscopy analysis. This work was supported by CONICYT-FONDECYT-Chile grants #1140345 (to V.A.B.), #1161219 (to F.A.), #11150624 (to M.V.G.), #1160731 (to A.F.C.) and #1160889 (to J.C.T.); CONICYT-FONDAP-Chile grant #15130011 (to F.A.); SeCTyP 06/J432 grant from Universidad Nacional de Cuyo and PICT2013-0305 grant from Agencia Nacional de Investigacion Cientifica y Tecnologica, Argentina (to M.I.C.).	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JAN 25	2019	10								73	10.1038/s41419-019-1306-x			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	HJ2SI	WOS:000457019800016	30683840	gold, Green Published			2022-04-25	
J	Wu, L; Yang, LL				Wu, Lei; Yang, Lili			The function and mechanism of HMGB1 in lung cancer and its potential therapeutic implications	ONCOLOGY LETTERS			English	Review						high-mobility group protein B1; lung cancer; proliferation; function	GLYCATION END-PRODUCTS; GROUP BOX-1 PROTEIN; BRONCHIAL EPITHELIAL-CELLS; TOLL-LIKE RECEPTORS; BACTERIAL CPG-DNA; HEPATOCELLULAR-CARCINOMA; INFLAMMATORY RESPONSES; ADENOCARCINOMA CELLS; REGULATES AUTOPHAGY; SODIUM-SALICYLATE	As a non-histone chromatin-associated protein, high-mobility group box-1 (HMGB1) performs a pivotal function in various human diseases, including autoimmune diseases, neurodegenerative diseases and cancer. Overexpression of HMGB1 has been demonstrated in numerous types of cancer, including breast cancer, colorectal cancer, lung cancer and hepatocellular carcinoma. However, the underlying mechanism of HMGB1 function in lung cancer remains to be elucidated. The present study aimed to analyze, and summarize the role and mechanism of HMGB1 in lung cancer by retrieving available literature regarding HMGB1 in association with lung cancer. It provides comprehensive information on the association of HMGB1 with the carcinogenesis and progression of lung cancer, and discusses the molecular mechanism of these processes. HMGB1 may induce tumorigenesis, metastasis and chemotherapy resistance in lung cancer. Overall, it is evident that HMGB1 serves an important role in the development and progression of lung cancer, and this review warrants further investigation into HMGB1 as a novel target for cancer therapy.	[Wu, Lei; Yang, Lili] Tianjin Med Univ, Tianjin Canc Inst & Hosp, Dept Immunol, Huanhuxi Rd, Tianjin 300060, Peoples R China; [Wu, Lei; Yang, Lili] Tianjin Med Univ, Natl Clin Res Ctr Canc, Tianjin Canc Inst & Hosp, Tianjin 300060, Peoples R China; [Wu, Lei; Yang, Lili] Tianjin Med Univ, Key Lab Canc Immunol & Biotherapy, Tianjin Canc Inst & Hosp, Tianjin 300060, Peoples R China		Yang, LL (corresponding author), Tianjin Med Univ, Tianjin Canc Inst & Hosp, Dept Immunol, Huanhuxi Rd, Tianjin 300060, Peoples R China.	yanglili@tjmuch.com			National Key Technology RD ProgramNational Key Technology R&D Program [2015BAI12B12]; Key Projects of Tianjin Health Industry [15KG145]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572265, 31500736]	The present study was supported by the National Key Technology R&D Program (grant no. 2015BAI12B12), Key Projects of Tianjin Health Industry (grant no. 15KG145) and the National Natural Science Foundation of China (grant no. 81572265 and 31500736).	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Lett.	MAY	2018	15	5					6799	6805		10.3892/ol.2018.8215			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GF3DN	WOS:000431825900094	29725415	Green Published, gold			2022-04-25	
J	Lizarraga-Verdugo, E; Ruiz-Garcia, E; Lopez-Camarillo, C; Bermudez, M; Avendano-Felix, M; Ramos-Payan, R; Romero-Quintana, G; Ayala-Ham, A; Villegas-Mercado, C; Perez-Plasencia, C; Aguilar-Medina, M				Lizarraga-Verdugo, Erik; Ruiz-Garcia, Erika; Lopez-Camarillo, Cesar; Bermudez, Mercedes; Avendano-Felix, Mariana; Ramos-Payan, Rosalio; Romero-Quintana, Geovanni; Ayala-Ham, Alfredo; Villegas-Mercado, Carlos; Perez-Plasencia, Carlos; Aguilar-Medina, Maribel			Cell Survival Is Regulated via SOX9/BCL2L1 Axis in HCT-116 Colorectal Cancer Cell Line	JOURNAL OF ONCOLOGY			English	Article							BCL-2 PROTEIN FAMILY; X-L; SOX9; EXPRESSION; GENE; METASTASIS; AUTOPHAGY; DIFFERENTIATION; INHIBITION; ACTIVATION	Colorectal cancer (CRC) is one of the most frequent types of malignancies and one of the major causes of cancer-related death worldwide. Sex-determining region Y (SRY)-box 9 protein (SOX9) is a member of the SOX family of transcription factors which are involved in the regulation of differentiation and development. Recently, several reports suggest an important role of SOX9 in tumorigenesis since its overexpression correlates with tumor progression and poor outcome in several types of cancer; however, its role in CRC is not clear until now. Therefore, in this work, we searched for novel SOX9-regulated genes involved in cell survival of CRC. We silenced SOX9 in the poorly differentiated HCT-116 cell line, using a specific siRNA, to identify differential expressed genes by DNA microarrays and analyzed the role or candidate genes in apoptosis and autophagy. Transcriptome analysis showed that diverse cellular pathways, associated with CRC carcinogenesis such as Wnt/beta-catenin, MAPK, TGF-beta, and mTOR, were modulated after SOX9 silencing. Interestingly, we found that SOX9 silencing promotes downregulation of BCL2L1 and overexpression of CASP3, proteins related to apoptosis, which was further confirmed in SW-480, a moderated-differentiated cell line, but not in HT-29, well-differentiated cell line. Moreover, inhibition of BCL2L1 by ABT-737 (BH3 mimetic) in SOX9-silenced HCT-116 cells resulted in an increased apoptosis percentage. However, downregulation of BCL2L1 was not enough to induce autophagy. This is the first report, suggesting that cell survival in poorly and moderated-differentiated CRC cells lines is regulated by SOX9/BCL2L1 axis, but not in well-differentiated cell lines.	[Lizarraga-Verdugo, Erik; Bermudez, Mercedes; Avendano-Felix, Mariana; Ramos-Payan, Rosalio; Romero-Quintana, Geovanni; Aguilar-Medina, Maribel] Univ Autonoma Sinaloa, Fac Ciencias Quim Biol, Culiacan, Sinaloa, Mexico; [Ruiz-Garcia, Erika; Perez-Plasencia, Carlos] Inst Nacl Cancerol, Mexico City, DF, Mexico; [Lopez-Camarillo, Cesar] Univ Autonoma Ciudad Mexico, Posgrad Ciencias Genom, Mexico City, DF, Mexico; [Ayala-Ham, Alfredo; Villegas-Mercado, Carlos] Univ Autonoma Sinaloa, Fac Odontol, Culiacan, Sinaloa, Mexico		Aguilar-Medina, M (corresponding author), Univ Autonoma Sinaloa, Fac Ciencias Quim Biol, Culiacan, Sinaloa, Mexico.	eriklizarraga.fcqb@uas.edu.mx; betzabe100@yahoo.com.mx; genomicas@yahoo.com.mx; bermudezcm@uas.edu.mx; mariana_melisa25@hotmail.com; rosaliorp@uas.edu.mx; geovanniromero@uas.edu.mx; endoalfredo@uas.edu.mx; carlosvillegas@uas.edu.mx; carlos.pplas@gmail.com; maribelaguilar@uas.edu.mx	Lopez-Camarillo, Cesar/I-1946-2019	Lopez-Camarillo, Cesar/0000-0002-9417-2609; Villegas-Mercado, Carlos/0000-0001-5729-4677; Ruiz-Garcia, Erika/0000-0002-0446-123X; Perez-Plasencia, Carlos/0000-0002-8593-8211; Ramos-Payan, Rosalio/0000-0001-7500-7571	Consejo Nacional de Ciencia y Tecnologia CONACYTConsejo Nacional de Ciencia y Tecnologia (CONACyT) [290311]	The authors acknowledge Consejo Nacional de Ciencia y Tecnologia CONACYT for Mariana Avendano-Felix (575985) and Erik Lizarraga-Verdugo (304939) fellowships. The authors acknowledge Consejo Nacional de Ciencia y Tecnologia CONACYT (grant 290311) for funding.	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Oncol.	APR 29	2020	2020								5701527	10.1155/2020/5701527			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	LN9TJ	WOS:000533273200002	32411238	gold, Green Published			2022-04-25	
J	Lee, HY; Son, SW; Moeng, S; Choi, SY; Park, JK				Lee, Han Yeoung; Son, Seung Wan; Moeng, Sokviseth; Choi, Soo Young; Park, Jong Kook			The Role of Noncoding RNAs in the Regulation of Anoikis and Anchorage-Independent Growth in Cancer	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						anoikis; anchorage-independent growth; metastasis; apoptosis; noncoding RNA; microRNA; long noncoding RNA; cancer	EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA CELLS; SUPPRESSES TUMOR-METASTASIS; FOCAL ADHESION KINASE; ADENOMATOUS POLYPOSIS-COLI; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER; UP-REGULATION; COLORECTAL-CANCER; LUNG-CANCER	Cancer is a global health concern, and the prognosis of patients with cancer is associated with metastasis. Multistep processes are involved in cancer metastasis. Accumulating evidence has shown that cancer cells acquire the capacity of anoikis resistance and anchorage-independent cell growth, which are critical prerequisite features of metastatic cancer cells. Multiple cellular factors and events, such as apoptosis, survival factors, cell cycle, EMT, stemness, autophagy, and integrins influence the anoikis resistance and anchorage-independent cell growth in cancer. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are dysregulated in cancer. They regulate cellular signaling pathways and events, eventually contributing to cancer aggressiveness. This review presents the role of miRNAs and lncRNAs in modulating anoikis resistance and anchorage-independent cell growth. We also discuss the feasibility of ncRNA-based therapy and the natural features of ncRNAs that need to be contemplated for more beneficial therapeutic strategies against cancer.	[Lee, Han Yeoung; Son, Seung Wan; Moeng, Sokviseth; Choi, Soo Young; Park, Jong Kook] Hallym Univ, Dept Biomed Sci, Chunchon 24252, South Korea; [Lee, Han Yeoung; Son, Seung Wan; Moeng, Sokviseth; Choi, Soo Young; Park, Jong Kook] Hallym Univ, Res Inst Biosci & Biotechnol, Chunchon 24252, South Korea		Park, JK (corresponding author), Hallym Univ, Dept Biomed Sci, Chunchon 24252, South Korea.	gksdudsd@gmail.com; miyanae@naver.com; sokvisethmoeng@yahoo.com; sychoi@hallym.ac.kr; jkp555@hallym.ac.kr		Park, Jong Kook/0000-0002-3946-5687	National Research Foundation of Korea (NRF) - Ministry of Education [2017R1D1A3B03035662, 2019R1A6A1A11036849]; National Research Foundation of Korea (NRF) - Korea government (MSIT) [2019R1A2C1089710]	This work was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A3B03035662) (J.K.P.) and (2019R1A6A1A11036849) (S.Y.C.); and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C1089710) (J.K.P.).	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J. Mol. Sci.	JAN	2021	22	2							627	10.3390/ijms22020627			34	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	PX4HT	WOS:000611318400001	33435156	Green Published, gold			2022-04-25	
J	Glibo, M; Serman, A; Karin-Kujundzic, V; Vlatkovic, IB; Miskovic, B; Vranic, S; Serman, L				Glibo, Mislav; Serman, Alan; Karin-Kujundzic, Valentina; Vlatkovic, Ivanka Bekavac; Miskovic, Berivoj; Vranic, Semir; Serman, Ljiljana			The role of glycogen synthase kinase 3 (GSK3) in cancer with emphasis on ovarian cancer development and progression: A comprehensive review	BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES			English	Review						GSK3; ovarian cancer; therapeutic target	FACTOR-KAPPA-B; WNT-SIGNALING PATHWAY; CELL-CYCLE ARREST; URSOLIC ACID; E-CADHERIN; MESENCHYMAL TRANSITION; 3-BETA INHIBITORS; BETA-CATENIN; COLORECTAL-CANCER; INDUCED APOPTOSIS	Glycogen synthase kinase 3 (GSK3) is a monomeric serine-threonine kinase discovered in 1980 in a rat skeletal muscle. It has been involved in various cellular processes including embryogenesis, immune response, inflammation, apoptosis, autophagy, wound healing, neurodegeneration, and carcinogenesis. GSK3 exists in two different isoforms, GSK3 alpha, and GSK3 beta, both containing seven antiparallel beta-plates, a short linking part and an alpha helix, but coded by different genes and variously expressed in human tissues. In the current review, we comprehensively appraise the current literature on the role of GSK3 in various cancers with emphasis on ovarian carcinoma. Our findings indicate that the role of GSK3 in ovarian cancer development cannot be decisively determined as the currently available data support both prooncogenic and tumor-suppressive effects. Likewise, the clinical impact of GSK3 expression on ovarian cancer patients and its potential therapeutic implications are also limited. Further studies are needed to fully elucidate the pathophysiological and clinical implications of GSK3 activity in ovarian cancer.	[Glibo, Mislav; Karin-Kujundzic, Valentina; Serman, Ljiljana] Univ Zagreb, Sch Med, Dept Biol, Zagreb, Croatia; [Serman, Alan; Karin-Kujundzic, Valentina; Vlatkovic, Ivanka Bekavac; Miskovic, Berivoj; Serman, Ljiljana] Univ Zagreb, Ctr Excellence Reprod & Regenerat Med, Sch Med, Zagreb, Croatia; [Serman, Alan; Vlatkovic, Ivanka Bekavac; Miskovic, Berivoj] Univ Zagreb, Sch Med, Dept Obstet & Gynecol, Zagreb, Croatia; [Serman, Alan; Vlatkovic, Ivanka Bekavac; Miskovic, Berivoj] Clin Hosp Sveti Duh, Clin Obstet & Gynecol, Sveti Duh 64, Zagreb 10000, Croatia; [Vranic, Semir] Qatar Univ, Coll Med, QU Hlth, Doha, Qatar		Serman, A (corresponding author), Clin Hosp Sveti Duh, Clin Obstet & Gynecol, Sveti Duh 64, Zagreb 10000, Croatia.	sermana@mef.hr	Vranic, Semir/I-6823-2019	Vranic, Semir/0000-0001-9743-7265	European Union through the Europe Regional Development Fund, Operational Programme Competitiveness and Cohesion [KK.01.1.1.01.0008]	This publication was co-financed by the European Union through the Europe Regional Development Fund, Operational Programme Competitiveness and Cohesion, under grant agreement No. KK.01.1.1.01.0008, Reproductive and Regenerative Medicine - Exploring New Platforms and Potentials.	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Basic Med. Sci.		2021	21	1					5	18		10.17305/bjbms.2020.5036			14	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	PU0CO	WOS:000608975800002	32767962	Green Published, gold			2022-04-25	
J	Kim, J; Kim, D; Jung, H; Lee, J; Hong, VS				Kim, Jeongeun; Kim, Donghee; Jung, Hyunho; Lee, Jinho; Hong, Victor Sukbong			Identification and Kinetic Characterization of Serum- and Glucocorticoid-Regulated Kinase Inhibitors Using a Fluorescence Polarization-Based Assay	SLAS DISCOVERY			English	Article						serum; and glucocorticoid-regulated kinase; SGK inhibitor; kinase-focused library; thiazolidine-2; 4-dione; molecular modeling		The serum- and glucocorticoid-regulated kinase (SGK) family consists of three isoforms (SGK1, SGK2, and SGK3) that have been implicated in the regulation of tumor growth, metastasis, autophagy, and epithelial ion transport. SGK1 and SGK3 play essential roles in protein kinase B (AKT or PKB)-independent phosphoinositide 3-kinases (PI3K)-mediated tumorigenesis, as evidenced by the significantly elevated expression levels of SGK1 and SGK3 in many cancers, including prostate cancer, colorectal carcinoma, estrogen-dependent breast cancer, and glioblastoma. Therefore, SGK is a potential target for anticancer therapy. A small kinase-focused library comprising 160 compounds was screened against SGK1 using a fluorescence polarization-based kinase assay that yielded a Z'-factor of 0.82. Among the 39 compounds obtained as initial hits in a primary screen, 12 compounds contained the thiazolidine-2,4-dione scaffold. The inhibitory mechanisms of the most potent hit, KMU010402, were further investigated using kinetic analyses, followed by determination of the inhibition constants for SGK1, SGK2, and SGK3. Molecular modeling was used to propose a potential binding mode of KMU010402 to SGK1.	[Kim, Jeongeun; Kim, Donghee; Jung, Hyunho; Lee, Jinho; Hong, Victor Sukbong] Keimyung Univ, Dept Chem, Coll Nat Sci, Daegu, South Korea		Lee, J; Hong, VS (corresponding author), Keimyung Univ, Dept Chem, 1095 Dalgubeoldaero, Daegu 42601, South Korea.	jinho@kmu.ac.kr; victorh@kmu.ac.kr					Arakawa T, 2007, BIOPHYS CHEM, V131, P62, DOI 10.1016/j.bpc.2007.09.004; Castel P, 2016, CANCER CELL, V30, P229, DOI 10.1016/j.ccell.2016.06.004; Chang F, 2003, LEUKEMIA, V17, P590, DOI 10.1038/sj.leu.2402824; CROSS DAE, 1995, NATURE, V378, P785, DOI 10.1038/378785a0; Gagliardi PA, 2012, NEOPLASIA, V14, P719, DOI 10.1593/neo.12856; Gong GQ, 2018, ACTA PHARMACOL SIN, V39, P1902, DOI 10.1038/s41401-018-0087-6; Greenawalt EJ, 2019, MOL CANCER RES, V17, P289, DOI 10.1158/1541-7786.MCR-18-0364; Hong F, 2008, MOL CELL, V30, P701, DOI 10.1016/j.molcel.2008.04.027; Huw LY, 2013, ONCOGENESIS, V2, DOI 10.1038/oncsis.2013.46; Janku F, 2018, NAT REV CLIN ONCOL, V15, P273, DOI 10.1038/nrclinonc.2018.28; Jiang NN, 2020, MOL BIOL REP, V47, P4587, DOI 10.1007/s11033-020-05435-1; Kobayashi T, 1999, BIOCHEM J, V344, P189, DOI 10.1042/0264-6021:3440189; Lee S, 2016, ASSAY DRUG DEV TECHN, V14, P50, DOI 10.1089/adt.2015.685; Liu WW, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0743-1; Nakanishi Y, 2016, CANCER RES, V76, P1193, DOI 10.1158/0008-5472.CAN-15-2201; Roskoski R, 2020, PHARMACOL RES, V152, DOI 10.1016/j.phrs.2019.104609; Sanner MF, 1999, J MOL GRAPH MODEL, V17, P57; Sharlow ER, 2008, NAT PROTOC, V3, P1350, DOI 10.1038/nprot.2008.111; Sherk AB, 2008, CANCER RES, V68, P7475, DOI 10.1158/0008-5472.CAN-08-1047; Sommer EM, 2013, BIOCHEM J, V452, P499, DOI 10.1042/BJ20130342; Sportsman JR, 2004, ASSAY DRUG DEV TECHN, V2, P205, DOI 10.1089/154065804323056549; Sportsman R, 2006, DRUG DISCOV SER, V5, P85; Tessier M, 2006, J BIOL CHEM, V281, P23978, DOI 10.1074/jbc.M604333200; Truhlar DG, 2007, J COMPUT CHEM, V28, P73, DOI 10.1002/jcc.20529; Vasudevan KM, 2009, CANCER CELL, V16, P21, DOI 10.1016/j.ccr.2009.04.012; Wang YZ, 2014, MOL ENDOCRINOL, V28, P935, DOI 10.1210/me.2013-1339; Wang YZ, 2011, MOL ENDOCRINOL, V25, P72, DOI 10.1210/me.2010-0294; Zhao B, 2007, PROTEIN SCI, V16, P2761, DOI 10.1110/ps.073161707; Zhu RZ, 2020, THER ADV MED ONCOL, V12, DOI 10.1177/1758835920940946	29	1	1	1	4	SAGE PUBLICATIONS INC	THOUSAND OAKS	2455 TELLER RD, THOUSAND OAKS, CA 91320 USA	2472-5552	2472-5560		SLAS DISCOV	SLAS Discov.	JUN	2021	26	5					655	662	24725552211002465	10.1177/24725552211002465		MAR 2021	8	Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry	SF2XG	WOS:000635765800001	33783250				2022-04-25	
J	Wu, C; Tang, ZY; Chen, HY; Zhang, J; Zhao, C				Wu, C.; Tang, Z-Y; Chen, H-Y; Zhang, J.; Zhao, C.			High-expression of lncRNA CEBPA-AS1 promotes liver cancer progression	EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES			English	Article						LncRNAs; CEBPA-AS1; Liver cancer; EMT; Invasion	LONG NONCODING RNA; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; EMT; METASTASIS; PROGNOSIS; AUTOPHAGY; CELLS; ATB	OBJECTIVE: Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in the progression of different cancers. The aim of this study was to detect the expression level of lncRNA CEBPA-AS1 in liver cancer and to study its influence on cell proliferation, invasion and prognosis. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, transwell assay, Western blot, Kaplan-Meier survival curve and Cox regression were used to evaluate lncRNA CEBPA-AS1 expression, cell proliferation, invasion, epithelial-mesenchymal transition (EMT)-related molecules expression and prognosis, respectively. RESULTS: The expression of lncRNA CEB-PA-AS1 increased significantly in liver cancer tissues (p<0.05). Meanwhile, CEBPA-AS1 expression was associated with tumor size, portal vein tumor thrombus and invasion and metastasis (p<0.05). In vitro experiments indicated that downregulation of lncRNA CEBPA-AS1 could effectively reduce cell proliferation, invasion and EMT process. CONCLUSIONS: LncRNA CEBPA-AS1 acts as an oncogene in liver cancer, which may be a novel biomarker in liver cancer progression.	[Wu, C.] Sun Yat Sen Univ, Dept Intervent, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China; [Tang, Z-Y] Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Hepatobiliary Surg, Nanning, Peoples R China; [Chen, H-Y] Southern Med Univ, Liver Tumor Ctr, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China; [Zhang, J.] Sun Yat Sen Univ, Dept Hepat Surg, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China; [Zhao, C.] Guangxi Med Univ, Dept Invas Technol, Canc Hosp, Nanning, Peoples R China		Zhang, J (corresponding author), Sun Yat Sen Univ, Dept Hepat Surg, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China.; Zhao, C (corresponding author), Guangxi Med Univ, Dept Invas Technol, Canc Hosp, Nanning, Peoples R China.	zhangjian629@sina.com; 710519137@qq.com			Free Application Project of Guangdong Provincial Natural Science Foundation [2018A0303130050]	Free Application Project of Guangdong Provincial Natural Science Foundation (2018A0303130050).	Battistelli C, 2017, ONCOGENE, V36, P942, DOI 10.1038/onc.2016.260; Block TM, 2003, ONCOGENE, V22, P5093, DOI 10.1038/sj.onc.1206557; But DYK, 2008, WORLD J GASTROENTERO, V14, P1652, DOI 10.3748/wjg.14.1652; Cao H, 2015, PATHOL RES PRACT, V211, P557, DOI 10.1016/j.prp.2015.05.010; Che DH, 2017, MOL IMMUNOL, V90, P197, DOI 10.1016/j.molimm.2017.06.018; Chen HW, 2013, MOL CARCINOGEN, V52, P647, DOI 10.1002/mc.21904; Feng JT, 2006, ONCOGENE, V25, P3810, DOI 10.1038/sj.onc.1209551; Fu XM, 2017, EUR REV MED PHARMACO, V21, P3239; Gasri-Plotnitsky L, 2017, ONCOTARGET, V8, P23775, DOI 10.18632/oncotarget.15864; Guo Y, 2018, CANCER BIOL THER, V19, P205, DOI 10.1080/15384047.2017.1416276; Harries LW, 2012, BIOCHEM SOC T, V40, P902, DOI 10.1042/BST20120020; He H, 2012, DIAGN MOL PATHOL, V21, P143, DOI 10.1097/PDM.0b013e318249fd8b; He R, 2017, BIOMED PHARMACOTHER, V95, P331, DOI 10.1016/j.biopha.2017.08.057; Huang ZQ, 2018, CELL PHYSIOL BIOCHEM, V46, P1341, DOI 10.1159/000489149; Jiang N, 2018, CLIN CHIM ACTA, V486, P26, DOI 10.1016/j.cca.2018.07.026; Ke D, 2017, ONCOTARGET, V8, P21516, DOI 10.18632/oncotarget.15628; Li GL, 2016, PURINERG SIGNAL, V12, P479, DOI 10.1007/s11302-016-9513-8; Li XM, 2016, ONCOTARGET, V7, P23197, DOI 10.18632/oncotarget.8099; Liu Y, 2018, BBA-MOL BASIS DIS, V1864, P420, DOI 10.1016/j.bbadis.2017.11.003; Ning XF, 2019, ONCOL RES, V27, P399, DOI 10.3727/096504018X15179675206495; Pan Q, 2017, CANCER LETT, V392, P26, DOI 10.1016/j.canlet.2017.01.039; Taylor DH, 2015, MOL REPROD DEV, V82, P932, DOI 10.1002/mrd.22581; Wang TT, 2017, BMC CANCER, V17, DOI 10.1186/s12885-017-3701-y; Xu H, 2018, CANCER LETT, V412, P69, DOI 10.1016/j.canlet.2017.09.030; Yang SC, 2017, MOL CANCER, V16, DOI 10.1186/s12943-017-0700-1; Zemmour D, 2017, P NATL ACAD SCI USA, V114, pE3472, DOI 10.1073/pnas.1700946114; Zhang QQ, 2018, J CELL BIOCHEM, V119, P4447, DOI 10.1002/jcb.26537; Zhang W, 2018, BIOCHIMIE, V144, P21, DOI 10.1016/j.biochi.2017.10.002	28	5	5	0	4	VERDUCI PUBLISHER	ROME	VIA GREGORIO VII, ROME, 186-00165, ITALY	1128-3602			EUR REV MED PHARMACO	Eur. Rev. Med. Pharmacol. Sci.		2019	23	19					8295	8302		10.26355/eurrev_201910_19140			8	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JH3RG	WOS:000492684500014	31646559				2022-04-25	
J	Yu, S; Wang, LJ; Cao, ZX; Gong, DY; Liang, QY; Chen, HT; Fu, HZ; Wang, WW; Tang, X; Xie, ZH; He, Y; Peng, C; Li, YZ				Yu, Si; Wang, Lijiao; Cao, Zhixing; Gong, Daoyin; Liang, Qianyi; Chen, Hanting; Fu, Huizhu; Wang, Wenwen; Tang, Xue; Xie, Zihao; He, Yang; Peng, Cheng; Li, Yuzhi			Anticancer effect of Polyphyllin in colorectal cancer cells through ROS-dependent autophagy and G2/M arrest mechanisms	NATURAL PRODUCT RESEARCH			English	Article						Polyphyllin; autophagy; ROS; G2/M arrest	PARIS-POLYPHYLLA; APOPTOSIS	Polyphyllin is a steroidal saponin isolated from the rhizoma of Paris polyphylla. In the present study, we aimed to investigate the anticancer effects of polyphyllin in colorectal cancer and to elucidate the potential underlying molecular mechanisms. Using, CCK8 assay, flow cytometry, laser confocal microscope analysis and western blot, the anticancer effects of the polyphyllin were analysed in colorectal cells. Our results indicate that polyphyllin significantly decreased cell viability of HCT 116 cells and induced autophagy. Furthermore, we found that polyphyllin induced autophagy in an ROS-dependent cell death and not related with PI3K/AKT/mTOR pathway. We also provide evidence that excessive ROS triggered by polyphyllin could induce G2/M phase arrest via regulating cycle proteins expression of cell cycle regulators, such as p21 and cyclinB1. In conclusion, polyphyllin exhibit anticancer effect through ROS-dependent autophagy and induces G2/M arrest in colorectal cancer. [GRAPHICS] .	[Yu, Si; Wang, Lijiao; Cao, Zhixing; Gong, Daoyin; Chen, Hanting; Tang, Xue; Xie, Zihao; Peng, Cheng; Li, Yuzhi] Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu, Sichuan, Peoples R China; [Yu, Si; Wang, Lijiao; Cao, Zhixing; Gong, Daoyin; Chen, Hanting; Tang, Xue; Xie, Zihao; Peng, Cheng; Li, Yuzhi] Minist Educ Key Lab Standardizat Chinese Herbal M, Chengdu, Sichuan, Peoples R China; [Yu, Si; Wang, Lijiao; Cao, Zhixing; Gong, Daoyin; Chen, Hanting; Tang, Xue; Xie, Zihao; Peng, Cheng; Li, Yuzhi] Chinese Med Resources Sichuan Province, Key Lab Breeding Base Co Founded Sichuan Prov & M, Key Lab Systemat Res Dev & Utilizat, Chengdu, Sichuan, Peoples R China; [Liang, Qianyi; Fu, Huizhu; Wang, Wenwen; He, Yang] Chengdu Univ Tradit Chinese Med, Sch Med Technol, Chengdu, Sichuan, Peoples R China		Peng, C; Li, YZ (corresponding author), Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu, Sichuan, Peoples R China.; Peng, C; Li, YZ (corresponding author), Minist Educ Key Lab Standardizat Chinese Herbal M, Chengdu, Sichuan, Peoples R China.; Peng, C; Li, YZ (corresponding author), Chinese Med Resources Sichuan Province, Key Lab Breeding Base Co Founded Sichuan Prov & M, Key Lab Systemat Res Dev & Utilizat, Chengdu, Sichuan, Peoples R China.	pengchengchengdu@126.com; liyuzhi5654@163.com					Arnold M, 2016, GUT; Blokhina O, 2010, PLANT PHYSIOL BIOCH, V48, P359, DOI 10.1016/j.plaphy.2010.01.007; Chang JL, 2015, J ETHNOPHARMACOL, V170, P117, DOI 10.1016/j.jep.2015.05.006; Gu LH, 2013, J TRADIT CHIN MED, V33, P325, DOI 10.1016/S0254-6272(13)60174-0; He L, 2011, BIOCHEM BIOPH RES CO, V409, P489, DOI 10.1016/j.bbrc.2011.05.032; Huo YA, 2009, EXP EYE RES, V89, P876, DOI 10.1016/j.exer.2009.07.012; Jing SS, 2017, NAT PROD RES, V31, P660, DOI 10.1080/14786419.2016.1219861; Ling Y, 2015, NAT PROD RES, V29, P1798, DOI 10.1080/14786419.2015.1007137; Liu B, 2012, CELL DEATH DIS, V4, p[e892, e892]; Liu J, 2015, BIOCHEM BIOPH RES CO, V463, P262, DOI 10.1016/j.bbrc.2015.05.042; Nagesh R, 2017, GENE REP, V6, P103, DOI 10.1016/j.genrep.2016.12.008; Prasad S, 2017, CANCER LETT, V387, P95, DOI 10.1016/j.canlet.2016.03.042; Shi YM, 2015, PHYTOMEDICINE, V22, P1139, DOI 10.1016/j.phymed.2015.08.014; Sun ZL, 2017, BIOMED PHARMACOTHER, V85, P303, DOI 10.1016/j.biopha.2016.11.030; Torre LA, 2016, CANCER EPIDEM BIOMAR, V25, P16, DOI 10.1158/1055-9965.EPI-15-0578; Tsujimoto Y, 2005, CELL DEATH DIFFER, V12, P1528, DOI 10.1038/sj.cdd.4401777; Xu CL, 2014, FITOTERAPIA, V99, P292, DOI 10.1016/j.fitote.2014.10.010	17	11	15	5	31	TAYLOR & FRANCIS LTD	ABINGDON	2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND	1478-6419	1478-6427		NAT PROD RES	Nat. Prod. Res.		2018	32	12					1489	1492		10.1080/14786419.2017.1353512			4	Chemistry, Applied; Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	GD9WN	WOS:000430863800023	28714320				2022-04-25	
J	Yu, TC; Guo, FF; Yu, YN; Sun, TT; Ma, D; Han, JX; Qian, Y; Kryczek, I; Sun, DF; Nagarsheth, N; Chen, YX; Chen, HY; Hong, J; Zou, WP; Fang, JY				Yu, TaChung; Guo, Fangfang; Yu, Yanan; Sun, Tiantian; Ma, Dan; Han, Jixuan; Qian, Yun; Kryczek, Ilona; Sun, Danfeng; Nagarsheth, Nisha; Chen, Yingxuan; Chen, Haoyan; Hong, Jie; Zou, Weiping; Fang, Jing-Yuan			Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy	CELL			English	Article							RESISTANCE; CELLS; COMMENSAL; OXALIPLATIN; SENSITIVITY; STATISTICS; MECHANISMS; MICROBIOTA; EXPRESSION; CETUXIMAB	Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes.	[Yu, TaChung; Guo, Fangfang; Yu, Yanan; Sun, Tiantian; Ma, Dan; Han, Jixuan; Qian, Yun; Sun, Danfeng; Chen, Yingxuan; Chen, Haoyan; Hong, Jie; Fang, Jing-Yuan] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes,Shanghai, Key Lab Gastroenterol & Hepatol,Shanghai Canc Ins, Minist Hlth,Div Gastroenterol & Hepatol,Renji Hos, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China; [Kryczek, Ilona; Sun, Danfeng; Nagarsheth, Nisha; Zou, Weiping] Univ Michigan, Ctr Comprehens Canc, Grad Programs Immunol & Canc Biol, Dept Surg,Sch Med, Ann Arbor, MI 48109 USA		Chen, YX; Chen, HY; Hong, J; Fang, JY (corresponding author), Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes,Shanghai, Key Lab Gastroenterol & Hepatol,Shanghai Canc Ins, Minist Hlth,Div Gastroenterol & Hepatol,Renji Hos, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China.; Zou, WP (corresponding author), Univ Michigan, Ctr Comprehens Canc, Grad Programs Immunol & Canc Biol, Dept Surg,Sch Med, Ann Arbor, MI 48109 USA.	yingxuanchen71@126.com; haoyanchen@shsmu.edu.cn; jiehong97@shsmu.edu.cn; wzou@med.umich.edu; jingyuanfang@sjtu.edu.cn		Nagarsheth, Nisha/0000-0002-9508-1530; fang, jingyuan/0000-0003-2282-0248	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81421001, 81320108024, 81530072, 81522008, 31371273, 31371420, 81572303, 81001070]; National Key Technology RD ProgramNational Key Technology R&D Program [2014BAI09B05]; Program for Professor of Special Appointment at Shanghai Institutions of Higher Learning [201268, QD2015003]; Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant [20152512, 20161309]; Chenxing Project of Shanghai Jiao-Tong University; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA211016]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA190176, R01CA211016] Funding Source: NIH RePORTER	This project was supported in part by grants from the National Natural Science Foundation of China (81421001, 81320108024, 81530072, 81522008 31371273, 31371420, 81572303, and 81001070), the National Key Technology R&D Program (2014BAI09B05), the Program for Professor of Special Appointment (Eastern Scholar No. 201268 and 2015 Youth Eastern Scholar NO. QD2015003) at Shanghai Institutions of Higher Learning, the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (no. 20152512, 20161309), the Chenxing Project of Shanghai Jiao-Tong University (H. Chen and J. Hong), and the National Cancer Institute (CA211016, W.Z). We thank Dr. Ming Zhong for collecting colocretal cancer tissues and patient information for this work. We thank Dr. Tingting Yan for graphic abstract conception.	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J	Nazim, UMD; Moon, JH; Lee, YJ; Seol, JW; Kim, YJ; Park, SY				Nazim, Uddin M. D.; Moon, Ji-Hong; Lee, You-Jin; Seol, Jae-Won; Kim, Yong Ju; Park, Sang-Youel			Glipizide sensitizes lung cancer cells to TRAIL-induced apoptosis via Akt/mTOR/autophagy pathways	ONCOTARGET			English	Article						glipizide; autophagy; TRAIL; apoptosis; lung cancer cells	DIABETES-MELLITUS; COLORECTAL-CANCER; AUTOPHAGY FLUX; RECEPTOR; DEATH; RISK; MECHANISMS; LIGAND; GROWTH; INHIBITION	The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with subsidiary agents is a promising anticancer strategy to conquer TRAIL resistance in malignant cells. Glipizide is a second-generation oral hypoglycemic medicine for the cure of type II diabetes because of its capability to selectively stimulate insulin secretion from beta-cells. In this study, we revealed that glipizide could trigger TRAIL-mediated apoptotic cell death in human lung adenocarcinoma cells. Pretreatment with glipizide downregulation of p-Akt and p-mTOR in different concentrations. In addition, LC3-II and p-Akt was suppressed in the presence of LY294002, a well-known inhibitor of P13K. Treatment with glipizide commenced in a slight increase in conversion rate of LC3-I to LC3-II and significantly decreased p62 expression levels in a dose-dependent manner. This indicates that glipizide encouraged autophagy flux activation in human lung cancer cells. Inhibition of autophagy flux applying a specific inhibitor and genetically modified ATG5 siRNA enclosed glipizide-mediated enhancing effect of TRAIL. These data demonstrate that inhibition of Akt/mTOR by glipizide sensitizes TRAIL-induced tumor cell death through activating autophagy flux and also suggest that glipizide may be a combination therapeutic target with TRAIL protein in TRAIL-resistant cancer cells.	[Nazim, Uddin M. D.; Moon, Ji-Hong; Lee, You-Jin; Seol, Jae-Won; Park, Sang-Youel] Chonbuk Natl Univ, Biosafety Res Inst, Coll Vet Med, Iksan 54596, Jeonbuk, South Korea; [Kim, Yong Ju] Chonbuk Natl Univ, Dept Herbal Med Resources, Coll Environm & Bioresources, Iksan 54596, Jeonbuk, South Korea		Park, SY (corresponding author), Chonbuk Natl Univ, Biosafety Res Inst, Coll Vet Med, Iksan 54596, Jeonbuk, South Korea.	sypark@chonbuk.ac.kr	Park, Sang-Youel/D-5966-2012	Park, Sang-Youel/0000-0003-0575-6045	National Research Foundation of Korea (NRF) - Korean government (MISP) [2016R1A2B2009293]	This study was supported by a grant from the National Research Foundation of Korea (NRF), funded by the Korean government (MISP) (2016R1A2B2009293).	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J	Fu, R; Ding, Y; Luo, J; Huang, KM; Tang, XJ; Li, DS; Guo, SW				Fu, Rui; Ding, Yan; Luo, Jie; Huang, Kuan Ming; Tang, Xiang Jun; Li, Dong Sheng; Guo, Shi Wen			Ten-eleven translocation 1 regulates methylation of autophagy-related genes in human glioma	NEUROREPORT			English	Article						autophagy; glioma; 5-hydroxymethylcytosine; 5-methylcytosine; ten-eleven translocation 1	MALIGNANT GLIOMAS; SIGNALING PATHWAY; COLORECTAL-CANCER; THERAPY; TET1; 5-HYDROXYMETHYLCYTOSINE; CHALLENGES; CELLS	Ten-eleven translocation 1 catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which plays an important role in epigenetics and is related to the malignant biological behavior of tumors. However, its regulatory role in glioma remains unclear. In this study, the levels of 5mC and 5hmC were detected using immunohistochemistry, dot-blot, hMeDIP-chip, and western blot in glioma tissues and normal brain tissues, whereas 5hmC differentially enriched genes were determined and further validated. The level of 5hmC in gliomas was decreased, whereas 5mC was increased. 5hmC highly enriched 10 functional protein-coding genes and 10 signaling pathways were identified using hMeGIP-chip in glioma tissues. Two autophagy-related genes, ATG13 and DNA damage-regulated autophagy modulator protein 1, with low enrichment of 5hmC in glioma tissues were verified in the promoter region, and hMeGIP-PCR further confirmed this result in U251 cells. Immunohistochemistry further confirmed that autophagy level in glioma tissues was lower than that of normal controls, and negatively correlated with WHO grade. This study indicates that ten-eleven translocation 1 may be involved in the development and progression of glioma through demethylation regulating a variety of cellular functions and signaling pathways, and autophagy is one of the regulatory mechanisms.	[Fu, Rui; Luo, Jie; Huang, Kuan Ming; Tang, Xiang Jun] Xi An Jiao Tong Univ, Hlth Sci Ctr, Affiliated Taihe Hosp, Dept Neurosurg, Xian, Shaanxi, Peoples R China; [Ding, Yan; Li, Dong Sheng] Hubei Univ Med, Taihe Hosp, Hubei Key Lab Embryon Stem Cell Res, Shiyan, Hubei, Peoples R China; [Guo, Shi Wen] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Neurosurg, Xian 710061, Shanxi, Peoples R China		Guo, SW (corresponding author), Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Neurosurg, Xian 710061, Shanxi, Peoples R China.	gsw1962@126.com		/0000-0002-4916-8125	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81602297]; Science and Technology Department of Hubei Province [2016CFB11, 2017CFB562]	This work was supported by the National Natural Science Foundation of China (grant number 81602297); and the Science and Technology Department of Hubei Province (grant numbers 2016CFB11 and 2017CFB562).	Ahsan S, 2014, ACTA NEUROPATHOL COM, V2, DOI 10.1186/2051-5960-2-59; Alers S, 2014, AUTOPHAGY, V10, P944, DOI 10.4161/auto.28987; Bian EB, 2014, J NEURO-ONCOL, V116, P429, DOI 10.1007/s11060-013-1328-7; Coulter JB, 2013, J BIOL CHEM, V288, P28792, DOI 10.1074/jbc.M113.491365; Crighton D, 2007, AUTOPHAGY, V3, P72, DOI 10.4161/auto.3438; Davis F G, 2001, Expert Rev Anticancer Ther, V1, P395, DOI 10.1586/14737140.1.3.395; Drabsch Y, 2012, CANCER METAST REV, V31, P553, DOI 10.1007/s10555-012-9375-7; Frosina G, 2015, CRIT REV ONCOL HEMAT, V96, P257, DOI 10.1016/j.critrevonc.2015.05.013; Fu R, 2017, BIOSCIENCE REP, V37, P1; Guan JJ, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2014.546; Guishard AF, 2018, J CLIN NEUROSCI, V47, P28, DOI 10.1016/j.jocn.2017.10.001; Hadjipanayis CG, 2009, J MOL MED, V87, P363, DOI 10.1007/s00109-009-0440-9; Hou LC, 2017, MED SCI MONITOR, V23, P5130, DOI 10.12659/MSM.904492; Ichimura N, 2015, CANCER PREV RES, V8, P702, DOI 10.1158/1940-6207.CAPR-14-0306; Jeschke J, 2016, CURR OPIN GENET DEV, V36, P16, DOI 10.1016/j.gde.2016.01.004; Kraus TFJ, 2012, INT J CANCER, V131, P1577, DOI 10.1002/ijc.27429; Lian H, 2016, ONCOTARGET, V7, P64512, DOI 10.18632/oncotarget.11412; Louis DN, 2007, ACTA NEUROPATHOL, V114, P97, DOI 10.1007/s00401-007-0243-4; Muller T, 2012, AM J PATHOL, V181, P675, DOI 10.1016/j.ajpath.2012.04.017; Neri F, 2015, ONCOGENE, V34, P4168, DOI 10.1038/onc.2014.356; Rajesh Y, 2017, ACTA PHARMACOL SIN, V38, P591, DOI 10.1038/aps.2016.167; Sahoo SS, 2017, ONCOTARGET, V8, P71400, DOI 10.18632/oncotarget.18069; Selim KA, 2017, DISEASES, V26, P5; Wallot-Hieke  N., 2017, AUTOPHAGY, P1; Wang HX, 2015, NEOPLASIA, V17, P239, DOI 10.1016/j.neo.2015.02.002; Wang X, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0683-9	26	4	4	2	10	LIPPINCOTT WILLIAMS & WILKINS	PHILADELPHIA	TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA	0959-4965	1473-558X		NEUROREPORT	Neuroreport	JUN 13	2018	29	9					731	738		10.1097/WNR.0000000000001024			8	Neurosciences	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology	GH0MM	WOS:000433096700006	29659445				2022-04-25	
J	Zabirnyk, O; Liu, W; Khalil, S; Sharma, A; Phang, JM				Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M.			Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy	CARCINOGENESIS			English	Article							ACTIVATED-RECEPTOR-GAMMA; OXIDATIVE STRESS; COLORECTAL-CANCER; LIGAND ACTIVATION; TUMOR-SUPPRESSOR; APOPTOSIS; CELLS; EXPRESSION; INDUCTION; 7-KETOCHOLESTEROL	Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy.	[Zabirnyk, Olga] NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA		Zabirnyk, O (corresponding author), NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res,NIH, Bldg 538,Room 144, Frederick, MD 21702 USA.	olga_zabirnyk@yahoo.com; phangj@mail.nih.gov	liu, wei/E-7340-2012		National Institutes of Health; National Cancer Institute; Center for Cancer ResearchUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI); NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIABC010744, ZIABC010743] Funding Source: NIH RePORTER	Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research.	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J	Zhang, ZR; Zhang, MX; Liu, H; Yin, W				Zhang, Zhirui; Zhang, Mengxiao; Liu, Hao; Yin, Wu			AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells	JOURNAL OF CELLULAR BIOCHEMISTRY			English	Article						autophagy; AZD9291; epidermal growth factor receptor (EGFR); phosphoinositide-3 kinase/protein kinase B (PI3K/Akt)	RECEPTOR-TYROSINE KINASE; COLORECTAL-CANCER; EGFR; OSIMERTINIB; RESISTANCE; MUTATION; MECHANISMS; T790M; DEATH; INDUCTION	AZD9291, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is highly selective against EGFR T790M-mutant non-small cell lung cancer (NSCLC). On investigating the growth inhibitory effects of AZD9291 on NSCLC and the underlying mechanism, we found that AZD9291 can trigger autophagy-mediated cell death in both A549 and H1975 cells by increasing the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3) and decreasing the expression of p62. In the presence of the autophagy inhibitor chloroquine, the AZD9291-induced increase in LC3 level was further augmented. AZD9291 decreased the levels of phosphoinositide-3 kinase (PI3K), protein kinase B (Akt), and phosphorylated Akt. AZD9291-induced cell death was enhanced by Akt knockdown, and the levels of both EGFR and phosphorylated EGFR were decreased by AZD9291. AZD9291 was also found to significantly suppress the tumor growth in H1975 xenograft nude mice. Thus, AZD9291 was found to induce autophagy, decrease in EGFR levels, and show a strong inhibitory effect on NSCLC both in vitro and in vivo. Furthermore, the PI3K/Akt signaling pathway was found to play a critical role in AZD9291-induced cell death.	[Zhang, Zhirui; Yin, Wu] Nanjing Univ, Coll Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China; [Zhang, Zhirui; Zhang, Mengxiao; Liu, Hao] Bengbu Med Coll, Fac Pharm, 2600 Donghai Rd, Bengbu 233000, Anhui, Peoples R China		Liu, H (corresponding author), Bengbu Med Coll, Fac Pharm, 2600 Donghai Rd, Bengbu 233000, Anhui, Peoples R China.; Yin, W (corresponding author), Nanjing Univ, Coll Life Sci, SKLPB, LBMP, Xianlin Campus,163 Xianlin Rd, Nanjing 210046, Jiangsu, Peoples R China.	liuhao6886@foxmail.com; wyin@nju.edu.cn			Education Department of Anhui Natural Science Research Project China [KJ2018A0238]; Key development project of Jiangsu Province [BE2017712]; Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica [JKLPSE201509]; Six talent peaks project in Jiangsu Province [YY-012]; Natural Science Fund of ChinaNational Natural Science Foundation of China (NSFC) [91540119, 81473293, 81673462, 31071250]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities; Priority Academic Program Development of Jiangsu Higher Education Institutions	Education Department of Anhui Natural Science Research Project China, Grant/Award Number: KJ2018A0238; Key development project of Jiangsu Province, Grant/Award Number: BE2017712; The Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Grant/Award Number: JKLPSE201509; Six talent peaks project in Jiangsu Province to Y.W., Grant/Award Number: YY-012; Natural Science Fund of China, Grant/Award Numbers: 91540119, 81473293, 81673462, 31071250; Fundamental Research Funds for the Central Universities; Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions	Ballard P, 2016, CLIN CANCER RES, V22, P5130, DOI 10.1158/1078-0432.CCR-16-0399; Berg M, 2012, DISCOV MED, V14, P207; Bersanelli M, 2016, J THORAC ONCOL, V11, pE121, DOI 10.1016/j.jtho.2016.05.019; 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Cell. Biochem.	JAN	2019	120	1					756	767		10.1002/jcb.27434			12	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	HB1XP	WOS:000450823500068	30145802				2022-04-25	
J	Gao, S; Zhao, ZY; Wu, R; Wu, LN; Tian, X; Zhang, ZY				Gao, Song; Zhao, Zhiying; Wu, Rong; Wu, Lina; Tian, Xin; Zhang, Zhenyong			MiR-146b inhibits autophagy in prostate cancer by targeting the PTEN/Akt/mTOR signaling pathway	AGING-US			English	Article						prostate cancer; microRNA-146b; PTEN; autophagy; AKT/m-TOR signaling pathway	PI3K/AKT/MTOR PATHWAY; CELL-PROLIFERATION; COLORECTAL-CANCER; LUNG-CANCER; APOPTOSIS; METASTASIS; MICRORNAS; SUPPRESSION; RESISTANCE; CARCINOMA	Prostate cancer (PCa) is considered as a common visceral cancer in males and the sixth major cause of cancer-related deaths in males worldwide. Significant diagnostic and therapeutic advances have been made in the past decades. However, an improved understanding of their molecular mechanism is still needed. In the present research, we first detected the expression of miR-146b by quantitative real-time PCR (qRT-PCR) and found that miR-146b expression was increased in PCa. Subsequently, we found that miR-146b play an important role in the viability and proliferation capacity of PCa cells functionally. To explore the mechanism, we performed western blot to examine the autophagy-related markers, and found that miR-146b may promote autophagy in PCa cells via activation of PTEN/AKT/mTOR signaling pathway. Furthermore, we performed the dual luciferase reporter assay to clarify the relationship between miR-146b and PTEN. In conclusion, this study demonstrated that miR-146b inhibited autophagy in PCa by targeting the PTEN/Akt/mTOR signaling pathway, and it could be a potential candidate for application in the treatment of PCa.	[Gao, Song; Wu, Rong; Wu, Lina; Tian, Xin; Zhang, Zhenyong] China Med Univ, Shengjing Hosp, Dept Clin Oncol 2, Shenyang 110022, Liaoning, Peoples R China; [Zhao, Zhiying] Northeastern Univ, Sch Comp Sci & Engn, Shenyang 110004, Liaoning, Peoples R China		Zhang, ZY (corresponding author), China Med Univ, Shengjing Hosp, Dept Clin Oncol 2, Shenyang 110022, Liaoning, Peoples R China.	zhangzy@sj-hospital.org					Armstrong CM, 2017, PROSTATE, V77, P1020, DOI 10.1002/pros.23358; Bartel DP, 2009, CELL, V136, P215, DOI 10.1016/j.cell.2009.01.002; Bitting RL, 2013, ENDOCR-RELAT CANCER, V20, pR83, DOI 10.1530/ERC-12-0394; Calle AS, 2018, CANCER SCI, V109, P2093, DOI 10.1111/cas.13642; Chen CX, 2018, BRAZ J MED BIOL RES, V51, DOI [10.1590/1414-431X20187080, 10.1590/1414-431x20187080]; Chen R, 2018, J CELL MOL MED, V22, P1855, DOI 10.1111/jcmm.13469; Chen SS, 2015, CELL PHYSIOL BIOCHEM, V35, P997, DOI 10.1159/000369755; De Amicis F, 2014, J CELL MOL MED, V18, P2252, DOI 10.1111/jcmm.12363; Deng XZ, 2015, CELL PHYSIOL BIOCHEM, V35, P71, DOI 10.1159/000369676; Fort RS, 2018, EXP HEMATOL ONCOL, V7, DOI 10.1186/s40164-018-0102-0; Fu Q, 2018, BIOMED PHARMACOTHER, V97, P120, DOI 10.1016/j.biopha.2017.10.115; Garzon R, 2009, ANNU REV MED, V60, P167, DOI 10.1146/annurev.med.59.053006.104707; Han F, 2018, J CELL BIOCHEM, V119, P1604, DOI 10.1002/jcb.26320; Hu XX, 2018, J CANCER, V9, P2603, DOI 10.7150/jca.24918; Huang EY, 2018, J CELL MOL MED, V22, P3661, DOI 10.1111/jcmm.13649; Huang ZQ, 2017, J CELL MOL MED, V21, P467, DOI 10.1111/jcmm.12990; Irimie AI, 2015, ONCOTARGETS THER, V8, P461, DOI 10.2147/OTT.S78358; Kanzawa T, 2003, CANCER RES, V63, P2103; Lapierre LR, 2015, AUTOPHAGY, V11, P867, DOI 10.1080/15548627.2015.1034410; Li JL, 2018, GENE, V665, P26, DOI 10.1016/j.gene.2018.04.086; Li W, 2018, NEUROSCI LETT, V675, P83, DOI 10.1016/j.neulet.2018.03.041; Liao HQ, 2015, ONCOL LETT, V10, P2055, DOI 10.3892/ol.2015.3551; Liu WW, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0743-1; Livesey KM, 2009, CURR OPIN INVEST DR, V10, P1269; Luo CL, 2016, BIOMED PHARMACOTHER, V82, P595, DOI 10.1016/j.biopha.2016.05.029; Ma JF, 2018, BIOMED RES INT, V2018, DOI 10.1155/2018/4780612; Mizushima N, 2008, NATURE, V451, P1069, DOI 10.1038/nature06639; Mraz M, 2009, BIOCHEM BIOPH RES CO, V390, P1, DOI 10.1016/j.bbrc.2009.09.061; Pei GQ, 2018, CELL PHYSIOL BIOCHEM, V46, P847, DOI 10.1159/000488742; Ramalinga M, 2015, ONCOTARGET, V6, P34446, DOI 10.18632/oncotarget.5920; Sharma K, 2014, EXCLI J, V13, P178; Shi ZJ, 2018, J CELL BIOCHEM, V119, P5813, DOI 10.1002/jcb.26768; Shi ZJ, 2018, J CELL MOL MED, V22, P2055, DOI 10.1111/jcmm.13515; Shi ZJ, 2017, INT J NEUROSCI, V127, P1104, DOI 10.1080/00207454.2017.1323208; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Sohn EJ, 2018, CANCER CELL INT, V18, DOI 10.1186/s12935-017-0500-0; Takayama KI, 2017, CANCERS, V9, pE102; Vera-Ramirez L, 2018, NAT COMMUN, V9, DOI 10.1038/s41467-018-04070-6; Wang Q, 2018, EXP THER MED, V15, P3028, DOI 10.3892/etm.2018.5792; Wu SJ, 2018, ONCOTARGETS THER, V11, P2593, DOI 10.2147/OTT.S157707; Xu S, 2017, BIOMED PHARMACOTHER, V96, P634, DOI 10.1016/j.biopha.2017.10.037; Yang CL, 2018, CELL PHYSIOL BIOCHEM, V46, P93, DOI 10.1159/000488412; Yang JL, 2018, BIOMED PHARMACOTHER, V103, P699, DOI 10.1016/j.biopha.2018.04.072; Yang ZNJ, 2011, MOL CANCER THER, V10, P1533, DOI 10.1158/1535-7163.MCT-11-0047; Yu X, 2018, ONCOTARGETS THER, V11, P1833, DOI 10.2147/OTT.S155716; Yu X, 2016, J CELL MOL MED, V20, P10, DOI 10.1111/jcmm.12650; Zhao N, 2019, J CELL BIOCHEM, V120, P12070, DOI 10.1002/jcb.26417; Zhu YZ, 2017, AM J CANCER RES, V7, P1136	48	25	27	1	16	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA	1945-4589			AGING-US	Aging-US	AUG	2018	10	8					2113	2121		10.18632/aging.101534			9	Cell Biology; Geriatrics & Gerontology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Geriatrics & Gerontology	GS1RN	WOS:000443308900026	30153654	Green Published, gold			2022-04-25	
J	Liu, JZ; Hu, YL; Feng, Y; Guo, YB; Li, YF; Yang, JL; Mao, QS; Xue, WJ				Liu, Jia-Zhou; Hu, Yi-Lin; Feng, Ying; Guo, Yi-Bing; Li, Yi-Fei; Yang, Jun-Ling; Mao, Qin-Sheng; Xue, Wan-Jiang			Rafoxanide promotes apoptosis and autophagy of gastric cancer cells by suppressing PI3K /Akt/mTOR pathway	EXPERIMENTAL CELL RESEARCH			English	Article						Rafoxanide; Gastric cancer; PI3K; Apoptosis; Autophagy	IMMATURE FASCIOLA-HEPATICA; DOUBLE-EDGED-SWORD; POOR-PROGNOSIS; DEATH; INHIBITION; ACTIVATION; EXPRESSION; RESISTANCE; CLOSANTEL; STRESS	Rafoxanide is commonly used as anti-helminthic medicine in veterinary medicine, a main compound of salicylanilide. Previous studies have reported that rafoxanide, as an inhibitor of BRAF V600E mutant protein, inhibits the growth of colorectal cancer, multiple myeloma, and skin cancer. However, its therapeutic effect on gastric cancer (GC) and the potential mechanism has not been investigated. Here, we have found that rafoxanide inhibited the proliferation of GC cells in vitro, arrested the cell cycle in the G0/G1 phase, and promoted apoptosis and autophagy in GC cells. Treatment with specific autophagy inhibitor 3-methyladenine drastically inhibited the apoptotic cell death effect by suppressing the switch from autophagy to apoptosis. Mechanistically, we found that rafoxanide inhibited the growth of GC cells in vitro by inhibiting the activity of the PI3K/Akt/mTOR signaling pathway. This process induced autophagy, which essentially resulted in the apoptosis of GC cells. Results from subcutaneous implanted tumor models in nude mice also indicated that rafoxanide inhibited the growth of GC cells in vivo. Taken together, our findings revealed that rafoxanide inhibited the growth of GC cells both in vitro and vivo, indicating a potential drug candidate for the treatment of GC.	[Liu, Jia-Zhou; Hu, Yi-Lin; Feng, Ying; Mao, Qin-Sheng; Xue, Wan-Jiang] Nantong Univ, Affiliated Hosp, Dept Gastrointestinal Surg, 20 Xisi St, Nantong 226001, Peoples R China; [Liu, Jia-Zhou; Hu, Yi-Lin; Feng, Ying; Guo, Yi-Bing; Yang, Jun-Ling; Xue, Wan-Jiang] Nantong Univ, Affiliated Hosp, Res Ctr Clin Med, 20 Xisi St, Nantong 226001, Peoples R China; [Li, Yi-Fei] Nantong Univ, Affiliated Hosp, Dept Pathol, 20 Xisi St, Nantong 226001, Peoples R China		Mao, QS; Xue, WJ (corresponding author), Nantong Univ, Affiliated Hosp, Dept Gastrointestinal Surg, 20 Xisi St, Nantong 226001, Peoples R China.	tdfymaoqsh@sina.com; xuewanjiang@ntu.edu.cn		Guo, Yibing/0000-0001-9723-0678	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672409]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2016M590489, 2017T100393]; Postdoctoral Science Foundation of Jiangsu ProvinceChina Postdoctoral Science Foundation [1601101C]; Jiangsu Provincial Medical Youth Talent [QNRC2016700]; Scientific and Technological Innovation and Demonstration Project of Nantong City [MS32016018, M512017001-6, MS12017007-5, MS12017008-5]; "333 Talent" Cultivating Project of Jiangsu Province [BRA2018394]; Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX18_0831]	This work was supported by the National Natural Science Foundation of China (No. 81672409), China Postdoctoral Science Foundation (2016M590489, 2017T100393), Postdoctoral Science Foundation of Jiangsu Province (1601101C), Jiangsu Provincial Medical Youth Talent (QNRC2016700), Scientific and Technological Innovation and Demonstration Project of Nantong City (MS32016018, M512017001-6, MS12017007-5, and MS12017008-5), "333 Talent" Cultivating Project of Jiangsu Province (BRA2018394), and Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX18_0831).	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Cell Res.	DEC 15	2019	385	2							111691	10.1016/j.yexcr.2019.111691			12	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	JU0XU	WOS:000501403300008	31678170				2022-04-25	
J	Zhao, Z; Han, FH; Yang, SB; Wu, JH; Zhan, WH				Zhao, Zhi; Han, Fanghai; Yang, Shibin; Wu, Jianhai; Zhan, Wenhua			Oxamate-mediated inhibition of lactate dehydrogenase induces protective autophagy in gastric cancer cells: Involvement of the Akt-mTOR signaling pathway	CANCER LETTERS			English	Article						Gastric cancer; Glycolysis; Lactate dehydrogenase; Oxamate; Autophagy	POOR-PROGNOSIS; COLORECTAL-CANCER; IN-VITRO; EXPRESSION; ASSOCIATION; HIF-1-ALPHA; METABOLISM; CARCINOMA; APOPTOSIS; SURVIVAL	Cancer cells produce a substantial amount of energy through aerobic glycolysis even in the presence of adequate oxygen. Lactate dehydrogenase (LDH), a key regulator of glycolysis, reversibly catalyzes the conversion of pyruvate to lactate. Recently, oxamate, an inhibitor of LDH, has been shown to be a promising anticancer agent. However, the detailed mechanism remains largely unclear. In this study, we demonstrate that oxamate inhibits the viability of human gastric cancer cells in a dose- and time-dependent manner. In addition, treatment with oxamate induces protective autophagy in gastric cancer cells. Moreover, autophagy inhibited by chloroquine or Beclin 1 small interfering RNA (siRNA) enhances oxamateinduced apoptosis and proliferation inhibition. Further study has shown that oxamate treatment significantly augments reactive oxygen species (ROS) production. Furthermore, cells pretreated with N-acetyl cyste(NAC), a ROS inhibitor, display significantly reduced ROS production and attenuated oxamateinduced autophagy. Finally, functional studies reveal that the Akt mTOR signaling pathway, a major negative regulator of autophagy, is inhibited by oxamate. Together, our results provide new insights regarding the biological and anti-proliferative activities of oxamate against gastric cancer, and may offer a promising therapeutic strategy for gastric cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.	[Zhao, Zhi; Han, Fanghai; Yang, Shibin; Wu, Jianhai; Zhan, Wenhua] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Guangzhou 510080, Guangdong, Peoples R China		Han, FH (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Guangzhou 510080, Guangdong, Peoples R China.	FH_Han@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81072049]	This study was supported by the National Natural Science Foundation of China (No.81072049).	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MAR 1	2015	358	1					17	26		10.1016/j.canlet.2014.11.046			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CB3DB	WOS:000349507300003	25524555				2022-04-25	
J	Takhsha, FS; Vangestel, C; Tanc, M; De Bruycker, S; Berg, M; Pintelon, I; Stroobants, S; De Meyer, GRY; van der Veken, P; Martinet, W				Takhsha, Farnaz Sedigheh; Vangestel, Christel; Tanc, Muhammet; De Bruycker, Sven; Berg, Maya; Pintelon, Isabel; Stroobants, Sigrid; De Meyer, Guido R. Y.; van der Veken, Pieter; Martinet, Wim			ATG4B Inhibitor UAMC-2526 Potentiates the Chemotherapeutic Effect of Gemcitabine in a Panc02 Mouse Model of Pancreatic Ductal Adenocarcinoma	FRONTIERS IN ONCOLOGY			English	Article						pancreatic ductal adenocarcinoma; autophagy; ATG4B; UAMC-2526; gemcitabine; proliferation; Panc02	CANCER-CELLS; AUTOPHAGY; PROLIFERATION; RESISTANCE; HYPOXIA; TARGET; MTOR	Resistance against anti-cancer therapy is one of the major challenges during treatment of multiple cancers. Gemcitabine is a standard first-line chemotherapeutic drug, yet autophagy is highly activated in the hypoxic microenvironment of solid tumors and enhances the survival of tumor cells against gemcitabine chemotherapy. Recently, we showed the add-on effect of autophagy inhibitor UAMC-2526 to prevent HT-29 colorectal tumor growth in CD1(-/-) Foxn1nu mice treated with oxaliplatin. In this study, we aimed to investigate the potential beneficial effects of UAMC-2526 in a syngeneic Panc02 mouse model of pancreatic ductal adenocarcinoma (PDAC). Our data showed that UAMC-2526 combined with gemcitabine significantly reduced tumor growth as compared to the individual treatments. However, in contrast to in vitro experiments with Panc02 cells in culture, we were unable to detect autophagy inhibition by UAMC-2526 in Panc02 tumor tissue, neither via western blot analysis of autophagy markers LC3 and p62, nor by transmission electron microscopy. In vitro experiments revealed that UAMC-2526 enhances the potential of gemcitabine to inhibit Panc02 cell proliferation without obvious induction of cell death. Altogether, we conclude that although the combination treatment of UAMC-2526 with gemcitabine did not inhibit autophagy in the Panc02 mouse model, it has a beneficial effect on tumor growth inhibition.	[Takhsha, Farnaz Sedigheh; De Meyer, Guido R. Y.; Martinet, Wim] Univ Antwerp, Lab Physiopharmacol, Antwerp, Belgium; [Vangestel, Christel; De Bruycker, Sven; Stroobants, Sigrid] Univ Antwerp, Mol Imaging Ctr Antwerp MICA, Antwerp, Belgium; [Vangestel, Christel; Stroobants, Sigrid] Univ Antwerp Hosp, Dept Nucl Med, Edegem, Belgium; [Tanc, Muhammet; van der Veken, Pieter] Univ Antwerp, Lab Med Chem, Antwerp, Belgium; [Tanc, Muhammet] Kings Coll London, Dept Imaging Chem & Biol, London, England; [De Bruycker, Sven] AP Univ Appl Sci & Arts Antwerp, Dept Sci & Technol, Antwerp, Belgium; [Berg, Maya; De Meyer, Guido R. Y.; van der Veken, Pieter; Martinet, Wim] Univ Antwerp, Infla Med Ctr Excellence, Antwerp, Belgium; [Pintelon, Isabel] Univ Antwerp, Lab Cell Biol & Histol, Antwerp, Belgium		Martinet, W (corresponding author), Univ Antwerp, Lab Physiopharmacol, Antwerp, Belgium.; Martinet, W (corresponding author), Univ Antwerp, Infla Med Ctr Excellence, Antwerp, Belgium.		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Oncol.	NOV 18	2021	11								750259	10.3389/fonc.2021.750259			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	XI6FG	WOS:000726204300001	34868951	gold, Green Published			2022-04-25	
J	Auger, C; Christou, N; Brunel, A; Perraud, A; Verdier, M				Auger, Clement; Christou, Niki; Brunel, Aude; Perraud, Aurelie; Verdier, Mireille			Autophagy and Extracellular Vesicles in Colorectal Cancer: Interactions and Common Actors?	CANCERS			English	Review						autophagy; extracellular vesicles; secretory autophagy; rab-GTPases; colorectal cancer	UNCONVENTIONAL SECRETORY PATHWAY; MULTIVESICULAR BODIES; STEM-CELLS; EXOSOMES; BIOGENESIS; PROTEINS; MICROVESICLES; RELEASE; FUSION; COMMUNICATION	Simple Summary Cancer stem cells (CSCs) are known for their ability to survive under stressful conditions. To this aim, they use autophagy to recycle their altered organelles and proteins by addressing them toward a lysosome for their degradation. CSCs can also communicate with their environment using the secretion of extracellular vesicles (EVs) which carry information, strengthening their ability to survive under such conditions. Both mechanisms are known for using common actors and have been described as implicated in colorectal cancer (CRC). However, CSCs remain difficult to target due to the lack of specific markers identified, especially in colorectal cancer. Then, the study of the crosstalk between autophagy and the secretion of EVs seems crucial regarding a better targeting of CSCs. Autophagy is a homeostatic process involved in the degradation of disabled proteins and organelles using lysosomes. This mechanism requires the recruitment of specialized proteins for vesicle trafficking, that may also be involved in other types of machinery such as the biogenesis and secretion of extracellular vesicles (EVs), and particularly small EVs called exosomes. Among these proteins, Rab-GTPases may operate in both pathways, thus representing an interesting avenue for further study regarding the interaction between autophagy and extracellular vesicle machinery. Both mechanisms are involved in the development of colorectal cancer (CRC), particularly in cancer stem cell (CSC) survival and communication, although they are not specific to CRC or CSCs. This highlights the importance of studying the crosstalk between autophagy and EVs biogenesis and release.	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J	D'Orazi, G; Cordani, M; Cirone, M				D'Orazi, Gabriella; Cordani, Marco; Cirone, Mara			Oncogenic pathways activated by pro-inflammatory cytokines promote mutant p53 stability: clue for novel anticancer therapies	CELLULAR AND MOLECULAR LIFE SCIENCES			English	Article						Inflammatory cytokines; Cancer; Mutant p53; Unfolded protein response; Oncogenic pathways; Autophagy	ENDOPLASMIC-RETICULUM STRESS; COLORECTAL-CANCER; PROTEIN-KINASE; CELL-SURVIVAL; P38 MAPK; AUTOPHAGY; MTOR; GAIN; CONTRIBUTES; INTERPLAY	Inflammation and cancerogenesis are strongly interconnected processes, not only because inflammation promotes DNA instability, but also because both processes are driven by pathways such as NF-kB, STAT3, mTOR and MAPKs. Interestingly, these pathways regulate the release of pro-inflammatory cytokines such as IL-6, TNF-alpha and IL-1 beta that in turn control their activation and play a crucial role in shaping immune response. The transcription factor p53 is the major tumor suppressor that is often mutated in cancer, contributing to tumor progression. In this overview, we highlight how the interplay between pro-inflammatory cytokines and pro-inflammatory/pro-oncogenic pathways, regulating and being regulated by UPR signaling and autophagy, affects the stability of mutp53 that in turn is able to control autophagy, UPR signaling, cytokine release and the activation of the same oncogenic pathways to preserve its own stability and promote tumorigenesis. Interrupting these positive feedback loops may represent a promising strategy in anticancer therapy, particularly against cancers carrying mutp53.	[D'Orazi, Gabriella] IRCCS Regina Elena Natl Canc Inst, Dept Res & Adv Technol, Rome, Italy; [Cordani, Marco] IMDEA Nanociencia, C Faraday 9,Ciudad Univ Cantoblanco, Madrid, Spain; [Cirone, Mara] Sapienza Univ Rome, Dept Expt Med, Lab Affiliated Pasteur Inst Italy Fdn Cenci Bolog, Rome, Italy		Cirone, M (corresponding author), Sapienza Univ Rome, Dept Expt Med, Lab Affiliated Pasteur Inst Italy Fdn Cenci Bolog, Rome, Italy.	mara.cirone@uniroma1.it	D'Orazi, Gabriella/T-2792-2019; Cordani, Marco/N-1247-2018	D'Orazi, Gabriella/0000-0001-6876-9105; Cordani, Marco/0000-0001-9342-4862; cirone, mara/0000-0002-2207-9624	Italian Association for Cancer Research (AIRC)Fondazione AIRC per la ricerca sul cancro [11377, 16742, 23040]; Istituto Pasteur Italia Fondazione Cenci BolognettiIstituto Pasteur Italia Fondazione Cenci Bolognetti	The research in the laboratory of GD has been supported by Grants from the Italian Association for Cancer Research (AIRC) (IG 2013, 11377; IG 2015, 16742); in the laboratory of Mara Cirone by Grants from the Italian Association for Cancer Research (AIRC) IG 2019 23040) and by Istituto Pasteur Italia Fondazione Cenci Bolognetti. The funding agencies played no role in the concept, design, or writing of this study.	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J	Scherz-Shouval, R; Weidberg, H; Gonen, C; Wilder, S; Elazar, Z; Oren, M				Scherz-Shouval, Ruth; Weidberg, Hilla; Gonen, Chagay; Wilder, Sylvia; Elazar, Zvulun; Oren, Moshe			p53-dependent regulation of autophagy protein LC3 supports cancer cell survival under prolonged starvation	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA			English	Article						apoptosis; posttranscriptional regulation	WILD-TYPE P53; TUMOR SUPPRESSORS; TUMORIGENESIS; MODULATION; EXPRESSION; APOPTOSIS; SESTRIN2; STRESS	The p53 tumor suppressor is mutated in a high percentage of human tumors. However, many other tumors retain wild-type ( wt) p53 expression, raising the intriguing possibility that they actually benefit from it. Recent studies imply a role for p53 in regulation of autophagy, a catabolic pathway by which eukaryotic cells degrade and recycle macromolecules and organelles, particularly under conditions of nutrient deprivation. Here, we show that, in many cell types, p53 confers increased survival in the face of chronic starvation. We implicate regulation of autophagy in this effect. In HCT116 human colorectal cancer cells exposed to prolonged nutrient deprivation, the endogenous wt p53 posttranscriptionally down-regulates LC3, a pivotal component of the autophagic machinery. This enables reduced, yet sustainable autophagic flux. Loss of p53 impairs autophagic flux and causes excessive LC3 accumulation upon starvation, culminating in apoptosis. Thus, p53 increases cell fitness by maintaining better autophagic homeostasis, adjusting the rate of autophagy to changing circumstances. We propose that some cancer cells retain wt p53 to benefit from the resultant increased fitness under limited nutrient supply.	[Scherz-Shouval, Ruth; Gonen, Chagay; Wilder, Sylvia; Oren, Moshe] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel; [Weidberg, Hilla; Elazar, Zvulun] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel		Oren, M (corresponding author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.	moshe.oren@weizmann.ac.il		Oren, Moshe/0000-0003-4311-7172; scherz-shouval, ruth/0000-0002-4570-121X	Sir Charles Clore postdoctoral fellowship; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R37 CA40099]; Robert Bosch Foundation; Israel Science FoundationIsrael Science Foundation; Israeli Cancer Research Foundation; M.D. Moross Institute for Cancer Research; Yad Abraham Center for Cancer Diagnosis and Therapy; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R37CA040099] Funding Source: NIH RePORTER	We thank Adi Kimchi (Weizmann Institute, Rehovot, Israel) and her team for helpful discussions and reagents, Vera Shinder for helpful discussions and technical guidance, Dan Michael for sharing ideas, Gilad Fuchs, Gil Hornung, and Noa Levi for scientific and technical assistance, and Bert Vogelstein (Johns Hopkins University, Baltimore) and Varda Rotter (Weizmann Institute, Rehovot, Israel) for the gift of cell lines. R.S.-S. is recipient of the Sir Charles Clore postdoctoral fellowship. Z.E. is incumbent of the Harold Korda Chair of Biology; M.O. is incumbent of the Andere Lwoff chair in Molecular Biology. This work was supported in part by Grant R37 CA40099 from the National Cancer Institute, a grant from the Robert Bosch Foundation, the Israel Science Foundation and the Israeli Cancer Research Foundation (to Z.E.), and the M.D. Moross Institute for Cancer Research and the Yad Abraham Center for Cancer Diagnosis and Therapy (to M.O.). The electron microscopy studies were conducted at the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at The Weizmann Institute of Science.	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Natl. Acad. Sci. U. S. A.	OCT 26	2010	107	43					18511	18516		10.1073/pnas.1006124107			6	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	673QG	WOS:000283677400053	20937856	Green Published			2022-04-25	
J	Xie, YC; Liu, J; Kang, R; Tang, DL				Xie, Yangchun; Liu, Jiao; Kang, Rui; Tang, Daolin			Mitophagy Receptors in Tumor Biology	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY			English	Review						mitophagy; cancer; cell death; autophagy; mitochondria	CANCER STEM-CELLS; MITOCHONDRIAL AUTOPHAGY; PINK1/PARKIN-MEDIATED MITOPHAGY; MOLECULAR-MECHANISMS; COLORECTAL-CANCER; DRUG-RESISTANCE; BNIP3; PARKIN; DEATH; NIX	Mitochondria are multifunctional organelles that regulate cancer biology by synthesizing macromolecules, producing energy, and regulating cell death. The understanding of mitochondrial morphology, function, biogenesis, fission and fusion kinetics, and degradation is important for the development of new anticancer strategies. Mitophagy is a type of selective autophagy that can degrade damaged mitochondria under various environmental stresses, especially oxidative damage and hypoxia. The key regulator of mitophagy is the autophagy receptor, which recognizes damaged mitochondria and allows them to enter autophagosomes by binding to MAP1LC3 or GABARAP, and then undergo lysosomal-dependent degradation. Many components of mitochondria, including mitochondrial membrane proteins (e.g., PINK1, BNIP3L, BNIP3, FUNDC1, NIPSNAP1, NIPSNAP2, BCL2L13, PHB2, and FKBP8) and lipids (e.g., cardiolipin and ceramides), act as mitophagy receptors in a context-dependent manner. Dysfunctional mitophagy not only inhibits, but also promotes, tumorigenesis. Similarly, mitophagy plays a dual role in chemotherapy, radiotherapy, and immunotherapy. In this review, we summarize the latest advances in the mechanisms of mitophagy and highlight the pathological role of mitophagy receptors in tumorigenesis and treatment.	[Xie, Yangchun] Cent South Univ, Xiangya Hosp 2, Dept Oncol, Changsha, Peoples R China; [Liu, Jiao] Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Peoples R China; [Kang, Rui; Tang, Daolin] Univ Texas Southwestern Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA		Xie, YC (corresponding author), Cent South Univ, Xiangya Hosp 2, Dept Oncol, Changsha, Peoples R China.; Tang, DL (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA.	xieyangchun88@csu.edu.cn; daolin.tang@utsouthwestern.edu	Kang, Rui/ABD-5291-2021; Tang, Daolin/ABD-5062-2021; Tang, Daolin/B-2905-2010	Kang, Rui/0000-0003-2725-1574; Tang, Daolin/0000-0002-1903-6180; Xie, Yangchun/0000-0003-2571-4774	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81802476]	YX was supported by the National Natural Science Foundation of China (No. 81802476).	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Cell. Dev. Biol.	NOV 11	2020	8								594203	10.3389/fcell.2020.594203			11	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	OV0CL	WOS:000591889100001	33262988	gold, Green Published			2022-04-25	
J	Cheng, YP; Li, SM; Chuang, WL; Li, CH; Chen, GJ; Chang, CC; Or, CHR; Lin, PY; Chang, CC				Cheng, Yen-Po; Li, Shiming; Chuang, Wan-Ling; Li, Chia-Hsuan; Chen, Guan-Jun; Chang, Ching-Chin; Or, Chi-Hung R.; Lin, Ping-Yi; Chang, Chia-Che			Blockade of STAT3 Signaling Contributes to Anticancer Effect of 5-Acetyloxy-6,7,8,4 '-Tetra-Methoxyflavone, a Tangeretin Derivative, on Human Glioblastoma Multiforme Cells	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						glioblastoma multiforme; STAT3; tangeretin; 5-acetyloxy-6; 7; 8; 4 '-tetramethoxyflavone; polymethoxyflavone; BCL-2; BCL-xL; apoptosis	POLYMETHOXYLATED FLAVONE; OXIDATIVE STRESS; BREAST-CANCER; IN-VITRO; AUTOPHAGY; TISSUE	Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor prognosis, largely due to resistance to current radiotherapy and Temozolomide chemotherapy. The constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) is evidenced as a pivotal driver of GBM pathogenesis and therapy resistance, and hence, is a promising GBM drug target. 5-acetyloxy-6,7,8,4 '-tetramethoxyflavone (5-AcTMF) is an acetylated derivative of Tangeretin which is known to exert anticancer effects on breast, colon, lung, and multiple myeloma; however, its effect on GBM remains elusive. Herein, we reported that 5-AcTMF suppressed the viability and clonogenicity along with inducing apoptosis in multiple human GBM cell lines. Mechanistic analyses further revealed that 5-AcTMF lowered the levels of Tyrosine 705-phosphorylated STAT3 (p-STAT3), a canonical marker of STAT3 activation, but also dampened p-STAT3 upregulation elicited by Interleukin-6. Notably, ectopic expression of dominant-active STAT3 impeded 5-AcTMF-induced suppression of viability and clonogenicity plus apoptosis induction in GBM cells, confirming the prerequisite of STAT3 blockage for the inhibitory action of 5-AcTMF on GBM cell survival and growth. Additionally, 5-AcTMF impaired the activation of STAT3 upstream kinase JAK2 but also downregulated antiapoptotic BCL-2 and BCL-xL in a STAT3-dependent manner. Moreover, the overexpression of either BCL-2 or BCL-xL abrogated 5-AcTMF-mediated viability reduction and apoptosis induction in GBM cells. Collectively, we, for the first time, revealed the anticancer effect of 5-AcTMF on GBM cells, which was executed via thwarting the JAK2-STAT3-BCL-2/BCL-xL signaling axis. Our findings further implicate the therapeutic potential of 5-AcTMF for GBM treatment.	[Cheng, Yen-Po] Yuanlin Changhua Christian Hosp, Dept Surg, Div Neurosurg, Changhua 50006, Taiwan; [Cheng, Yen-Po; Li, Chia-Hsuan; Chen, Guan-Jun; Chang, Ching-Chin; Chang, Chia-Che] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 40227, Taiwan; [Li, Shiming] Huanggang Normal Univ, Hubei Key Lab Proc & Applicat Catalyt Mat, Huanggang 438000, Peoples R China; [Li, Shiming] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA; [Chuang, Wan-Ling; Lin, Ping-Yi] Changhua Christian Hosp, Transplant Med & Surg Res Ctr, Changhua 50006, Taiwan; [Or, Chi-Hung R.] Tungs Taichung MetroHarbor Hosp, Dept Anesthesiol, Taichung 43503, Taiwan; [Lin, Ping-Yi; Chang, Chia-Che] China Med Univ Hosp, Dept Med Res, Taichung 40447, Taiwan; [Chang, Chia-Che] Natl Chung Hsing Univ, Rong Hsing Res Ctr Translat Med, PhD Program Translat Med, Dept Life Sci,iEGG & Anim Biotechnol Res Ctr, Taichung 40227, Taiwan; [Chang, Chia-Che] Asia Univ, Dept Biotechnol, Taichung 41354, Taiwan		Chang, CC (corresponding author), Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 40227, Taiwan.; Lin, PY (corresponding author), Changhua Christian Hosp, Transplant Med & Surg Res Ctr, Changhua 50006, Taiwan.; Lin, PY; Chang, CC (corresponding author), China Med Univ Hosp, Dept Med Res, Taichung 40447, Taiwan.; Chang, CC (corresponding author), Natl Chung Hsing Univ, Rong Hsing Res Ctr Translat Med, PhD Program Translat Med, Dept Life Sci,iEGG & Anim Biotechnol Res Ctr, Taichung 40227, Taiwan.; Chang, CC (corresponding author), Asia Univ, Dept Biotechnol, Taichung 41354, Taiwan.	69221@cch.org.tw; chia_che@dragon.nchu.edu.tw		Chang, Chia-Che/0000-0003-3509-3713	iEGG; Animal Biotechnology Center from The Feature Areas Research Center Program within Ministry of Education (MOE) in Taiwan	This research was financially supported by The iEGG and Animal Biotechnology Center from The Feature Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.	Braidy N, 2017, CNS NEUROL DISORD-DR, V16, P387, DOI 10.2174/1871527316666170328113309; Brantley EC, 2008, MOL CANCER RES, V6, P675, DOI 10.1158/1541-7786.MCR-07-2180; Chang N, 2017, MOL CELL ENDOCRINOL, V451, P53, DOI 10.1016/j.mce.2017.01.004; Datla KP, 2001, NEUROREPORT, V12, P3871, DOI 10.1097/00001756-200112040-00053; Davis ME, 2016, CLIN J ONCOL NURS, V20, P2, DOI 10.1188/16.CJON.S1.2-8; Fox BM, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20081853; Ganguly Debolina, 2018, Oncotarget, V9, P22095, DOI 10.18632/oncotarget.25188; Han XT, 2017, ONCOTARGET, V8, P100931, DOI 10.18632/oncotarget.21753; Jensen KV, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0189670; Kohsaka S, 2012, MOL CANCER THER, V11, P1289, DOI 10.1158/1535-7163.MCT-11-0801; Lai CS, 2013, ROY SOC CH, V344, P281; Lee B, 2018, ANIM CELLS SYST, V22, P54, DOI 10.1080/19768354.2018.1426627; Li SM, 2008, ACS SYM SER, V987, P191; Li YR, 2016, CANCER BIOL THER, V17, P48, DOI 10.1080/15384047.2015.1108491; Lin GS, 2014, MED ONCOL, V31, DOI 10.1007/s12032-014-0924-5; Linder B, 2019, CANCERS, V11, DOI 10.3390/cancers11030333; Luwor RB, 2013, J CLIN NEUROSCI, V20, P907, DOI 10.1016/j.jocn.2013.03.006; Ma NH, 2014, J FUNCT FOODS, V11, P528, DOI 10.1016/j.jff.2014.08.009; Masliantsev K, 2018, ONCOTARGET, V9, P3968, DOI 10.18632/oncotarget.23374; Okuyama S, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18030489; Ostrom QT, 2018, NEURO-ONCOLOGY, V20, P1, DOI 10.1093/neuonc/noy131; Ouedraogo ZG, 2017, MOL NEUROBIOL, V54, P5780, DOI 10.1007/s12035-016-0103-0; Pearson JRD, 2017, SIGNAL TRANSDUCT TAR, V2, DOI 10.1038/sigtrans.2017.40; Periyasamy K, 2015, CANCER CHEMOTH PHARM, V75, P263, DOI 10.1007/s00280-014-2629-z; Reardon DA, 2017, SEMIN IMMUNOPATHOL, V39, P225, DOI 10.1007/s00281-016-0616-7; Shu ZP, 2014, INT IMMUNOPHARMACOL, V19, P275, DOI 10.1016/j.intimp.2014.01.011; Stoyanov GS, 2018, MED ONCOL, V35, DOI 10.1007/s12032-018-1083-x; Sundaram R, 2015, J FUNCT FOODS, V16, P315, DOI 10.1016/j.jff.2015.03.024; Takahashi K, 2006, CELL, V126, P663, DOI 10.1016/j.cell.2006.07.024; Tung Y., 2019, CURR PHARM REP, V5, P98, DOI DOI 10.1007/S40495-019-00170-Z; Wang JH, 2014, CELL BIOCHEM BIOPHYS, V70, P1255, DOI 10.1007/s12013-014-0049-7; Wang X., 2018, J FOOD BIOACT, V3, P76; Wu CF, 2019, J CELL BIOCHEM, V120, P4883, DOI 10.1002/jcb.27762; Yamamoto K, 1999, MOL CELL BIOL, V19, P8469; Yuan G, 2014, J BIOL CHEM, V289, P10607, DOI 10.1074/jbc.M113.528760; Zhi D, 2014, FOOD SCI HUM WELL, V3, P197, DOI [10.1080/15384047.2015.1108491, DOI 10.1080/15384047.2015.1108491, 10.1016/j.fshw.2014.12.003, DOI 10.1016/J.FSHW.2014.12.003]	36	8	9	3	6	MDPI	BASEL	ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND	1422-0067			INT J MOL SCI	Int. J. Mol. Sci.	JUL 1	2019	20	13							3366	10.3390/ijms20133366			14	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	IL1EG	WOS:000477041100250	31323961	gold, Green Published			2022-04-25	
J	Maisonneuve, C; Tsang, DKL; Foerster, EG; Robert, LM; Mukherjee, T; Prescott, D; Tattoli, I; Lemire, P; Winer, DA; Winer, S; Streutker, CJ; Geddes, K; Cadwell, K; Ferrero, RL; Martin, A; Girardin, SE; Philpott, DJ				Maisonneuve, Charles; Tsang, Derek K. L.; Foerster, Elisabeth G.; Robert, Lukian Maxence; Mukherjee, Tapas; Prescott, Dave; Tattoli, Ivan; Lemire, Paul; Winer, Daniel A.; Winer, Shawn; Streutker, Catherine J.; Geddes, Kaoru; Cadwell, Ken; Ferrero, Richard L.; Martin, Alberto; Girardin, Stephen E.; Philpott, Dana J.			Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells	CELL REPORTS			English	Article							MULTIPLE INTESTINAL NEOPLASIA; IMMUNE RECEPTOR NOD1; NF-KAPPA-B; MURAMYL DIPEPTIDE; SUPPRESSOR-CELLS; BACTERIAL PEPTIDOGLYCAN; ALTERNATIVE ACTIVATION; IMMUNOACTIVE PEPTIDES; HOST RECOGNITION; T-CELLS	Pioneering studies from the early 1980s suggested that bacterial peptidoglycan-derived muramyl peptides (MPs) could exert either stimulatory or immunosuppressive functions depending, in part, on chronicity of exposure. However, this Janus-faced property of MPs remains largely unexplored. Here, we demonstrate the immunosuppressive potential of Nod1, the bacterial sensor of diaminopimelic acid (DAP)-containing MPs. Using a model of self-limiting peritonitis, we show that systemic Nod1 activation promotes an autophagy-dependent reprogramming of macrophages toward an alternative phenotype. Moreover, Nod1 stimulation induces the expansion of myeloid-derived suppressor cells (MDSCs) and maintains their immunosuppressive potential via arginase-1 activity. Supporting the role of MDSCs and tumor-associated macrophages in cancer. we demonstrate that myeloid-intrinsic Nod1 expression sustains intra-tumoral arginase-1 levels to foster an immunosuppressive and tumor-permissive microenvironment during colorectal cancer (CRC) development. Our findings support the notion that bacterial products, via Nod1 detection, modulate the immunosuppressive activity of myeloid cells and fuel tumor progression in CRC.	[Maisonneuve, Charles; Tsang, Derek K. L.; Foerster, Elisabeth G.; Robert, Lukian Maxence; Mukherjee, Tapas; Prescott, Dave; Tattoli, Ivan; Winer, Daniel A.; Geddes, Kaoru; Martin, Alberto; Girardin, Stephen E.; Philpott, Dana J.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada; [Tattoli, Ivan; Lemire, Paul; Winer, Daniel A.; Winer, Shawn; Streutker, Catherine J.; Girardin, Stephen E.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada; [Winer, Daniel A.] Univ Toronto, Toronto Gen Hosp, Dept Pathol, Toronto, ON M5S 1A8, Canada; [Winer, Shawn; Streutker, Catherine J.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada; [Cadwell, Ken] New York Grossman Univ, Kimmel Ctr Biol & Med, Grossman Sch Med, Skirball Inst, New York, NY 10016 USA; [Cadwell, Ken] NYU, Dept Microbiol, Grossman Sch Med, New York, NY 10016 USA; [Cadwell, Ken] NYU, Dept Med, Div Gastroenterol & Hepatol, Grossman Sch Med, New York, NY 10016 USA; [Winer, Daniel A.] Buck Inst Res Aging, Novato, CA 94945 USA; [Ferrero, Richard L.] Monash Univ, Dept Mol & Translat Sci, Clayton, Vic 3800, Australia; [Ferrero, Richard L.] Hudson Inst Med Res, Ctr Innate Immun & Infect Dis, Clayton, Vic 3168, Australia; [Ferrero, Richard L.] Monash Univ, Biomed Discovery Inst, Dept Microbiol, Clayton, Vic 3800, Australia		Philpott, DJ (corresponding author), Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.	dana.philpott@utoronto.ca	Tattoli, Ivan/H-2600-2017	Tattoli, Ivan/0000-0001-7925-4609; Prescott, David/0000-0002-9798-9526; Foerster, Elisabeth/0000-0002-3271-0782; Cadwell, Ken/0000-0002-5860-0661	Canadian Cancer Society Research InstituteCanadian Cancer Society (CCS) [703185]; Canadian Institutes for Health Research (CIHR) Team Grant-Environments, Genes, and Chronic DiseaseCanadian Institutes of Health Research (CIHR) [ECD-144628]; Canada's National Microbiology Laboratory; National Health and Medical Research Council (NHMRC) of AustraliaNational Health and Medical Research Council (NHMRC) of Australia [APP1107930]; Victorian State Government Operational Infrastructure Scheme; Queen Elizabeth II/Aventis Pasteur Graduate Scholarship in Science and Technology	The authors of this paper would like to thank Dionne White and Joanna Warzyszynska for their expert FACS assistance and the University of Toronto Department of Comparative Medicine animal facility for their assistance. This work was supported by grants from the Canadian Cancer Society Research Institute (703185 to D.J.P. and A.M.); a Canadian Institutes for Health Research (CIHR) Team Grant-Environments, Genes, and Chronic Disease (ECD-144628 to D.J.P., S.E.G., and A.M.); Canada's National Microbiology Laboratory; the National Health and Medical Research Council (NHMRC) of Australia (APP1107930); and the Victorian State Government Operational Infrastructure Scheme. R.L.F. is an NHMRC Senior Research Fellow (APP1079904). C.M. was supported by the Queen Elizabeth II/Aventis Pasteur Graduate Scholarship in Science and Technology.	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J	Kang, Y; Jia, YL; Wang, QL; Zhao, QR; Song, M; Ni, R; Wang, J				Kang, Yan; Jia, Yaoli; Wang, Qilong; Zhao, Qianru; Song, Meng; Ni, Ran; Wang, Jing			Long Noncoding RNA KCNQ1OT1 Promotes the Progression of Non-Small Cell Lung Cancer via Regulating miR-204-5p/ATG3 Axis	ONCOTARGETS AND THERAPY			English	Article						KCNQ1OT1; miR-204-5p; ATG3; NSCLC	LNCRNA KCNQ1OT1; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; TUMOR-SUPPRESSOR; PROLIFERATION; METASTASIS; EXPRESSION; INVASION; A549	Purpose: Non-small cell lung cancer (NSCLC) is the first leading cause of cancer-related death globally. Long noncoding RNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) was involved in the progression of multiple cancers by sponging target miRNA. We aimed to explore the pathological mechanism of KCNQ1OT1 in NSCLC progression. Methods: The expression of KCNQ1OT1, miR-204-5p and autophagy-related gene 3 (ATG3) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry assay were conducted for the detection of cell proliferation and apoptosis, respectively. Western blot assay was performed to examine the protein levels of B-cell lymphoma-2 (BCL-2), BCL2-Associated X (Bax), cleaved caspase-3, cleaved caspase-9 and LC3 II /LC3 I and P62. The interaction between miR-204-5p and KCNQ1OT1 or ATG3 was validated by dual-luciferase reporter system and RNA immunoprecipitation (RIP) assay. Murine xenograft assay was conducted to explore the function of KCNQ1OT1 in vivo Immunohistochemistry (IHC) staining assay was used for the analysis of ki67-positive cell percentage. Results: The expression of KCNQ1OT1 and ATG3 was up-regulated whereas miR-204-5p was down-regulated in NSCLC tumors and cells. MiR-204-5p was inversely con elated with KCNQ1OT1 or ATG3. In addition, KCNQ1OT1 knockdown facilitated apoptosis, inhibited autophagy and proliferation of NSCLC cells in vitro and blocked tumor growth in vivo. However, the miR-204-5p inhibitor reversed the effects. More importantly, ATG3 was a target gene of miR-204-5p and ATG3 overexpression restored the effect of miR-204-5p on NSCLC cell progression. Conclusion: KCNQ1OT1 promotes cell proliferation and autophagy and inhibits cell apoptosis via regulating miR-204-5p/ATG3 axis, providing a promising target for NSCLC therapy.	[Kang, Yan; Wang, Qilong; Ni, Ran; Wang, Jing] Zhengzhou Univ, Affiliated Hosp 1, Dept Resp Med 2, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China; [Jia, Yaoli] Xuchang Cent Hosp, Dept Resp Med, Xuchang, Henan, Peoples R China; [Zhao, Qianru] Zhengzhou Univ, Affiliated Hosp 1, Dept Geriatr Med, Zhengzhou, Henan, Peoples R China; [Song, Meng] Zhengzhou Univ, Coll Publ Hlth, Dept Epidemiol & Hlth Stat, Zhengzhou, Henan, Peoples R China		Ni, R; Wang, J (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Resp Med 2, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China.	anxian218911qco@126.com; shijin199410ut@126.com					Ai XH, 2018, BMC CANCER, V18, DOI 10.1186/s12885-018-4224-x; Bian YZ, 2019, CANCER BIOL THER, V20, P886, DOI 10.1080/15384047.2019.1579959; Chang RM, 2014, HEPATOLOGY, V60, P1251, DOI 10.1002/hep.27221; Chung TKH, 2012, INT J CANCER, V130, P1036, DOI 10.1002/ijc.26060; Cui M, 2019, J CELL BIOCH; Dong ZW, 2019, J CELL PHYSIOL, V234, P11304, DOI 10.1002/jcp.27788; Feng WL, 2018, CELL PHYSIOL BIOCHEM, V49, P432, DOI 10.1159/000492978; Gao W, 2017, J CANCER, V8, P2356, DOI 10.7150/jca.19470; Gao XR, 2018, BIOL CHEM, V399, P375, DOI 10.1515/hsz-2017-0215; Hu HQ, 2018, BIOCHEM BIOPH RES CO, V503, P2400, DOI 10.1016/j.bbrc.2018.06.168; Hua L, 2018, CELL BIOL INT, V42, P1240, DOI 10.1002/cbin.10995; Imam JS, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0052397; Jia H, 2019, PATHOL RES PRACT, V215, P697, DOI 10.1016/j.prp.2018.12.039; Jiang GB, 2016, CELL BIOCHEM FUNCT, V34, P505, DOI 10.1002/cbf.3223; Li C, 2019, J CELL PHYSL; Li M, 2019, BIOCHIMIE, V158, P224, DOI 10.1016/j.biochi.2018.12.003; Li N, 2018, GYNECOL ONCOL, V150, P343, DOI 10.1016/j.ygyno.2018.06.013; Li Q, 2016, INT J MOL MED, V37, P1067, DOI 10.3892/ijmm.2016.2513; Li YC, 2019, ONCOTARGETS THER, V12, P2649, DOI 10.2147/OTT.S188054; Liu LY, 2015, BIOCHEM BIOPH RES CO, V457, P621, DOI 10.1016/j.bbrc.2015.01.037; Liu TM, 2018, BIOCHEM BIOPH RES CO, V503, P1503, DOI 10.1016/j.bbrc.2018.07.070; Luan WK, 2017, ONCOTARGETS THER, V10, P1237, DOI 10.2147/OTT.S128819; Luan XT, 2018, J GYNECOL ONCOL, V29, DOI 10.3802/jgo.2018.29.e95; Moravcikova E, 2017, INT J CANCER, V141, P2050, DOI 10.1002/ijc.30906; Shao J, 2019, J CELL PHYSIOL, V234, P17269, DOI 10.1002/jcp.28344; Sumbul AT, 2014, TUMOR BIOL, V35, P12713, DOI 10.1007/s13277-014-2596-3; Sun HW, 2018, ARCH BIOCHEM BIOPHYS, V658, P7, DOI 10.1016/j.abb.2018.09.019; Sun X, 2018, THORAC CANCER, V9, P523, DOI 10.1111/1759-7714.12599; Tang QL, 2018, INT J ONCOL, V53, P1732, DOI 10.3892/ijo.2018.4493; Wang CG, 2019, EXP MOL PATHOL, V107, P77, DOI 10.1016/j.yexmp.2019.01.012; Wang H, 2018, ONCOL REP, V39, P247, DOI 10.3892/or.2017.6088; Wang XJ, 2016, BIOMED PHARMACOTHER, V82, P202, DOI 10.1016/j.biopha.2016.04.060; Wang YZ, 2018, CANCER BIOMARK, V22, P721, DOI 10.3233/CBM-181228; Wang YX, 2018, CANCER CELL INT, V18, DOI 10.1186/s12935-018-0628-6; Xie YD, 2019, BIOMED PHARMACOTHER, V109, P679, DOI 10.1016/j.biopha.2018.10.097; Yin Y, 2014, CLIN CANCER RES, V20, P6187, DOI 10.1158/1078-0432.CCR-14-1030; You JW, 2018, MED SCI MONITOR, V24, P2126, DOI 10.12659/MSM.909627; Zhang SY, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0793-5; Zheng L, 2019, EUR REV MED PHARMACO, V23, P6944, DOI 10.26355/eurrev_201908_18734	39	40	40	0	4	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2019	12						10787	10797		10.2147/OTT.S226044			11	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	JV1NO	WOS:000502135400001	31849486	gold, Green Published			2022-04-25	
J	Gutierrez-Salmeron, M; Garcia-Martinez, JM; Martinez-Useros, J; Fernandez-Acenero, MJ; Viollet, B; Olivier, S; Chauhan, J; Lucena, SR; De la Vieja, A; Goding, CR; Chocarro-Calvo, A; Garcia-Jimenez, C				Gutierrez-Salmeron, Maria; Manuel Garcia-Martinez, Jose; Martinez-Useros, Javier; Jesus Fernandez-Acenero, Maria; Viollet, Benoit; Olivier, Severine; Chauhan, Jagat; Lucena, Silvia R.; De la Vieja, Antonio; Goding, Colin R.; Chocarro-Calvo, Ana; Garcia-Jimenez, Custodia			Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer	PLOS BIOLOGY			English	Article							PROTEIN-KINASE; HISTONE ACETYLTRANSFERASE; GENE-EXPRESSION; P300 ACETYLATION; PHOSPHORYLATION; TRANSCRIPTION; MECHANISMS; METFORMIN; METABOLISM; AUTOPHAGY	Coordination of gene expression with nutrient availability supports proliferation and homeostasis and is shaped by protein acetylation. Yet how physiological/pathological signals link acetylation to specific gene expression programs and whether such responses are cell-type-specific is unclear. AMP-activated protein kinase (AMPK) is a key energy sensor, activated by glucose limitation to resolve nutrient supply-demand imbalances, critical for diabetes and cancer. Unexpectedly, we show here that, in gastrointestinal cancer cells, glucose activates AMPK to selectively induce EP300, but not CREB-binding protein (CBP). Consequently, EP300 is redirected away from nuclear receptors that promote differentiation towards beta-catenin, a driver of proliferation and colorectal tumorigenesis. Importantly, blocking glycogen synthesis permits reactive oxygen species (ROS) accumulation and AMPK activation in response to glucose in previously nonresponsive cells. Notably, glycogen content and activity of the ROS/AMPK/EP300/beta-catenin axis are opposite in healthy versus tumor sections. Glycogen content reduction from healthy to tumor tissue may explain AMPK switching from tumor suppressor to activator during tumor evolution.	[Gutierrez-Salmeron, Maria; Manuel Garcia-Martinez, Jose; Lucena, Silvia R.; Chocarro-Calvo, Ana; Garcia-Jimenez, Custodia] Univ Rey Juan Carlos, Fac Hlth Sci, Area Physiol, Madrid, Spain; [Martinez-Useros, Javier] Univ Hosp Fdn Jimenez Diaz UAM, OncoHlth Inst, Translat Oncol Div, Hlth Res Inst, Madrid, Spain; [Jesus Fernandez-Acenero, Maria] Hosp Gregorio Maranon, Dept Surg Pathol, Madrid, Spain; [Viollet, Benoit; Olivier, Severine] Univ Paris, Inst Cochin, INSERM, CNRS, Paris, France; [Chauhan, Jagat; Goding, Colin R.; Chocarro-Calvo, Ana] Univ Oxford, Ludwig Inst Canc Res, Nuffield Dept Med, Oxford, England; [De la Vieja, Antonio] Inst Salud Carlos III, Unidad Tumores Endocrinos UFIEC, Madrid, Spain; [De la Vieja, Antonio] CiberOnc, Madrid, Spain		Chocarro-Calvo, A; Garcia-Jimenez, C (corresponding author), Univ Rey Juan Carlos, Fac Hlth Sci, Area Physiol, Madrid, Spain.; Chocarro-Calvo, A (corresponding author), Univ Oxford, Ludwig Inst Canc Res, Nuffield Dept Med, Oxford, England.	ana.chocarro@urjc.es; custodia.garcia@urjc.es	Chocarro-Calvo, Ana/AAM-3213-2020; García-Jiménez, Custodia/AAS-7744-2020; De la Vieja, Antonio/I-4774-2013; Viollet, Benoit/N-2397-2019; Viollet, Benoit/O-6927-2017; Lucena, Silvia Rocio/M-5703-2014	Chocarro-Calvo, Ana/0000-0003-1476-4848; García-Jiménez, Custodia/0000-0003-0146-4424; De la Vieja, Antonio/0000-0002-1187-1907; Viollet, Benoit/0000-0002-0121-0224; Viollet, Benoit/0000-0002-0121-0224; Garcia Martinez, Jose Manuel/0000-0002-6498-5174; Fernandez-Acenero/0000-0002-2439-3553; Gutierrez-Salmeron, Maria/0000-0002-6818-6951; Olivier, Severine/0000-0002-7653-2295; Lucena, Silvia Rocio/0000-0002-1803-3922	Spanish governmentSpanish GovernmentEuropean Commission [AEI,Mineco/FEDER SAF2016-79837-R, PID2019-110998RB-100, MICIU/FEDER: RTI2018-099343-B-100]; European UnionEuropean Commission [PIEF-GA-2013-626098]; EMBO Postdoctoral Long-Term Fellowship [ALTF 800-2013]; Comunidad de Madrid: Ayudas Atraccion de TalentoComunidad de Madrid [2017-T1/BMD-5334]; Comunidad de MadridComunidad de Madrid [FEDER-PEJD-2017-POST/BMD-3906]; Ludwig Institute for Cancer Research; INSERMInstitut National de la Sante et de la Recherche Medicale (Inserm)European Commission; CNRSCentre National de la Recherche Scientifique (CNRS)European Commission; Universite Paris Descartes; SFD (Societe Francophone du Diabete); Region Ile-deFranceRegion Ile-de-France	The financial support of the Spanish government (Grant Numbers: AEI, Mineco/FEDER SAF2016-79837-R and PID2019-110998RB-100 to CG-J and MICIU/FEDER: RTI2018-099343-B-100 to AV)(http://www.ciencia.gob.es/portal/site/MICINN/aei) is gratefully acknowledged. A.C-C. was supported by a European Union Marie Curie FP7-PEOPLE-2013-IEF (PIEF-GA-2013-626098), EMBO Postdoctoral Long-Term Fellowship (ALTF 800-2013) and by Comunidad de Madrid: Ayudas Atraccion de Talento (2017-T1/BMD-5334); (https://gestiona3.madrid.org/quadrivium/convocatorias/home/talento).SR.L.was supported by Comunidad de Madrid/FEDER-PEJD-2017-POST/BMD-3906. (https://gestiona3.madrid.org/quadrivium/convocatorias/) J.C. and C.R.G. were supported by the Ludwig Institute for Cancer Research (https://www.ludwig.ox.ac.uk/).B.V.was funded by INSERM, CNRS, Universite Paris Descartes (http://www.idf.inserm.fr/) and SFD (Societe Francophone du Diabete: https://www.sfdiabete.org/) and S.O. by the Region Ile-deFrance. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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Biol.	JUN	2020	18	6							e3000732	10.1371/journal.pbio.3000732			29	Biochemistry & Molecular Biology; Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics	MH6AU	WOS:000546810300001	32603375	Green Published, gold			2022-04-25	
J	Li, XN; Wang, ZJ; Ye, CX; Zhao, BC; Li, ZL; Yang, Y				Li, Xiang-Nan; Wang, Zhen-Jun; Ye, Chun-Xiang; Zhao, Bao-Cheng; Li, Zhu-Lin; Yang, Yong			RNA sequencing reveals the expression profiles of circRNA and indicates that circDDX17 acts as a tumor suppressor in colorectal cancer	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH			English	Article						Colorectal cancer; Circular RNAs; High-throughput sequencing; Bioinformatic analysis; CircDDX17; Tumor suppressor	CIRCULAR RNAS; PROGNOSTIC MARKER; CONFERS; AUTOPHAGY	BackgroundCircular RNA (circRNA) is a novel class of noncoding RNAs with functions in various pathophysiological activities. However, the expression profiles and functions of circRNAs in colorectal cancer (CRC) remain largely unknown.MethodsHigh-throughput RNA sequencing (RNA-seq) was performed to assess circRNA expression profiles in 4 paired CRC tissues, and significantly dysregulated circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of dysregulated circRNAs. Target miRNAs of circRNAs were predicted using miRanda software, and were further analyzed combining DIANA-miRPath v.3 platform (Reverse Search module) with KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer (Entry: map05210 and map05206). CircRNA-miRNA interaction networks were constructed using Cytoscape software. Expression levels of a significantly down-regulated circRNA, circDDX17 (hsa_circ_0002211), was detected by qRT-PCR in 60 paired CRC tissues. CircDDX17 was knockdown by siRNA, and the biological functions of circDDX17 were examined in CRC cell lines.ResultsTotally 448 differentially expressed circRNAs were identified, including 394 up-regulated and 54 down-regulated circRNAs. qRT-PCR validation confirmed the reliability of the RNA-Seq data. GO and KEGG analyses revealed that these dysregulated circRNAs were potentially implicated in CRC pathogenesis. Analyses by combining miRanda and miRPath softwares with KEGG pathways suggested that the miRNAs targeted by the top 10 dysregulated circRNAs were associated with the KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer, indicating that circRNA-miRNA interactions might play important functional roles in the initiation and progression of CRC. The results of qRT-PCR for circDDX17 in 60 paired CRC tissues showed that circDDX17 was significantly down-regulated in CRC tissues and associated with unfavorable clinicopathological parameters. In vitro experiments showed that silencing of circDDX17 promoted CRC cell proliferation, migration, invasion, and inhibited apoptosis.ConclusionsIn conclusion, we have identified numerous circRNAs that are dysregulated in CRC tissues compared with adjacent normal mucosa tissues. Bioinformatic analyses suggested that these dysregulated circRNAs might play important functional roles in CRC tumorigenesis. CircDDX17 functions as a tumor suppressor and could serve as a potential biomarker and a therapeutic target for CRC.	[Li, Xiang-Nan; Wang, Zhen-Jun; Ye, Chun-Xiang; Zhao, Bao-Cheng; Li, Zhu-Lin; Yang, Yong] Capital Med Univ, Beijing Chao Yang Hosp, Dept Gen Surg, 8 Gongtinan Rd, Beijing 100020, Peoples R China		Wang, ZJ (corresponding author), Capital Med Univ, Beijing Chao Yang Hosp, Dept Gen Surg, 8 Gongtinan Rd, Beijing 100020, Peoples R China.	Drzhenjun@163.com		Wang, Zhen-jun/0000-0001-6885-9354	National High-Tech R & D Program of China (863 Program) [2015AA033602]; 1351 Personnel Training Program of Beijing Chao-Yang Hospital Affiliated to Capital Medical University [CYXZ-2017-09]	This study was supported by the National High-Tech R & D Program of China (863 Program) (2015AA033602); 1351 Personnel Training Program of Beijing Chao-Yang Hospital Affiliated to Capital Medical University (CYXZ-2017-09).	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Exp. Clin. Cancer Res.	DEC 27	2018	37								325	10.1186/s13046-018-1006-x			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HF8NM	WOS:000454499100002	30591054	gold, Green Published	Y	N	2022-04-25	
J	Koehler, BC; Jassowicz, A; Scherr, AL; Lorenz, S; Radhakrishnan, P; Kautz, N; Elssner, C; Weiss, J; Jaeger, D; Schneider, M; Schulze-Bergkamen, H				Koehler, Bruno Christian; Jassowicz, Adam; Scherr, Anna-Lena; Lorenz, Stephan; Radhakrishnan, Praveen; Kautz, Nicole; Elssner, Christin; Weiss, Johanna; Jaeger, Dirk; Schneider, Martin; Schulze-Bergkamen, Henning			Pan-Bcl-2 inhibitor Obatoclax is a potent late stage autophagy inhibitor in colorectal cancer cells independent of canonical autophagy signaling	BMC CANCER			English	Article						Autophagy; Colorectal cancer; Apoptosis; Autophagy related gene; LC3; p62 (SQSTM1); Obatoclax; Chloroquine	REGULATES AUTOPHAGY; THERAPEUTIC TARGET; INDUCED APOPTOSIS; ACRIDINE-ORANGE; BCL-2 FAMILY; BH3 MIMETICS; RESISTANCE; BECLIN-1; LC3; CHLOROQUINE	Background: Colorectal cancer is the third most common malignancy in humans and novel therapeutic approaches are urgently needed. Autophagy is an evolutionarily highly conserved cellular process by which cells collect unnecessary organelles or misfolded proteins and subsequently degrade them in vesicular structures in order to refuel cells with energy. Dysregulation of the complex autophagy signaling network has been shown to contribute to the onset and progression of cancer in various models. The Bcl-2 family of proteins comprises central regulators of apoptosis signaling and has been linked to processes involved in autophagy. The antiapoptotic members of the Bcl-2 family of proteins have been identified as promising anticancer drug targets and small molecules inhibiting those proteins are in clinical trials. Methods: Flow cytometry and colorimetric assays were used to assess cell growth and cell death. Long term 3D cell culture was used to assess autophagy in a tissue mimicking environment in vitro. RNA interference was applied to modulate autophagy signaling. Immunoblotting and q-RT PCR were used to investigate autophagy signaling. Immunohistochemistry and fluorescence microscopy were used to detect autophagosome formation and autophagy flux. Results: This study demonstrates that autophagy inhibition by obatoclax induces cell death in colorectal cancer (CRC) cells in an autophagy prone environment. Here, we demonstrate that pan-Bcl-2 inhibition by obatoclax causes a striking, late stage inhibition of autophagy in CRC cells. In contrast, ABT-737, a Mcl-1 sparing Bcl-2 inhibitor, failed to interfere with autophagy signaling. Accumulation of p62 as well as Light Chain 3 (LC3) was observed in cells treated with obatoclax. Autophagy inhibition caused by obatoclax is further augmented in stressful conditions such as starvation. Furthermore, our data demonstrate that inhibition of autophagy caused by obatoclax is independent of the essential pro-autophagy proteins Beclin-1, Atg7 and Atg12. Conclusions: The objective of this study was to dissect the contribution of Bcl-2 proteins to autophagy in CRC cells and to explore the potential of Bcl-2 inhibitors for autophagy modulation. Collectively, our data argue for a Beclin-1 independent autophagy inhibition by obatoclax. Based on this study, we recommend the concept of autophagy inhibition as therapeutic strategy for CRC.	[Koehler, Bruno Christian; Jassowicz, Adam; Scherr, Anna-Lena; Lorenz, Stephan; Kautz, Nicole; Jaeger, Dirk; Schulze-Bergkamen, Henning] Univ Heidelberg Hosp, Dept Med Oncol, Internal Med 6, Natl Ctr Tumor Dis, Heidelberg, Germany; [Radhakrishnan, Praveen; Schneider, Martin] Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, D-69120 Heidelberg, Germany; [Weiss, Johanna] Heidelberg Univ, Univ Heidelberg Hosp, Dept Clin Pharmacol & Pharmacoepidemiol, D-69120 Heidelberg, Germany; [Schulze-Bergkamen, Henning] Marien Hosp, Dept Internal Med 2, Wesel, Germany		Koehler, BC (corresponding author), Univ Heidelberg Hosp, Dept Med Oncol, Internal Med 6, Natl Ctr Tumor Dis, Heidelberg, Germany.	bruno.koehler@nct-heidelberg.de					Bai H, 2012, ONCOGENE, V31, P4397, DOI 10.1038/onc.2011.613; Basit F, 2013, CELL DEATH DIFFER, V20, P1161, DOI 10.1038/cdd.2013.45; Bonapace L, 2010, J CLIN INVEST, V120, P1310, DOI 10.1172/JCI39987; Burdelski C, 2015, CLIN CANCER RES, V21, P3471, DOI 10.1158/1078-0432.CCR-14-0620; 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Wroblewski D, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0084073; Yazbeck VY, 2014, ORAL ONCOL, V50, P120, DOI 10.1016/j.oraloncology.2013.10.013; Zhai H, 2015, ONCOTARGET; Zhang ZL, 2015, BIOMED PHARMACOTHER, V74, P17, DOI 10.1016/j.biopha.2015.06.003	66	22	22	0	11	BMC	LONDON	CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	1471-2407			BMC CANCER	BMC Cancer	NOV 19	2015	15								919	10.1186/s12885-015-1929-y			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CW8UR	WOS:000365275400002	26585594	Green Published, gold			2022-04-25	
J	Lin, X; Lai, XJ; Feng, W; Yu, XF; Gu, Q; Zheng, X				Lin, Xiao; Lai, Xiaojing; Feng, Wei; Yu, Xiaofu; Gu, Qing; Zheng, Xiao			MiR-30a sensitized lung cancer against neoadjuvant chemotherapy by depressing autophagy	JAPANESE JOURNAL OF CLINICAL ONCOLOGY			English	Article						NSCLC; neoadjuvant chemotherapy; miR-30a; autophagy; sensitivity; cisplatin; pemetrexed	RENAL-CELL CARCINOMA; INDUCED APOPTOSIS; COLORECTAL-CANCER; 1ST-LINE THERAPY; DOWN-REGULATION; INHIBITION; MICRORNA; EXPRESSION; CHEMORESISTANCE; GEMCITABINE	Objective: This study was aimed at exploring whether miR-30a enhanced sensitivity of non-small-cell lung cancer (NSCLC) cells against neoadjuvant chemotherapy through an autophagy-dependent way. Methods: We totally recruited 304 NSCLC patients who have underwent chemotherapy, as well as 185 NSCLC patients who did not receive chemotherapy. NSCLC cell lines (i.e. H1299 and H460) were also purchased, and they were transfected by miR-30a mimic/inhibitor. Furthermore, cisplatin (DDP)/pemetrexed (PEM) resistance of NSCLC cells was assessed utilizing MTT assay, and autophagic proteins isolated from NSCLC tissues and cells were quantitated by western blotting. Results: Lowly expressed miR-30a was reflective of lymph node metastasis, advanced TNM stage and poor 5-year survival among NSCLC patients treated by neoadjuvant chemotherapy (i.e. combined treatment of DDP and PEM) (P < 0.05). Moreover, DDP combined with PEM attenuated viability and proliferation, but, on the contrary, promoted autophagy of H1299 and H460 cell lines (P < 0.05). However, miR-30a undermined resistance of NSCLC cells against DDP and PEM (P < 0.05), and it suppressed DDP/PEM-induced autophagy and promoted DDP/PEM-triggered apoptosis of NSCLC cells (P < 0.05). Conclusions: Intentionally elevating miR-30a expression was conducive to improving NSCLC prognosis after neoadjuvant chemotherapy, for its depressing drug-caused autophagy and resistance.	[Lin, Xiao; Lai, Xiaojing; Feng, Wei; Yu, Xiaofu; Gu, Qing; Zheng, Xiao] Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Thorac Radiotherapy, 1 Banshan East Rd, Hangzhou 310022, Zhejiang, Peoples R China		Zheng, X (corresponding author), Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Thorac Radiotherapy, 1 Banshan East Rd, Hangzhou 310022, Zhejiang, Peoples R China.	neayozhengxiao@163.com					Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; Arndt GM, 2009, BMC CANCER, V9, DOI 10.1186/1471-2407-9-374; Calvert H, 2003, SEMIN ONCOL, V30, P2, DOI 10.1053/sonc.2003.37267; Chen N, 2009, BBA-MOL CELL RES, V1793, P1516, DOI 10.1016/j.bbamcr.2008.12.013; Chen S, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0950-x; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Cheng CW, 2012, BREAST CANCER RES TR, V134, P1081, DOI 10.1007/s10549-012-2034-4; Cummins JM, 2006, P NATL ACAD SCI USA, V103, P3687, DOI 10.1073/pnas.0511155103; Fleeman N, 2010, HEALTH TECHNOL ASSES, V14, P47, DOI [10.3310/hta14Suppl1/07, 10.3310/hta14suppl1/07]; Heinzelmann J, 2011, WORLD J UROL, V29, P367, DOI 10.1007/s00345-010-0633-4; Hou YJ, 2011, LAB INVEST, V91, P1146, DOI 10.1038/labinvest.2011.97; Huang QB, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0067294; Iaccarino I, 2011, CELL DEATH DIFFER, V18, P565, DOI 10.1038/cdd.2010.174; Ichihara E, 2015, J THORAC ONCOL, V10, P486, DOI 10.1097/JTO.0000000000000434; Katz B, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0113700; Khan SA, 2005, LANCET, V366, P1303, DOI 10.1016/S0140-6736(05)67530-7; Kondo Y, 2005, NAT REV CANCER, V5, P726, DOI 10.1038/nrc1692; Kumar MS, 2007, NAT GENET, V39, P673, DOI 10.1038/ng2003; Kumarakulasinghe NB, 2015, RESPIROLOGY, V20, P370, DOI 10.1111/resp.12490; Landi D, 2012, CANCER-AM CANCER SOC, V118, P4670, DOI 10.1002/cncr.27435; Lebovitz CB, 2015, AUTOPHAGY, V11, P1668, DOI 10.1080/15548627.2015.1067362; Li WF, 2016, TUMOR BIOL, V37, P5885, DOI 10.1007/s13277-015-4456-1; Li X, 2009, CELL, V137, P273, DOI 10.1016/j.cell.2009.01.058; Liu ZY, 2014, FEBS LETT, V588, P3089, DOI 10.1016/j.febslet.2014.06.037; Liu ZF, 2014, J CELL MOL MED, V18, P610, DOI 10.1111/jcmm.12209; Longo L, 2008, MOL CANCER THER, V7, P2476, DOI 10.1158/1535-7163.MCT-08-0361; Maione Paolo, 2010, Ther Adv Med Oncol, V2, P251, DOI 10.1177/1758834010366707; Nasrallah H, 2012, MED ONCOL, V29, P212, DOI 10.1007/s12032-010-9790-y; O'Donovan TR, 2011, AUTOPHAGY, V7, P509, DOI 10.4161/auto.7.5.15066; Prochnik SE, 2007, DEV GENES EVOL, V217, P73, DOI 10.1007/s00427-006-0116-1; Richetta C, 2013, CELL MICROBIOL, V15, P368, DOI 10.1111/cmi.12043; Sato K, 2007, CANCER RES, V67, P9677, DOI 10.1158/0008-5472.CAN-07-1462; Scagliotti GV, 2012, J CLIN ONCOL, V30, P172, DOI 10.1200/JCO.2010.33.7089; Shi QX, 2019, CHEMOSPHERE, V215, P710, DOI 10.1016/j.chemosphere.2018.10.019; Siegel RL, 2018, CA-CANCER J CLIN, V68, P7, DOI 10.3322/caac.21442; Sun WL, 2011, AUTOPHAGY, V7, P1035, DOI 10.4161/auto.7.9.16521; Tanida I, 2005, AUTOPHAGY, V1, P84, DOI 10.4161/auto.1.2.1697; Thatcher N, 2015, LANCET ONCOL, V16, P763, DOI 10.1016/S1470-2045(15)00021-2; Toton E, 2014, J PHYSIOL PHARMACOL, V65, P459; Wang CL, 2017, CELL PHYSIOL BIOCHEM, V43, P2405, DOI 10.1159/000484394; Wang SY, 2017, J PHARMACOL SCI, V134, P197, DOI 10.1016/j.jphs.2017.07.001; Weidberg H, 2010, EMBO J, V29, P1792, DOI 10.1038/emboj.2010.74; Xu RD, 2016, ONCOL REP, V35, P1757, DOI 10.3892/or.2015.4497; Yadunandam AK, 2012, INT J ONCOL, V41, P1036, DOI 10.3892/ijo.2012.1506; Yang X, 2017, CELL PHYSIOL BIOCHEM, V43, P1126, DOI 10.1159/000481754; Zeng LY, 2012, BMC GENOMICS, V13, DOI 10.1186/1471-2164-13-S8-S14; Zhang HD, 2017, INT J MOL MED, V40, P1235, DOI 10.3892/ijmm.2017.3084; Zheng B, 2015, BIOCHEM BIOPH RES CO, V459, P234, DOI 10.1016/j.bbrc.2015.02.084; Zhong M, 2013, CELL PHYSIOL BIOCHEM, V31, P209, DOI 10.1159/000343362; Zhu H, 2009, AUTOPHAGY, V5, P816, DOI 10.4161/auto.9064; Zou ZY, 2016, BIOCHEM J, V473, P2131, DOI 10.1042/BCJ20160177	51	4	4	1	1	OXFORD UNIV PRESS	OXFORD	GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND	0368-2811	1465-3621		JPN J CLIN ONCOL	Jpn. J. Clin. Oncol.	MAY	2021	51	5					675	684		10.1093/jjco/hyaa272		FEB 2021	10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	SA4HC	WOS:000649258300002	33537721	Bronze			2022-04-25	
J	Rebecca, VW; Nicastri, MC; McLaughlin, N; Fennelly, C; McAfee, Q; Ronghe, A; Nofal, M; Lim, CY; Witze, E; Chude, CI; Zhang, G; Alicea, GM; Piao, SF; Murugan, S; Ojha, R; Levi, SM; Wei, Z; Barber-Rotenberg, JS; Murphy, ME; Mills, GB; Lu, YL; Rabinowitz, J; Marmorstein, R; Liu, Q; Liu, SJ; Xu, XW; Herlyn, M; Zoncu, R; Brady, DC; Speicher, DW; Winkler, JD; Amaravadi, RK				Rebecca, Vito W.; Nicastri, Michael C.; McLaughlin, Noel; Fennelly, Colin; McAfee, Quentin; Ronghe, Amruta; Nofal, Michel; Lim, Chun-Yan; Witze, Eric; Chude, Cynthia I.; Zhang, Gao; Alicea, Gretchen M.; Piao, Shengfu; Murugan, Sengottuvelan; Ojha, Rani; Levi, Samuel M.; Wei, Zhi; Barber-Rotenberg, Julie S.; Murphy, Maureen E.; Mills, Gordon B.; Lu, Yiling; Rabinowitz, Joshua; Marmorstein, Ronen; Liu, Qin; Liu, Shujing; Xu, Xiaowei; Herlyn, Meenhard; Zoncu, Roberto; Brady, Donita C.; Speicher, David W.; Winkler, Jeffrey D.; Amaravadi, Ravi K.			A Unified Approach to Targeting the Lysosome's Degradative and Growth Signaling Roles	CANCER DISCOVERY			English	Article							AUTOPHAGY INHIBITION; PANCREATIC ADENOCARCINOMA; MONITORING AUTOPHAGY; AMINO-ACIDS; CELL-DEATH; CANCER; IDENTIFICATION; METABOLISM; RESISTANCE; PROTEINS	Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e., autophagy and macropinocytosis) while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQ) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy. Central nitrogen methylation of the DQ linker enhances lysosomal localization and potency. An in situ photoaffinity pulldown identified palmitoyl-protein thioesterase 1 (PPT1) as the molecular target of DQ661. PPT1 inhibition concurrently impairs mTOR and lysosomal catabolism through the rapid accumulation of palmitoylated proteins. DQ661 inhibits the in vivo tumor growth of melanoma, pancreatic cancer, and colorectal cancer mouse models and can be safely combined with chemotherapy. Thus, lysosome-directed PPT1 inhibitors represent a new approach to concurrently targeting mTORC1 and lysosomal catabolism in cancer. SIGNIFICANCE: This study identifies chemical features of dimeric compounds that increase their lysosomal specificity, and a new molecular target for these compounds, reclassifying these compounds as targeted therapies. Targeting PPT1 blocks mTOR signaling in a manner distinct from catalytic inhibitors, while concurrently inhibiting autophagy, thereby providing a new strategy for cancer therapy. (C) 2017 AACR.	[Rebecca, Vito W.; Fennelly, Colin; McAfee, Quentin; Chude, Cynthia I.; Piao, Shengfu; Murugan, Sengottuvelan; Ojha, Rani; Levi, Samuel M.; Amaravadi, Ravi K.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA; [Nicastri, Michael C.; McLaughlin, Noel; Levi, Samuel M.; Winkler, Jeffrey D.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA; [Ronghe, Amruta; Zhang, Gao; Alicea, Gretchen M.; Murphy, Maureen E.; Liu, Qin; Herlyn, Meenhard; Speicher, David W.] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, 3601 Spruce St, Philadelphia, PA 19104 USA; [Ronghe, Amruta; Zhang, Gao; Alicea, Gretchen M.; Murphy, Maureen E.; Liu, Qin; Herlyn, Meenhard; Speicher, David W.] Wistar Inst Anat & Biol, Melanoma Res Ctr, 3601 Spruce St, Philadelphia, PA 19104 USA; [Nofal, Michel; Rabinowitz, Joshua] Princeton Univ, Dept Chem & Integrat Genom, Princeton, NJ 08544 USA; [Lim, Chun-Yan; Zoncu, Roberto] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA; [Witze, Eric; Brady, Donita C.] Univ Penn, Abramson Family Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA; [Wei, Zhi] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA; [Barber-Rotenberg, Julie S.; Marmorstein, Ronen] Univ Penn, Dept Biochem & Biophys, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA; [Mills, Gordon B.; Lu, Yiling] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA; [Liu, Shujing; Xu, Xiaowei] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA; [Winkler, Jeffrey D.; Amaravadi, Ravi K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA		Winkler, JD (corresponding author), Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.; Amaravadi, RK (corresponding author), Univ Penn, 8th Floor BRB,421 Curie Blvd, Philadelphia, PA 19104 USA.	winkler@sas.upenn.edu; ravi.amaravadi@uphs.upenn.edu	, AndyWei/H-4415-2012; Ojha, Rani/ABF-9507-2020	Wei, Zhi/0000-0001-6059-4267; /0000-0002-9823-351X; Levi, Samuel/0000-0003-0973-3991; Mills, Gordon/0000-0002-0144-9614; Chude, Cynthia/0000-0002-8595-9151; Liu, Shujing/0000-0002-2958-093X; Murphy, Maureen/0000-0001-7644-7296	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01CA169134, P01 CA114046, P30 CA016520, SPORE P50 CA174523, 1R01CA198015, CA016672, P30CA010815]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P50CA093372, DP2CA195761, R01CA169134, R50CA221838, P50CA174523, P30CA010815, P30CA016520, R01CA139319, R01CA198015, P01CA114046, P30CA016672] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [F30AR065870] Funding Source: NIH RePORTER	This work was entirely supported by NIH grants R01CA169134, P01 CA114046, P30 CA016520, SPORE P50 CA174523, 1R01CA198015, CA016672, and P30CA010815.	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NOV	2017	7	11					1266	1283		10.1158/2159-8290.CD-17-0741			18	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FL5BY	WOS:000414247300011	28899863	Green Accepted			2022-04-25	
J	Zhang, ZD; Wang, AH; Li, H; Zhi, H; Lu, F				Zhang, Zhongde; Wang, Aihua; Li, Hui; Zhi, Hui; Lu, Feng			RETRACTED: STAT3-dependent TXNDC17 expression mediates Taxol resistance through inducing autophagy in human colorectal cancer cells (Retracted article. See vol. 730, 2020)	GENE			English	Article; Retracted Publication						TXNDC17; Autophagy; Taxol resistance; Colorectal cancer cell	THIOREDOXIN-RELATED PROTEIN; TARGETING AUTOPHAGY; GROWTH-FACTOR; 14 KDA; STAT3; SURVIVAL; INDUCTION; PROMOTES; TRP14	Taxol (paclitaxel) is one of the taxane class of anticancer drugs as a first-line chemotherapeutic agent against many cancers including colorectal cancer, breast cancer, non-small cell lung cancer, ovarian cancer and so on. It is verified to induce cytotoxicity in a concentration and time-dependent manner. Numerous novel formulations of Taxol have been remanufactured for better therapeutic effect. Though Taxol works as a common anticancer drug for a long time in clinical practice, drug resistance is a major limitation of its long-term administration. In-depth research on drug resistance is still in progress and researchers have made some achievements, however, the mechanism or key molecule related to Taxol resistance in colorectal cancer still remains to be explored. In the present study, we observed that the high expression of TXNDC17 (thioredoxin domain containing 17) was associated with Taxol resistance in colorectal cancer cells. And TXNDC17 mediated Taxol resistance was related with increased basal autophagy level. Taxol exposure induced high levels of phospho-STAT3 (Tyr 705) and TXNDC17; and increase of basal autophagy in colorectal cancer cells. TXNDC17 overexpression cells obtained Taxol resistance and a high level of autophagy, and it is not surprising that stable downregulation of TXNDC17 accordingly reversed these phenomena. Interestingly, STAT3 could similarly work as TXNDC17 in spite of slighter effect compared to TXNDC17. And it has been proved that phospho-STAT3 (Tyr 705) possesses transcriptional regulation activity through forming dimmers. Many research revealed that transcription factor STAT3 affected more than 1000 gene products, and TXNDC17 is predicted to be a target gene of STAT3 at UCSC database. For the first time, we found STAT3 could bind promoter region of TXNDC17 (-623 bp to -58 bp relative to the transcription start site (TSS)) for regulating its expression. These results suggest the possibility that TXNDC17 could play an important role in Taxol resistance via enhancing autophagy in human colorectal cancer cells. TXNDC17 may become a potential target of colorectal cancer therapeutics. (C) 2016 Elsevier B.V. All rights reserved.	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J	Beyer, S; Schwalm, S; Pfeilschifter, J; Huwiler, A				Beyer, Sandra; Schwalm, Stephanie; Pfeilschifter, Josef; Huwiler, Andrea			Renal Mesangial Cells Isolated from Sphingosine Kinase 2 Transgenic Mice Show Reduced Proliferation and are More Sensitive to Stress-Induced Apoptosis	CELLULAR PHYSIOLOGY AND BIOCHEMISTRY			English	Article						Mesangial cells; Proliferation; Apoptosis; Autophagy; S1P; Transgenic SK-2 mice	UNILATERAL URETERAL OBSTRUCTION; EPIDERMAL-GROWTH-FACTOR; SPHINGOLIPID METABOLISM; INHIBITOR ABC294640; KIDNEY FIBROSIS; BREAST-CANCER; COLON-CANCER; LINE MCF7; IN-VIVO; 1-PHOSPHATE	Background/Aims: Sphingosine 1-phosphate (S1P) is considered as a key molecule regulating various cell functions including cell growth and death. It is produced by two sphingosine kinases (SK) denoted as SK-1 and SK-2. Whereas SK-1 has been extensively studied and has been appointed a role in promoting cell growth, the function of SK-2 is controversial, and both proproliferative and pro-apoptotic functions have been suggested. In this study we investigated whether renal mesangial cells isolated from transgenic mice overexpressing the human Sphk2 gene (hSK2-tg) showed an altered cell response towards growth-inducing and apoptotic stimuli. Methods: hSK2-tg mice were generated by using a Quick KnockinR strategy. Renal mesangial cells were isolated by a differential sieving method and further cultivated in vitro. Lipids were quantified by mass spectrometry. Protein expression was determined by Western blot analysis, cell proliferation was determined by 3H-thymidine incorporation, and apoptosis was determined by a DNA fragmentation ELISA. Results: We show here that kidneys and mesangial cells from hSK2-tg mice express the hSK2 as well as the endogenous mouse mSK2. hSK2 and mSK2 predominantly resided in the cytosol of quiescent transgenic cells. However, S1P accumulated strongly in the nucleus and only minimally in the cytosol of transgenic cells. Functionally, hSK2-tg cells proliferated less than control cells under normal growth conditions and were also more sensitive towards stress-induced apoptosis. On the molecular level, this was reflected by reduced ERK and Akt/PKB activation, and upon staurosporine treatment, by a sensitized mitochondrial pathway as manifested by reduced anti-apoptotic Bcl-XL expression and increased cleavage of caspase-9, downstream caspase-3 and PARP-1. Conclusion: Altogether, these data demonstrate that SK-2 exerts an antiproliferative and apoptosissensitizing effect in renal mesangial cells which suggests that selective inhibitors of SK-2 may promote proliferation and reduce apoptosis and this may have impact on the outcome of proliferation-associated diseases such as mesangioproliferative glomerulonephritis. (C) 2018 The Author(s) Published by S. Karger AG, Basel	[Beyer, Sandra; Schwalm, Stephanie; Pfeilschifter, Josef] Univ Klinikum, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany; [Beyer, Sandra; Schwalm, Stephanie; Pfeilschifter, Josef] Goethe Univ, Frankfurt, Germany; [Huwiler, Andrea] Univ Bern, Inselspital, Inst Pharmacol, INO F, CH-3010 Bern, Switzerland		Huwiler, A (corresponding author), Univ Bern, Inselspital, Inst Pharmacol, INO F, CH-3010 Bern, Switzerland.	Huwiler@pki.unibe.ch		, Stephanie/0000-0002-2198-6898	Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [310030-153346, 310030-175561/1]; German Research FoundationGerman Research Foundation (DFG) [SFB1039, PF361/6-1]	This work was supported by the Swiss National Science Foundation (310030-153346 and 310030-175561/1) and the German Research Foundation (SFB1039; PF361/6-1). We thank Isolde Romer and Simone Albert for excellent technical assistance.	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Physiol. Biochem.		2018	47	6					2522	2533		10.1159/000491625			12	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	GO6KR	WOS:000440152000028	29991026	Green Published, gold			2022-04-25	
J	Liu, HH; Zhao, JQ; Fu, RZ; Zhu, CH; Fan, DD				Liu, Huanhuan; Zhao, Jiaqi; Fu, Rongzhan; Zhu, Chenhui; Fan, Daidi			The ginsenoside Rk3 exerts anti-esophageal cancer activity in vitro and in vivo by mediating apoptosis and autophagy through regulation of the PI3K/Akt/mTOR pathway	PLOS ONE			English	Article							CELL-CYCLE ARREST; COLORECTAL-CANCER; DUAL ROLE; STATISTICS; CROSSTALK; ANTITUMOR; DEATH	The rare ginsenoside Rk3 is a bioactive component derived from ginseng and Panax notoginseng that has been proven to possess anti-lung cancer activity. However, the effect of Rk3 on human esophageal cancer has not yet been reported. In this study, we aimed to explore its anticancer curative effect and potential molecular mechanisms in the Eca109 and KYSE150 cell lines. We found that Rk3 was able to significantly repress cell proliferation and colony formation in both Eca109 and KYSE150 cells in vitro. In the KYSE150 xenograft model, Rk3 obviously inhibited tumor growth and exhibited little toxicity in organs. Moreover, Rk3 could trigger G1 phase arrest and induce apoptosis and autophagy. Interestingly, apoptosis induced by Rk3 could be partly abrogated by 3-MA (an autophagy inhibitor), implying that autophagy could enhance apoptosis. Further studies indicated that pretreatment with the Akt inhibitor GSK690693 or the mTOR inhibitor rapamycin promoted Rk3-induced apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway is related to Rk3-induced apoptosis and autophagy. In conclusion, the present study is the first to clarify that Rk3 can inhibit Eca109 and KYSE150 cell proliferation through activating apoptosis and autophagy by blocking the PI3K/Akt/mTOR pathway, suggesting that Rk3 may be a promising antitumor agent for esophageal cancer. In addition, this study provides ideas and an experimental basis for further research on the anti-esophageal cancer effects of the ginsenoside Rk3 and its mechanism.	[Liu, Huanhuan; Fu, Rongzhan; Zhu, Chenhui; Fan, Daidi] Northwest Univ, Sch Chem Engn, Shaanxi Key Lab Degradable Biomed Mat, Xian, Shaanxi, Peoples R China; [Liu, Huanhuan; Fu, Rongzhan; Zhu, Chenhui; Fan, Daidi] Northwest Univ, Sch Chem Engn, Shaanxi R&D Ctr Biomat & Fermentat Engn, Xian, Shaanxi, Peoples R China; [Liu, Huanhuan; Fu, Rongzhan; Zhu, Chenhui; Fan, Daidi] Northwest Univ, Res Inst, Biotech & Biomed, Xian, Shaanxi, Peoples R China; [Zhao, Jiaqi] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China		Zhu, CH; Fan, DD (corresponding author), Northwest Univ, Sch Chem Engn, Shaanxi Key Lab Degradable Biomed Mat, Xian, Shaanxi, Peoples R China.; Zhu, CH; Fan, DD (corresponding author), Northwest Univ, Sch Chem Engn, Shaanxi R&D Ctr Biomat & Fermentat Engn, Xian, Shaanxi, Peoples R China.; Zhu, CH; Fan, DD (corresponding author), Northwest Univ, Res Inst, Biotech & Biomed, Xian, Shaanxi, Peoples R China.	zch@nwu.edu.cn; fandaidi@nwu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21576222, 21576223, 21576160, 21878247, 21838009, 21808184]; Shaanxi Key Laboratory of Degradable Biomedical Materials Program [16JS106, 2016SZSj-35]	This study was financially supported by the National Natural Science Foundation of China (21576222 to CZ, 21576223, 21576160, 21878247 to CZ, 21838009 to DF, 21808184 to RF) and Shaanxi Key Laboratory of Degradable Biomedical Materials Program (16JS106, 2016SZSj-35 to DF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Li, ZX; Wen, CM; Li, JL; Meng, HM; Ji, C; Han, ZC; An, GL; Yang, L				Li, Zixuan; Wen, Chunmei; Li, Jialu; Meng, Huimin; Ji, Cheng; Han, Zhichao; An, Gangli; Yang, Lin			Zkscan3 gene is a potential negative regulator of plasma cell differentiation	EUROPEAN JOURNAL OF INFLAMMATION			English	Article						plasma cell; X-inactive-specific transcript; zkscan3	AUTOPHAGY	We previously showed that the ZKSCAN3 gene codes for a zinc-finger transcription factor that regulates the expression of important genes and plays crucial roles in the development, metastasis, and pathogenesis of rectal cancer, prostate cancer, myeloma, and so on, and in the regulation of autophagy. However, its biological functions under normal physiological conditions remain unclear. In addition, our previous studies showed that the ZKSCAN3 gene may negatively regulate B cell functions. Therefore, we constructed a zkscan3-knockout mouse model and observed that knockout mice contained a greater number of plasma cells than wild-type mice. We also found that the number of plasma cells was significantly increased in either colorectal cancer xenografts or under lipopolysaccharide-induced conditions. RNA-seq and quantitative-polymerase chain reaction assay indicated that the X-inactive-specific transcript is upregulated in B cells of zkscan3-knockout mice, which may represent a potential mechanism how zkscan3 modulates plasma cell differentiation.	[Li, Zixuan; Wen, Chunmei; Li, Jialu; Meng, Huimin; Ji, Cheng; Han, Zhichao; An, Gangli; Yang, Lin] Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou, Jiangsu, Peoples R China; [An, Gangli; Yang, Lin] Soochow Univ, Collaborat Innovat Ctr Hematol, Suzhou, Peoples R China; [An, Gangli; Yang, Lin] Soochow Univ, State Key Lab Radiat Med & Protect, Suzhou, Peoples R China; [Yang, Lin] Persongen BioTherapeut Suzhou Co Ltd, Suzhou, Peoples R China		An, GL; Yang, L (corresponding author), Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou, Jiangsu, Peoples R China.	gangli_an@suda.edu.cn; yanglin@suda.edu.cn			Priority Academic Program Development of Jiangsu Higher Education Institutions; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31471283]; National Key R&D Program of China [2016YFC1303403]; Collaborative Innovation Major Project [XYXT2015304]; Six Talent Peaks Project in Jiangsu Province [SWYY-CXTD-010]; Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, PR China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, PR China; Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu, PR China [GZN1201803]	The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions; National Natural Science Foundation of China (Grant No. 31471283); National Key R&D Program of China (2016YFC1303403); Collaborative Innovation Major Project (Grant No. XYXT2015304); Six Talent Peaks Project in Jiangsu Province (No. SWYY-CXTD-010); the Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu, PR China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, PR China; and the Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu, PR China (No. GZN1201803).	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J. Inflamm.	MAY	2019	17								2058739219850008	10.1177/2058739219850008			11	Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Immunology	HZ5RK	WOS:000468910000001		gold			2022-04-25	
J	Arun, RP; Sivanesan, D; Patra, B; Varadaraj, S; Verma, RS				Arun, Raj Pranap; Sivanesan, Divya; Patra, Bamadeb; Varadaraj, Sudha; Verma, Rama Shanker			Simulated microgravity increases polyploid giant cancer cells and nuclear localization of YAP	SCIENTIFIC REPORTS			English	Article							AUTOPHAGY MAINTAINS; HIPPO PATHWAY; STEM-CELLS; DIFFERENTIATION; EXPRESSION; MTOR; HOMEOSTASIS; RENEWAL; CD44; OCT4	Physical cues are vital in determining cellular fate in cancer. In vitro 3D culture do not replicate forces present in vivo. These forces including tumor interstitial fluid pressure and matrix stiffness behave as switches in differentiation and metastasis, which are intricate features of cancer stem cells (CSCs). Gravity determines the effect of these physical factors on cell fate and functions as evident from microgravity experiments on space and ground simulations. Here, we described the role of simulation of microgravity (SMG) using rotary cell culture system (RCCS) in increasing stemness in human colorectal cancer cell HCT116. We observed distinct features of cancer stem cells including CD133/CD44 dual positive cells and migration in SMG which was not altered by autophagy induction or inhibition. 3D and SMG increased autophagy, but the flux was staggered under SMG. Increased unique giant cancer cells housing complete nuclear localization of YAP were observed in SMG. This study highlights the role of microgravity in regulating stemness in CSC and importance of physical factors in determining the same.	[Arun, Raj Pranap; Sivanesan, Divya; Patra, Bamadeb; Varadaraj, Sudha; Verma, Rama Shanker] Indian Inst Technol Madras, Stem Cell & Mol Biol Lab, Bhupat & Jyoti Mehta Sch Biosci, Dept Biotechnol, Madras 600036, Tamil Nadu, India		Verma, RS (corresponding author), Indian Inst Technol Madras, Stem Cell & Mol Biol Lab, Bhupat & Jyoti Mehta Sch Biosci, Dept Biotechnol, Madras 600036, Tamil Nadu, India.	vermars@iitm.ac.in	Patra, Bamadeb/AAL-6915-2020; Patra, Bamadeb/F-1696-2016	Patra, Bamadeb/0000-0003-1309-2162; Patra, Bamadeb/0000-0003-1309-2162; Arun, Raj Pranap/0000-0001-5746-4728	Defence Research Development organizationDefence Research & Development Organisation (DRDO) [DLS/81/48222/LSRB-273/SHDD/2013]; Indian Institute of Technology Madras; Ministry of Human Resource Department, India	We wish to thank the Defence Research Development organization for supporting this work (DLS/81/48222/LSRB-273/SH&DD/2013). Raj Pranap Arun, Divya Sivanesan, Bamdeb Patra and Sudha Varadaraj wish to thank Indian Institute of Technology Madras, and Ministry of Human Resource Department, India for their fellowship. We thank Dr. Ganesh and Mr. M. Anandharasan from DSS infotech (Olympus, USA) for their support procuring confocal images. We thank R.S. Anand, Anna University, Chennai for his contribution in design of this work.	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Wang YJ, 2015, AM J PHYSIOL-CELL PH, V309, pC709, DOI 10.1152/ajpcell.00212.2015; Weber GF, 1997, P ASSOC AM PHYSICIAN, V109, P1; Wojnacki J, 2018, J BIOL CHEM, V293, P4575, DOI 10.1074/jbc.H118.002041; Yu FX, 2015, CELL, V163, P811, DOI 10.1016/j.cell.2015.10.044; Zanconato F, 2016, CANCER CELL, V29, P783, DOI 10.1016/j.ccell.2016.05.005; Zha YH, 2017, EXP THER MED, V14, P199, DOI 10.3892/etm.2017.4512; Zhang M, 2013, AM J PATHOL, V182, P565, DOI 10.1016/j.ajpath.2012.10.015; Zhang S, 2014, ONCOGENE, V33, P116, DOI 10.1038/onc.2013.96; Zhao H., 2009, CANCER RES, V69, P5080, DOI [10.1158/0008-5472.SABCS-09-5080, DOI 10.1158/0008-5472.SABCS-09-5080]; Zhou JY, 2016, ONCOTARGET, V7, P7657, DOI 10.18632/oncotarget.7084	71	17	17	2	7	NATURE PUBLISHING GROUP	LONDON	MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	2045-2322			SCI REP-UK	Sci Rep	JUL 23	2019	9								10684	10.1038/s41598-019-47116-5			12	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	IK6SP	WOS:000476718900070	31337825	Green Published, gold			2022-04-25	
J	Li, J; Wang, SW; Zhang, DS; Sun, Y; Zhu, CY; Fei, Q; Hu, J; Zhang, C; Sun, YM				Li, Juan; Wang, Shu-Wei; Zhang, Dong-Sheng; Sun, Ye; Zhu, Chun-Yan; Fei, Qiang; Hu, Jun; Zhang, Chuan; Sun, Yue-Ming			FTY720-induced enhancement of autophagy protects cells from FTY720 cytotoxicity in colorectal cancer	ONCOLOGY REPORTS			English	Article						FTY720; colorectal cancer; autophagy; cytoprotection; drug resistance; CIP2A	OVARIAN-CANCER; PP2A; LC3; PROLIFERATION; EXPRESSION; INHIBITOR; APOPTOSIS; EFFICACY; ASSAYS; CIP2A	FTY720, also known as fingolimod, is a widely used immunomodulator in multiple sclerosis and multiple organ transplantation. It is also an important protein phosphatase 2A (PP2A) activator. Based on this, a number of studies have recently demonstrated the cytotoxic effect of FTY720 in various cancers. Yet in colorectal cancer (CRC), the underlying mechanisms of FTY720 cytotoxicity remain less clear, especially the relationship between a drug and autophagy. We demonstrate here for the first time that FTY720 promotes the appearance of autophagic hallmarks such as autophagosome formation and light chain 3 (LC3)-II accumulation, indicating the participation of autophagy in FTY720 cytotoxicity on CRC. Moreover, inhibition of autophagy using 3-methyladenine (3-MA), a specific inhibitor of autophagy, enhanced FTY720 cytotoxicity, indicating the protective role of autophagy against the drug's own cytotoxic effect. The protective autophagy was likely affected by cancerous inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor that is closely related with poor prognosis and drug resistance. Consequently, our data not only demonstrate a new mechanism underlying the cytotoxic effect of FTY720 in CRC, but also a new strategy for CRC treatment, especially in cases resistant to conventional chemotherapies because of high CIP2A levels.	[Li, Juan; Zhang, Dong-Sheng; Sun, Ye; Zhu, Chun-Yan; Fei, Qiang; Zhang, Chuan; Sun, Yue-Ming] Nanjing Med Univ, Dept Colorectal Surg, Affiliated Hosp 1, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China; [Wang, Shu-Wei] Nanjing Univ Chinese Med, Dept Gen Surg, Wuxi Affiliated Hosp, Wuxi, Peoples R China; [Hu, Jun] First Peoples Hosp Changzhou, Dept Hepatobiliary Surg, Changzhou 214000, Jiangsu, Peoples R China		Sun, YM (corresponding author), Nanjing Med Univ, Dept Colorectal Surg, Affiliated Hosp 1, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China.	sym890207@163.com			Department of Health of the Jiangsu Province, China	This study was supported by a grant from the Fund of Department of Health of the Jiangsu Province, China.	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Rep.	MAY	2016	35	5					2833	2842		10.3892/or.2016.4668			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DJ3AS	WOS:000374077700038	26985637	Bronze			2022-04-25	
J	Wang, ZH; Guo, K; Gao, P; Pu, QQ; Lin, P; Qin, SG; Xie, N; Hur, J; Li, CL; Huang, CH; Wu, M				Wang, Zhihan; Guo, Kai; Gao, Pan; Pu, Qinqin; Lin, Ping; Qin, Shugang; Xie, Na; Hur, Junguk; Li, Changlong; Huang, Canhua; Wu, Min			Microbial and genetic-based framework identifies drug targets in inflammatory bowel disease	THERANOSTICS			English	Article						Inflammatory bowel disease; cyclic GMP-AMP synthase (cGAS); host transcriptome-microbiome interaction; drug repurposing; brefeldin-a	GMP-AMP SYNTHASE; OXIDATIVE STRESS; GUT MICROBIOTA; ACTIVATION; COLITIS; PATHOGENESIS; ASSOCIATION; AUTOPHAGY; IMMUNITY; PATHWAY	Rationale: With increasing incidence and prevalence of inflammatory bowel disease (IBD), it has become one of the major public health threats, and there is an urgent need to develop new therapeutic agents. Although the pathogenesis of IBD is still unclear, previous research has provided evidence for complex interplays between genetic, immune, microbial, and environmental factors. Here, we constructed a gene-microbiota interaction-based framework to discover IBD biomarkers and therapeutics. Methods: We identified candidate biomarkers for IBD by analyzing the publicly available transcriptomic and microbiome data from IBD cohorts. Animal models of IBD and diarrhea were established. The inflammation-correlated microbial and genetic variants in gene knockout mice were identified by 16S rRNA sequences and PCR array. We performed bioinformatic analysis of microbiome functional prediction and drug repurposing. Our validation experiments with cells and animals confirmed anti-inflammatory properties of a drug candidate. Results: We identified the DNA-sensing enzyme cyclic GMP-AMP synthase (cGAS) as a potential biomarker for IBD in both patients and murine models. cGAS knockout mice were less susceptible to DSS-induced colitis. cGAS-associated gut microbiota and host genetic factors relating to IBD pathogenesis were also identified. Using a computational drug repurposing approach, we predicted 43 candidate drugs with high potency to reverse colitis-associated gene expression and validated that brefeldin-a mitigates inflammatory response in colitis mouse model and colon cancer cell lines. Conclusions: By integrating computational screening, microbiota interference, gene knockout techniques, and in vitro and in vivo validation, we built a framework for predicting biomarkers and host-microbe interaction targets and identifying repurposing drugs for IBD, which may be tested further for clinical application. This approach may also be a tool for repurposing drugs for treating other diseases.	[Wang, Zhihan; Xie, Na; Li, Changlong; Huang, Canhua] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Sichuan, Peoples R China; [Wang, Zhihan; Gao, Pan; Pu, Qinqin; Lin, Ping; Qin, Shugang; Hur, Junguk; Wu, Min] Univ North Dakota, Sch Med & Hlth Sci, Dept Biomed Sci, Grand Forks, ND 58202 USA; [Guo, Kai] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA; [Gao, Pan] Wuhan Univ, Med Res Inst, Wuhan 430071, Peoples R China; [Lin, Ping] Army Med Univ, Daping Hosp, Inst Surg Res, State Key Lab Trauma Burns & Combined Injury, Chongqing 400038, Peoples R China; [Qin, Shugang; Huang, Canhua] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Qin, Shugang; Huang, Canhua] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China; [Qin, Shugang; Huang, Canhua] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China		Li, CL (corresponding author), Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Sichuan, Peoples R China.; Wu, M (corresponding author), Univ North Dakota, Sch Med & Hlth Sci, Dept Biomed Sci, Grand Forks, ND 58202 USA.; Huang, CH (corresponding author), Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China.; Huang, CH (corresponding author), Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China.; Huang, CH (corresponding author), Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China.; Huang, CH (corresponding author), Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Sichuan, Peoples R China.	changlongli@scu.edu.cn; hcanhua@hotmail.com; min.wu@und.edu		Guo, Kai/0000-0002-4651-781X	National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 AI138203, AI109317, P20 GM103442, GM113123]; National Key Research and Development Project [2020YFA0509400, 2020YFC2002705]; Guangdong Basic and Applied Basic Research Foundation [2019B030302012]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81821002, 81790251]; Science and Technology Department of Sichuan Province [2019YJ0050]; (NIH)/NIGMSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P20GM113123, U54GM128729]; UND SMHS funds; Servier Medical Art (SMART)	The authors thank Charlie Rice (Rockefeller University) for kindly providing Cgastm1a(EUCOMM)Hmgu mice. This project was supported by the National Institutes of Health (NIH) grants R01 AI138203, AI109317 grants, P20 GM103442, and GM113123 to MW, the National Key Research and Development Project (2020YFA0509400, 2020YFC2002705), Guangdong Basic and Applied Basic Research Foundation (2019B030302012), and National Natural Science Foundation of China (81821002 and 81790251) to CH, and the Science and Technology Department of Sichuan Province (No. 2019YJ0050) to CL. The Human core, Histology core, and Imaging core at UND were acknowledged for the support of the work. Histological services were provided by the UND Histology Core Facility supported (NIH)/NIGMS award P20GM113123, DaCCoTA CTR NIH grant U54GM128729, and UND SMHS funds. Figures 1A and 5I were created by modifying illustrations provided by Servier Medical Art (SMART, smart.servier.com) licensed under a Creative Commons Attribution 3.0 Unported License and Vecteezy.com.	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Zhu QF, 2014, J IMMUNOL, V193, P4779, DOI 10.4049/jimmunol.1402051	76	2	2	5	8	IVYSPRING INT PUBL	LAKE HAVEN	PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA	1838-7640			THERANOSTICS	Theranostics		2021	11	15					7491	7506		10.7150/thno.59196			16	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	UJ8SC	WOS:000691548300004	34158863	gold, Green Published			2022-04-25	
J	Devkota, AK; Tavares, CDJ; Warthaka, M; Abramczyk, O; Marshall, KD; Kaoud, TS; Gorgulu, K; Ozpolat, B; Dalby, KN				Devkota, Ashwini K.; Tavares, Clint D. J.; Warthaka, Mangalika; Abramczyk, Olga; Marshall, Kyle D.; Kaoud, Tamer S.; Gorgulu, Kivanc; Ozpolat, Bulent; Dalby, Kevin N.			Investigating the Kinetic Mechanism of Inhibition of Elongation Factor 2 Kinase by NH125: Evidence of a Common in Vitro Artifact	BIOCHEMISTRY			English	Article							DEPENDENT PROTEIN-KINASE; MALIGNANT GLIOMA-CELLS; HEAVY-CHAIN-KINASE; COLON-CANCER CELLS; FACTOR-II KINASE; RAT GLIAL-CELLS; PROMISCUOUS INHIBITORS; INDUCED AUTOPHAGY; MAMMALIAN-CELLS; PHOSPHORYLATION	Evidence that elongation factor 2 kinase (eEF-2K) has potential as a target for anticancer therapy and possibly for the treatment of depression is emerging. Here the steady-state kinetic mechanism of eEF-2K is presented using a peptide substrate and is shown to conform to an ordered sequential mechanism with ATP binding first. Substrate inhibition by the peptide was observed and revealed to be competitive with ATP, explaining the observed ordered mechanism. Several small molecules are reported to inhibit eEF-2K activity with the most notable being the histidine kinase inhibitor NH125, which has been used in a number of studies to characterize eEF-2K activity in cells. While NH125 was previously reported to inhibit eEF-2K in vitro with an IC50 of 60 nM, its mechanism of action was not established. Using the same kinetic assay, the ability of an authentic sample of NH125 to inhibit eEF-2K was assessed over a range of substrate and inhibitor concentrations. A typical dose-response curve for the inhibition of eEF-2K by NH125 is best fit to an IC50 of 18 +/- 0.25 mu M and a Hill coefficient of 3.7 +/- 0.14, suggesting that NH125 is a weak inhibitor of eEF-2K under the experimental conditions of a standard in vitro kinase assay. To test the possibility that NH125 is a potent inhibitor of eEF2 phosphorylation, we assessed its ability to inhibit the phosphorylation of eEF2. Under standard kinase assay conditions, NH125 exhibits a similar weak ability to inhibit the phosphorylation of eEF2 by eEF-2K. Notably, the activity of NH125 is severely abrogated by the addition of 0.1% Triton to the kinase assay through a process that can be reversed upon dilution. These studies suggest that NH125 is a nonspecific colloidal aggregator in vitro, a notion further supported by the observation that NH125 inhibits other protein kinases, such as ERK2 and TRPM7 in a manner similar to that of eEF-2K. As NH125 is reported to inhibit eEF-2K in a cellular environment, its ability to inhibit eEF2 phosphorylation was assessed in MDA-MB-231 breast cancer, A549 lung cancer, and HEK-293T cell lines using a Western blot approach. No sign of a decrease in the level of eEF2 phosphorylation was observed up to 12 h following addition of NH125 to the media. Furthermore, contrary to the previously reported literatures, NH125 induced the phosphorylation of eEF-2.	[Devkota, Ashwini K.; Tavares, Clint D. J.; Dalby, Kevin N.] Univ Texas Austin, Grad Program Cell & Mol Biol, Austin, TX 78712 USA; [Warthaka, Mangalika; Abramczyk, Olga; Marshall, Kyle D.; Kaoud, Tamer S.; Dalby, Kevin N.] Univ Texas Austin, Coll Pharm, Div Med Chem, Austin, TX 78712 USA; [Kaoud, Tamer S.; Dalby, Kevin N.] Univ Texas Austin, Grad Program Pharm, Austin, TX 78712 USA; [Ozpolat, Bulent] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Unit 422, Houston, TX 77030 USA		Dalby, KN (corresponding author), Univ Texas Austin, Grad Program Cell & Mol Biol, 107 W Dean Keaton,Biomed Engn Bldg, Austin, TX 78712 USA.	bozpolat@mdanderson.org; kinases@me.com	Kaoud, Tamer S/C-3618-2019; Dalby, Kevin N/A-1905-2013; Görgülü, Kıvanç/AAV-6525-2020; Gorgulu, Kivanc/M-6950-2017	Dalby, Kevin N/0000-0001-9272-5129; Görgülü, Kıvanç/0000-0002-1613-1422; Gorgulu, Kivanc/0000-0002-1613-1422; Marshall, Kyle/0000-0003-3366-1174; Gorgulu, Kivanc/0000-0002-0855-9939; Abramczyk, Olga/0000-0002-7595-3223; Kaoud, Tamer/0000-0003-1298-8725	Welch FoundationThe Welch Foundation [F-1390]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM59802, P01GM078195]; Egyptian Ministry of Higher EducationScience and Technology Development Fund (STDF); NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM059802, P01GM078195] Funding Source: NIH RePORTER	This research was supported in part by grants from the Welch Foundation (F-1390) to K.N.D. and the National Institutes of Health to K.N.D. (GM59802). A grant from the National Institutes of Health (P01GM078195) supported K.N.D. T.S.K. acknowledges a scholarship from the Egyptian Ministry of Higher Education.	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J	Jia, YF; Yu, DF; Huang, QH; Zhang, XD; Qiu, LQ; Cao, RH; Du, RL; Liu, WB				Jia, Yifan; Yu, Difei; Huang, Qiuhua; Zhang, Xiaodong; Qiu, Liqin; Cao, Rihui; Du, Runlei; Liu, Wenbin			Design and Synthesis of 4(1H)-quinolone Derivatives as Autophagy Inducing Agents by Targeting ATG5 Protein	LETTERS IN DRUG DESIGN & DISCOVERY			English	Article						Synthesis; quinolone; antiproliferative; autophagy; mechanism of action; ATG5 protein	BAX GENE-TRANSFER; BIOLOGICAL EVALUATION; QUINOLINE DERIVATIVES; ANTITUMOR-ACTIVITY; IN-VITRO; CANCER; P53; MUTATION; ACCUMULATION	Background: Quinolines have been characterized as a class of potential antitumor agents, and a large number of natural and synthetic quinolines acting as antitumor agents were reported. Methods: A series of 7-chloro-4(1H)-quinolone derivatives were synthesized. The antiproliferative effect of these compounds was evaluated by MTT assay against five human tumor cell lines. The mechanism of action of the selected compound 7h was also investigated. Results and Discussion: Most of the compounds had more potent antiproliferative activities than the lead compound 7-chloro-4(1H)-quinolone 6b. Compound 7h was found to be the most potent antiproliferative agent against human tumor cell lines. Further investigation demonstrated that compound 7h triggered ATG5-dependent autophagy of colorectal cancer cells by promoting the functions of LC3 proteins. Conclusion: These results were useful for designing and discovering more potent novel antitumor agents endowed with better pharmacological profiles.	[Jia, Yifan] Wuhan Univ, Dept Pain Management, Renmin Hosp, Wuhan 430060, Peoples R China; [Liu, Wenbin] Wuhan Polytech Univ, Coll Hlth Sci & Nursing, Wuhan 430023, Peoples R China; [Yu, Difei; Zhang, Xiaodong; Du, Runlei] Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China; [Huang, Qiuhua; Qiu, Liqin; Cao, Rihui] Sun Yat Sen Univ, Sch Chem, Guangzhou 510275, Peoples R China		Liu, WB (corresponding author), Wuhan Polytech Univ, Coll Hlth Sci & Nursing, Wuhan 430023, Peoples R China.; Du, RL (corresponding author), Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China.; Cao, RH (corresponding author), Sun Yat Sen Univ, Sch Chem, Guangzhou 510275, Peoples R China.	caorihui@mail.sysu.edu.cn; runleidu@whu.edu.cn; liuwenbin_1@yeah.net			Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [S2013010012138, 2016A030313349]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872271, 31501148, 81402994]	This work was supported by grants from the Natural Science Foundation of Guangdong Province [S2013010012138 and 2016A030313349] and the National Natural Science Foundation of China grant [81872271, 31501148, and 81402994].	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Drug Des. Discov.		2020	17	7					884	890		10.2174/1570180816666191122113045			7	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	MI4HM	WOS:000547371000007					2022-04-25	
J	Ma, HL; Li, YW; Wang, XX; Wu, H; Qi, GH; Li, RR; Yang, N; Gao, M; Yan, S; Yuan, CZ; Kong, BH				Ma, Hanlin; Li, Yingwei; Wang, Xiangxiang; Wu, Huan; Qi, Gonghua; Li, Rongrong; Yang, Ning; Gao, Min; Yan, Shi; Yuan, Cunzhong; Kong, Beihua			PBK, targeted by EVI1, promotes metastasis and confers cisplatin resistance through inducing autophagy in high-grade serous ovarian carcinoma	CELL DEATH & DISEASE			English	Article							ORIGINATED PROTEIN-KINASE; PDZ-BINDING KINASE; PBK/TOPK EXPRESSION; THERAPEUTIC TARGET; CELL-PROLIFERATION; COLORECTAL-CANCER; PROSTATE-CANCER; TOPK; PROGNOSIS; GROWTH	High-grade serous ovarian carcinoma (HGSOC) is the most lethal type of gynecologic malignancy. Chemoresistance is the main reason for the poor prognosis of HGSOC. PDZ-binding kinase (PBK) promotes the malignant progression of various carcinomas. However, the roles and clinical significance of PBK in HGSOC remain unclear. Here, we reported that PBK was overexpressed in HGSOC tissues and cell lines. High PBK expression was associated with a poor prognosis, metastasis, and cisplatin resistance of HGSOC. Overexpression of PBK promoted autophagy and enhanced cisplatin resistance via the ERK/mTOR signaling pathway. Further study showed that inhibition of autophagy by chloroquine or bafilomycin A1 reversed PBK-induced cisplatin resistance. Overexpression of PBK decreased ovarian cancer responsiveness to cisplatin treatment through inducing autophagy in vivo. We also demonstrated that the PBK inhibitor OTS514 augmented the growth inhibition effect of cisplatin in vitro and in vivo. Moreover, ecotropic viral integration site-1 (EVI1) could regulate PBK expression through directly targeting the PBK promoter region. In conclusion, high PBK expression was correlated with a poor prognosis, metastasis, and cisplatin resistance through promoting autophagy in HGSOC. PBK might be a promising target for the early diagnosis and individual treatment of ovarian cancer.	[Ma, Hanlin; Li, Yingwei; Wang, Xiangxiang; Wu, Huan; Qi, Gonghua; Li, Rongrong; Yang, Ning; Gao, Min; Yan, Shi; Yuan, Cunzhong; Kong, Beihua] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Shandong, Peoples R China; [Ma, Hanlin; Li, Rongrong; Yang, Ning; Gao, Min; Yan, Shi; Yuan, Cunzhong; Kong, Beihua] Shandong Univ, Qilu Hosp, Gynecol Oncol Key Lab Shandong Prov, Jinan 250012, Shandong, Peoples R China; [Li, Yingwei] Shandong Univ, Inst Oncol, Sch Med, Jinan 250012, Shandong, Peoples R China		Kong, BH (corresponding author), Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Shandong, Peoples R China.; Kong, BH (corresponding author), Shandong Univ, Qilu Hosp, Gynecol Oncol Key Lab Shandong Prov, Jinan 250012, Shandong, Peoples R China.	kongbeihuasdu@gmail.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81874107, 81572554, 81502245]; Program for Interdisciplinary Basic Research of Shandong University [2018JC014]	This work was financially supported by National Natural Science Foundation of China (81874107, 81572554, and 81502245) and the Program for Interdisciplinary Basic Research of Shandong University (2018JC014).	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FEB 18	2019	10								166	10.1038/s41419-019-1415-6			15	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	HN8NU	WOS:000460452900004	30778048	Green Published, gold			2022-04-25	
J	Oliveira, CSF; Pereira, H; Alves, S; Castro, L; Baltazar, F; Chaves, SR; Preto, A; Corte-Real, M				Oliveira, C. S. F.; Pereira, H.; Alves, S.; Castro, L.; Baltazar, F.; Chaves, S. R.; Preto, A.; Corte-Real, M.			Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria	CELL DEATH & DISEASE			English	Article							CHAIN FATTY-ACIDS; LYSOSOMAL MEMBRANE PERMEABILIZATION; CARCINOMA CELLS; DEATH; PROPIONIBACTERIA; PROGRESSION; EXPRESSION; MACHINERY; NECROSIS; THERAPY	Acetate is a short-chain fatty acid secreted by Propionibacteria from the human intestine, known to induce mitochondrial apoptotic death in colorectal cancer (CRC) cells. We previously established that acetate also induces lysosome membrane permeabilization in CRC cells, associated with release of the lysosomal protease cathepsin D (CatD), which has a well-established role in the mitochondrial apoptotic cascade. Unexpectedly, we showed that CatD has an antiapoptotic role in this process, as pepstatin A (a CatD inhibitor) increased acetate-induced apoptosis. These results mimicked our previous data in the yeast system showing that acetic acid activates a mitochondria-dependent apoptosis process associated with vacuolar membrane permeabilization and release of the vacuolar protease Pep4p, ortholog of mammalian CatD. Indeed, this protease was required for cell survival in a manner dependent on its catalytic activity and for efficient mitochondrial degradation independently of autophagy. In this study, we therefore assessed the role of CatD in acetate-induced mitochondrial alterations. We found that, similar to acetic acid in yeast, acetate-induced apoptosis is not associated with autophagy induction in CRC cells. Moreover, inhibition of CatD with small interfering RNA or pepstatin A enhanced apoptosis associated with higher mitochondrial dysfunction and increased mitochondrial mass. This effect seems to be specific, as inhibition of CatB and CatL with E-64d had no effect, nor were these proteases significantly released to the cytosol during acetate-induced apoptosis. Using yeast cells, we further show that the role of Pep4p in mitochondrial degradation depends on its protease activity and is complemented by CatD, indicating that this mechanism is conserved. In summary, the clues provided by the yeast model unveiled a novel CatD function in the degradation of damaged mitochondria when autophagy is impaired, which protects CRC cells from acetate-induced apoptosis. CatD inhibitors could therefore enhance acetate-mediated cancer cell death, presenting a novel strategy for prevention or therapy of CRC.	[Oliveira, C. S. F.; Pereira, H.; Alves, S.; Castro, L.; Chaves, S. R.; Preto, A.; Corte-Real, M.] Univ Minho, Dept Biol, CBMA Ctr Mol & Environm Biol, P-4710057 Braga, Portugal; [Oliveira, C. S. F.] Univ Porto, ICBAS Inst Biomed Sci Abel Salazar, P-4100 Oporto, Portugal; [Baltazar, F.] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga, Portugal; [Baltazar, F.] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal		Corte-Real, M (corresponding author), Univ Minho, Dept Biol, Ctr Mol & Environm Biol, Campus Gualtar, P-4710057 Braga, Portugal.	mcortereal@bio.uminho.pt	Alves, Sara/U-5006-2019; Corte-Real, Manuela/B-6328-2013; F, Baltazar/A-8720-2010; Alves, Sara/L-3253-2015; Chaves, Susana R/H-8786-2013; Preto, Ana/H-8112-2012	Corte-Real, Manuela/0000-0002-1423-1331; F, Baltazar/0000-0002-1770-4544; Alves, Sara/0000-0003-0404-5954; Chaves, Susana R/0000-0002-6004-9872; Preto, Ana/0000-0002-7302-0630; Castro, Lisandra/0000-0003-3048-933X; Ferro Oliveira, Claudia Suellen/0000-0002-0113-9528; Pereira, Helena/0000-0002-0104-8714	FEDER through POFC - COMPETE; Fundacao para a Ciencia e TecnologiaPortuguese Foundation for Science and TechnologyEuropean Commission [PEst-OE/BIA/UI4050/2014, FCTANR/BEX-BCM/0175/2012, SFRH/BD/77449/2011, SFRH/BD/73139/2010, SFRH/BD/93589/2013, SFRH/BPD/89980/2012]	We thank Frank Madeo (University of Graz) for plasmids pESC, pESC-PEP4 and pESC-DPM, and Elisabete Fernandes (University of Minho) for the pESC-CTSD construct. This work was supported by FEDER through POFC - COMPETE and by Fundacao para a Ciencia e Tecnologia through projects PEst-OE/BIA/UI4050/2014 and FCTANR/BEX-BCM/0175/2012, as well as fellowships to CSF Oliveira (SFRH/BD/77449/2011), H Pereira (SFRH/BD/73139/2010), L Castro (SFRH/BD/93589/2013) and S Chaves (SFRH/BPD/89980/2012).	Altobelli E, 2014, PREV MED, V62, P132, DOI 10.1016/j.ypmed.2014.02.010; Carmona-Gutierrez D, 2011, CELL DEATH DIS, V2, DOI 10.1038/cddis.2011.43; Comalada M, 2006, J CANCER RES CLIN, V132, P487, DOI 10.1007/s00432-006-0092-x; Goncalves P, 2013, CURR DRUG METAB, V14, P994; Groth-Pedersen L, 2013, CANCER LETT, V332, P265, DOI 10.1016/j.canlet.2010.05.021; Hah YS, 2012, CANCER LETT, V323, P208, DOI 10.1016/j.canlet.2012.04.012; Handy DE, 2012, ANTIOXID REDOX SIGN, V16, P1323, DOI 10.1089/ars.2011.4123; Iwase T, 2013, SCI REP-UK, V3, DOI 10.1038/srep03081; Jan G, 2002, CELL DEATH DIFFER, V9, P179, DOI 10.1038/sj.cdd.4400935; Janku F, 2011, NAT REV CLIN ONCOL, V8, P528, DOI 10.1038/nrclinonc.2011.71; Kirana Chandra, 2012, Int J Proteomics, V2012, P245819, DOI 10.1155/2012/245819; Klionsky DJ, 2005, J CELL SCI, V118, P7, DOI 10.1242/jcs.01620; Lan A, 2007, APOPTOSIS, V12, P573, DOI 10.1007/s10495-006-0010-3; Macfarlane GT, 2008, J APPL MICROBIOL, V104, P305, DOI 10.1111/j.1365-2672.2007.03520.x; Margaryan NV, 2010, CANCER BIOL THER, V10, DOI 10.4161/cbt.10.5.12534; Marques C, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.29; Mathew R, 2007, NAT REV CANCER, V7, P961, DOI 10.1038/nrc2254; Maynadier M, 2013, J CONTROL RELEASE, V171, P251, DOI 10.1016/j.jconrel.2013.07.017; Mehrpour M, 2010, CELL RES, V20, P748, DOI 10.1038/cr.2010.82; Oberle C, 2010, CELL DEATH DIFFER, V17, P1167, DOI 10.1038/cdd.2009.214; Okamoto K, 1998, J CELL BIOL, V142, P613, DOI 10.1083/jcb.142.3.613; Pereira C, 2010, MOL MICROBIOL, V76, P1398, DOI 10.1111/j.1365-2958.2010.07122.x; Pereira H, 2013, FEBS LETT, V587, P200, DOI 10.1016/j.febslet.2012.11.025; Repnik U, 2012, BBA-PROTEINS PROTEOM, V1824, P22, DOI 10.1016/j.bbapap.2011.08.016; Sagulenko V, 2008, CARCINOGENESIS, V29, P1869, DOI 10.1093/carcin/bgn147; Szajda SD, 2008, HEPATO-GASTROENTEROL, V55, P388; Talieri M, 2004, CANCER LETT, V205, P97, DOI 10.1016/j.canlet.2003.09.033; Tang Y, 2011, CELL DEATH DIFFER, V18, P602, DOI 10.1038/cdd.2010.117; Tang Y, 2011, AUTOPHAGY, V7, P235, DOI 10.4161/auto.7.2.14277; Troy AM, 2004, EUR J CANCER, V40, P1610, DOI 10.1016/j.ejca.2004.03.011; Xie ZP, 2007, NAT CELL BIOL, V9, P1102, DOI 10.1038/ncb1007-1102; Yamamoto A, 1998, CELL STRUCT FUNCT, V23, P33, DOI 10.1247/csf.23.33; Zeng HW, 2014, WORLD J GASTRO ONCOL, V6, P41, DOI 10.4251/wjgo.v6.i2.41; Zhu YM, 2011, CANCER LETT, V309, P119, DOI 10.1016/j.canlet.2011.06.004	34	38	38	1	12	NATURE PUBLISHING GROUP	LONDON	MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	2041-4889			CELL DEATH DIS	Cell Death Dis.	JUN	2015	6								e1788	10.1038/cddis.2015.157			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	CM2MO	WOS:000357514700014	26086961	gold, Green Published			2022-04-25	
J	Liu, D; Meng, X; Wu, DL; Qiu, ZD; Luo, HM				Liu, Da; Meng, Xue; Wu, Donglu; Qiu, Zhidong; Luo, Haoming			A Natural Isoquinoline Alkaloid With Antitumor Activity: Studies of the Biological Activities of Berberine	FRONTIERS IN PHARMACOLOGY			English	Review						berberine; biological activities; antitumor; autophagy; epigenetic effects	INDUCED NEUROPATHIC PAIN; HUMAN GASTRIC-CARCINOMA; CELL-CYCLE ARREST; CANCER-CELLS; TRANSPOSABLE ELEMENTS; INDUCED APOPTOSIS; COPTIDIS RHIZOMA; DNA METHYLATION; GENE-EXPRESSION; MITOCHONDRIAL PATHWAY	Coptis, a traditional medicinal plant, has been used widely in the field of traditional Chinese medicine for many years. More recently, the chemical composition and bioactivity of Coptis have been studied worldwide. Berberine is a main component of Rhizoma Coptidis. Modern medicine has confirmed that berberine has pharmacological activities, such as anti-inflammatory, analgesic, antimicrobial, hypolipidemic, and blood pressure-lowering effects. Importantly, the active ingredient of berberine has clear inhibitory effects on various cancers, including colorectal cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, and cervical cancer. Cancer, ranked as one of the world's five major incurable diseases by WHO, is a serious threat to the quality of human life. Here, we try to outline how berberine exerts antitumor effects through the regulation of different molecular pathways. In addition, the berberine-mediated regulation of epigenetic mechanisms that may be associated with the prevention of malignant tumors is described. Thus, this review provides a theoretical basis for the biological functions of berberine and its further use in the clinical treatment of cancer.	[Liu, Da; Meng, Xue; Wu, Donglu; Qiu, Zhidong; Luo, Haoming] Changchun Univ Chinese Med, Dept Pharm, Changchun, Jilin, Peoples R China; [Liu, Da; Meng, Xue; Wu, Donglu; Qiu, Zhidong; Luo, Haoming] Changchun Univ Chinese Med, Key Lab Effect Components Tradit Chinese Med, Changchun, Jilin, Peoples R China		Qiu, ZD; Luo, HM (corresponding author), Changchun Univ Chinese Med, Dept Pharm, Changchun, Jilin, Peoples R China.; Qiu, ZD; Luo, HM (corresponding author), Changchun Univ Chinese Med, Key Lab Effect Components Tradit Chinese Med, Changchun, Jilin, Peoples R China.	Qiuzd@ccucm.edu.cn; luo.haoming@163.com	Luo, Haoming/AAF-5322-2019		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81803680]; Jilin Province Science and Technology Development Project in China [20170307031, YY20180520050JH]	This work was supported by the National Natural Science Foundation of China (Grant No. 81803680). Jilin Province Science and Technology Development Project in China (Grant Nos. 20170307031 and YY20180520050JH).	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Pharmacol.	FEB 14	2019	10								9	10.3389/fphar.2019.00009			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	HL4KO	WOS:000458687800001	30837865	Green Published, gold			2022-04-25	
J	Han, XR; Zhang, X; Wang, Q; Wang, L; Yu, SW				Han, Xinru; Zhang, Xiang; Wang, Qian; Wang, Lu; Yu, Shuwen			Antitumor potential of Hedyotis diffusa Willd: A systematic review of bioactive constituents and underlying molecular mechanisms	BIOMEDICINE & PHARMACOTHERAPY			English	Review						Hedyotis diffusa Willd; Antitumor activity; Apoptosis; Proliferation; Cell cycle termination; Anti-inflammation	CELL-CYCLE ARREST; NF-KAPPA-B; COLORECTAL-CANCER CELLS; IN-VITRO; PROTOCATECHUIC ACID; INHIBITS PROLIFERATION; LIQUID-CHROMATOGRAPHY; EXTRACELLULAR-MATRIX; SIGNALING PATHWAY; CARCINOMA-CELLS	Cancer is a major cause of death in the world. Chemotherapy can extend the life of cancer patients to some extent, but the quality of life is reduced. Therefore, the quest for more efficient and less toxic medication strategies is still at the forefront of current research. Hedyotis diffusa Willd (HDW), a Chinese herb medicine, has received great attention in the past two decades and has been well documented in clinics for antitumor activity in a variety of human cancers. This review discussed a total of 58 different kinds of active antitumor components isolated from HDW, including iridoids, flavonoids, flavonol glycosides, anthraquinones, phenolic acids, and their derivatives, sterols, and volatile oils. Their antitumor activities include inhibition of tumor cell proliferation, induction of tumor cell apoptosis and tumor angiogenesis, regulation of the host immune response, anti-inflammatory and antioxidant, and protective autophagy. Besides, we provide up-to-date and systematic evidence for HDW antitumor activities and the possible underlying molecular mechanisms and reference for further development of novel drugs and dosage formulation in control of human cancers.	[Han, Xinru; Zhang, Xiang; Wang, Qian; Wang, Lu; Yu, Shuwen] Shandong First Med Univ, Dept Pharm, Cent Hosp, Jinan 250013, Shandong, Peoples R China		Wang, L; Yu, SW (corresponding author), Shandong First Med Univ, Dept Pharm, Cent Hosp, Jinan 250013, Shandong, Peoples R China.	lulucc@163.com; yaoxuebu2020@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81803570]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2019M652411]; Postdoctoral Innovation Project of Shandong Province [201902044]; Jinan Science and Technology Bureau [201907111]	This work was supported by the National Natural Science Foundation of China (81803570), China Postdoctoral Science Foundation (2019M652411), the Postdoctoral Innovation Project of Shandong Province (201902044), and the Jinan Science and Technology Bureau (201907111).	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Pharmacother.	OCT	2020	130								110735	10.1016/j.biopha.2020.110735			12	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	OH6JX	WOS:000582697900131	34321173	gold			2022-04-25	
J	Vacchelli, E; Semeraro, M; Enot, DP; Chaba, K; Colame, VP; Dartigues, P; Perier, A; Villa, I; Rusakiewicz, S; Gronnier, C; Goere, D; Mariette, C; Zitvogel, L; Kroemer, G				Vacchelli, Erika; Semeraro, Michaela; Enot, David P.; Chaba, Kariman; Colame, Vichnou Poirier; Dartigues, Peggy; Perier, Aurelie; Villa, Irene; Rusakiewicz, Sylvie; Gronnier, Caroline; Goere, Diane; Mariette, Christophe; Zitvogel, Laurence; Kroemer, Guido			Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy	ONCOTARGET			English	Article						immunogenic cell death; autophagy; ATG16L1; pattern recognition receptor; apoptosis	TUMOR MICROENVIRONMENT; CHEMOTHERAPY; EXPRESSION; CHEMORADIOTHERAPY; ASSOCIATION; LYMPHOCYTES; REGRESSION; MECHANISM; EFFICACY	Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3(+) regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8(+) cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy.	[Vacchelli, Erika; Semeraro, Michaela; Enot, David P.; Chaba, Kariman; Colame, Vichnou Poirier; Perier, Aurelie; Rusakiewicz, Sylvie; Goere, Diane; Zitvogel, Laurence; Kroemer, Guido] Gustave Roussy Canc Campus, Villejuif, France; [Vacchelli, Erika; Enot, David P.; Chaba, Kariman; Kroemer, Guido] INSERM, U1138, Paris, France; [Vacchelli, Erika; Enot, David P.; Chaba, Kariman; Kroemer, Guido] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France; [Vacchelli, Erika; Chaba, Kariman; Kroemer, Guido] Univ Paris 05, Sorbonne Paris Cite, Paris, France; [Vacchelli, Erika; Kroemer, Guido] Univ Paris 06, Paris, France; [Semeraro, Michaela; Colame, Vichnou Poirier; Perier, Aurelie; Rusakiewicz, Sylvie; Zitvogel, Laurence] INSERM, U1015, Villejuif, France; [Semeraro, Michaela; Colame, Vichnou Poirier; Perier, Aurelie; Rusakiewicz, Sylvie; Zitvogel, Laurence] Ctr Clin Invest Biotherapies Canc CICBT 1428, Villejuif, France; [Enot, David P.; Kroemer, Guido] Gustave Roussy Canc Campus, Metabol & Cell Biol Platforms, Villejuif, France; [Dartigues, Peggy] Gustave Roussy Canc Campus, Dept Pathol, Villejuif, France; [Villa, Irene] Gustave Roussy Canc Campus, Dept Pathol, Digital Pathol, Villejuif, France; [Gronnier, Caroline; Mariette, Christophe] Claude Huriez Univ Hosp, Dept Digest & Oncol Surg, Lille, France; [Gronnier, Caroline; Mariette, Christophe] North France Univ, Lille, France; [Goere, Diane] Gustave Roussy Canc Campus, Dept Surg Oncol, Villejuif, France; [Zitvogel, Laurence] Univ Paris 11, Fac Med, Le Kremlin Bicetre, France; [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France		Kroemer, G (corresponding author), Gustave Roussy Canc Campus, Villejuif, France.	laurence.zitvogel@gustaveroussy.fr; kroemer@orange.fr	KROEMER, Guido/B-4263-2013; Vacchelli, Erika/E-5212-2018; Kroemer, Guido/AAY-9859-2020	KROEMER, Guido/0000-0002-9334-4405; Vacchelli, Erika/0000-0001-8010-0594; , GOERE/0000-0001-6306-2354	Ligue National contre le Cancer (Equipe labelisees); Agence National de la Recherche (ANR) - Projets blancsFrench National Research Agency (ANR); ANRFrench National Research Agency (ANR); Association pour la recherche sur le cancer (ARC)Fondation ARC pour la Recherche sur le Cancer; Canceropole Ile-de-FranceRegion Ile-de-France; Institut National du Cancer (INCa)Institut National du Cancer (INCA) France; Fondation Bettencourt-Schueller; Fondation de FranceFondation de France; Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale; European Commission (ArtForce)European CommissionEuropean Commission Joint Research Centre; European Research Council (ERC)European Research Council (ERC); LabEx Immuno-Oncology; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); Paris Alliance of Cancer Research Institutes (PACRI)	G.K. and L.Z. are supported by the Ligue National contre le Cancer (Equipe labelisees); Agence National de la Recherche (ANR) - Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI).	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J	Wang, ZY; Song, D; Huang, P				Wang, Ziyao; Song, Dan; Huang, Ping			MicroRNA-340 inhibits tumor cell proliferation, migration and invasion, and induces apoptosis in hepatocellular carcinoma	MOLECULAR MEDICINE REPORTS			English	Article						microRNA-340; hepatocellular carcinoma; proliferation; apoptosis; migration; invasion; S-phase kinase-associated protein 2	CANCER CELLS; COLORECTAL-CANCER; METASTASIS; EXPRESSION; PROGRESSION; AUTOPHAGY; PATHWAY	MicroRNAs (miRs) are short RNAs that serve a role in the origination and progression of hepatocellular carcinoma (HCC). miR-340 has been identified to be a novel tumor suppressor. The present study investigated the antitumor function of miR-340 in HCC. In the present study, it was detected that miR-340 was significantly decreased in HCC cancer tissues and human HCC cell lines using reverse transcription-quantitative polymerase chain reaction analysis. Cell Counting kit-8 and apoptosis assays demonstrated that miR-340 reduced cell proliferation and induced cellular apoptosis in HCC cell lines. A Transwell invasion assay demonstrated that miR-340 suppressed the migration and invasion of HCC cell lines. In addition, S-phase kinase-associated protein 2 (SKP2), which may be repressed by miR-340 in HCC cell lines, was identified to be a potential target of miR-340. The results of the present study revealed that miR-340 serves a tumor suppressor role by influencing the proliferation, apoptosis, migration and invasion of HCC cell lines, which may be explained by the downregulation of SKP2 by miR-340.	[Wang, Ziyao; Song, Dan; Huang, Ping] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Natl Key Clin Dept, 1 Youyi Rd, Chongqing 400000, Peoples R China		Huang, P (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Natl Key Clin Dept, 1 Youyi Rd, Chongqing 400000, Peoples R China.	huangpchina@sina.com					Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; Cai HQ, 2014, INT J MOL SCI, V15, P560, DOI 10.3390/ijms15010560; Callegari Elisa, 2013, Onco Targets Ther, V6, P1167, DOI 10.2147/OTT.S36161; Fernandez S, 2015, ONCOGENE, V34, P3240, DOI 10.1038/onc.2014.267; de Cedron MG, 2016, J LIPID RES, V57, P193, DOI 10.1194/jlr.R061812; Hou LK, 2016, ONCOTARGET, V7, P26016, DOI 10.18632/oncotarget.8421; Huang DQ, 2015, ONCOTARGET, V6, P9257, DOI 10.18632/oncotarget.3288; Huang K, 2016, ONCOL REP, V35, P887, DOI 10.3892/or.2015.4458; Huang X, 2013, EMBO J, V32, P2204, DOI 10.1038/emboj.2013.133; Lee SW, 2015, MOL CELL, V57, P1022, DOI 10.1016/j.molcel.2015.01.015; Li PQ, 2016, CELL PHYSIOL BIOCHEM, V38, P1915, DOI 10.1159/000445553; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; McGlynn KA, 2015, CLIN LIVER DIS, V19, P223, DOI 10.1016/j.cld.2015.01.001; Mohammadi-Yeganeh S, 2016, TUMOR BIOL, V37, P8993, DOI 10.1007/s13277-015-4513-9; Negrini M, 2007, J CELL SCI, V120, P1833, DOI 10.1242/jcs.03450; Peschansky VJ, 2014, EPIGENETICS-US, V9, P3, DOI 10.4161/epi.27473; Strong AMP, 2014, ARCH BIOCHEM BIOPHYS, V563, P118, DOI 10.1016/j.abb.2014.07.012; Sun Y, 2012, ONCOL REP, V28, P1346, DOI 10.3892/or.2012.1958; Szabo G, 2013, NAT REV GASTRO HEPAT, V10, P542, DOI 10.1038/nrgastro.2013.87; Takeyama H, 2014, MOL CANCER THER, V13, P976, DOI 10.1158/1535-7163.MCT-13-0571; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; Wei PT, 2016, DNA CELL BIOL, V35, P33, DOI 10.1089/dna.2015.3021; Wu SY, 2016, WORLD J GASTROENTERO, V22, P176, DOI 10.3748/wjg.v22.i1.176; Xu P, 2016, J ORAL MAXIL SURG, V74, P844, DOI 10.1016/j.joms.2015.09.038; Yu WF, 2016, GENE, V577, P193, DOI 10.1016/j.gene.2015.11.045; Zhang JS, 2012, CANCER METAST REV, V31, P653, DOI 10.1007/s10555-012-9368-6; Zhang XY, 2009, HEPATOLOGY, V50, P490, DOI 10.1002/hep.23008; Zucman-Rossi J, 2015, GASTROENTEROLOGY, V149, P1226, DOI 10.1053/j.gastro.2015.05.061	28	8	8	0	3	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1791-2997	1791-3004		MOL MED REP	Mol. Med. Rep.	NOV	2017	16	5					7649	7656		10.3892/mmr.2017.7583			8	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	FM0ZU	WOS:000414698900248	28944918	Bronze			2022-04-25	
J	Samdal, H; Sandmoe, MA; Olsen, LC; Jarallah, EAH; Hoiem, TS; Schonberg, SA; Pettersen, CHH				Samdal, Helle; Sandmoe, Malin A.; Olsen, Lene C.; Jarallah, Elaf A. H.; Hoiem, Therese S.; Schonberg, Svanhild A.; Pettersen, Caroline H. H.			Basal level of autophagy and MAP1LC3B-II as potential biomarkers for DHA-induced cytotoxicity in colorectal cancer cells	FEBS JOURNAL			English	Article						autophagy; colorectal cancer; docosahexaenoic acid; MAP1LC3B; omega-3	OXIDATIVE STRESS; P53 MUTATIONS; MUTANT P53; ER STRESS; EXPRESSION; INHIBITION; APOPTOSIS; THERAPY; GROWTH; DEATH	The omega-3 fatty acid docosahexaenoic acid (DHA) is known as an anticancer agent. Colorectal cancer (CRC) cells exhibit different sensitivity toward DHA, but the mechanisms involved are still unclear. Gene expression profiling of 10 CRC cell lines demonstrated a correlation between the level of DHA sensitivity and different biological stress responses, such as endoplasmic reticulum (ER) stress, oxidative stress, and autophagy. The basal level of autophagy and MAP1LC3B-II protein correlated with DHA sensitivity in the cell lines studied. DHA induced oxidative stress, ER stress, and autophagy in DHA-sensitive DLD-1 cells, while the less sensitive LS411N cells were affected to a much lesser extent. Co-treatment with DHA and the autophagy inducer rapamycin reduced DHA sensitivity in DLD-1 and HCT-8 cells, while co-treatment with DHA and the autophagy inhibitors chloroquine and 3-methyladenine increased the DHA sensitivity in LS411N and LS513 cells. Differentially expressed genes correlating with DHA sensitivity and the level of autophagy demonstrated an overlap in biological pathways involved. Results indicate the basal level of autophagy and MAP1LC3B-II protein as potential biomarkers for DHA sensitivity in CRC cells. DatabasesProtocol and data for gene expression experiments have been submitted to ArrayExpress with accession number E-MTAB-5750.	[Samdal, Helle; Sandmoe, Malin A.; Olsen, Lene C.; Jarallah, Elaf A. H.; Hoiem, Therese S.; Schonberg, Svanhild A.; Pettersen, Caroline H. H.] Norwegian Univ Sci & Technol, Dept Clin & Mol Med, NTNU, Fac Med & Hlth Sci, Trondheim, Norway; [Olsen, Lene C.] Norwegian Univ Sci & Technol, Bioinformat Core Facil BioCore, NTNU, Trondheim, Norway; [Pettersen, Caroline H. H.] Trondheim Reg & Univ Hosp, Dept Surg, St Olavs Hosp, Trondheim, Norway		Pettersen, CHH (corresponding author), Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Fac Med & Hlth Sci, Labs Enteret 5th Floor East, N-7006 Trondheim, Norway.	caroline.h.pettersen@ntnu.no		Olsen, Lene Christin/0000-0002-5869-4952; Pettersen, Caroline/0000-0003-0658-0061	Joint Research Committee between St. Olavs Hospital; Faculty of Medicine and Health Sciences, NTNU (FFU); Faculty of Medicine and Health Sciences, NTNU; Cancer Research Fund at St. Olavs Hospital; Central Norway Regional Health Authority; Research Council of Norway through "Smaforsk' grant	We appreciate the technical assistance by Grete Klippenvag Pettersen and Almaz Nigatu Tesfahun. Gene expression analysis was performed at the Genomics Core Facility, Norwegian University of Science and Technology (NTNU). This work was supported by grants from the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU (FFU), The Faculty of Medicine and Health Sciences, NTNU, the Cancer Research Fund at St. Olavs Hospital, the Central Norway Regional Health Authority and the Research Council of Norway through "Smaforsk' grant.	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M., 2009, WORLD, DOI 10.1200/JC0.2009.23.6018; Xiong HY, 2010, CANCER LETT, V288, P68, DOI 10.1016/j.canlet.2009.06.039; Xu GR, 2017, GENE, V604, P33, DOI 10.1016/j.gene.2016.12.016; Xu J, 2011, NAT CHEM BIOL, V7, P285, DOI 10.1038/nchembio.546; Yusof AS, 2012, ASIAN PAC J CANCER P, V13, P4713, DOI 10.7314/APJCP.2012.13.9.4713; Zand H, 2007, MOL CELL BIOCHEM, V304, P71, DOI 10.1007/s11010-007-9487-5	58	5	5	0	8	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1742-464X	1742-4658		FEBS J	FEBS J.	JUL	2018	285	13					2446	2467		10.1111/febs.14488			22	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	GM1QS	WOS:000437845500007	29723445	Green Submitted, Bronze			2022-04-25	
J	Guo, GF; Jiang, WQ; Zhang, B; Cai, YC; Xu, RH; Chen, XX; Wang, F; Xia, LP				Guo, Gui-Fang; Jiang, Wen-Qi; Zhang, Bei; Cai, Yu-Chen; Xu, Rui-Hua; Chen, Xu-Xian; Wang, Fang; Xia, Liang-Ping			Autophagy-related proteins Beclin-1 and LC3 predict cetuximab efficacy in advanced colorectal cancer	WORLD JOURNAL OF GASTROENTEROLOGY			English	Article						Beclin-1; Cetuximab; Colorectal neoplasms; Drug therapy; LC3	MULTICENTER RANDOMIZED-TRIAL; 1ST-LINE TREATMENT; FLUOROURACIL; EXPRESSION; MUTATIONS; CELLS; GENE; EGFR; KRAS; CHEMOTHERAPY	AIM: To investigate the utility of Beclin-1 and LC3, two autophagy-related proteins, in predicting the cetuximab efficacy in advanced colorectal cancer (ACRC). METHODS: The data of 85 patients with ACRC treated at the Sun Yat-sen University Cancer Center from March 1, 2005 to December 31, 2008 were studied, including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing chemotherapy. Beclin-1 and LC3 expression was evaluated by immunohistochemistry, and KRAS status was evaluated by polymerase chain reaction. RESULTS: Beclin-1 and LC3 expression in ACRC was significantly correlated (r = 0.44, P < 0.01); however, LC3 was more highly expressed in cancerous tissues than in normal tissues (Z = -2.63, P < 0.01). In the cetuximab-containing chemotherapy group, patients with low LC3 expression had higher objective response rates (ORRs) than those with high LC3 expression (52.9% vs 17.9%, P = 0.01), and patients with low Beclin-1 expression had a longer median progression-free survival (PFS) than their counterparts with higher Beclin-1 expression (9.0 mo vs 3.0 mo, P = 0.01). However, neither of these predictive relationships was detected in the group treated with non-cetuximab-containing chemotherapy. Patients with wild-type KRAS had higher ORRs (42.3% vs 9.1%, P = 0.049) and disease control rates (DCRs) (73.1% vs 36.4%, P = 0.035), and longer median PFS (5.5 mo vs 2.5 mo, P = 0.02) than those with mutant KRAS in the cetuximab-containing chemotherapy group. Neither Beclin-1 (P = 0.52) nor LC3 (P = 0.32) expression was significantly correlated with KRAS status. CONCLUSION: Patients with low Beclin-1 expression had a longer PFS than those with high Beclin-1 expression, and patients with low LC3 expression had a higher ORR in ACRC patients treated with cetuximab-containing chemotherapy. (C) 2011 Baishideng. All rights reserved.	[Guo, Gui-Fang; Jiang, Wen-Qi; Zhang, Bei; Cai, Yu-Chen; Xu, Rui-Hua; Chen, Xu-Xian; Wang, Fang; Xia, Liang-Ping] Sun Yat Sen Univ, State Key Lab Oncol, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China; [Guo, Gui-Fang; Zhang, Bei; Chen, Xu-Xian; Wang, Fang; Xia, Liang-Ping] Sun Yat Sen Univ, VIP Reg, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China; [Jiang, Wen-Qi; Xu, Rui-Hua] Sun Yat Sen Univ, Dept Med Oncol, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China		Xia, LP (corresponding author), Sun Yat Sen Univ, State Key Lab Oncol, Ctr Canc, 651 E Dongfeng Rd, Guangzhou 510060, Guangdong, Peoples R China.	xialiangping@163.com	Xu, Rui-Hua/AAW-4766-2021	Xu, Rui-Hua/0000-0001-9771-8534	Science and Technology Planning Project of Guangdong Province, China [2010B031600317]; Administration of Traditional Chinese Medicine of Guangdong Province, China [20111169]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81071872]	Supported by Grants from Science and Technology Planning Project of Guangdong Province, China, No. 2010B031600317; Administration of Traditional Chinese Medicine of Guangdong Province, China, No. 20111169; National Natural Science Foundation of China, No. 81071872	Ahn CH, 2007, APMIS, V115, P1344, DOI 10.1111/j.1600-0463.2007.00858.x; Allegra CJ, 2009, J CLIN ONCOL, V27, P2091, DOI 10.1200/JCO.2009.21.9170; Bokemeyer C, 2009, J CLIN ONCOL, V27, P663, DOI 10.1200/JCO.2008.20.8397; Cuervo AM, 2004, TRENDS CELL BIOL, V14, P70, DOI 10.1016/j.tcb.2003.12.002; Douillard JY, 2000, LANCET, V355, P1041, DOI 10.1016/S0140-6736(00)02034-1; Eberhard DA, 2008, J CLIN ONCOL, V26, P983, DOI 10.1200/JCO.2007.12.9858; Giacchetti S, 2000, J CLIN ONCOL, V18, P136, DOI 10.1200/JCO.2000.18.1.136; Giannopoulou E, 2009, ANTICANCER RES, V29, P5077; Guo GF, 2010, MED ONCOL       1117; Guo Gui-fang, 2010, Zhonghua Zhong Liu Za Zhi, V32, P777; Guo Gui-Fang, 2009, Ai Zheng, V28, P1317; Jaeger PA, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0011102; Klionsky DJ, 2000, SCIENCE, V290, P1717, DOI 10.1126/science.290.5497.1717; Klionsky DJ, 2003, DEV CELL, V5, P539, DOI 10.1016/S1534-5807(03)00296-X; Lee JW, 2007, APMIS, V115, P750, DOI 10.1111/j.1600-0463.2007.apm_640.x; Li XQ, 2010, AUTOPHAGY, V6, P1066, DOI 10.4161/auto.6.8.13366; Li XQ, 2010, CANCER RES, V70, P5942, DOI 10.1158/0008-5472.CAN-10-0157; Li ZD, 2008, PROG BIOCHEM BIOPHYS, V35, P1282; Liang XH, 1999, NATURE, V402, P672, DOI 10.1038/45257; Martinet W, 2006, J HISTOCHEM CYTOCHEM, V54, P85, DOI 10.1369/jhc.5A6743.2005; Mizushima N, 2004, INT J BIOCHEM CELL B, V36, P2491, DOI 10.1016/j.biocel.2004.02.005; Rocken C, 2008, Pathologe, V29 Suppl 2, P200, DOI 10.1007/s00292-008-1041-z; Sato K, 2007, CANCER RES, V67, P9677, DOI 10.1158/0008-5472.CAN-07-1462; Shintani T, 2004, SCIENCE, V306, P990, DOI 10.1126/science.1099993; Tatsumi K, 2008, J MOL DIAGN, V10, P520, DOI 10.2353/jmoldx.2008.080024; Theodoropoulos GE, 2009, ANTICANCER RES, V29, P785; Van Cutsem E, 2009, EJC SUPPL, V7, P345, DOI 10.1016/S1359-6349(09)71172-3; Van Cutsem E, 2009, NEW ENGL J MED, V360, P1408, DOI 10.1056/NEJMoa0805019; Weihua Z, 2008, CANCER CELL, V13, P385, DOI 10.1016/j.ccr.2008.03.015; Yoshioka A, 2008, INT J ONCOL, V33, P461, DOI 10.3892/ijo_00000028	30	58	61	1	15	BAISHIDENG PUBLISHING GROUP INC	PLEASANTON	8226 REGENCY DR, PLEASANTON, CA 94588 USA	1007-9327	2219-2840		WORLD J GASTROENTERO	World J. Gastroenterol.	NOV 21	2011	17	43					4779	4786		10.3748/wjg.v17.i43.4779			8	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	861FG	WOS:000298004000005	22147978	hybrid, Green Published, Green Submitted			2022-04-25	
J	Zheng, HC; Gong, BC; Zhao, S				Zheng, Hua-Chuan; Gong, Bao-Cheng; Zhao, Shuang			The meta and bioinformatics analysis of GRP78 expression in gastric cancer	ONCOTARGET			English	Article						GRP78; gastric cancer; meta analysis; bioinformatics analysis	CELL-SURFACE GRP78; ER STRESS; COLORECTAL-CANCER; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; POOR-PROGNOSIS; PROTEIN GRP78; UP-REGULATION; TUMOR-GROWTH; METASTASIS	GRP78 is a molecular chaperone located in endoplasmic reticulum, and induces folding and assembly of newly-synthesized proteins, proteasome degradation of aberrant proteins, and translocation of secretory proteins, autophagy, and epithelialmesenchymal transition. We performed a systematic meta-and bioinformatics analysis through multiple online databases up to March 14, 2017. It was found that up-regulated GRP78 expression in gastric cancer, compared with normal mucosa at both protein and mRNA levels (p < 0.05). GRP78 expression was positively correlated with depth of invasion, TNM staging and dedifferentiation of gastric cancer (p < 0.05), while its mRNA expression was negatively correlated with depth of invasion, histological grading and dedifferentiation (p < 0.05). A positive association between GRP78 expression and unfavorable overall survival was found in patients with gastric cancer (p < 0.005). A higher GRP78 mRNA expression was positively correlated with overall and progression-free survival rates of all cancer patients, even stratified by aggressive parameters, or as an independent factor (p < 0.05). These findings indicated that GRP78 expression might be employed as a potential marker to indicate gastric carcinogenesis and subsequent progression, even prognosis.	[Zheng, Hua-Chuan] China Med Univ, Dept Expt Oncol, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China; China Med Univ, Anim Ctr, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China		Zheng, HC (corresponding author), China Med Univ, Dept Expt Oncol, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China.	zheng_huachuan@hotmail.com			Liaoning BaiQianWan Program; Award for Liaoning Distinguished Professor; Key Scientific and Technological Project of Liaoning Province [2015408001]; National Natural Scientific Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472544, 81672700]	This study was supported by Liaoning BaiQianWan Program, Award for Liaoning Distinguished Professor, a Key Scientific and Technological Project of Liaoning Province (2015408001) and National Natural Scientific Foundation of China (81472544; 81672700).	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J	Zhang, J; Gao, SH; Zhang, YD; Yi, HX; Xu, MX; Xu, JL; Liu, H; Ding, ZC; He, HB; Wang, HM; Hao, Z; Sun, LK; Liu, Y; Wei, F				Zhang, Jian; Gao, Shuohui; Zhang, Yandong; Yi, Huixin; Xu, Mengxian; Xu, Jialun; HuanLiu; Ding, Zhichen; He, Hongbin; Wang, Hongmei; Hao, Zhuo; Sun, Liankun; Liu, Yan; Wei, Feng			MiR-216a-5p inhibits tumorigenesis in Pancreatic Cancer by targeting TPT1/mTORC1 and is mediated by LINC01133	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES			English	Article						LINC01133; pancreatic cancer; miR-216a-5p; TPT1; tumor progression	TRANSLATIONALLY-CONTROLLED 1; TUMOR PROTEIN; HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION; COLORECTAL-CANCER; PROGRESSION; METASTASIS; STATISTICS; ACTIVATION; INVASION	MiR-216a-5p has opposite effects on tumorigenesis and progression in the context of different tumors, acting as either a tumor suppressor or an oncogene. However, the expression and function of miR-216a-5p in pancreatic cancer (PC) is not well characterized. In this study, we found miR-216a-5p was significantly downregulated in PC tissues and cell lines, which showed a negative correlation with peripancreatic lymph, perineural invasion and TNM stage of PCs patients. We made use of functional assays to reveal that miR-216a-5p inhibited growth and migration of PC cells in vitro and in vivo. Then, by employing the bioinformatics analysis and luciferase reporter assay, we demonstrated TPT1 was a potential target of miR-216a-5p, which contributes to tumor malignance by mediating mTORC1 pathway-associated autophagy. Furthermore, bioinformatics analysis and RNA pulldown confirmed that miR-216a-5p was mediated by LINC01133, which sponge miR-216a-5p, as a competing endogenous RNA (ceRNA). Collectively, our study revealed an important role of LINC01133/miR-216a-5p/TPT1 axis in the genesis and progression of PCs, which provides potential biomarkers for clinical diagnosis and therapy of PCs.	[Zhang, Jian; Zhang, Yandong; HuanLiu; Ding, Zhichen; Wei, Feng] Jilin Univ, Dept Hepatobiliary & Pancreas Surg, Hosp 1, Changchun, Peoples R China; [Yi, Huixin; Xu, Mengxian; Hao, Zhuo; Liu, Yan] Acad Mil Med Sci, Inst Mil Vet Med, Genet Engn Lab PLA, Changchun, Peoples R China; [Gao, Shuohui] Jilin Univ, Dept Gastrointestinal Colorectal Surg, China Japan Union Hosp, Changchun, Peoples R China; [Sun, Liankun] Jilin Univ, Coll Basic Med Sci, Dept Pathophysiol, Changchun, Peoples R China; [Xu, Jialun] Jilin Univ, Key Lab Zoonosis Res, Coll Vet Med, Minist Educ, Changchun, Peoples R China; [He, Hongbin; Wang, Hongmei] Shandong Normal Univ, Coll Life Sci, Ruminant Dis Res Ctr, Jinan, Peoples R China		Wei, F (corresponding author), Jilin Univ, Hosp 1, Changchun, Peoples R China.; Liu, Y (corresponding author), Acad Mil Med Sci, Changchun, Peoples R China.	liu820512@163.com; wei_feng@jlu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972273, 31972720, 81772291]; Science & Technology Department of Jilin Province [20190701008GH, 20160101053JC]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2018T110253]; Bethune B Project of Jilin University [450060521279]	The work was supported by grants from the National Natural Science Foundation of China (Nos. 81972273 to Feng Wei, 31972720 for Yan Liu, 81772291 to Shuohui Gao), the Science & Technology Department of Jilin Province (Nos. 20190701008GH and 20160101053JC), the China Postdoctoral Science Foundation (No. 2018T110253), and the Bethune B Project of Jilin University (No. 450060521279).	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J. Biol. Sci.		2020	16	14					2612	2627		10.7150/ijbs.46822			16	Biochemistry & Molecular Biology; Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics	MT6VW	WOS:000555111400010	32792860	Green Published, gold			2022-04-25	
J	Liu, HY; Zhang, HS; Liu, MY; Li, HM; Wang, XY; Wang, M				Liu, Hui-Yun; Zhang, Hong-Sheng; Liu, Min-Yao; Li, Hong-Ming; Wang, Xin-Yu; Wang, Miao			GLS1 depletion inhibited colorectal cancer proliferation and migration via redox/Nrf2/autophagy-dependent pathway	ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS			English	Article						GLS1; Redox; Autophagy; Colorectal cancer	GLUTAMINE-METABOLISM; AUTOPHAGY; ROS	Cancer cells can metabolize glutamine to replenish TCA cycle intermediates for cell survival. Glutaminase (GLS1) is over-expressed in multiple cancers, including colorectal cancer (CRC). However, the role of GLS1 in colorectal cancer development has not yet fully elucidated. In this study, we found that GLS1 levels were significantly increased in CRC cells. Knockdown of GLS1 by shRNAs as well as GLS1 inhibitor BPTES decreased DLD1 and SW480 cell proliferation, colony formation and migration. Knockdown of GLS1 as well as BPTES induced reactive oxygen species (ROS) production, down-regulation of GSH/GSSG ratio, an decrease in Nrf2 protein expression and an increase in cytoplasmic Nrf2 protein expression in DLD1 and SW480 cells. Furthermore, Knockdown of GLS1 as well as BPTES inhibited autophagy pathway, antioxidant NAC and Nrf2 activator could reversed inhibition of GLS1-mediated an decrease in autophagic flux in DLD1 and SW480 cells. Depletion of GLS1-induced inhibition of DLD1 and SW480 CRC cell proliferation, colony formation and migration was reversed by autophagy inducer rapamycin. These results suggest that targeting GLS1 might be a new potential therapeutic target for the treatment of CRC.	[Liu, Hui-Yun; Zhang, Hong-Sheng; Liu, Min-Yao; Li, Hong-Ming; Wang, Xin-Yu; Wang, Miao] Beijing Univ Technol, Fac Environm & Life, Pingleyuan 100, Beijing 100124, Peoples R China		Zhang, HS (corresponding author), Beijing Univ Technol, Fac Environm & Life, Pingleyuan 100, Beijing 100124, Peoples R China.	zhanghs@bjut.edu.cn			Beijing Natural Science FoundationBeijing Natural Science Foundation [7192014]; Open Project of Key Laboratory of Genomics and Precision Medicine, Chinese Academy of Sciences; National Laboratory of Biomacromolecules [2017kf02]; practical training plan for the cross training of high level talents in Beijing Universities [2017271]; Beijing International Science and Technology Cooperation Base of Antivirus Drug	This study was supported by Beijing Natural Science Foundation (No. 7192014) ; the Open Project of Key Laboratory of Genomics and Precision Medicine, Chinese Academy of Sciences; the National Laboratory of Biomacromolecules (No. 2017kf02) ; the practical training plan for the cross training of high level talents in Beijing Universities (No. 2017271) ; Beijing International Science and Technology Cooperation Base of Antivirus Drug. We would like to thank Li Yan (Research Center for EcoEnvironmental Sciences, Chinese Academy of Sciences) and XiaoYan Zhang (Beijing Normal University) for helping confocal fluorescent microscope of GFPLC3.	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Biochem. Biophys.	SEP 15	2021	708								108964	10.1016/j.abb.2021.108964		JUN 2021	9	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	TE4RM	WOS:000669998500014	34119480				2022-04-25	
J	Zhang, ZZ; Ju, FY; Chen, F; Wu, HY; Chen, JY; Zhong, J; Shao, LM; Zheng, S; Wang, LJ; Xue, M				Zhang, Zizhen; Ju, Fangyu; Chen, Fei; Wu, Haoyue; Chen, Jingyu; Zhong, Jing; Shao, Liming; Zheng, Sheng; Wang, Liangjing; Xue, Meng			GDC-0326 Enhances the Effects of 5-Fu in Colorectal Cancer Cells by Inducing Necroptotic Death	ONCOTARGETS AND THERAPY			English	Article						GDC-0326; 5-fluorouracil; colorectal cancer; combination therapy	DRUG-COMBINATION; AUTOPHAGY; NVP-BYL719; EXPRESSION; APOPTOSIS	Aim: Chemoresistance to 5-fluorouracil (5-Fu) is common in colorectal cancer (CRC). Programmed necrosis (necroptosis) is an alternative form of programmed cell death regulated by receptor-interacting protein kinase (RIPK) 1 and 3, assumed as a novel target of cancer therapy. In this study, we aimed to explore whether a novel small molecular agent GDC-0326 could facilitate the effect of 5-Fu through necroptosis. Main Methods: Cell Counting Kit-8 (CCK-8) assay and colony formation were performed to confirm the function of GDC-0326 in CRC cells. Western blot and immunofluorescence were conducted to measure the altered expressions of RIPK1/RIPK3 induced by GDC-0326. Subcutaneous tumor models were used to evaluate the chemotherapeutic effects and concomitant side effects of GDC-0326 in vivo. Key Findings: We found that GDC-0326 effectively suppressed the growth of CRC cells in a dose-dependent manner. The induction of necroptosis by GDC-0326 was correlated with the modulation of RIPK1 and RIPK3. Necrostatin-1 and GSK-872, inhibitors of RIPK1 and RIPK3, respectively, could rescue the cell death induced by GDC-0326. In addition, in vitro and in vivo studies showed that 5-Fu plus GDC-0326 evinced a better antitumor efficacy by suppressing tumor growth and increasing tumor necrosis with no increased toxicity. Significance: This study demonstrates that GDC-0326 plus 5-Fu has augmented antitumor efficacy and acceptable safety, which might be a promising therapeutic strategy for CRC patients in the future.	[Zhang, Zizhen; Ju, Fangyu; Chen, Fei; Chen, Jingyu; Zhong, Jing; Shao, Liming; Zheng, Sheng; Wang, Liangjing; Xue, Meng] Zhejiang Univ, Dept Gastroenterol, Affiliated Hosp 2, Sch Med, Hangzhou 310020, Peoples R China; [Zhang, Zizhen; Ju, Fangyu; Chen, Fei; Chen, Jingyu; Zhong, Jing; Shao, Liming; Zheng, Sheng; Wang, Liangjing; Xue, Meng] Zhejiang Univ, Inst Gastroenterol, Hangzhou 310000, Peoples R China; [Zhang, Zizhen; Ju, Fangyu; Chen, Fei; Chen, Jingyu; Zhong, Jing; Shao, Liming; Zheng, Sheng; Wang, Liangjing; Xue, Meng] Zhejiang Univ, Canc Ctr, Hangzhou 310000, Peoples R China; [Wu, Haoyue] Zhejiang Univ, Inst Genet, Sch Med, Hangzhou 310012, Peoples R China; [Wu, Haoyue] Zhejiang Univ, Dept Genet, Sch Med, Hangzhou 310012, Peoples R China		Wang, LJ; Xue, M (corresponding author), Zhejiang Univ, Dept Gastroenterol, Affiliated Hosp 2, Sch Med, Hangzhou 310020, Peoples R China.; Wang, LJ; Xue, M (corresponding author), Zhejiang Univ, Inst Gastroenterol, Hangzhou 310000, Peoples R China.; Wang, LJ; Xue, M (corresponding author), Zhejiang Univ, Canc Ctr, Hangzhou 310000, Peoples R China.	wangljzju@zju.edu.cn; xuemeng@zju.edu.cn	Zhang, Zizhen/AAA-1539-2022		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81802348]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LY18H160009, LY16H160031]	This work was supported by the National Natural Science Foundation of China (grant nos. 82073229 and 81702308), Zhejiang Provincial Natural Science Foundation (grant nos. LY18H160009 and LY16H160031), and the National Natural Science Foundation of China (grant no. 81802348).	Ashton JC, 2015, CANCER RES, V75, P2400, DOI 10.1158/0008-5472.CAN-14-3763; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Chen CY, 2017, AM J TRANSL RES, V9, P5507; Chou TC, 2010, CANCER RES, V70, P440, DOI 10.1158/0008-5472.CAN-09-1947; Christofferson DE, 2010, CURR OPIN CELL BIOL, V22, P263, DOI 10.1016/j.ceb.2009.12.003; Ding Z, 2019, PHARMACEUTICS, V11, DOI 10.3390/pharmaceutics11070328; Dittrich L, 2021, J CLIN MED, V10, DOI 10.3390/jcm10010072; Feng Y, 2018, NANOSCALE RES LETT, V13, DOI 10.1186/s11671-018-2716-x; Fletcher JI, 2010, NAT REV CANCER, V10, P147, DOI 10.1038/nrc2789; Fritsch C, 2014, MOL CANCER THER, V13, P1117, DOI 10.1158/1535-7163.MCT-13-0865; Furet P, 2013, BIOORG MED CHEM LETT, V23, P3741, DOI 10.1016/j.bmcl.2013.05.007; Gao JW, 2018, ONCOL REP, V40, P1971, DOI 10.3892/or.2018.6634; Heffron TP, 2016, J MED CHEM, V59, P985, DOI 10.1021/acs.jmedchem.5b01483; Ji MY, 2018, AM J CANCER RES, V8, P2402; Kroemer G, 2009, CELL DEATH DIFFER, V16, P3, DOI 10.1038/cdd.2008.150; Li YM, 2019, HEPATOLOGY, V70, P1564, DOI 10.1002/hep.30676; Linkermann A, 2014, NEW ENGL J MED, V370, P455, DOI 10.1056/NEJMra1310050; Liu F, 2020, CANCER MED-US, V9, P1079, DOI 10.1002/cam4.2746; Lu XH, 2020, INT J BIOL SCI, V16, P1427, DOI 10.7150/ijbs.42962; McNamara CR, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0056576; Mishra SK, 2019, BBA-MOL CELL BIOL L, V1864, P158, DOI 10.1016/j.bbalip.2018.11.002; Scheiblecker L, 2020, PHARMACEUTICALS-BASE, V13, DOI 10.3390/ph13120418; Sinzger M, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-38907-x; Soler A, 2016, CLIN CANCER RES, V22, P5805, DOI 10.1158/1078-0432.CCR-15-3051; Tigu AB, 2020, MOLECULES, V25, DOI 10.3390/molecules25081947; Vivanco I, 2002, NAT REV CANCER, V2, P489, DOI 10.1038/nrc839; Wang JH, 2020, CANCERS, V12, DOI 10.3390/cancers12113171; Wang WC, 2016, BIOCHEM PHARMACOL, V121, P8, DOI 10.1016/j.bcp.2016.09.024; Wosikowski K, 1997, CLIN CANCER RES, V3, P2405; Xin Y, 2016, CANCER LETT, V379, P24, DOI 10.1016/j.canlet.2016.05.023; Zhang J, 2011, GASTROENTEROLOGY, V141, P50, DOI 10.1053/j.gastro.2011.05.010; Zhang L, 2015, TOXICOL LETT, V236, P43, DOI 10.1016/j.toxlet.2015.04.015; Zhang YH, 2020, PHARMACOL RES, V155, DOI 10.1016/j.phrs.2020.104717; Zhang ZB, 2020, NATURE, V579, P415, DOI 10.1038/s41586-020-2071-9; Zheng W, 2018, BIOMED PHARMACOTHER, V106, P175, DOI 10.1016/j.biopha.2018.06.111; Zhu YH, 2020, CELL DEATH DIS, V11, DOI 10.1038/s41419-020-03164-8	36	0	0	1	3	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2021	14						2519	2530		10.2147/OTT.S302334			12	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	RM7LT	WOS:000639841200001	33880032	gold, Green Published			2022-04-25	
J	Zhu, JL; Cai, YS; Xu, K; Ren, XY; Sun, J; Lu, SM; Chen, JH; Xu, P				Zhu, Jialin; Cai, Yongsong; Xu, Ke; Ren, Xiaoyu; Sun, Jian; Lu, Shemin; Chen, Jinghong; Xu, Peng			Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy-dependent pathway in human synovial sarcoma cells	ONCOLOGY REPORTS			English	Article						Beclin1; proliferation; autophagy; apoptosis; synovial sarcoma	CANCER CELLS; OVARIAN-CANCER; BREAST-CANCER; PI3K/AKT/MTOR PATHWAY; COLORECTAL-CANCER; SIGNALING PATHWAY; MULTIPLE-MYELOMA; DOWN-REGULATION; APOPTOSIS; EXPRESSION	Beclin1 is an important autophagy-related protein, which is involved in both autophagy and apoptosis. In recent years, the antitumor effect of Beclin1 has received increased attention. In the present study, we established a stable Beclin1-overexpressing cell line with SW982 human synovial sarcoma cells. We found that Beclin1 overexpression decreased the cell viability, inhibited proliferation and induced apoptosis in SW982 cells. The expression levels of Bcl-2 and PCNA were decreased, while the levels of cleaved-caspase-3 and cleaved-PARP were increased. Beclin1 is closely related with autophagy, thus the autophagy-related markers LC3 and p62 were detected by western blot analysis, and transmission electron microscopy was used to observe autophagosomes. The results showed that the expression level of LC3II was increased and that of p62 was decreased. Moreover, many double membrane-enclosed autophagosomes were found in cells with Beclinl overexpression, which indicated that the autophagic activity was enhanced. To explore the effect of autophagy on the viability of SW982 cells, Atg5 was knocked down using siRNA to inhibit the autophagic activity. We found that autophagy contributed to the decrease in cell viability. Knockdown of Atg5 increased the viability and decreased the apoptotic rate of SW982 cells with Beclinl overexpression. The expression level of Bcl-2 was increased, while the expression levels of cleaved-caspase-3 and cleaved-PARP were decreased. We also found that the Akt/Bcl-2/caspase-9 pathway was involved. The phosphorylation of AKT was positively correlated with cell viability. The cleavage of caspase-9 was increased by Beclin1 overexpression and decreased by inhibition of autophagy. Altogether, our results suggested that both autophagy and apoptosis contributed to the antitumor effect of Beclin1 in SW982 cells.	[Zhu, Jialin; Cai, Yongsong; Xu, Ke; Ren, Xiaoyu; Xu, Peng] Xi An Jiao Tong Univ, Hlth Sci Ctr, Xian Hong Hui Hosp, Dept Joint Surg, 555 Friendship East St, Xian 710054, Shaanxi, Peoples R China; [Sun, Jian; Lu, Shemin] Xi An Jiao Tong Univ, Hlth Sci Ctr, Dept Genet & Mol Biol, Xian 710061, Shaanxi, Peoples R China; [Chen, Jinghong] Xi An Jiao Tong Univ, Hlth Sci Ctr, Inst Endem Dis,Sch Publ Hlth, Key Lab Trace Elements & Endem Dis,Natl Hlth & Fa, Xian 710061, Shaanxi, Peoples R China		Xu, P (corresponding author), Xi An Jiao Tong Univ, Hlth Sci Ctr, Xian Hong Hui Hosp, Dept Joint Surg, 555 Friendship East St, Xian 710054, Shaanxi, Peoples R China.	sousou369@163.com	Lu, Shemin/AAI-6479-2021; Lu, Shemin/M-3350-2018	Lu, Shemin/0000-0002-5535-8320; Lu, Shemin/0000-0001-8250-850X	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81271948, 81601877, 81171742]	The present study was supported by the National Natural Science Foundation of China (grant nos. 81271948, 81601877 and 81171742).	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Rep.	OCT	2018	40	4					1927	1936		10.3892/or.2018.6599			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GR8JZ	WOS:000442971200010	30066884	Green Submitted, Green Published, hybrid			2022-04-25	
J	Wang, SS; Du, H; Sun, PS				Wang, Sisi; Du, Hui; Sun, Peisen			Long Noncoding RNA NEAT1 Contributes to the Tumorigenesis of Colorectal Cancer Through Regulating SLC38A1 Expression by Sponging miR-138	CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS			English	Article						colorectal cancer; miR-138; NEAT1	CELL-PROLIFERATION; PROMOTES; MIGRATION; TRANSPORTERS; PROGRESSION; PROGNOSIS; APOPTOSIS	Background: Colorectal cancer (CRC), a malignant tumor, has become a highly relevant social problem. Nuclear paraspeckle assembly transcript 1 (NEAT1) was reported as an oncogenic long noncoding RNA in diverse tumors, including CRC. Nevertheless, the mechanism of NEAT1 in CRC remains unknown. Materials and Methods: The expression levels of NEAT1 and solute carrier family 38 member 1 (SLC38A1) in CRC tissues and cells were detected by real-time quantitative polymerase chain reaction. The protein levels of p62, microtubule-associated protein light (LC3-I), LC3-II, and SLC38A1 were examined by Western blot assay. Cell proliferation, apoptosis, and invasion were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), and flow cytometry and transwell assays, respectively. The interaction between miR-138 and NEAT1 or SLC38A1 was predicted by StarBase or TargetScan, and verified by the dual-luciferase reporter assay. The effect of NEAT1 on tumor growth was determined in CRC mice model. Results: The expression of NEAT1 and SLC38A1 was upregulated in CRC tissues and cells. NEAT1 knockdown or SLC38A1 downregulation restrained cell proliferation and invasion, and accelerated cell apoptosis and autophagy of CRC cells. NEAT1 acted as a sponge of miR-138 to regulate SLC38A1 expression. Furthermore, NEAT1 deficiency suppressed tumor growth in vivo. Conclusion: These studies disclosed that NEAT1 knockdown inhibited CRC progression by miR-138/SLC38A1 axis, providing an underlying target for CRC treatment.	[Wang, Sisi; Du, Hui] Qingdao Municipal Hosp, Blood Purificat Ctr, Qingdao, Peoples R China; [Sun, Peisen] Qingdao Municipal Hosp, Hlth Management Ctr, Qingdao, Peoples R China		Sun, PS (corresponding author), Qingdao Municipal Hosp, Hlth Management Ctr, 1 Jiaozhou Rd, Shibei Dist, Shandong, Peoples R China.	hlitwz@163.com					Albers A, 2001, PFLUG ARCH EUR J PHY, V443, P92, DOI 10.1007/s004240100663; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Bai XX, 2017, CELL PHYSIOL BIOCHEM, V43, P757, DOI 10.1159/000481559; Bartel DP, 2009, CELL, V136, P215, DOI 10.1016/j.cell.2009.01.002; Bian ZH, 2018, CLIN CANCER RES, V24, P4808, DOI 10.1158/1078-0432.CCR-17-2967; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Broer A, 2016, J BIOL CHEM, V291, P13194, DOI 10.1074/jbc.M115.700534; Bror S, 2014, PFLUG ARCH EUR J PHY, V466, P155, DOI 10.1007/s00424-013-1393-y; Chai YQ, 2016, CANCER MED-US, V5, P1588, DOI 10.1002/cam4.710; Diao LY, 2018, ONCOTARGETS THER, V11, P2797, DOI 10.2147/OTT.S165147; He C, 2019, BIOSCIENCE REP, V39, DOI 10.1042/BSR20181465; Huarte M, 2015, NAT MED, V21, P1253, DOI 10.1038/nm.3981; Jiang P, 2019, ONCOL LETT, V18, P2109, DOI 10.3892/ol.2019.10524; Li Y, 2017, DIS MARKERS, V2017, DOI 10.1155/2017/5314649; Liu JW, 2019, DIGEST DIS SCI, V64, P1868, DOI 10.1007/s10620-019-05506-9; Long LM, 2013, J TRANSL MED, V11, DOI 10.1186/1479-5876-11-275; Luo Y, 2019, CANCER LETT, V440, P11, DOI 10.1016/j.canlet.2018.10.002; Mackenzie B, 2004, PFLUG ARCH EUR J PHY, V447, P784, DOI 10.1007/s00424-003-1117-9; Nyhan MJ, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2123-6; Peng W, 2017, PATHOL ONCOL RES, V23, P651, DOI 10.1007/s12253-016-0172-4; Pritchard CC, 2011, GUT, V60, P116, DOI 10.1136/gut.2009.206250; Shan YJ, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0759-7; Si YR, 2019, CELL MOL BIOL LETT, V24, DOI 10.1186/s11658-019-0175-8; Wang K, 2013, BMC CANCER, V13, DOI 10.1186/1471-2407-13-343; Wang R, 2016, J CANCER RES CLIN, V142, P2291, DOI 10.1007/s00432-016-2238-9; Wu GZ, 2018, ARTIF CELL NANOMED B, V46, P579, DOI 10.1080/21691401.2018.1464459; Xie J, 2014, BMC GASTROENTEROL, V14, DOI 10.1186/1471-230X-14-70; Xie J, 2013, CHINESE J CANCER RES, V25, P514, DOI 10.3978/j.issn.1000-9604.2013.09.03; Xu WB, 2017, BIOMED PHARMACOTHER, V95, P1112, DOI 10.1016/j.biopha.2017.09.019; Yang QQ, 2017, INT J ONCOL, V50, P1801, DOI 10.3892/ijo.2017.3941; Yu HM, 2019, CELL PROLIFERAT, V52, DOI 10.1111/cpr.12526; Zhang JL, 2018, PATHOL ONCOL RES, V24, P109, DOI 10.1007/s12253-017-0233-3; Zhang M, 2018, J HEMATOL ONCOL, V11, DOI 10.1186/s13045-018-0656-7; Zhao L, 2018, J CELL PHYSIOL, V233, P4044, DOI 10.1002/jcp.26072; Zhong F, 2018, ACTA BIOCH BIOPH SIN, V50, P1190, DOI 10.1093/abbs/gmy130; Zhou FF, 2017, J HUAZHONG U SCI-MED, V37, P30, DOI 10.1007/s11596-017-1690-3	36	3	3	0	2	MARY ANN LIEBERT, INC	NEW ROCHELLE	140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA	1084-9785	1557-8852		CANCER BIOTHER RADIO	Cancer Biother. Radiopharm.	NOV 1	2021	36	9					793	802		10.1089/cbr.2020.3608		JUL 2020	10	Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging	XK8JL	WOS:000586245200001	32700988				2022-04-25	
J	Jiang, Y; Wang, XQ; Hu, DD				Jiang, Ying; Wang, Xiaoqin; Hu, Daode			Furanodienone induces G0/G1 arrest and causes apoptosis via the ROS/MAPKs-mediated caspase-dependent pathway in human colorectal cancer cells: a study in vitro and in vivo	CELL DEATH & DISEASE			English	Article							OXIDATIVE STRESS; REACTIVE OXYGEN; SIGNALING PATHWAY; UP-REGULATION; NITRIC-OXIDE; MITOCHONDRIA; ACTIVATION; AUTOPHAGY; TARGET; CYCLE	Furanodienone, a major bioactive constituents of sesquiterpene derived from Rhizoma Curcumae, has been proven to possess the potent anticancer efficacy on human breast cancer cells. Here, we investigated the cytotoxicity of furanodienone on human colorectal carcinoma cell lines in vitro and in vivo, as well as its underlying molecular mechanisms in the induction of apoptosis. In this study, we found that furanodienone significantly inhibited proliferation of RKO and HT-29 cells, induced mitochondrial dysfunction characterized by collapse of mitochondrial transmembrane potential and reduction of ATP level, and promoted the production of reactive oxygen species (ROS) that functions upstream of caspase-dependent apoptosis. The antioxidant N-acetyl cysteine, a ROS scavenger, abolished this apoptosis induced by furanodienone. In addition, furanodienone elevated the expression of p-p38, p-JNK, but decreased p-ERK, as a result of the produced ROS. The specific inhibitors U0126, SP600125 and SB202190 attenuated the expression of MAPKs, and regulated the expression of cleaved caspase-8, - 9 and - 3. Furthermore, the potential inhibitory effect of furanodienone on CRC cells was also corroborated in mouse xenograft model. In conclusion, the results demonstrated that furanodienone-triggered ROS plays a pivotal role in apoptosis as an upstream molecule-modulating activity of caspases in mitochondrial pathway via stimulating MAPKs signaling pathway. Our finding may provide a novel candidate for development of antitumor drugs targeting on colorectal cancer.	[Jiang, Ying; Wang, Xiaoqin; Hu, Daode] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Clin Pharmacol, 100 Haining Rd, Shanghai 200080, Hongkou, Peoples R China		Hu, DD (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Clin Pharmacol, 100 Haining Rd, Shanghai 200080, Hongkou, Peoples R China.	shanghaiyao@sina.com			Shanghai Committee of Science and TechnologyShanghai Science & Technology Committee [16401901400]; Health Bureau of Shanghai, China [2011ZJ021]; State Key Laboratory of Clinical Pharmacology Department of Shanghai General Hospital, Shanghai, China	We gratefully acknowledge the financial support of the Shanghai Committee of Science and Technology (16401901400), the Health Bureau of Shanghai, China (2011ZJ021) and the State Key Laboratory of Clinical Pharmacology Department of Shanghai General Hospital, Shanghai, China.	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MAY	2017	8								e2815	10.1038/cddis.2017.220			14	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	EW0QG	WOS:000402195700068	28542135	gold, Green Published			2022-04-25	
J	Huang, SB; Yang, ZNJ; Yu, CR; Sinicrope, FA				Huang, Shengbing; Yang, Zhineng J.; Yu, Chunrong; Sinicrope, Frank A.			Inhibition of mTOR Kinase by AZD8055 Can Antagonize Chemotherapy-induced Cell Death through Autophagy Induction and Down-regulation of p62/Sequestosome 1	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							PANCREATIC-CANCER CELLS; MAMMALIAN TARGET; COLORECTAL-CANCER; APOPTOSIS; PHOSPHORYLATION; ACTIVATION; GROWTH; TUMORIGENESIS; DEGRADATION; CASPASE-8	AZD8055 is an ATP-competitive inhibitor of mammalian target of rapamycin (mTOR) that forms two multiprotein complexes, mTORC1 and mTORC2, and negatively regulates autophagy. We demonstrate that AZD8055 stimulates and potentiates chemotherapy-mediated autophagy, as shown by LC3I-II conversion and down-regulation of the ubiquitin-binding protein p62/sequestosome 1. AZD8055-induced autophagy was pro-survival as shown by its ability to attenuate cell death and DNA damage (p-H2AX), and to enhance clonogenic survival by cytotoxic chemotherapy. Autophagy inhibition by siRNA against Beclin 1 or LC3B, or by chloroquine, partially reversed the cytoprotective effect of AZD8055 that was independent of cell cycle inhibition. The pro-survival role of autophagy was confirmed using ectopic expression of Beclin 1 that conferred cytoprotection. To determine whether autophagy-mediated down-regulation of p62/sequestosome 1 contributes to its pro-survival role, we generated p62 knockdown cells using shRNA that showed protection from chemotherapy-induced cell death and DNA damage. We also overexpressed wild-type (wt) p62 that promoted chemotherapy-induced cell death, whereas mutated p62 at functional domains (PB1, UBA) failed to do so. The ability of ectopic wt p62 to promote cell death was blocked by AZD8055. AZD8055 was shown to inhibit phosphorylation of the autophagy-initiating kinase ULK1 at Ser(757) and inhibited known targets of mTORC1 (p-mTOR Ser(2448), p70S6K, p-S6, p4EBP1) and mTORC2 (p-mTOR Ser(2481), p-AKT Ser(473)). Knockdown of mTOR, but not Raptor or Rictor, reduced p-ULK1 at Ser(757) and enhanced chemotherapy-induced autophagy that resulted in a similar cytoprotective effect as shown for AZD8055. In conclusion, AZD8055 inhibits mTOR kinase and ULK1 phosphorylation to induce autophagy whose pro-survival effect is due, in part, to down-regulation of p62.	[Sinicrope, Frank A.] Mayo Clin, Rochester, MN 55905 USA; Mayo Canc Ctr, Rochester, MN 55905 USA		Sinicrope, FA (corresponding author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA.	sinicrope.frank@mayo.edu			NCI, National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [1 K05 CA142885-01]; Mayo Cancer Center [CA15083]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA015083, K05CA142885] Funding Source: NIH RePORTER	This work was supported, in whole or in part, by NCI, National Institutes of Health Grant 1 K05 CA142885-01 (Senior Scientist Award, to F. A. S.), and the Mayo Cancer Center core Grant CA15083.	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Biol. Chem.	NOV 18	2011	286	46					40002	40012		10.1074/jbc.M111.297432			11	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	846TI	WOS:000296925700033	21949121	hybrid, Green Published			2022-04-25	
J	Kobayashi, Y; Kashima, H; Rahmanto, YS; Banno, K; Yu, Y; Matoba, Y; Watanabe, K; Iijima, M; Takeda, T; Kunitomi, H; Iida, M; Adachi, M; Nakamura, K; Tsuji, K; Masuda, K; Nomura, H; Tominaga, E; Aoki, D				Kobayashi, Yusuke; Kashima, Hiroyasu; Rahmanto, Yohan Suryo; Banno, Kouji; Yu, Yu; Matoba, Yusuke; Watanabe, Keiko; Iijima, Moito; Takeda, Takashi; Kunitomi, Haruko; Iida, Miho; Adachi, Masataka; Nakamura, Kanako; Tsuji, Kosuke; Masuda, Kenta; Nomura, Hiroyuki; Tominaga, Eiichiro; Aoki, Daisuke			Drug repositioning of mevalonate pathway inhibitors as antitumor agents for ovarian cancer	ONCOTARGET			English	Article						ovarian cancer; drug repositioning; statin; bisphosphonate; mevalonate pathway	TUBAL INTRAEPITHELIAL CARCINOMA; METABOLIC REQUIREMENTS; CELL-PROLIFERATION; COLORECTAL-CANCER; STATIN USE; GLUTATHIONE; MODEL; APOPTOSIS; SURVIVAL; RISK	Drug repositioning is an alternative strategy redirecting existing drugs for new disease. We have previously reported an antitumor effect of statins, antidyslipidemic drugs, on ovarian cancer in vitro and in vivo. In this study, we investigated the antitumor effects of other mevalonate pathway inhibitors and the mechanism of the antitumor effect from a metabolic perspective. The effects of inhibitors of the mevalonate pathway on tumor cell growth were evaluated in vitro. Bisphosphonates that inhibit this pathway are commonly used as antiosteoporotic drugs, and antitumor effects of the bisphosphonate were examined in vitro and in vivo. Metabolites in SKOV3 ovarian cancer cells were analyzed before and after lovastatin treatment, using capillary electrophoresis-mass spectrometry. All mevalonate pathway inhibitors showed concentration-dependent inhibitory effects on tumor cell growth. Particularly marked effects were obtained with inhibitors of farnesyltransferase and geranylgeranyltransferase. The bisphosphonate was also shown to have an antitumor effect in vivo. The expression of autophagy marker LC3A/3B was increased in cells after treatment. In metabolomics analysis, lovastatin treatment increased the metabolites involved in the tricarboxylic acid cycle while reducing the metabolites associated with glycolysis. Also it decreased glutathione and resulted to work with chemotherapeutic agents synergistically. Inhibition at any point in the mevalonate pathway, and especially of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, suppresses growth of ovarian cancer cells. Inhibition of this pathway may induce autophagy, cause a shift to activation of the tricarboxylic acid cycle and enhance susceptibility to chemotherapy. Drug repositioning targeting mevalonate pathway for ovarian cancer deserves consideration for clinical application.	[Kobayashi, Yusuke; Banno, Kouji; Matoba, Yusuke; Watanabe, Keiko; Iijima, Moito; Takeda, Takashi; Kunitomi, Haruko; Iida, Miho; Adachi, Masataka; Nakamura, Kanako; Tsuji, Kosuke; Masuda, Kenta; Nomura, Hiroyuki; Tominaga, Eiichiro; Aoki, Daisuke] Keio Univ, Dept Obstet & Gynecol, Sch Med, Tokyo, Japan; [Kobayashi, Yusuke; Kashima, Hiroyasu; Rahmanto, Yohan Suryo; Yu, Yu] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA; [Kashima, Hiroyasu] Shinshu Univ, Sch Med, Dept Obstet & Gynecol, Nagano, Japan; [Yu, Yu] Curtin Univ, Curtin Hlth Innovat Res Inst, Sch Pharm, Perth, WA, Australia		Kobayashi, Y (corresponding author), Keio Univ, Dept Obstet & Gynecol, Sch Med, Tokyo, Japan.; Kobayashi, Y (corresponding author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.	kobax@a2.keio.jp	Suryo Rahmanto, Yohan/K-8043-2018; Adachi, Masataka/M-3477-2015; Takeda, Takashi/AAB-1391-2019; Yu, Yu/AAD-7947-2019; Adachi, Masataka/T-7247-2019; Kobayashi, Yusuke/M-5174-2019	Suryo Rahmanto, Yohan/0000-0003-1453-7872; Adachi, Masataka/0000-0003-2974-8795; Takeda, Takashi/0000-0001-6686-5742; Yu, Yu/0000-0002-0209-0586; Adachi, Masataka/0000-0003-2974-8795; Kobayashi, Yusuke/0000-0002-4503-2845	KAKENHI (Japan Society for the Promotion of Science)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [16K20205]; Translational Research Network Program from Ministry of Education, Culture, Sports, Science and Technology (MEXT); Japan Society of Gynecologic OncologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science; Uehara Memorial FoundationUehara Memorial Foundation; Kanzawa Medical Research FoundationKanzawa Medical Research Foundation; Kobayashi Foundation for Cancer ResearchKobayashi Foundation for Cancer Research; Keio University Medical Science Fund	This works was supported by KAKENHI (Japan Society for the Promotion of Science, Grant-in-aid; 16K20205), Translational Research Network Program from Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Society of Gynecologic Oncology, the Uehara Memorial Foundation, Kanzawa Medical Research Foundation, Kobayashi Foundation for Cancer Research, and Keio University Medical Science Fund.	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J	Goulielmaki, M; Assimomytis, N; Rozanc, J; Taki, E; Christodoulou, I; Alexopoulos, LG; Zoumpourlis, V; Pintzas, A; Papahatjis, D				Goulielmaki, Maria; Assimomytis, Nikos; Rozanc, Jan; Taki, Eleni; Christodoulou, Ioannis; Alexopoulos, Leonidas G.; Zoumpourlis, Vassilis; Pintzas, Alexandros; Papahatjis, Demetris			DPS-2: A Novel Dual MEK/ERK and PI3K/AKT pathway Inhibitor with Powerful Ex Vivo and In Vivo Anticancer Properties	TRANSLATIONAL ONCOLOGY			English	Article							METASTATIC COLORECTAL-CANCER; ESTROGEN-RECEPTOR MODULATORS; MEK INHIBITORS; COMBINED BRAF; DOUBLE-BLIND; ERK PATHWAY; OPEN-LABEL; KINASE; KRAS; RAF	Development of novel bioactive compounds against KRAS and/or BRAF mutant colorectal cancer (CRC) is currently an urgent need in oncology. In addition, single or multitarget kinase inhibitors against MEK/ERK and PI3K/AKT pathways are of potential therapeutic advantage. A new compound based on the benzothiophene nucleus was synthesized, based on previous important outcomes on other pharmaceutical preparations, to be tested as potential anticancer agent. Treatments by 2-5 mu M DPS-2 of several CRC and melanoma cell lines bearing either BRAF or KRAS mutations have shown a remarkable effect on cell viability in 2D and 3D cultures. More detailed analysis has shown that DPS-2 can kill cancer cells by apoptosis, reducing at the same time their autophagy properties. After testing activities of several signaling pathways, the compound was found to have a dual inhibition of two major proliferative/survival pathways, MEK/ERK and PI3K/AKT, in both CRC and melanoma, thus providing a mechanistic evidence for its potent anticancer activity. Antitumor activity of DPS-2 was further validated in vivo, as DPS-2 treatment of mouse xenografts of Colo-205 colorectal cancer cells remarkably reduced their tumor formation properties. Our findings suggest that DPS-2 has significant anti-KRAS/ anti-BRAF mutant CRC activity in preclinical models, potentially providing a novel treatment strategy for these difficult-to-treat tumors, which needs to be further exploited.	[Goulielmaki, Maria; Assimomytis, Nikos; Taki, Eleni; Christodoulou, Ioannis; Zoumpourlis, Vassilis; Pintzas, Alexandros; Papahatjis, Demetris] Natl Hellen Res Fdn, Athens 11636, Greece; [Rozanc, Jan; Alexopoulos, Leonidas G.] TEPA Lefkippos Demokritos, 15343 Ag Paraskevi, Athens, Greece; [Alexopoulos, Leonidas G.] Natl Tech Univ Athens, Sch Mech Engn, Zografos 15780, Greece; [Rozanc, Jan] Univ Luxembourg, Life Sci Res Unit, Belvaux, Luxembourg		Papahatjis, D (corresponding author), Vas Konstantinou 48, Athens 11635, Greece.	dpapah@eie.gr	Alexopoulos, Leonidas/AAN-1148-2021	Rozanc, Jan/0000-0003-4283-6087; ASSIMOMYTIS, NIKOS/0000-0003-3589-9995; Alexopoulos, Leonidas G/0000-0003-0425-166X	European Regional Development Fund of the European Union under the O.P. Competitiveness, Entrepreneurship and Innovation NSRF 2007-2013; European Regional Development Fund of the European Union under Regional Operational Program of Attica (STHENOS project within GSRT'S KRIPIS) [MIS 447985]; EU Horizon 2020-Mel-Plex [642295]; Hellenic Foundation for Research and Innovation (HFRI) [2400]; General Secretariat for Research and Technology (GSRT)Greek Ministry of Development-GSRT [2400]; project "STHENOS-b'' - Operational Programme "Competitiveness, Entrepreneurship and Innovation" (NSRF 2014-2020) [MIS 5002398]; EU (European Regional Development Fund)	This work was supported by Greece and the European Regional Development Fund of the European Union under the O.P. Competitiveness, Entrepreneurship and Innovation NSRF 2007-2013 and the Regional Operational Program of Attica (STHENOS project MIS 447985 within GSRT'S KRIPIS) and the grant EU Horizon 2020-Mel-Plex (grant no. 642295). The salary of the Phd candidate M.G. was supported by the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT) under the HFRI PhD Fellowship grant (GA no. 2400). We also acknowledge support of this work by the project "STHENOS-b'' (MIS 5002398), which is funded by the Operational Programme "Competitiveness, Entrepreneurship and Innovation" (NSRF 2014-2020) and cofinanced by Greece and the EU (European Regional Development Fund).	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Oncol.	JUL	2019	12	7					932	950		10.1016/j.tranon.2019.04.005			19	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IB2SL	WOS:000470118900008	31096110	Green Published, gold			2022-04-25	
J	Huang, YH; Lei, J; Yi, GH; Huang, FY; Li, YN; Wang, CC; Sun, Y; Dai, HF; Tan, GH				Huang, Yong-Hao; Lei, Jing; Yi, Guo-Hui; Huang, Feng-Ying; Li, Yue-Nan; Wang, Cai-Chun; Sun, Yan; Dai, Hao-Fu; Tan, Guang-Hong			Coroglaucigenin induces senescence and autophagy in colorectal cancer cells	CELL PROLIFERATION			English	Article							CARDIAC-GLYCOSIDES; NATURAL-PRODUCTS; CELLULAR SENESCENCE; DRUG DISCOVERY; EVOLVING ROLE; THERAPY; CYCLE; CDK4; NEUROBLASTOMA; INHIBITION	Objectives: Coroglaucigenin (CGN), a natural product isolated from Calotropis gigantean by our research group, has been identified as a potential anti-cancer agent. However, the molecular mechanisms involved remain poorly understood. Materials and methods: Cell viability and cell proliferation were detected by MTT and BrdU assays. Flow cytometry, SA-beta-gal assay, western blotting and immunofluorescence were performed to determine CGN-induced apoptosis, senescence and autophagy. Western blotting, siRNA transfection and coimmunoprecipitation were carried out to investigate the mechanisms of CGN-induced senescence and autophagy. The anti-tumour activities of combination therapy with CGN and chloroquine were observed in mice tumour models. Results: We demonstrated that CGN inhibits the proliferation of colorectal cancer cells both in vitro and in vivo. We showed that the inhibition of cell proliferation by CGN is independent of apoptosis, but is associated with cell-cycle arrest and senescence in colorectal cancer cells. Notably, CGN induces protective autophagy that attenuates CGN-mediated cell proliferation. Functional studies revealed that CGN disrupts the association of Hsp90 with both CDK4 and Akt, leading to CDK4 degradation and Akt dephosphorylation, eventually resulting in senescence and autophagy, respectively. Combination therapy with CGN and chloroquine resulted in enhanced anti-tumour effects in vivo. Conclusions: Our results demonstrate that CGN induces senescence and autophagy in colorectal cancer cells and indicate that combining it with an autophagy inhibitor may be a novel strategy suitable for CGN-mediated anti-cancer therapy.	[Huang, Yong-Hao; Lei, Jing; Yi, Guo-Hui; Huang, Feng-Ying; Li, Yue-Nan; Wang, Cai-Chun; Sun, Yan; Tan, Guang-Hong] Hainan Med Coll, Key Lab Trop Dis & Translat Med, Minist Educ, Haikou, Hainan, Peoples R China; [Huang, Yong-Hao; Lei, Jing; Yi, Guo-Hui; Huang, Feng-Ying; Li, Yue-Nan; Wang, Cai-Chun; Sun, Yan; Tan, Guang-Hong] Hainan Med Coll, Hainan Prov Key Lab Trop Med, Haikou, Hainan, Peoples R China; [Dai, Hao-Fu] Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Haikou, Hainan, Peoples R China; [Yi, Guo-Hui] Hainan Med Coll, Publ Res Lab, Haikou, Hainan, Peoples R China		Sun, Y; Tan, GH (corresponding author), Hainan Med Coll, Key Lab Trop Dis & Translat Med, Minist Educ, Haikou, Hainan, Peoples R China.; Sun, Y; Tan, GH (corresponding author), Hainan Med Coll, Hainan Prov Key Lab Trop Med, Haikou, Hainan, Peoples R China.; Dai, HF (corresponding author), Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Haikou, Hainan, Peoples R China.	18712798207@163.com; daihaofu@itbb.org.cn; tanhoho@163.com		Tan, Guang-Hong/0000-0002-6406-0331	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC)	National Natural Science Foundation of China	Acosta JC, 2012, TRENDS CELL BIOL, V22, P211, DOI 10.1016/j.tcb.2011.11.006; Anders L, 2011, CANCER CELL, V20, P620, DOI 10.1016/j.ccr.2011.10.001; Campaner S, 2010, NAT CELL BIOL, V12, P54, DOI 10.1038/ncb2004; Cerella C, 2013, MITOCHONDRION, V13, P225, DOI 10.1016/j.mito.2012.06.003; Collado M, 2010, NAT REV CANCER, V10, P51, DOI 10.1038/nrc2772; Elgendy M, 2011, MOL CELL, V42, P23, DOI 10.1016/j.molcel.2011.02.009; Garcia-Prat L, 2016, NATURE, V529, P37, DOI 10.1038/nature16187; Gewirtz DA, 2014, CANCER RES, V74, P647, DOI 10.1158/0008-5472.CAN-13-2966; Gheorghiade M, 2006, CIRCULATION, V113, P2556, DOI 10.1161/CIRCULATIONAHA.105.560110; Gordaliza M, 2007, CLIN TRANSL ONCOL, V9, P767, DOI 10.1007/s12094-007-0138-9; Green DR, 2014, CELL, V157, P65, DOI 10.1016/j.cell.2014.02.049; He CC, 2009, ANNU REV GENET, V43, P67, DOI 10.1146/annurev-genet-102808-114910; Janku F, 2011, NAT REV CLIN ONCOL, V8, P528, DOI 10.1038/nrclinonc.2011.71; Jiang SH, 2017, NATURE, V544, P460, DOI 10.1038/nature22032; Jung CH, 2010, FEBS LETT, V584, P1287, DOI 10.1016/j.febslet.2010.01.017; Kang C, 2016, AUTOPHAGY, V12, P898, DOI 10.1080/15548627.2015.1121361; Koehn FE, 2005, NAT REV DRUG DISCOV, V4, P206, DOI 10.1038/nrd1657; Kroemer G, 2010, MOL CELL, V40, P280, DOI 10.1016/j.molcel.2010.09.023; Lee YJ, 2014, NATURE, V510, P547, DOI 10.1038/nature13267; Liu DH, 2011, BIOL PHARM BULL, V34, P1072, DOI 10.1248/bpb.34.1072; Liu R, 2014, AUTOPHAGY, V10, P1241, DOI 10.4161/auto.28912; Lorenz OR, 2014, MOL CELL, V53, P941, DOI 10.1016/j.molcel.2014.02.003; Mahalingam D, 2009, BRIT J CANCER, V100, P1523, DOI 10.1038/sj.bjc.6605066; Malumbres M, 2009, NAT REV CANCER, V9, P153, DOI 10.1038/nrc2602; Maoyuan W, 2008, MODERN PHARM RES, V1, P4; Marino G, 2014, NAT REV MOL CELL BIO, V15, P81, DOI 10.1038/nrm3735; McConkey DJ, 2000, CANCER RES, V60, P3807; Mishra BB, 2011, EUR J MED CHEM, V46, P4769, DOI 10.1016/j.ejmech.2011.07.057; Molenaar JJ, 2008, CANCER RES, V68, P2599, DOI 10.1158/0008-5472.CAN-07-5032; Newman RA, 2008, MOL INTERV, V8, P36, DOI 10.1124/mi.8.1.8; Otto T, 2017, NAT REV CANCER, V17, P93, DOI 10.1038/nrc.2016.138; Prassas I, 2008, NAT REV DRUG DISCOV, V7, P926, DOI 10.1038/nrd2682; Puyol M, 2010, CANCER CELL, V18, P63, DOI 10.1016/j.ccr.2010.05.025; Rader J, 2013, CLIN CANCER RES, V19, P6173, DOI 10.1158/1078-0432.CCR-13-1675; Roninson IB, 2003, CANCER RES, V63, P2705; Sherr CJ, 2016, CANCER DISCOV, V6, P353, DOI 10.1158/2159-8290.CD-15-0894; Shi LS, 2010, J NAT PROD, V73, P1214, DOI 10.1021/np9005212; Sun M, 2017, ONCOTARGET, V8, P32807, DOI 10.18632/oncotarget.16454; Tian LM, 2011, EXP DERMATOL, V20, P836, DOI 10.1111/j.1600-0625.2011.01324.x; VanArsdale T, 2015, CLIN CANCER RES, V21, P2905, DOI 10.1158/1078-0432.CCR-14-0816; Wu CH, 2007, P NATL ACAD SCI USA, V104, P13028, DOI 10.1073/pnas.0701953104; Yang PM, 2010, CANCER RES, V70, P7699, DOI 10.1158/0008-5472.CAN-10-1626; Young ARJ, 2009, GENE DEV, V23, P798, DOI 10.1101/gad.519709; Yu QY, 2006, CANCER CELL, V9, P23, DOI 10.1016/j.ccr.2005.12.012; Zhang H, 2004, J MOL MED, V82, P488, DOI 10.1007/s00109-004-0549-9; Zhang HL, 2016, TRENDS MOL MED, V22, P671, DOI 10.1016/j.molmed.2016.06.001; Zou XH, 2002, GENE DEV, V16, P2923, DOI 10.1101/gad.1033002	47	8	8	1	7	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0960-7722	1365-2184		CELL PROLIFERAT	Cell Prolif.	AUG	2018	51	4							e12451	10.1111/cpr.12451			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	GO3UR	WOS:000439922800007	29484762	Green Published			2022-04-25	
J	Cao, X; Yang, M; Wei, RC; Zeng, Y; Gu, JF; Huang, WD; Yang, DQ; Li, HL; Ding, M; Wei, N; Zhang, KJ; Xu, B; Liu, XR; Qian, QJ; Liu, XY				Cao, X.; Yang, M.; Wei, R-C; Zeng, Y.; Gu, J-F; Huang, W-D; Yang, D-Q; Li, H-L; Ding, M.; Wei, N.; Zhang, K-J; Xu, B.; Liu, X-R; Qian, Q-J; Liu, X-Y			Cancer targeting Gene-Viro-Therapy of liver carcinoma by dual-regulated oncolytic adenovirus armed with TRAIL gene	GENE THERAPY			English	Article						cancer targeting Gene-Viro-Therapy; dual-regulated oncolytic adenovirus; tumor necrosis factor-related apoptosis-inducing ligand; autophagy; apoptosis	HUMAN HEPATOCELLULAR-CARCINOMA; PROGRAMMED CELL-DEATH; ANTITUMOR-ACTIVITY; ALPHA-FETOPROTEIN; TUMOR-CELLS; COLORECTAL-CANCER; SURVIVIN PROMOTER; MALIGNANT GLIOMA; HUMAN HEPATOMA; SV40 ENHANCER	Liver cancer is a common and aggressive malignancy, but available treatment approaches remain suboptimal. Cancer targeting Gene-Viro-Therapy (CTGVT) has shown excellent anti-tumor effects in a preclinical study. CTGVT takes advantage of both gene therapy and virotherapy by incorporating an anti-tumor gene into an oncolytic virus vector. Potent anti-tumor activity is achieved by virus replication and exogenous expression of the anti-tumor gene. A dual-regulated oncolytic adenoviral vector designated Ad.AFP.E1A.E1B (Delta 55) (Ad.AFP.D55 for short thereafter) was constructed by replacing the native viral E1A promoter with the simian virus 40 enhancer/alpha-fetoprotein (AFP) composite promoter (AFPep) based on an E1B-55K-deleted construct, ZD55. Ad.AFP.D55 showed specific replication and cytotoxicity in AFP-positive hepatoma cells. It also showed enhanced safety in normal cells when compared with the mono-regulated vector ZD55. To improve the anti-hepatoma activities of the virus, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene was introduced into Ad.AFP.D55. Ad.AFP.D55-TRAIL exhibited remarkable anti-tumor activities in vitro and in vivo. Treatment with Ad.AFP.D55-TRAIL can induce both autophagy owing to the Ad.AFP.D55 vector and caspase-dependent apoptosis owing to the TRAIL protein. Therefore, Ad.AFP.D55-TRAIL could be a potential anti-hepatoma agent with anti-tumor activities due to AFP-specific replication and TRAIL-induced apoptosis. Gene Therapy (2011) 18, 765-777; doi:10.1038/gt.2011.16; published online 17 March 2011	[Cao, X.; Gu, J-F; Huang, W-D; Yang, D-Q; Li, H-L; Ding, M.; Wei, N.; Zhang, K-J; Liu, X-R; Liu, X-Y] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China; [Yang, M.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA; [Wei, R-C] Guangxi Normal Univ, Sch Life Sci, Guilin, Peoples R China; [Zeng, Y.] Chinese Acad Sci, Inst Pasteur Shanghai, Mol Virol Lab, Shanghai 200031, Peoples R China; [Li, H-L] Southwestern Univ, Chongqing Engn Res Ctr Floriculture, Dept Hort & Garden, Chongqing, Peoples R China; [Xu, B.] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gen Surg, Shanghai 200092, Peoples R China; [Qian, Q-J; Liu, X-Y] Zhejiang Sci Tech Univ, Xinyuan Inst Med & Biotechnol, Hangzhou, Zhejiang, Peoples R China; [Qian, Q-J] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Gene & Virus Therapy, Shanghai, Peoples R China		Liu, XY (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yueyang Rd, Shanghai 200031, Peoples R China.	xyliu@sibs.ac.cn			National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30623003]; Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [06DZ22032]; National Basic Research Program of China (973 Program)National Basic Research Program of China [2004 CB51804]; Hi-Tech Research Development Program of China (863 Program)National High Technology Research and Development Program of China [2007AA 021006]; Chinese Academy of ScienceChinese Academy of Sciences [KSCX2-YW-R -09, R-04]; Zhejiang Sci-Tech UniversityZhejiang University of Science & Technology [0616033]	We are grateful to Professor Mu-Jun Zhao for providing the EGFP-LC3 plasmid, Professor Hong-Bin Ji for providing the BEAS-2B cell line, Professor You-Cheng Xu for critical reading the manuscript, Dr Han Di for help with the molecular cloning and Ms Lan-Ying Sun for help with the cell culture. This study was supported by grants from the National Nature Science Foundation of China (No. 30623003), the Science and Technology Commission of Shanghai Municipality (No. 06DZ22032), the National Basic Research Program of China (973 Program) (No. 2004 CB51804), the Hi-Tech Research Development Program of China (863 Program) (No. 2007AA 021006), the Key Project of the Chinese Academy of Science (No. KSCX2-YW-R -09, R-04) and the Zhejiang Sci-Tech University Grant 0616033.	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AUG	2011	18	8					765	777		10.1038/gt.2011.16			13	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine	806CE	WOS:000293779500003	21412282	Bronze			2022-04-25	
J	Zhang, J; Yang, SZ; Xu, B; Wang, T; Zheng, Y; Liu, F; Ren, FG; Jiang, J; Shi, HT; Zou, BC; Lu, XL; Lu, SM; Dong, L				Zhang, Jing; Yang, Suzhen; Xu, Bing; Wang, Ting; Zheng, Ying; Liu, Fei; Ren, Fenggang; Jiang, Jiong; Shi, Haitao; Zou, Baicang; Lu, Xiaolan; Lu, Shemin; Dong, Lei			p62 functions as an oncogene in colorectal cancer through inhibiting apoptosis and promoting cell proliferation by interacting with the vitamin D receptor	CELL PROLIFERATION			English	Article						apoptosis; colorectal cancer; proliferation; SQSTM1; p62; vitamin D receptor	DOWN-REGULATION; ACTIVATION; CARCINOGENESIS; CROSSROADS; CARCINOMA; AUTOPHAGY; PROTECTS; SYSTEM; CYCLE	Objectives The role of p62 in cancer is controversial. Evidence has shown that p62 is upregulated in different cancers and promotes tumour growth, such as in liver cancer and lung cancer. However, a recent study showed that the downregulation of p62 in hepatic stellate cells (HSCs) promotes hepatocellular carcinoma (HCC) development. How p62 is regulated in colorectal cancer (CRC) remains largely unknown. In this study, we aimed to investigate the roles and molecular mechanisms of p62 in CRC. Materials and Methods The expression levels of p62 in CRC tissues and adjacent non-tumour tissues were determined by immunohistochemistry (IHC). Stable p62-overexpression HCT116 cells and p62-knockdown SW480 cells were established with lentiviral vectors. The role of p62 in CRC was investigated in in vitro and in vivo functional studies. The relationship between p62 and the vitamin D receptor (VDR) was investigated by coimmunoprecipitation (Co-IP) assays. Results p62 was significantly upregulated in CRC, and a high p62 level was an independent risk factor for a poor prognosis in CRC patients. p62 promoted CRC migration and invasion by inhibiting apoptosis and promoting cell proliferation in vitro, and p62 aggravated tumour growth and metastasis in vivo. Co-IP assays indicated that p62 interacts with the VDR and may target the NRF2-NQO1 axis. Conclusions Our study suggested that p62 functions as an oncogene in CRC through inhibiting apoptosis and promoting cell proliferation by interacting with the VDR.	[Zhang, Jing; Yang, Suzhen; Wang, Ting; Zheng, Ying; Jiang, Jiong; Shi, Haitao; Zou, Baicang; Dong, Lei] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Digest Dis & Gastrointestinal Motil Res Room, Xian, Shaanxi, Peoples R China; [Xu, Bing] Xi An Jiao Tong Univ, Dept Digest Dis & Gastrointestinal Motil Res Room, Xian, Shaanxi, Peoples R China; [Liu, Fei] Xi An Jiao Tong Univ, Coll Stomatol, Clin Res Ctr Shanxi Prov Dent & Maxillofacial Dis, Xian, Shaanxi, Peoples R China; [Ren, Fenggang] Xi An Jiao Tong Univ, Natl Local Joint Engn Res Ctr Precis Surg & Regen, Xian, Shaanxi, Peoples R China; [Lu, Xiaolan] Shanghai Pudong Hosp, Fudan Affiliated Pudong Med Ctr, Dept Digest Dis, Shanghai, Peoples R China; [Lu, Shemin] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Xian, Shaanxi, Peoples R China		Dong, L (corresponding author), Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Digest Dis & Gastrointestinal Motil Res Room, Xian, Shaanxi, Peoples R China.; Lu, SM (corresponding author), Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Xian, Shaanxi, Peoples R China.	lushemin@xjtu.edu.cn; dong556@126.com	Lu, Shemin/AAI-6479-2021; Ren, Fenggang/A-1942-2015; Lu, Shemin/M-3350-2018	Lu, Shemin/0000-0002-5535-8320; Ren, Fenggang/0000-0002-9239-9279; Lu, Shemin/0000-0001-8250-850X	Central government guide the development of local science and technology special funds [2016ZY-HM-01]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81801310]; Key research and development program of shanxi province [2017SF-100, 2018ZDXMSF-055]; Shanxi provincial science & technology plan project [2016KTZDSF02-02]	Central government guide the development of local science and technology special funds, Grant/Award Number: 2016ZY-HM-01; National Natural Science Foundation of China, Grant/Award Number: 81801310; Key research and development program of shanxi province, Grant/Award Number: 2017SF-100 and 2018ZDXMSF-055; Shanxi provincial science & technology plan project, Grant/Award Number: 2016KTZDSF02-02	Aleem E, 2004, CELL CYCLE, V3, P35; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Merchan BB, 2017, J STEROID BIOCHEM, V167, P203, DOI 10.1016/j.jsbmb.2016.11.020; Bendris N, 2015, CELL CYCLE, V14, P1786, DOI 10.1080/15384101.2014.998085; Binefa G, 2014, WORLD J GASTROENTERO, V20, P6786, DOI 10.3748/wjg.v20.i22.6786; Bressenot A, 2009, J HISTOCHEM CYTOCHEM, V57, P289, DOI 10.1369/jhc.2008.952044; Chandel N, 2012, AM J PHYSIOL-CELL PH, V303, pC607, DOI 10.1152/ajpcell.00076.2012; Duran A, 2008, CANCER CELL, V13, P343, DOI 10.1016/j.ccr.2008.02.001; Duran A, 2016, CANCER CELL, V30, P595, DOI 10.1016/j.ccell.2016.09.004; Evan GI, 2001, NATURE, V411, P342, DOI 10.1038/35077213; Ferrer-Mayorga G, 2017, GUT, V66, P1449, DOI 10.1136/gutjnl-2015-310977; Galluzzi L, 2014, CELL, V159, P1263, DOI 10.1016/j.cell.2014.11.006; Gearhart J, 2007, NEW ENGL J MED, V357, P1469, DOI 10.1056/NEJMp078126; Grant WB, 2006, ANTICANCER RES, V26, P2687; Hanahan D, 2000, CELL, V100, P57, DOI 10.1016/S0092-8674(00)81683-9; Inami Y, 2011, J CELL BIOL, V193, P275, DOI 10.1083/jcb.201102031; Kaur J, 2015, NAT REV MOL CELL BIO, V16, P461, DOI 10.1038/nrm4024; Lamkanfi M, 2010, INT J BIOCHEM CELL B, V42, P21, DOI 10.1016/j.biocel.2009.09.013; Lee LR, 2013, CANCER PREV RES, V6, P731, DOI 10.1158/1940-6207.CAPR-12-0493; Majewski K, 2018, J BIOL REG HOMEOS AG, V32, P321; Matthews D, 2010, J STEROID BIOCHEM, V121, P362, DOI 10.1016/j.jsbmb.2010.03.061; Moan J, 2008, P NATL ACAD SCI USA, V105, P668, DOI 10.1073/pnas.0710615105; Moscat J, 2009, CELL, V137, P1001, DOI 10.1016/j.cell.2009.05.023; Murray A, 2017, ENDOCR-RELAT CANCER, V24, P181, DOI 10.1530/ERC-16-0463; Nakai K, 2014, AM J HYPERTENS, V27, P586, DOI 10.1093/ajh/hpt160; Nakayama S, 2017, CANCER MED-US, V6, P1264, DOI 10.1002/cam4.1093; Plum LA, 2010, NAT REV DRUG DISCOV, V9, P941, DOI 10.1038/nrd3318; Prentice A, 2008, NUTR REV, V66, pS153, DOI 10.1111/j.1753-4887.2008.00100.x; Riachy R, 2006, APOPTOSIS, V11, P151, DOI 10.1007/s10495-006-3558-z; Shen JL, 2017, OXID MED CELL LONGEV, V2017, DOI 10.1155/2017/9091879; Soung YH, 2003, ONCOGENE, V22, P8048, DOI 10.1038/sj.onc.1206727; Umemura A, 2016, CANCER CELL, V29, P935, DOI 10.1016/j.ccell.2016.04.006; Wei Z, 2018, CELL, V173, P1135, DOI 10.1016/j.cell.2018.04.013; Yamamoto M, 2018, PHYSIOL REV, V98, P1169, DOI 10.1152/physrev.00023.2017; Yao TB, 2015, ANTIOXID REDOX SIGN, V22, P633, DOI 10.1089/ars.2014.5887; Ye CF, 2018, J BIOL REG HOMEOS AG, V32, P497; Zhang C, 2016, LIVER INT, V36, P68, DOI 10.1111/liv.12888; Zhang YB, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.77; Zheng Y, 2017, BONE RES, V5, DOI 10.1038/boneres.2017.23	39	12	15	3	11	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0960-7722	1365-2184		CELL PROLIFERAT	Cell Prolif.	MAY	2019	52	3							e12585	10.1111/cpr.12585			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	IA0TW	WOS:000469271700021	30793399	Green Published, gold			2022-04-25	
J	Lachenmayer, A; Toffanin, S; Cabellos, L; Alsinet, C; Hoshida, Y; Villanueva, A; Minguez, B; Tsai, HW; Ward, SC; Thung, S; Friedman, SL; Llovet, JM				Lachenmayer, Anja; Toffanin, Sara; Cabellos, Laia; Alsinet, Clara; Hoshida, Yujin; Villanueva, Augusto; Minguez, Beatriz; Tsai, Hung-Wen; Ward, Stephen C.; Thung, Swan; Friedman, Scott L.; Llovet, Josep M.			Combination therapy for hepatocellular carcinoma: Additive preclinical efficacy of the HDAC inhibitor panobinostat with sorafenib	JOURNAL OF HEPATOLOGY			English	Article						Hepatocellular carcinoma; Liver cancer; Histone modification; Signaling pathways; Molecular therapies	HISTONE DEACETYLASE INHIBITORS; TARGETED THERAPIES; COLORECTAL-CANCER; LBH589; EXPRESSION; SIGNATURE; AUTOPHAGY; RELAPSE; MODELS; GROWTH	Background & Aims: Hepatocellular carcinoma (HCC) is a heterogeneous cancer in which sorafenib is the only approved systemic therapy. Histone deacetylases (HDAC) are commonly dysregulated in cancer and therefore represent promising targets for therapies, however their role in HCC pathogenesis is still unknown. We analyzed the expression of 11 HDACs in human HCCs and assessed the efficacy of the pan-HDAC inhibitor panobinostat alone and in combination with sorafenib in preclinical models of liver cancer. Methods: Gene expression and copy number changes were analyzed in a cohort of 334 human HCCs, while the effects of panobinostat and sorafenib were evaluated in three liver cancer cell lines and a murine xenograft model. Results: Aberrant HDAC expression was identified and validated in 91 and 243 HCCs, respectively. Upregulation of HDAC3 and HDAC5 mRNAs was significantly correlated with DNA copy number gains. Inhibiting HDACs with panobinostat led to strong anti-tumoral effects in vitro and vivo, enhanced by the addition of sorafenib. Cell viability and proliferation declined, while apoptosis and autophagy increased. Panobinostat increased histone H3 and HSP90 acetylation, downregulated BIRC5 (survivin) and upregulated CDH1. Combination therapy with panobinostat and sorafenib significantly decreased vessel density, and most significantly decreased tumor volume and increased survival in HCC xenografts. Conclusions: Aberrant expression of several HDACs and copy number gains of HDAC3 and HDAC5 occur in HCC. Treatment with panobinostat combined with sorafenib demonstrated the highest preclinical efficacy in HCC models, providing the rationale for clinical studies with this novel combination. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.	[Lachenmayer, Anja; Toffanin, Sara; Cabellos, Laia; Alsinet, Clara; Minguez, Beatriz; Tsai, Hung-Wen; Ward, Stephen C.; Thung, Swan; Friedman, Scott L.; Llovet, Josep M.] Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, Div Liver Dis,Dept Med,Tisch Canc Inst,Dept Patho, New York, NY 10029 USA; [Lachenmayer, Anja] Univ Hosp Dusseldorf, Dept Gen Visceral & Pediat Surg, Dusseldorf, Germany; [Toffanin, Sara] Natl Canc Inst, Dept Surg & Expt Oncol, Hepatooncol Grp, I-20133 Milan, Italy; [Alsinet, Clara; Villanueva, Augusto; Llovet, Josep M.] Univ Barcelona, CIBERehd, IDIBAPS, Barcelona Clin Liver Canc Grp BCLC,Translat Res L, Catalonia, Spain; [Alsinet, Clara; Villanueva, Augusto; Llovet, Josep M.] Univ Barcelona, CIBERehd, IDIBAPS, Liver Unit,Hosp Clin, Catalonia, Spain; [Hoshida, Yujin] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA; [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain		Llovet, JM (corresponding author), Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, Div Liver Dis,Dept Med,Tisch Canc Inst,Dept Patho, Box 1123,1425 Madison Ave,Room 11-70, New York, NY 10029 USA.	Josep.Llovet@mssm.edu	Augusto, Villanueva/F-9378-2012; Llovet, Josep M/ABB-6264-2021; Cabellos, Laia/L-4629-2017; Hoshida, Yujin/R-7513-2019; Llovet, Josep M/D-4340-2014; Ward, Stephen/C-5222-2013; Mínguez, Beatriz/N-4456-2014	Augusto, Villanueva/0000-0003-3585-3727; Llovet, Josep M/0000-0003-0547-2667; Llovet, Josep M/0000-0003-0547-2667; Mínguez, Beatriz/0000-0002-7276-9666	Bayer Pharmaceutical; NIH Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1RO1DK37340, 1RO1DK56621]; US National Institutes of Diabetes and Digestive and Kidney DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [1R01DK076986-01]; European CommissionEuropean CommissionEuropean Commission Joint Research Centre [259744]; Samuel Waxman Cancer Research Foundation; Spanish National Health InstituteSpanish Government [SAF-2010-16055]; Landon Foundation-American Association for Cancer Research; German Research Foundation (DFG)German Research Foundation (DFG); National Cancer Institute, Milan, ItalyUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI); Instituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Commission; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK056621, R01DK037340, R01DK076986] Funding Source: NIH RePORTER; ICREAICREA Funding Source: Custom	Prof. Llovet has a Consultancy Agreement and received research support from Bayer Pharmaceutical. The other authors have no conflict of interest to declare.; The underlying research reported in this study was funded by the NIH Institutes of Health.; Josep M Llovet is supported by grants from the US National Institutes of Diabetes and Digestive and Kidney Diseases (1R01DK076986-01), the European Commission's Framework Programme 7 (HEPTROMIC, proposal No. 259744), the Samuel Waxman Cancer Research Foundation and the Spanish National Health Institute (SAF-2010-16055). The study was supported by the Landon Foundation-American Association for Cancer Research Innovator Award for International Collaboration in Cancer Research. Scott Friedman has grants from the National Institutes of Health (1RO1DK37340, 1RO1DK56621). Anja Lachenmayer was supported by a fellowship from the German Research Foundation (DFG) and Sara Toffanin received a fellowship from National Cancer Institute, Milan, Italy. Clara Alsinet is supported by a grant from the Instituto de Salud Carlos III.	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Hepatol.	JUN	2012	56	6					1343	1350		10.1016/j.jhep.2012.01.009			8	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	948OK	WOS:000304512300021	22322234	Green Accepted			2022-04-25	
J	Chang, CT; Hseu, YC; Thiyagarajan, V; Huang, HC; Hsu, LS; Huang, PJ; Liu, JY; Liao, JW; Yang, HL				Chang, Chia-Ting; Hseu, You-Cheng; Thiyagarajan, Varadharajan; Huang, Hui-Chi; Hsu, Li-Sung; Huang, Pei-Jane; Liu, Jer-Yuh; Liao, Jiunn-Wang; Yang, Hsin-Ling			Antrodia salmonea induces G(2) cell-cycle arrest in human triple-negative breast cancer (MDA-MB-231) cells and suppresses tumor growth in athyrnic nude mice	JOURNAL OF ETHNOPHARMACOLOGY			English	Article						Antrodia salmonea; Breast cancer; MDA-MB-231cells; G(2) cell-cycle arrest; Apoptosis; Autophagy	LEUKEMIA HL-60 CELLS; IN-VITRO; HEPATOCELLULAR-CARCINOMA; SELECTIVE-INHIBITION; MEDICINAL MUSHROOM; COLORECTAL-CANCER; COX-2 INHIBITORS; DOWN-REGULATION; PHASE ARREST; APOPTOSIS	Ethnopharmacological relevance: Antrodia salmonea (AS), is a well-known folk medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, and anti-inflammatory effects. Materials and methods: In the present study, we examined the effects of AS on cell-cycle arrest in vitro in MDA-MB-231 cells and on tumor regression in vivo using an athymic nude mice model. Results: AS (0-200 mu g/mL) treatment significantly induced G(2) cell-cycle arrest in MDA-MB-231 cells by reducing the levels of cyclin B1, cyclin A, cyclin E, and CDC2 proteins. In addition, N-acetylcysteine (NAC) pretreatment prevented AS induced G(2) cell-cycle arrest, indicating that ROS accumulation and subsequent cell cycle arrest might be a major mechanism of AS-induced cytotoxicity. Further, AS treatment decreased COX-2 expression and induced PARP cleavage was significantly reversed by NAC pretreatment in MDA-MB-231 cells. The in vivo study results revealed that AS treatment was effective in terms of delaying the tumor incidence and reducing the tumor growth in MDA-MB-231-xenografted nude mice. TUNEL assay, immunohistochemical staining and Western blotting confirmed that AS significantly modulated the xenografted tumor progression as demonstrated by induction of apoptosis, autophagy, and cell-cycle arrest. Conclusion: Our data strongly suggest that Antrodia salmonea could be an anti-cancer agent for human breast cancer.	[Chang, Chia-Ting; Yang, Hsin-Ling] China Med Univ, Coll Biopharmaceut & Food Sci, Inst Nutr, 91 Hsueh Shih Rd, Taichung 40402, Taiwan; [Hseu, You-Cheng; Thiyagarajan, Varadharajan] China Med Univ, Coll Biopharmaceut & Food Sci, Dept Cosmeceut, Cosmeceut, Taichung 40402, Taiwan; [Hseu, You-Cheng; Huang, Pei-Jane] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 41354, Taiwan; [Huang, Hui-Chi] China Med Univ, Sch Chinese Pharmaceut Sci & Chinese Med Resource, Coll Biopharmaceut & Food Sci, Taichung 40402, Taiwan; [Hsu, Li-Sung] Chung Shan Med Univ, Inst Biochem & Biotechnol, Taichung 40402, Taiwan; [Liu, Jer-Yuh] China Med Univ, Grad Inst Canc Biol, Taichung 40402, Taiwan; [Liao, Jiunn-Wang] Natl Chung Hsing Univ, Grad Inst Vet Pathol, Taichung 402, Taiwan		Yang, HL (corresponding author), China Med Univ, Coll Biopharmaceut & Food Sci, Inst Nutr, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.	hlyang@mail.cmu.edu.tw		Liao, Jiunn-Wang/0000-0001-7374-1203	Ministry of Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [MOST-104-2320-B-039-040-MY3, MOST-103-2320-B-039-038-MY3, NSC-103-2622-B-039-001-CC2, CMU103-ASIA-12, CMU 103-ASIA-09]; Asia University; China Medical University, TaiwanChina Medical University	This work was supported by the grants MOST-104-2320-B-039-040-MY3, MOST-103-2320-B-039-038-MY3, NSC-103-2622-B-039-001-CC2, CMU103-ASIA-12, and CMU 103-ASIA-09 from the Ministry of Science and Technology, Asia University, and China Medical University, Taiwan.	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Ethnopharmacol.	JAN 20	2017	196						9	19		10.1016/j.jep.2016.12.018			11	Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine	EJ9ER	WOS:000393529900002	27986611				2022-04-25	
J	Tezcan, G; Garanina, EE; Zhuravleva, MN; Hamza, S; Rizvanov, AA; Khaiboullina, SF				Tezcan, Gulcin; Garanina, Ekaterina E.; Zhuravleva, Margarita N.; Hamza, Shaimaa; Rizvanov, Albert A.; Khaiboullina, Svetlana F.			Rab GTPase Mediating Regulation of NALP3 in Colorectal Cancer	MOLECULES			English	Article						colorectal cancer; NALP3; inflammasome signalling; vesicle trafficking pathway; Rab GTPase	NF-KAPPA-B; INFLAMMASOME ACTIVATION; PROTEIN SECRETION; NLRP3; PROGRESSION; MECHANISM; AUTOPHAGY; COLITIS; IDENTIFICATION; MACROPHAGES	The NALP3 inflammasome signaling contributes to inflammation within tumor tissues. This inflammation may be promoted by the vesicle trafficking of inflammasome components and cytokines. Rab5, Rab7 and Rab11 regulate vesicle trafficking. However, the role of these proteins in the regulation of inflammasomes remains largely unknown. To elucidate the role of these Rab proteins in inflammasome regulation, HCT-116, a colorectal cancer (CRC) cell line expressing pDsRed-Rab5 wild type (WT), pDsRed-Rab5 dominant-negative (DN), pDsRed-Rab7 WT, pDsRed-Rab7 DN, pDsRed-Rab11 WT and pDsRed-Rab11 DN were treated with lipopolysaccharide (LPS)/nigericin. Inflammasome activation was analyzed by measuring the mRNA expression of NLRP3, Pro-CASP1, RAB39A and Pro-IL-1 beta, conducting immunofluorescence imaging and western blotting of caspase-1 and analysing the secretion levels of IL-1 beta using enzyme-linked immunosorbent assay (ELISA). The effects of Rabs on cytokine release were evaluated using MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel-Premixed 41 Plex. The findings showed that LPS/nigericin-treated cells expressing Rab5-WT indicated increased NALP3 expression and secretion of the IL-1 beta as compared to Rab5-DN cells. Caspase-1 was localized in the nucleus and cytosol of Rab5-WT cells but was localized in the cytosol in Rab5-DN cells. There were no any effects of Rab7 and Rab11 expression on the regulation of inflammasomes. Our results suggest that Rab5 may be a potential target for the regulation of NALP3 in the treatment of the CRC inflammation.	[Tezcan, Gulcin; Garanina, Ekaterina E.; Zhuravleva, Margarita N.; Hamza, Shaimaa; Rizvanov, Albert A.; Khaiboullina, Svetlana F.] Kazan Fed Univ, Inst Fundamental Med & Biol, Kazan 420008, Russia; [Tezcan, Gulcin] Bursa Uludag Univ, Dept Fundamental Sci, Fac Dent, TR-16240 Bursa, Turkey; [Khaiboullina, Svetlana F.] Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA		Khaiboullina, SF (corresponding author), Kazan Fed Univ, Inst Fundamental Med & Biol, Kazan 420008, Russia.; Khaiboullina, SF (corresponding author), Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA.	gulcintezcan@gmail.com; kathryn.cherenkova@gmail.com; k.i.t.t.1807@gmail.com; shaimaa.hamza@mail.ru; rizvanov@gmail.com; sv.khaiboullina@gmail.com	Hamza, Shaimaa/AAE-4652-2022; Rizvanov, Albert/H-4486-2013; Tezcan, Gulcin/AAH-3843-2020; Zhuravleva, Margarita N/M-3926-2016	Rizvanov, Albert/0000-0002-9427-5739; Zhuravleva, Margarita N/0000-0001-8592-5325; Hamza, Shaimaa/0000-0002-5012-4760; Tezcan, Gulcin/0000-0002-5956-8755	RFBRRussian Foundation for Basic Research (RFBR) [18-34-01000]; Russian Government Program of Competitive Growth of Kazan Federal University; Ministry of Education and Science of Russian FederationMinistry of Education and Science, Russian Federation [0671-2020-0058]	The reported study was funded by RFBR Grant #18-34-01000. This research was supported by the Russian Government Program of Competitive Growth of Kazan Federal University. A.A. Rizvanov was supported by the state assignment no. 0671-2020-0058 of the Ministry of Education and Science of Russian Federation. The study was partially accomplished in the Centre of the National Technology Initiative at the M.M. Shemyakin-Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences.	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J	Aly, RGO; El-Enbaawy, MIH; Abd El-Rahman, SS; Ata, NS				Aly, Rasha G. O.; El-Enbaawy, Mona I. H.; Abd El-Rahman, Sahar S.; Ata, Nagwa S.			Antineoplastic activity of Salmonella Typhimurium outer membrane nanovesicles	EXPERIMENTAL CELL RESEARCH			English	Article						Bacterial outer membrane vesicles; Salmonella, antitumor; Apoptosis; Autophagy; Angiogenesis	ENDOTHELIAL GROWTH-FACTOR; DOWN-REGULATION; VESICLES; CANCER; CELLS; MODELS; INDUCE; CHEMOTHERAPY; EXPRESSION; AUTOPHAGY	Nano-sized Gram-negative bacterial outer membrane vesicles possess unique structural and immunostimulatory effects that could be exploited to regress tumors by alerting the host immune system and reversing the immunosuppressive tumor microenvironment. The current study was conducted to investigate the antitumor activity of the outer membrane vesicles (ST-OMVs) of Salmonella Typhimurium ATCC 14028, in vitro in human colorectal carcinoma (HTC116), breast cancer (MCF-7), and hepatocellular carcinoma (HepG2) cell lines and in vivo in Ehrlich solid carcinoma-bearing mice model either as a mono-immunotherapy or as an adjuvant to a commonly used conventional chemotherapy. In addition, we investigated the safety of ST-OMVs. Adult Swiss albino female mice with transplanted Ehrlich solid carcinoma were treated with either ST-OMVs, paclitaxel or a combination of both. Tumor volume, growth inhibition rate, quantitative RT-PCR of Bax and VEGF genes expression, histopathology and immune-expression of caspase-3, Beclin-1, CD49b and Ki-67 were all analyzed. Our results showed that ST-OMVs significantly decreased tumor volume, significantly increased tumor growth inhibition rate, upregulated the immunohistochemical expression of caspase-3, Beclin-1, and CD49b (enhanced recruitment of NK cells). Furthermore, ST-OMVs down-regulated the expression of Ki-67, increased Bax gene expression and decreased VEGF gene expression as detected by qRT-PCR analysis. Histologically, ST-OMVs promoted apoptosis, decreased tumor invasion and mitotic activities. Moreover, ST-OMVs showed a remarkable cytotoxic activity in various investigated in vitro cancer cell lines. Our findings demonstrate potential antitumor activity of ST-OMVs that might be used as a promising safe antitumor immunotherapy or an adjuvant to conventional chemotherapeutic drugs, resolving some of their problems.	[Aly, Rasha G. O.] Directorate Vet Med, Luxor, Egypt; [El-Enbaawy, Mona I. H.] Fac Vet Med, Dept Microbiol, Cairo, Egypt; [Abd El-Rahman, Sahar S.] Fac Vet Med, Dept Pathol, Cairo, Egypt; [Ata, Nagwa S.] Natl Res Ctr, Dept Microbiol, Cairo, Egypt		Abd El-Rahman, SS (corresponding author), Fac Vet Med, Dept Pathol, Cairo, Egypt.	saharsamirmah@cu.edu.eg		Abd El-Rahman, Sahar S/0000-0001-8638-1737			ABDULAMIR AS, 2013, CANC THER, V8, P10; Alaniz RC, 2007, J IMMUNOL, V179, P7692, DOI 10.4049/jimmunol.179.11.7692; Arruebo Manuel, 2011, Cancers (Basel), V3, P3279, DOI 10.3390/cancers3033279; Bancroft J.D., 2008, THEORY PRACTICE HIST; Barbuti AM, 2015, CANCERS, V7, P2360, DOI 10.3390/cancers7040897; Bincoletto C, 2005, INT IMMUNOPHARMACOL, V5, P679, DOI 10.1016/j.intimp.2004.11.015; Bitto NJ, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18061287; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Buchser WJ, 2012, CANCER RES, V72, P2970, DOI 10.1158/0008-5472.CAN-11-3396; Cespedes M V, 2006, Clin Transl Oncol, V8, P318; Chang WW, 2014, INT J MOL SCI, V15, P14546, DOI 10.3390/ijms150814546; Durrett R, 2013, NOT AMS, V60, P304, DOI [DOI 10.1090/noti953, 10.1090/noti953, DOI 10.1090/NOTI953]; El-Bahy AA., 2012, ADV CANC RES TREAT, V125978, DOI [10.5171/2012.125978, DOI 10.5171/2012.125978]; Ellis TN, 2010, MICROBIOL MOL BIOL R, V74, P81, DOI 10.1128/MMBR.00031-09; Ferrara N, 2004, ONCOLOGIST, V9, P2, DOI 10.1634/theoncologist.9-suppl_1-2; Glas R, 2000, J EXP MED, V191, P129, DOI 10.1084/jem.191.1.129; Harmey JH, 2002, BIOESSAYS, V24, P280, DOI 10.1002/bies.10043; Hiroshima Y, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0134324; Hiroshima Y, 2013, CELL CYCLE, V12, P2774, DOI 10.4161/cc.25872; HSU SM, 1981, J HISTOCHEM CYTOCHEM, V29, P577, DOI 10.1177/29.4.6166661; Huang ST, 2018, INT J ONCOL, V53, P1105, DOI 10.3892/ijo.2018.4449; Jang SC, 2015, SMALL, V11, P456, DOI 10.1002/smll.201401803; Kim OY, 2017, NAT COMMUN, V8, DOI 10.1038/s41467-017-00729-8; Kinouchi Shinichiro, 2003, Yonago Acta Medica, V46, P109; Kiraz Y, 2016, TUMOR BIOL, V37, P8471, DOI 10.1007/s13277-016-5035-9; Lau TM, 1999, MOL HUM REPROD, V5, P57, DOI 10.1093/molehr/5.1.57; Lee CH, 2014, GENE THER, V21, P309, DOI 10.1038/gt.2013.86; Lee JC, 2012, FEMS MICROBIOL LETT, V331, P17, DOI 10.1111/j.1574-6968.2012.02549.x; Lee WH, 2015, EXP MOL MED, V47, DOI 10.1038/emm.2015.59; Liu Q, 2016, SCI REP-UK, V6, DOI 10.1038/srep34776; Liu ZP, 2015, AM J CANCER RES, V5, P792; Maeda H, 2013, ADV DRUG DELIVER REV, V65, P71, DOI 10.1016/j.addr.2012.10.002; Moorthi C, 2011, J PHARM PHARM SCI, V14, P67, DOI 10.18433/J30C7D; Navale AM, 2013, INT J PHARM SCI RES, V4, P19, DOI 10.13040/IJPSR.0975-8232.4(1).19-28; O'Donoghue EJ, 2016, CELL MICROBIOL, V18, P1508, DOI 10.1111/cmi.12655; Ozaslan M, 2011, AFR J BIOTECHNOL, V10, P2375; Park KS, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0011334; Parker H, 2010, INFECT IMMUN, V78, P5054, DOI 10.1128/IAI.00299-10; Peng J, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0112744; Repetto G, 2008, NAT PROTOC, V3, P1125, DOI 10.1038/nprot.2008.75; Rosenberg SA, 2002, J IMMUNOTHER, V25, P218, DOI 10.1097/00002371-200205000-00004; Scholzen T, 2000, J CELL PHYSIOL, V182, P311, DOI 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9; Seidel UJE, 2013, FRONT IMMUNOL, V4, DOI 10.3389/fimmu.2013.00076; Shi CS, 2010, SCI SIGNAL, V3, DOI 10.1126/scisignal.2000751; Sisto F, 2003, INFECT IMMUN, V71, P465, DOI 10.1128/IAI.71.1.465-473.2003; Sorensen EW, 2010, J IMMUNOL, V184, P1858, DOI 10.4049/jimmunol.0903210; Stathis A., 2012, ESMO HDB CLIN PHARM; Talmadge JE, 2007, AM J PATHOL, V170, P793, DOI 10.2353/ajpath.2007.060929; Thay B, 2014, INFECT IMMUN, V82, P4034, DOI 10.1128/IAI.01980-14; Tu DG, 2016, ONCOTARGET, V7, P37513, DOI 10.18632/oncotarget.7038; Wang H, 2001, CLIN CANCER RES, V7, P3613; Yuan JS, 2006, BMC BIOINFORMATICS, V7, DOI 10.1186/1471-2105-7-85; Zhu LY, 2019, CELL MOL BIOL LETT, V24, DOI 10.1186/s11658-019-0164-y; Zuberi A, 2016, ILAR J, V57, P178, DOI 10.1093/ilar/ilw021	54	4	4	1	8	ELSEVIER INC	SAN DIEGO	525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA	0014-4827	1090-2422		EXP CELL RES	Exp. Cell Res.	FEB 1	2021	399	1							112423	10.1016/j.yexcr.2020.112423			11	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	PT7RR	WOS:000608809600004	33338480				2022-04-25	
J	Awi, NJ; Yap, HY; Armon, S; Low, JSH; Peh, KB; Peh, SC; Lee, CS; Teow, SY				Awi, Noel Jacques; Yap, Hooi-Yeen; Armon, Subasri; Low, John Seng-Hooi; Peh, Kaik-Boo; Peh, Suat-Cheng; Lee, C. Soon; Teow, Sin-Yeang			Association between autophagy and KRAS mutation with clinicopathological variables in colorectal cancer patients	MALAYSIAN JOURNAL OF PATHOLOGY			English	Article						Autophagy proteins; KRAS mutation; prognosis; Malaysian; Indonesian; LC3A; LC3B; p62; colorectal cancer	KIRSTEN RAS MUTATIONS; POOR-PROGNOSIS; BIOMARKERS; CELLS	Autophagy is a host defensive mechanism responsible for eliminating harmful cellular components through lysosomal degradation. Autophagy has been known to either promote or suppress various cancers including colorectal cancer (CRC). KRAS mutation serves as an important predictive marker for epidermal growth factor receptor (EGFR)-targeted therapies in CRC. However, the relationship between autophagy and KRAS mutation in CRC is not well-studied. In this single-centre study, 92 formalin-fixed paraffin-embedded (PIPE) tissues of CRC patients (42 Malaysian Chinese and 50 Indonesian) were collected and KRAS mutational status was determined by quantitative PCR (qPCR) (n=92) while the expression of autophagy effector (p62, LC3A and LC3B) was examined by immunohistochemistry (II-IC) (n=48). The outcomes of each were then associated with the clinicopathological variables (n=48). Our findings demonstrated that the female CRC patients have a higher tendency in developing KRAS mutation in the Malaysian Chinese population (p<0.05). Expression of autophagy effector LC3A was highly associated with the tumour grade in CRC (p<0.001) but not with other clinicopathological parameters. Lastly, the survival analysis did not yield a statistically significant outcome. Overall, this small cohort study concluded that KRAS mutation and autophagy effectors are not good prognostic markers for CRC patients.	[Awi, Noel Jacques; Yap, Hooi-Yeen; Peh, Suat-Cheng; Teow, Sin-Yeang] Sunway Univ, Dept Med Sci, Sch Med & Life Sci, Jalan Univ, Subang Jaya 47500, Selangor Darul, Malaysia; [Armon, Subasri] Hosp Kuala Lumpur, Pathol Dept, Jalan Pahang, Kuala Lumpur 50586, Malaysia; [Low, John Seng-Hooi; Peh, Suat-Cheng] Sunway Med Ctr, Jalan Lagoon Selatan, Subang Jaya 47500, Selangor Darul, Malaysia; [Peh, Kaik-Boo] Mahkota Med Ctr, Jalan Merdeka, Melaka 75000, Malaysia; [Lee, C. Soon] Western Sydney Univ, Sch Med, Discipline Pathol, Sydney, NSW, Australia		Teow, SY (corresponding author), Sunway Univ, Subang Jaya 47500, Selangor Darul, Malaysia.	ronaldt@sunway.edu.my	Teow, Sin-Yeang/J-2253-2019	Teow, Sin-Yeang/0000-0002-3824-0224	Sunway University [GRTIN-RSF-SHMS-DMS-03-2020]; National Cancer Council Malaysia (MAKNA) Cancer Research Award [EXT-SIDS-SIHD-MAKNA-2017-01]; Sunway Medical Centre Research Funds [SRC/002/2017/FR, SRC/003/2017/FR]; Sunway University Postgraduate Degree by Research Scholarship	This work was funded by Sunway University Internal Research Grant 2020 (GRTIN-RSF-SHMS-DMS-03-2020) , National Cancer Council Malaysia (MAKNA) Cancer Research Award (CRA) 2016 (EXT-SIDS-SIHD-MAKNA-2017-01) , and Sunway Medical Centre Research Funds (SRC/002/2017/FR and SRC/003/2017/FR) . Noel Jacques Awi and Hooi-Yeen Yap are recipients of Sunway University Postgraduate Degree by Research Scholarship.	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J. Pathol.	AUG	2021	43	2					269	279					11	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	UJ7SV	WOS:000691482100007	34448791				2022-04-25	
J	Nakamura, Y; Arakawa, H				Nakamura, Yasuyuki; Arakawa, Hirofumi			Discovery of Mieap-regulated mitochondrial quality control as a new function of tumor suppressor p53	CANCER SCIENCE			English	Review						Autophagy; cancer metabolism; mitochondrial quality control; reactive oxygen species; tumor suppressor p53	CELL-CYCLE CHECKPOINT; P53-DEPENDENT APOPTOSIS; SV40-TRANSFORMED CELLS; CANCER-CELLS; P53-INDUCIBLE REGULATOR; CANDIDATE MEDIATOR; POTENTIAL MEDIATOR; COLORECTAL-CANCER; OXIDATIVE STRESS; COMPLEX-III	The tumor suppressor p53 gene is frequently mutated in human cancers, and the p53 protein suppresses cancer. However, the mechanism behind the p53-mediated tumor suppression is still unclear. Recently, the mitochondria-eating protein (Mieap) was identified as a p53-inducible protein. Mieap induces the accumulation of lysosomal proteins within mitochondria (Mieap-induced accumulation of lysosome-like organelles within mitochondria, or MALM) in response to mitochondrial damage, and eliminates the oxidized mitochondrial proteins to repair unhealthy mitochondria. Furthermore, Mieap also induces vacuole-like structures (Mieap-induced vacuole, or MIV) to eat and degrade unhealthy mitochondria. Therefore, Mieap controls mitochondrial quality by repairing or eliminating unhealthy mitochondria by MALM or MIV, respectively. This mechanism is not mediated by canonical autophagy. Mieap-deficient Apc(Min/+) mice show strikingly high rates of intestinal tumor development as well as advanced-grade adenomas and adenocarcinomas. The p53/Mieap/BCL2 interacting protein 3 mitochondrial quality control pathway is frequently inactivated in human colorectal cancers. Defects in Mieap-regulated mitochondrial quality control lead to accumulation of unhealthy mitochondria in cancer cells. Cancer-specific unhealthy mitochondria could contribute to cancer development and aggressiveness through mitochondrial reactive oxygen species and altered metabolism. Mieap-regulated mitochondrial quality control is a newly discovered function of p53 that plays a critical role in tumor suppression.	[Nakamura, Yasuyuki; Arakawa, Hirofumi] Natl Canc Ctr, Res Inst, Div Canc Biol, Tokyo, Japan		Arakawa, H (corresponding author), Natl Canc Ctr, Res Inst, Div Canc Biol, Chuo Ku, 5-1-1 Tsukiji, Tokyo 1040045, Japan.	harakawa@ncc.go.jp	Arakawa, Hirofumi/L-3459-2013	Arakawa, Hirofumi/0000-0001-6077-0638	AMEDJapan Agency for Medical Research and Development (AMED) [15ck0106006h0002]; KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [22501021, 23659178, 24240117, 25430124, 25670169]	AMED, (Grant/Award Number: '15ck0106006h0002') KAKENHI, (Grant/Award Number: '22501021','23659178','24240117','25430124','25670169')	Adimoolam S, 2002, P NATL ACAD SCI USA, V99, P12985, DOI 10.1073/pnas.202485699; Arakawa H, 2004, NAT REV CANCER, V4, P978, DOI 10.1038/nrc1504; BARAK Y, 1993, EMBO J, V12, P461, DOI 10.1002/j.1460-2075.1993.tb05678.x; Beloribi-Djefaflia S, 2016, ONCOGENESIS, V5, DOI 10.1038/oncsis.2015.49; 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MAY	2017	108	5					809	817		10.1111/cas.13208			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EW2AH	WOS:000402298000001	28222492	hybrid, Green Published			2022-04-25	
J	Saito, K; Iizuka, Y; Ohta, S; Takahashi, S; Nakamura, K; Saya, H; Yoshida, K; Kawakami, Y; Toda, M				Saito, Katsuya; Iizuka, Yukihiko; Ohta, Shigeki; Takahashi, Satoshi; Nakamura, Kenta; Saya, Hideyuki; Yoshida, Kazunari; Kawakami, Yutaka; Toda, Masahiro			Functional analysis of a novel glioma antigen, EFTUD1	NEURO-ONCOLOGY			English	Article						autophagy; EFTUD1; glioma; ribosome biogenesis; SEREX	SHWACHMAN-DIAMOND-SYNDROME; PROGRAMMED CELL-DEATH; MTOR INHIBITOR RAD001; 60S RIBOSOMAL-SUBUNIT; BREAST-CANCER CELLS; P53-DEPENDENT APOPTOSIS; COLORECTAL-CANCER; TUMOR PROGRESSION; INDUCED AUTOPHAGY; SYNDROME PROTEIN	Background. A cDNA library made from 2 glioma cell lines, U87MG and T98G, was screened by serological identification of antigens by recombinant cDNA expression (SEREX) using serum from a glioblastoma patient. Elongation factor Tu GTP binding domain containing protein 1 (EFTUD1), which is required for ribosome biogenesis, was identified. A cancer microarray database showed overexpression of EFTUD1 in gliomas, suggesting that EFTUD1 is a candidate molecular target for gliomas. Methods. EFTUD1 expression in glioma cell lines and glioma tissue was assessed by Western blot, quantitative PCR, and immunohistochemistry. The effect on ribosome biogenesis, cell growth, cell cycle, and induction of apoptosis and autophagy in glioma cells during the downregulation of EFTUD1 was investigated. To reveal the role of autophagy, the autophagy-blocker, chloroquine (CQ), was used in glioma cells downregulating EFTUD1. The effect of combining CQ with EFTUD1 inhibition in glioma cells was analyzed. Results. EFTUD1 expression in glioma cell lines and tissue was higher than in normal brain tissue. Downregulating EFTUD1 induced G1 cell-cycle arrest and apoptosis, leading to reduced glioma cell proliferation. The mechanism underlying this antitumor effect was impaired ribosome biogenesis via EFTUD1 inhibition. Additionally, protective autophagy was induced by glioma cells as an adaptive response to EFTUD1 inhibition. The antitumor effect induced by the combined treatment was significantly higher than that of either EFTUD1 inhibition or CQ alone. Conclusion. These results suggest that EFTUD1 represents a novel therapeutic target and that the combination of EFTUD1 inhibition with autophagy blockade may be effective in the treatment of gliomas.	[Saito, Katsuya; Takahashi, Satoshi; Yoshida, Kazunari; Toda, Masahiro] Keio Univ, Sch Med, Dept Neurosurg, Tokyo 1608582, Japan; [Iizuka, Yukihiko; Ohta, Shigeki; Toda, Masahiro] Keio Univ, Sch Med, Neuroimmunol Res Grp, Tokyo 1608582, Japan; [Ohta, Shigeki] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan; [Nakamura, Kenta; Kawakami, Yutaka] Keio Univ, Sch Med, Inst Adv Med Res, Div Cellular Signaling, Tokyo 1608582, Japan; [Saya, Hideyuki] Keio Univ, Sch Med, Inst Adv Med Res, Div Gene Regulat, Tokyo 1608582, Japan		Toda, M (corresponding author), Keio Univ, Sch Med, Dept Neurosurg, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.	todam@z2.keio.jp	Ohta, Shigeki/Y-4455-2019; Takahashi, Satoshi/V-7869-2019; nakamura, asuka/S-7235-2016; Kawakami, Yutaka/E-7429-2013; Saya, Hideyuki/J-4325-2013	Ohta, Shigeki/0000-0003-2994-4278; Takahashi, Satoshi/0000-0002-0168-1261; Kawakami, Yutaka/0000-0003-4836-2855; Saya, Hideyuki/0000-0001-6610-1902	Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [22390283]	This research was supported by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (B), Grant number 22390283.	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J	Liu, L; Wang, HJ; Meng, T; Lei, C; Yang, XH; Wang, QS; Jin, B; Zhu, JF				Liu, Lin; Wang, Hai-Jiang; Meng, Tao; Lei, Cheng; Yang, Xin-Hui; Wang, Qi-San; Jin, Bo; Zhu, Jin-Feng			lncRNA GAS5 Inhibits Cell Migration and Invasion and Promotes Autophagy by Targeting miR-222-3p via the GAS5/PTEN-Signaling Pathway in CRC	MOLECULAR THERAPY-NUCLEIC ACIDS			English	Article							COLORECTAL-CANCER; EXPRESSION; MICRORNA	Colorectal cancer (CRC) is a frequently occurring lethal disorder with heterogeneous outcomes and drug responses. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) play a critical role in carcinogenesis. Hence, the aim of this study was to investigate the role of lncRNA growth arrest-specific 5 (GAS5) in CRC cells via mediation of the microRNA-222-3p (miR-222-3p)/GAS5/phosphatase and tensin homolog (PTEN)-signaling pathway. HCT116 and SW480 cells were collected and treated with small interfering (si)-lncRNA GAS5, overexpressing (oe)-lncRNA GAS5, miR222- 3p mimic, miR-222-3p inhibitor, or si-lncRNA GAS5 + miR-222-3p mimic. The miR-222-3p level and mRNA and protein levels of GAS5, Beclin1, light-chain 3B (LC3B), PTEN, and Akt were detected. Besides, cell migration, invasion, and apoptosis as well as acidic vesicular organelles (AVOs) were examined respectively. Xenografts in nude mice were also performed to detect tumorigenesis in vivo. Results suggested that the downregulation of lncRNA GAS5 decreased the expressions of Beclin1, LC3B, and PTEN. When treated with oe-lncRNA GAS5 or miR-222-3p inhibitor, HCT116 and SW480 cells exhibited suppressed invasion and migration abilities and increased apoptotic cells and autophagosome and AVO activities. Moreover, overexpression of GAS5 inhibited the tumorigenesis of CRC cells in vivo. Taken together, lncRNA GAS5 upregulated the expression of PTEN by functioning as a competing endogenous RNA (ceRNA) of miR-222-3p, thus inhibiting CRC cell migration and invasion and promoting cell autophagy.	[Liu, Lin; Wang, Hai-Jiang; Meng, Tao; Lei, Cheng; Yang, Xin-Hui; Wang, Qi-San; Jin, Bo; Zhu, Jin-Feng] Xinjiang Med Univ, Dept Abdomen Surg, Canc Hosp, 789 Suzhou East St, Urumqi 830011, Xinjiang Uygur, Peoples R China		Liu, L (corresponding author), Xinjiang Med Univ, Dept Abdomen Surg, Canc Hosp, 789 Suzhou East St, Urumqi 830011, Xinjiang Uygur, Peoples R China.	13899843593@163.com					Bian DH, 2017, AM J TRANSL RES, V9, P1509; Burada F, 2015, WORLD J GASTRO ONCOL, V7, P271, DOI 10.4251/wjgo.v7.i11.271; Chen G, 2013, NUCLEIC ACIDS RES, V41, pD983, DOI 10.1093/nar/gks1099; Dhar S, 2015, BBA-MOL CELL RES, V1853, P265, DOI 10.1016/j.bbamcr.2014.11.004; Dziki Lukasz, 2015, Pol Przegl Chir, V87, P459, DOI 10.1515/pjs-2015-0088; Gao HL, 2017, CANCER CELL INT, V17, DOI 10.1186/s12935-017-0447-1; Guo C, 2015, J BIOMED SCI, V22, DOI 10.1186/s12929-015-0213-4; Han Y, 2014, ASIAN PAC J CANCER P, V15, P4583, DOI 10.7314/APJCP.2014.15.11.4583; Iman M, 2016, RECENT PAT ANTI-CANC, V11, P434, DOI 10.2174/1574892811999160628114857; Khoshinani HM, 2017, JPN J RADIOL, V35, P664, DOI 10.1007/s11604-017-0679-y; Krell J, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0098561; Kuo TY, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0031587; Li J, 2018, CANCER CELL INT, V18, DOI 10.1186/s12935-017-0478-7; Liu BY, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0087563; Liu SH, 2014, GASTROENTEROLOGY, V147, P847, DOI 10.1053/j.gastro.2014.06.006; Pickard MR, 2015, GENES-BASEL, V6, P484, DOI 10.3390/genes6030484; Rossi Marianna Nicoletta, 2014, Int J Cell Biol, V2014, P473857, DOI 10.1155/2014/473857; Saito Y, 2003, GENE THER, V10, P1961, DOI 10.1038/sj.gt.3302100; Sawai H, 2008, BMC GASTROENTEROL, V8, DOI 10.1186/1471-230X-8-56; Shi YG, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0122679; Sun XW, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0164590; Thomas J, 2015, INT J MOL SCI, V16, P28063, DOI 10.3390/ijms161226080; Tokarz P, 2012, ACTA BIOCHIM POL, V59, P467; Wu SH, 2015, INT J CLIN EXP PATHO, V8, P3882; Xu J, 2017, J ECON ENTOMOL, V110, P683, DOI 10.1093/jee/tow297; Yang Y, 2017, ONCOL LETT, V13, P3151, DOI 10.3892/ol.2017.5841; Yin DD, 2014, MED ONCOL, V31, DOI 10.1007/s12032-014-0253-8; Yuan SJ, 2017, HUM GENE THER, V28, P690, DOI 10.1089/hum.2017.041; Zhao XH, 2015, MOL THER, V23, P1899, DOI 10.1038/mt.2015.170	29	68	70	3	6	CELL PRESS	CAMBRIDGE	50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA	2162-2531			MOL THER-NUCL ACIDS	Mol. Ther.-Nucl. Acids	SEP 6	2019	17						644	656		10.1016/j.omtn.2019.06.009			13	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	JA6XF	WOS:000487984400057	31400607	Green Published, gold			2022-04-25	
J	Hsieh, YY; Lo, HL; Yang, PM				Hsieh, Yao-Yu; Lo, Hsiang-Ling; Yang, Pei-Ming			EZH2 inhibitors transcriptionally upregulate cytotoxic autophagy and cytoprotective unfolded protein response in human colorectal cancer cells	AMERICAN JOURNAL OF CANCER RESEARCH			English	Article						Autophagy; colorectal cancer; ER stress; EZH2; unfolded protein response	ENDOPLASMIC-RETICULUM STRESS; METHYLTRANSFERASE EZH2; BREAST-CANCER; ER STRESS; GENE; DEATH; PHOSPHORYLATION; EXPRESSION; APOPTOSIS; LYMPHOMA	Enhancer of zeste homolog 2 (EZH2) has been emerged as novel anticancer target. Various EZH2 small-molecule inhibitors have been developed in recent years. A major class of EZH2 inhibitors are S-adenosyl-L-methionine (SAM)-competitive inhibitors, such as EPZ005687, EI1, GSK126, UNC1999 and GSK343. Autophagy, a physiological process of self-digestion, is involved in the turnover of proteins or intracellular organelles. It can serve as cytoprotective or cytotoxic function in cancer. Our previous study has found that UNC1999 and GSK343 are potent autophagy inducers. In this study, the underlying molecular mechanisms were further investigated. Our results showed that UNC1999 and GSK343 transcriptionally upregulated autophagy of human colorectal cancer (CRC) cells through inducing LC3B gene expression. Besides, UNC1999/GSK343-induced autophagy was partially dependent on ATG7 but independent to EZH2 inhibition. Microarray and PCR array analyses identified that UNC1999 and GSK343 also induced endoplasmic reticulum (ER) stress and unfolded protein response (UPR). UNC1999/GSK343-induced ER stress/UPR contributed to the survival of cancer cells, which was opposite to UNC1999/GSK343-induced autophagy that promoted cell death.	[Hsieh, Yao-Yu; Lo, Hsiang-Ling; Yang, Pei-Ming] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan; [Hsieh, Yao-Yu; Lo, Hsiang-Ling; Yang, Pei-Ming] Acad Sinica, Taipei, Taiwan; [Hsieh, Yao-Yu] Taipei Meidcal Univ, Shuang Ho Hosp, Div Hematol & Oncol, New Taipei, Taiwan; [Lo, Hsiang-Ling; Yang, Pei-Ming] Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Coll Med Sci & Technol, 250 Wu Hsing St, Taipei 11031, Taiwan		Yang, PM (corresponding author), Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Coll Med Sci & Technol, 250 Wu Hsing St, Taipei 11031, Taiwan.	yangpm@tmu.edu.tw	Yang, Pei-Ming/G-3763-2014	Yang, Pei-Ming/0000-0002-4004-2518	Ministry of Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [MOST103-2311-B-038-003, MOST104-2320-B-038-005]; Taipei Medical University-Shuang Ho Hospital [103TMU-SHH-02, 104TMU-SHH-03]; Research team of prevention and therapy of colorectal cancer in Taipei Medical University [TMU-T104-01]; Comprehensive Cancer Center of Taipei Medical University fund by the Health and welfare surcharge of tobacco products [MOHW105-TDU-B-212-134001]	This work was supported by the Ministry of Science and Technology (MOST103-2311-B-038-003 and MOST104-2320-B-038-005); Taipei Medical University-Shuang Ho Hospital (103TMU-SHH-02 and 104TMU-SHH-03); Research team of prevention and therapy of colorectal cancer in Taipei Medical University (TMU-T104-01); and Comprehensive Cancer Center of Taipei Medical University fund by the Health and welfare surcharge of tobacco products (MOHW105-TDU-B-212-134001).	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J. Cancer Res.		2016	6	8					1661	1680					20	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DW0YQ	WOS:000383369900007	27648357				2022-04-25	
J	Newton, IP; Kenneth, NS; Appleton, PL; Nathke, I; Rocha, S				Newton, Ian P.; Kenneth, Niall S.; Appleton, Paul L.; Naethke, Inke; Rocha, Sonia			Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1 alpha Have an Antagonistic Connection	MOLECULAR BIOLOGY OF THE CELL			English	Article							NF-KAPPA-B; BETA-CATENIN; TUMOR-SUPPRESSOR; CANCER-CELLS; RESPONSIVE ELEMENT; COLORECTAL-CANCER; GENE-EXPRESSION; APC; AUTOPHAGY; PATHWAY	The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines the availability of beta-catenin. Another common feature of solid tumors is the presence of hypoxia as indicated by the up-regulation of hypoxia-inducible factors (HIFs) such as HIF-1 alpha. Here, we demonstrate a novel link between APC and hypoxia and show that APC and HIF-1 alpha antagonize each other. Hypoxia results in reduced levels of APC mRNA and protein via a HIF-1 alpha-dependent mechanism. HIF-1 alpha represses the APC gene via a functional hypoxia-responsive element on the APC promoter. In contrast, APC-mediated repression of HIF-1 alpha requires wild-type APC, low levels of beta-catenin, and nuclear factor-kappa B activity. These results reveal down-regulation of APC as a new mechanism that contributes to the survival advantage induced by hypoxia and also show that loss of APC mutations produces a survival advantage by mimicking hypoxic conditions.	[Kenneth, Niall S.; Rocha, Sonia] Univ Dundee, Coll Life Sci, Wellcome Trust Ctr Gene Regulat & Express, Dundee DD1 5EH, Scotland; [Newton, Ian P.; Appleton, Paul L.; Naethke, Inke] Univ Dundee, Coll Life Sci, Div Cell & Dev Biol, Dundee DD1 5EH, Scotland		Rocha, S (corresponding author), Univ Dundee, Coll Life Sci, Wellcome Trust Ctr Gene Regulat & Express, Dundee DD1 5EH, Scotland.	s.rocha@dundee.ac.uk		Nathke, Inke/0000-0003-2420-4385; KENNETH, NIALL/0000-0001-8528-1021; Rocha, Sonia/0000-0002-2413-4981	Cancer Research UKCancer Research UK; Association for International Cancer Research; Research Council UKUK Research & Innovation (UKRI); University of Dundee; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [G0601098] Funding Source: UKRI; Cancer Research UKCancer Research UK [11243] Funding Source: researchfish; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [G0601098] Funding Source: researchfish	We thank Prof. T. Waldman for providing the IIA beta cells and Dr. O. Sansom for providing the APC-Cre mouse tissue. This study was mainly funded by a Cancer Research UK program grant (to I.P.N., P. L. A., and I.S.N.) and Association for International Cancer Research project grant (to N.S.K.). S. R. is funded by a Research Council UK fellowship, University of Dundee, with additional support from a Medical Research Council New Investigator Research Grant.	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Biol. Cell	NOV 1	2010	21	21					3630	3638		10.1091/mbc.E10-04-0312			9	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	672KR	WOS:000283582400002	20844082	Green Published, Green Submitted			2022-04-25	
J	Hu, YL; Yin, Y; Liu, HY; Feng, YY; Bian, ZH; Zhou, LY; Zhang, JW; Fei, BJ; Wang, YG; Huang, ZH				Hu, Ya-Ling; Yin, Yuan; Liu, He-Yong; Feng, Yu-Yang; Bian, Ze-Hua; Zhou, Le-Yuan; Zhang, Ji-Wei; Fei, Bo-Jian; Wang, Yu-Gang; Huang, Zhao-Hui			Glucose deprivation induces chemoresistance in colorectal cancer cells by increasing ATF4 expression	WORLD JOURNAL OF GASTROENTEROLOGY			English	Article						Glucose deprivation; ATF4; Oxaliplatin; 5-Fluorouracil; Chemoresistance	UNFOLDED PROTEIN RESPONSE; MULTIDRUG-RESISTANCE; CARCINOMA-CELLS; AUTOPHAGY; APOPTOSIS; SURVIVAL; HYPOXIA; PATHWAY; PERK/ATF4/LAMP3-ARM; SENSITIVITY	AIM: To investigate the role of activating transcription factor 4 (ATF4) in glucose deprivation (GD) induced colorectal cancer (CRC) drug resistance and the mechanism involved. METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RTPCR and Western blot were used to detect the mRNA and protein expression of drug resistance gene 1 (MDR1), respectively. RESULTS: GD protected CRC cells from drug-induced apoptosis (oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug resensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.	[Hu, Ya-Ling; Yin, Yuan; Liu, He-Yong; Feng, Yu-Yang; Bian, Ze-Hua; Zhou, Le-Yuan; Zhang, Ji-Wei; Fei, Bo-Jian; Huang, Zhao-Hui] Jiangnan Univ, Affiliated Hosp, Wuxi Oncol Inst, 200 Huihe Rd, Wuxi 214062, Jiangsu, Peoples R China; [Wang, Yu-Gang] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA		Huang, ZH (corresponding author), Jiangnan Univ, Affiliated Hosp, Wuxi Oncol Inst, 200 Huihe Rd, Wuxi 214062, Jiangsu, Peoples R China.	hzhwxsy@126.com	Huang, Zhaohui/S-9410-2019; Yin, Yuan/AAG-1707-2020	Huang, Zhaohui/0000-0002-0117-9976; 	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81000867, 81272299, 81301784, 81301920]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20150004, BK20151108]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [NOJUSRP51619B]; Medical Key Professionals Program of Jiangsu Province [RC2011031]; "333" Talents Project of Jiangsu Province; Hospital Management Center of Wuxi [YGZXM1524]	Supported by National Natural Science Foundation of China, No. 81000867, No. 81272299, No. 81301784 and No. 81301920; Natural Science Foundation of Jiangsu Province, No. BK20150004 and No. BK20151108; the Fundamental Research Funds for the Central Universities, No. NOJUSRP51619B; Medical Key Professionals Program of Jiangsu Province, No. RC2011031; "333" Talents Project of Jiangsu Province, and Hospital Management Center of Wuxi, No. YGZXM1524.	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Gastroenterol.	JUL 21	2016	22	27					6235	6245		10.3748/wjg.v22.i27.6235			11	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	DS4RV	WOS:000380769700012	27468213	hybrid, Green Published			2022-04-25	
J	Fu, XJ; Zhao, WW; Li, KK; Zhou, JY; Chen, XH				Fu, Xiaojing; Zhao, Wenwen; Li, Kangkang; Zhou, Jingyi; Chen, Xuehong			Cryptotanshinone Inhibits the Growth of HCT116 Colorectal Cancer Cells Through Endoplasmic Reticulum Stress-Mediated Autophagy	FRONTIERS IN PHARMACOLOGY			English	Article						cryptotanshinone; colorectal cancer; apoptosis; autophagy; endoplasmic reticulum stress	UNFOLDED-PROTEIN-RESPONSE; INDUCED-APOPTOSIS; PATHWAY; DEATH; ACID	Among cancers, colorectal cancer (CRC) has one of the highest annual incidence and death rates. Considering severe adverse reactions associated with classical chemotherapy medications, traditional Chinese medicines have become potential drug candidates. In the current study, the effects of cryptotanshinone (CPT), a major component of Salvia miltiorrhiza Bunge (Danshen) on CRC and underlying mechanism were explored. First of all, data from in vitro experiments and in vivo zebrafish models indicated that CPT selectively inhibited the growth and proliferation of HCT116 and SW620 cells while had little effect on SW480 cells. Secondly, both ER stress and autophagy were associated with CRC viability regulation. Interestingly, ER stress inhibitor and autophagy inhibitor merely alleviated cytotoxic effects on HCT116 cells in response to CPT stimulation, while have little effect on SW620 cells. The significance of apoptosis, autophagy and ER stress were verified by clinical data from CRC patients. In summary, the current study has revealed the anti-cancer effects of CPT in CRC by activating autophagy signaling mediated by ER stress. CPT is a promising drug candidate for CRC treatment.	[Fu, Xiaojing; Zhao, Wenwen; Li, Kangkang; Zhou, Jingyi; Chen, Xuehong] Qingdao Univ, Sch Basic Med, Qingdao, Peoples R China; [Zhao, Wenwen] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China		Chen, XH (corresponding author), Qingdao Univ, Sch Basic Med, Qingdao, Peoples R China.	chen-xuehong@163.com		chen, xuehong/0000-0003-0102-4023	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81803766]; Key Research and Discovery Program of Shandong Province [2019GSF107072]; Natural Science Foundation of Shandong ProvinceNatural Science Foundation of Shandong Province [ZR2018BH036]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2019M652336]; Shandong Key Research and Development Program Project [2018GSF118124]; Qingdao Postdoctoral Application Research Project	This study was supported by the National Natural Science Foundation of China (81803766), the Key Research and Discovery Program of Shandong Province (2019GSF107072), the Natural Science Foundation of Shandong Province (ZR2018BH036) China Postdoctoral Science Foundation (2019M652336), and the Qingdao Postdoctoral Application Research Project and Shandong Key Research and Development Program Project (2018GSF118124).	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Pharmacol.	JUN 17	2021	12								653232	10.3389/fphar.2021.653232			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	TC5HA	WOS:000668668700001	34220498	gold, Green Published			2022-04-25	
J	Fu, R; Yang, P; Li, ZW; Liu, W; Amin, S; Li, ZY				Fu, Rong; Yang, Peng; Li, Zongwei; Liu, Wen; Amin, Sajid; Li, Zhuoyu			Avenanthramide A triggers potent ROS-mediated anti-tumor effects in colorectal cancer by directly targeting DDX3	CELL DEATH & DISEASE			English	Article							CELL-DEATH; OAT; METABOLISM; MODULATION; AUTOPHAGY; ACIDITY; STRESS	Colorectal cancer (CRC) is a common malignant gastrointestinal tumor with high mortality worldwide. Drug resistance and cytotoxicity to normal cells are the main causes of chemotherapeutic treatment failure in CRC. Therefore, extracting the bioactive compounds from natural products with anti-carcinogenic activity and minimal side-effects is a promising strategy against CRC. The present study aims to evaluate the anti-carcinogenic properties of avenanthramides (AVNs) extracted from oats bran and clarify the underlying molecular mechanisms. We demonstrated that AVNs treatment suppressed mitochondrial bioenergetic generation, resulting in mitochondrial swelling and increased reactive oxygen species (ROS) production. Further study indicated that AVNs treatment significantly reduced DDX3 expression, an oncogenic RNA helicase highly expressed in human CRC tissues. DDX3 overexpression reversed the ROS-mediated CRC apoptosis induced by AVNs. Of note, we identified Avenanthramide A (AVN A) as the effective ingredient in AVNs extracts. AVN A blocked the ATPase activity of DDX3 and induced its degradation by directly binding to the Arg287 and Arg294 residues in DDX3. In conclusion, these innovative findings highlight that AVNs extracts, in particular its bioactive compound AVN A may crack the current hurdles in the way of CRC treatment.	[Fu, Rong; Yang, Peng; Liu, Wen; Amin, Sajid; Li, Zhuoyu] Shanxi Univ, Inst Biotechnol, Key Lab Chem Biol & Mol Engn, Natl Minist Educ, Taiyuan 030006, Shanxi, Peoples R China; [Fu, Rong; Yang, Peng] Shanxi Univ, Inst Biomed Sci, Taiyuan 030006, Shanxi, Peoples R China; [Li, Zongwei] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Ctr Canc Immunol Res, Houston, TX 77030 USA; [Li, Zhuoyu] Shanxi Univ, Sch Life Sci, Taiyuan 030006, Shanxi, Peoples R China		Li, ZY (corresponding author), Shanxi Univ, Inst Biotechnol, Key Lab Chem Biol & Mol Engn, Natl Minist Educ, Taiyuan 030006, Shanxi, Peoples R China.; Li, ZY (corresponding author), Shanxi Univ, Inst Biomed Sci, Taiyuan 030006, Shanxi, Peoples R China.	lzy@sxu.edu.cn	Li, Zongwei/AAM-4135-2021; Amin, Sajid/AAW-6491-2020		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31800657, 31770382]; "1331 Project" Key Innovation Center and Team of Shanxi Province; Shanxi Province Science Foundation for Key Projects [201801D111001]; Shanxi Province Science Foundation for Youths [201601D021107]; Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi [2016121]	This work was supported by the National Natural Science Foundation of China (No. 31800657 and 31770382), "1331 Project" Key Innovation Center and Team of Shanxi Province (Prof. Zhuoyu Li), Shanxi Province Science Foundation for Key Projects (No. 201801D111001), Shanxi Province Science Foundation for Youths (No. 201601D021107), Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (No. 2016121). We are grateful to the product specialists, Rui Zhang and Jiawei Wu from GE Healthcare for their technical assistance in Recognition and recovery of DDX3-bound ingredients and SPR affinity analysis. We also acknowledge to Dr. Jinping Jia and Prof. Jianbin Chao from Scientific Instrument Center of Shanxi University for their assistance on HPLC/MS and 1H NMR.	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AUG 7	2019	10								593	10.1038/s41419-019-1825-5			14	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	IO3LH	WOS:000479281300003	31391454	gold, Green Published			2022-04-25	
J	Zhao, YY; Wang, LF; Wang, YS; Dong, SY; Yang, SJ; Guan, YF; Wu, X				Zhao, Yanyan; Wang, Lufang; Wang, Yanshi; Dong, Siyu; Yang, Shaojie; Guan, Yifu; Wu, Xin			Astragaloside IV inhibits cell proliferation in vulvar squamous cell carcinoma through the TGF-beta/Smad signaling pathway	DERMATOLOGIC THERAPY			English	Article						apoptosis; Astragaloside IV; autophagy; proliferation; TGF-beta; Smad pathway; vulvar squamous cell carcinoma	COLORECTAL-CANCER; CHINESE MEDICINE; DOWN-REGULATION; APOPTOSIS; LINES; G1	Objective To explore the inhibition of the proliferation of vulvar squamous cell carcinoma (VSCC) by astragaloside IV. Methods MTT examined the cell proliferation of VSCC. Flow cytometry analyzed cell cycle and apoptosis. Western blot assay detected the expression of some relevant proteins. Results AS-IV reduced the proliferation of SW962 cells in a concentration- and time-dependent manner, induced cell-cycle arresting in G0/G1 phase, as demonstrated by the up-regulation of P53 and P21 expression, and the down-regulation of cyclin D1 expression. AS-IV enhanced the expression of Bax and cleaved-caspase 3, and suppressed Bcl-2 and Bcl-xl expression, which resulted in apoptosis increased. Furthermore, the expression of Beclin-1 and LC3-B was upregulated and that of P62 was downregulated, which suggested that AS-IV could increase the incidence of autophagy in SW962 cells. After inhibiting autophagy by 3-methyladenine (3-MA), cell apoptosis decreased upon AS-IV treatment. Similarly, TGF-beta 1 stimulated SW962 cells, cell proliferation enhanced, and the expression of TGF-beta RII and Smad4 was decreased. Furthermore, the expression of proteins that promote apoptosis and autophagy decreased. After AS-IV treatment, the expression levels of the above proteins exhibited the opposite effect. Conclusion AS-IV inhibits cell proliferation and induces apoptosis and autophagy through the TGF-beta/Smad signaling pathway in VSCC.	[Zhao, Yanyan; Wang, Lufang; Wang, Yanshi; Dong, Siyu; Yang, Shaojie; Wu, Xin] China Med Univ, Dept Gynecol, Affiliated Hosp 1, Shenyang 110001, Liaoning, Peoples R China; [Guan, Yifu] China Med Univ, Dept Biochem & Mol Biol, Shenyang, Liaoning, Peoples R China		Wu, X (corresponding author), China Med Univ, Dept Gynecol, Affiliated Hosp 1, Shenyang 110001, Liaoning, Peoples R China.	xinwu.1964@aliyun.com		Zhao, yanyan/0000-0002-6940-2206			Bertoli C, 2013, NAT REV MOL CELL BIO, V14, P518, DOI 10.1038/nrm3629; Canavan TP, 2002, AM FAM PHYSICIAN, V66, P1269; Fei ZW, 2016, J CLIN BIOCHEM NUTR, V58, P105, DOI 10.3164/jcbn.15-64; Hill-Daniel Jamie, 2015, FP Essent, V438, P31; Ikushima H, 2010, NAT REV CANCER, V10, P415, DOI 10.1038/nrc2853; Jiang K, 2017, INT IMMUNOPHARMACOL, V42, P195, DOI 10.1016/j.intimp.2016.10.001; Kaminska B., 2016, ACTA BIOCHIM POL, V52, P329; Kao ST, 2001, LIFE SCI, V69, P1485, DOI 10.1016/S0024-3205(01)01226-7; Li B, 2017, BIOCHEM BIOPH RES CO, V491, P98, DOI 10.1016/j.bbrc.2017.07.052; Li FL, 2012, EVID-BASED COMPL ALT, V2012, DOI 10.1155/2012/956107; Li M, 2017, NEUROSCI LETT, V639, P114, DOI 10.1016/j.neulet.2016.12.046; Lin SC, 2016, INT J BIOCHEM CELL B, V71, P24, DOI 10.1016/j.biocel.2015.12.003; Luo XC, 2016, INT IMMUNOPHARMACOL, V35, P22, DOI 10.1016/j.intimp.2016.03.020; Ma YH, 2015, INT J MOL MED, V35, P1667, DOI 10.3892/ijmm.2015.2188; Maiuri MC, 2007, NAT REV MOL CELL BIO, V8, P741, DOI 10.1038/nrm2239; Maiuri MC, 2007, EMBO J, V26, P2527, DOI 10.1038/sj.emboj.7601689; Martelossi C. G. C., 2016, EUR CYTOKINE NETW, V27, P81; Ren S, 2013, J TRADIT CHIN MED, V33, P413, DOI 10.1016/S0254-6272(13)60189-2; Schiemann WP, 2007, EXPERT REV ANTICANC, V7, P609, DOI 10.1586/14737140.7.5.609; SCHMIDT W, 1992, GEBURTSH FRAUENHEILK, V52, P462, DOI 10.1055/s-2007-1023789; Song Y, 2011, PHYTOTHER RES, V25, P909, DOI 10.1002/ptr.3354; Wang LF, 2018, MOL MED REP, V17, P4299, DOI 10.3892/mmr.2018.8455; Wang SX, 2018, BIOMED PHARMACOTHER, V102, P1037, DOI 10.1016/j.biopha.2018.03.127; Wang Y., 2016, SHANXI MED J, V45, P627; Wu ZM, 2018, CANCER MED-US, V7, P1546, DOI 10.1002/cam4.1419; Xia QM, 2014, J CANCER RES THER, V10, P1, DOI 10.4103/0973-1482.139741; Xie T, 2016, ONCOL RES, V24, P447, DOI 10.3727/096504016X14685034103590; Yuan W, 2008, PLANTA MED, V74, P1259, DOI 10.1055/s-2008-1081290; Zhou XJ, 2017, INT IMMUNOPHARMACOL, V42, P18, DOI 10.1016/j.intimp.2016.11.006; Zhu JH, 2018, PHYTOTHER RES, V32, P1289, DOI 10.1002/ptr.6057	30	5	6	0	1	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1396-0296	1529-8019		DERMATOL THER	Dermatol. Ther.	JUL-AUG	2019	32	4							e12802	10.1111/dth.12802			7	Dermatology	Science Citation Index Expanded (SCI-EXPANDED)	Dermatology	IP7SN	WOS:000480248400054	30536730				2022-04-25	
J	Hwang, WC; Kim, MK; Song, JH; Choi, KY; Min, DS				Hwang, Won Chan; Kim, Mi Kyoung; Song, Ju Hyun; Choi, Kang-Yell; Min, Do Sik			Inhibition of phospholipase D2 induces autophagy in colorectal cancer cells	EXPERIMENTAL AND MOLECULAR MEDICINE			English	Article							MAMMALIAN AUTOPHAGY; BREAST-CANCER; MTOR; EXPRESSION; ISOFORM; HOMOLOG; PROTEIN; GROWTH; LC3; PLD	Autophagy is a conserved lysosomal self-digestion process used for the breakdown of long-lived proteins and damaged organelles, and it is associated with a number of pathological processes, including cancer. Phospholipase D (PLD) isozymes are dysregulated in various cancers. Recently, we reported that PLD1 is a new regulator of autophagy and is a potential target for cancer therapy. Here, we investigated whether PLD2 is involved in the regulation of autophagy. A PLD2-specific inhibitor and siRNA directed against PLD2 were used to treat HT29 and HCT116 colorectal cancer cells, and both inhibition and genetic knockdown of PLD2 in these cells significantly induced autophagy, as demonstrated by the visualization of light chain 3 (LC3) puncta and autophagic vacuoles as well as by determining the LC3-II protein level. Furthermore, PLD2 inhibition promoted autophagic flux via the canonical Atg5-, Atg7- and AMPK-Ulk1-mediated pathways. Taken together, these results suggest that PLD2 might have a role in autophagy and that its inhibition might provide a new therapeutic basis for targeting autophagy.	[Hwang, Won Chan; Kim, Mi Kyoung; Song, Ju Hyun; Min, Do Sik] Pusan Natl Univ, Dept Mol Biol, Coll Nat Sci, Pusan 609735, South Korea; [Choi, Kang-Yell; Min, Do Sik] Yonsei Univ, Translat Res Ctr Prot Funct Control, Seoul 120749, South Korea; [Choi, Kang-Yell] Yonsei Univ, Dept Biotechnol, Coll Life Sci & Biotechnol, Seoul 120749, South Korea		Min, DS (corresponding author), Pusan Natl Univ, Dept Mol Biol, Coll Nat Sci, 30 Jangjeon Dong, Pusan 609735, South Korea.	minds@pusan.ac.kr			National Research Foundation of Korea (NRF) - Korean government (MEST)Ministry of Education, Science and Technology, Republic of KoreaNational Research Foundation of KoreaKorean Government [2012002009]; Translational Research Center for Protein Function Control Grant [NSF 2009-0092960]	This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST; No. 2012002009) and a Translational Research Center for Protein Function Control Grant (NSF 2009-0092960). We thank Dr G Velasco (Complutense University), M Komatsu (Tokyo Metropolitan Institute of Medical Science) and M Kundu (St Jude Children's Hospital) for materials.	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J	Fiorito, S; Flahaut, E; Rapino, S; Paolucci, F; Andreola, F; Moroni, N; Pittaluga, E; Zonfrillo, M; Valenti, G; Mastrofrancesco, A; Groppi, F; Sabbioni, E; Bakalis, E; Zerbetto, F; Serafino, A				Fiorito, Silvana; Flahaut, Emmanuel; Rapino, Stefania; Paolucci, Francesco; Andreola, Federica; Moroni, Noemi; Pittaluga, Eugenia; Zonfrillo, Manuela; Valenti, Giovanni; Mastrofrancesco, Arianna; Groppi, Flavia; Sabbioni, Enrico; Bakalis, Evangelos; Zerbetto, Francesco; Serafino, Annalucia			Redox active Double Wall Carbon Nanotubes show intrinsic anti-proliferative effects and modulate autophagy in cancer cells	CARBON			English	Article							METALLIC IMPURITIES; NEURONAL GROWTH; INTERFACING NEURONS; CCVD SYNTHESIS; APOPTOSIS; ELECTROCHEMISTRY; ELECTRODES; OXIDATION; STIMULATION; HYPOXIA	In Double-Walled-Carbon-Nanotubes (DWCNTs) the outer shell screens the inner one from the external environment. As a consequence, the electronic properties of the smaller tube are enhanced and DWCNTs have therefore been advocated for a number of uses. In their raw form they may contain small metallic clusters, left over from the catalytic process, that can give them a redox activity characterized by redox potentials in the range of one hundred millivolts and able to affect biological systems. Indeed, we find that redox active raw-DWCNTs inhibit rat colorectal cancer cell proliferation by blocking cells in the G2 phase through ROS generation by tumor cells. We show that raw-DWCNTs could also modulate autophagy in tumor cells through induction of intracellular acidification. To the best of our knowledge, this is the first time that DWCNTs have been found to inhibit proliferation and modulate autophagy in cancer cells. Our work further supports previous studies that provided promising results on the possibility of future applications of Carbon Nanotubes (CNTs) in nanomedicine. (C) 2014 Elsevier Ltd. All rights reserved.	[Fiorito, Silvana] Univ Roma La Sapienza, Dipartimento Med Clin, I-00185 Rome, Italy; [Flahaut, Emmanuel] Univ Toulouse 3, CNRS CIRIMAT, F-31062 Toulouse, France; [Rapino, Stefania; Paolucci, Francesco; Valenti, Giovanni; Bakalis, Evangelos; Zerbetto, Francesco] Univ Bologna, Dipartimento Chim G Ciamician, I-40126 Bologna, Italy; [Fiorito, Silvana; Andreola, Federica; Moroni, Noemi; Pittaluga, Eugenia; Zonfrillo, Manuela; Serafino, Annalucia] CNR, Inst Translat Pharmacol, I-00133 Rome, Italy; [Mastrofrancesco, Arianna] IRCCS, San Gallicano Dermatol Inst, Rome, Italy; [Groppi, Flavia] Univ Milan, Segrate, MI, Italy; [Groppi, Flavia] Ist Nazl Fis Nucl, Lab Radiochim LASA, Segrate, MI, Italy; [Sabbioni, Enrico] CeSI, Fdn Univ G DAnnunzio, Chieti, Italy		Fiorito, S (corresponding author), Univ Roma La Sapienza, Dipartimento Med Clin, Viale Univ 37, I-00185 Rome, Italy.	silvana.fiorito@uniroma1.it	FLAHAUT, Emmanuel/B-7964-2009; Zerbetto, Francesco/D-2503-2014; Zonfrillo, Manuela/A-3172-2016; Paolucci, Francesco/A-8708-2008; Serafino, Annalucia/AAC-1719-2019; Mastrofrancesco, Arianna/K-2433-2018; Bakalis, Evangelos/AAY-4577-2020; Valenti, Giovanni/M-5876-2017; Groppi, Flavia/S-4052-2019	FLAHAUT, Emmanuel/0000-0001-8344-6902; Zerbetto, Francesco/0000-0002-2419-057X; Zonfrillo, Manuela/0000-0001-6457-2380; Paolucci, Francesco/0000-0003-4614-8740; Serafino, Annalucia/0000-0002-1142-4752; Mastrofrancesco, Arianna/0000-0003-1231-3832; Valenti, Giovanni/0000-0002-6223-2072; Groppi, Flavia/0000-0002-8987-8375; Bakalis, Evangelos/0000-0002-0036-7887			Ambrosi A, 2010, CHEM-EUR J, V16, P1786, DOI 10.1002/chem.200902534; Bottini M, 2006, TOXICOL LETT, V160, P121, DOI 10.1016/j.toxlet.2005.06.020; Chen Y, 2008, CELL DEATH DIFFER, V15, P171, DOI 10.1038/sj.cdd.4402233; Chen Y, 2009, CELL DEATH DIFFER, V16, P1040, DOI 10.1038/cdd.2009.49; Chiche J, 2010, J CELL MOL MED, V14, P771, DOI 10.1111/j.1582-4934.2009.00994.x; Comes F, 2007, CELL DEATH DIFFER, V14, P693, DOI 10.1038/sj.cdd.4402076; 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Wong CH, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0009996; Zhang HY, 2009, TOXICOL SCI, V110, P376, DOI 10.1093/toxsci/kfp101	53	5	5	1	53	PERGAMON-ELSEVIER SCIENCE LTD	OXFORD	THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND	0008-6223	1873-3891		CARBON	Carbon	NOV	2014	78						589	600		10.1016/j.carbon.2014.07.046			12	Chemistry, Physical; Materials Science, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Materials Science	AO6LP	WOS:000341463900061		Green Published, Green Accepted			2022-04-25	
J	Li, DT; Wang, PP; Luo, YH; Zhao, MY; Chen, F				Li, Daotong; Wang, Pengpu; Luo, Yinghua; Zhao, Mengyao; Chen, Fang			Health benefits of anthocyanins and molecular mechanisms: Update from recent decade	CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION			English	Review						Anthocyanins; benefits; mechanism; anti-cancer activity; anti-inflammation activity; neuroprotective activity	E-DEFICIENT MICE; SPINAL-CORD-INJURY; RICH EXTRACT; IN-VITRO; ENDOTHELIAL-CELLS; COLON-CANCER; HEPATOCELLULAR-CARCINOMA; CARDIOVASCULAR-DISEASE; MART. FRUIT; MOUSE MODEL	Anthocyanins are one of the most widespread families of natural pigments in the plant kingdom. Their health beneficial effects have been documented in many in vivo and in vitro studies. This review summarizes the most recent literature regarding the health benefits of anthocyanins and their molecular mechanisms. It appears that several signaling pathways, including mitogen- activated protein kinase, nuclear factor B-k, AMP- activated protein kinase, and Wnt/ beta- catenin, as well as some crucial cellular processes, such as cell cycle, apoptosis, autophagy, and biochemical metabolism, are involved in these beneficial effects and may provide potential therapeutic targets and strategies for the improvement of a wide range of diseases in future. In addition, specific anthocyanin metabolites contributing to the observed in vivo biological activities, structure- activity relationships as well as additive and synergistic efficacy of anthocyanins are also discussed. Abbreviations: ABCA1: ATP- binding cassette transporter A1; ABCG1: ATP- binding cassette transporter G1; ACC: acetyl- CoA carboxylase; ACO: acyl- CoA oxidase; AD: Alzheimer's disease; AIF: apoptosis- inducing factor; AMPK: AMPactivated protein kinase; AP- 1: activator protein- 1; aP2: adipocyte fatty acid binding protein; apo E-/-: apolipoprotein E- deficient; APP: amyloid precursor protein; Atg5: autophagy- related gene 5; ATGL: adipose triglyceride lipase; ATP: adenosine triphosphate; Ab: amyloid- beta peptide; C/ EBP delta: CCAAT/ enhancer- binding protein; COX- 2: cyclooxygenase- 2; CPT1A: carnitine palmitoyltransferase- 1A; CRP: C- reactive protein; eIF2 alpha: eukaryotic initiation factor 2asubunit; Endo G: endonuclease G; ERK: extracellular signal-regulated kinase; FFAs: free fatty acids; FoxO1: forkhead box O1; G6Pase: glucose-6-phosphatase; GFAT: glutamine: fructose 6-phosphate aminotransferase; Glut2: glucose transporter 2; Glut4: glucose transporter 4; GSK3b: glycogen synthase kinase 3 beta; HBP: hexosamine biosynthetic pathway; IL: interleukin; iNOS: inducible nitric oxide synthase; JNK: c-Jun N-terminal kinase; LPL: lipoprotein lipaseand; LPS: lipopolysaccharide; MAPK: mitogen-activated protein kinase; MMP: matrix metalloproteinase; mtGPAT1: mitochondrial acyl-CoA: glycerol-sn-3-phosphate acyltransferase 1; mTOR: mammalian target of rapamycin; NF-kB: nuclear factor kB; NO: nitric oxide; OGD: oxygen-glucose deprivation; oxLDL: oxidative modification of low-density lipoprotein; PARP: poly ADP-ribose polymerase; PCA: protocatechuic acid; PD: Parkinson's disease; PEPCK: phosphoenol pyruvate carboxykinase; PGE(2): prostaglandin E2; PhIP: 2-amino-1-methyl-6-phenylimidazo [ 4,5-b] pyridine; PKCz: protein kinase C z; PPAR gamma: peroxisome proliferator-activated receptor gamma; Pt: petunidin; RCT: reverse cholesterol transport; ROS: reactive oxygen species; RR-ARFs: anthocyanin-rich fractions from red raspberries; SCI: spinal cord injury; SGLT1: sodium-dependent glucose transporter 1; STAT3: signal transducers and activators of transcription 3; TG: triglycerides; TNF: tumor necrosis factor; TRAFs: tumor necrosis factor receptor-associated factors; UCP2: uncoupling protein 2; UDP-GlcNAc: UDP-N-acetylglucosamine production	[Li, Daotong; Wang, Pengpu; Zhao, Mengyao; Chen, Fang] China Agr Univ, Natl Engn Res Ctr Fruit & Vegetable Proc, Key Lab Fruits & Vegetables Proc, Coll Food Sci & Nutr Engn,Minist Agr, Beijing, Peoples R China; [Li, Daotong; Wang, Pengpu; Zhao, Mengyao; Chen, Fang] China Agr Univ, Engn Res Ctr Fruits & Vegetables Proc, Minist Educ, Beijing, Peoples R China; [Luo, Yinghua] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA		Chen, F (corresponding author), China Agr Univ, Coll Food Sci & Nutr Engn, 17,East Qinghua Rd, Beijing 100083, Peoples R China.	chenfangch@sina.com		Zhao, Mengyao/0000-0002-5038-8504	Program for New Century Excellent Talents in University (NCET)Program for New Century Excellent Talents in University (NCET) [12-0520]; National Basic Research Program of China (973 Program)National Basic Research Program of China [2012CB720805]; National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81102152]; National Science & Technology Support Plan of the Chinese Ministry of EducationMinistry of Education, China [2011BAD39B00]	This work was supported by Program for New Century Excellent Talents in University (NCET) No. 12-0520, the National Basic Research Program of China (973 Program) No. 2012CB720805, and the National Natural Science Foundation of China (NSFC) No. 81102152, and the National Science & Technology Support Plan of the Chinese Ministry of Education No. 2011BAD39B00.	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J	Abate, M; Festa, A; Falco, M; Lombardi, A; Luce, A; Grimaldi, A; Zappavigna, S; Sperlongano, P; Irace, C; Caraglia, M; Misso, G				Abate, Marianna; Festa, Agostino; Falco, Michela; Lombardi, Angela; Luce, Amalia; Grimaldi, Anna; Zappavigna, Silvia; Sperlongano, Pasquale; Irace, Carlo; Caraglia, Michele; Misso, Gabriella			Mitochondria as playmakers of apoptosis, autophagy and senescence	SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY			English	Review						Mitochondrion; Metabolism; Apoptosis; Autophagy; Senescence; Cancer	CYTOCHROME-C RELEASE; TUMOR-SUPPRESSOR GENE; BCL-2 FAMILY PROTEINS; BREAST-CANCER CELLS; I-LIKE RECEPTORS; OXIDATIVE STRESS; CELLULAR SENESCENCE; COLORECTAL-CANCER; OUTER-MEMBRANE; DNA-DAMAGE	Mitochondria are the key energy-producing organelles and cellular source of reactive species. They are responsible for managing cell life and death by a balanced homeostasis passing through a network of structures, regulated principally via fission and fusion. Herein we discuss about the most advanced findings considering mitochondria as dynamic biophysical systems playing compelling roles in the regulation of energy metabolism in both physiologic and pathologic processes controlling cell death and survival. Precisely, we focus on the mitochondrial commitment to the onset, maintenance and counteraction of apoptosis, autophagy and senescence in the bioenergetic reprogramming of cancer cells. In this context, looking for a pharmacological manipulation of cell death processes as a successful route for future targeted therapies, there is major biotechnological challenge in underlining the location, function and molecular mechanism of mitochondrial proteins. Based on the critical role of mitochondrial functions for cellular health, a better knowledge of the main molecular players in mitochondria disfunction could be decisive for the therapeutical control of degenerative diseases, including cancer.	[Abate, Marianna; Festa, Agostino; Falco, Michela; Lombardi, Angela; Luce, Amalia; Grimaldi, Anna; Zappavigna, Silvia; Caraglia, Michele; Misso, Gabriella] Univ Campania Luigi Vanvitelli, Dept Precis Med, I-80138 Naples, Italy; [Sperlongano, Pasquale] Univ Campania Luigi Vanvitelli, Sch Med, Unit Gen & Geriatr Surg, I-80137 Naples, Italy; [Irace, Carlo] Univ Naples Federico II, Sch Med, Dept Pharm, Via Domenico Montesano 49, I-80131 Naples, Italy; [Caraglia, Michele] Biogem, IRGS, Via Camporeale, I-83031 Avellino, Italy		Caraglia, M; Misso, G (corresponding author), Univ Campania Luigi Vanvitelli, Dept Precis Med, I-80138 Naples, Italy.; Irace, C (corresponding author), Univ Naples Federico II, Sch Med, Dept Pharm, Via Domenico Montesano 49, I-80131 Naples, Italy.	carlo.irace@unina.it; michele.caraglia@unicampania.it; gabriella.misso@unicampania.it	ABATE, MARIANNA/AAG-4679-2019; Caraglia, Michele/AAK-4569-2020	Caraglia, Michele/0000-0003-2408-6091; ABATE, MARIANNA/0000-0002-2297-3706; 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Cell Dev. Biol.	FEB	2020	98				SI		139	153		10.1016/j.semcdb.2019.05.022			15	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	KD5XE	WOS:000507938200016	31154010		Y	N	2022-04-25	
J	Jing, Z; Sui, XB; Yao, JL; Xie, JS; Jiang, LM; Zhou, YB; Pan, HM; Han, WD				Jing, Zhao; Sui, Xinbing; Yao, Junlin; Xie, Jiansheng; Jiang, Liming; Zhou, Yubin; Pan, Hongming; Han, Weidong			SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKII gamma/AKT-mediated pathway	CANCER LETTERS			English	Article						SKF-96365; Autophagy; Apoptosis; Colorectal cancer; CaMKII	OPERATED CA2+ ENTRY; KINASE II-GAMMA; CYTOCHROME-C; THERAPEUTIC TARGET; CRITICAL REGULATOR; BREAST-CANCER; AKT/MTOR; RELEASE; STIM1; MITOCHONDRIA	Store-operated Ca2+ entry (SOCE) inhibitors are emerging as an attractive new generation of anti-cancer drugs. Here, we report that SKF-96365, an SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. In the meantime, SKF-96365 also induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibited the calcium/calmodulin-dependent protein kinase Il gamma(CaMKIl gamma)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKII gamma or ART abolished the effects of SKF-96365 on cancer cells, suggesting a critical role of the CaMKII gamma/AKT signaling pathway in SFK-96365-induced biological effects. Moreover, Hydroxychloroquine (HCQ), an FDA-approved drug used to inhibit autophagy, could significantly augment the anti-cancer effect of SFK-96365 in a mouse xenograft model. To our best knowledge, this is the first report to demonstrate that calcium/CaMKII gamma/AKT signaling can regulate apoptosis and autophagy simultaneously in cancer cells, and the combination of the SOCE inhibitor SKF-96365 with autophagy inhibitors represents a promising strategy for treating patients with colorectal cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.	[Jing, Zhao; Sui, Xinbing; Yao, Junlin; Jiang, Liming; Pan, Hongming; Han, Weidong] Zhejiang Univ, Coll Med, Dept Med Oncol, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China; [Xie, Jiansheng; Pan, Hongming; Han, Weidong] Zhejiang Univ, Sch Med, Biomed Res Ctr, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China; [Zhou, Yubin] Texas A&M Univ, Hlth Sci Ctr, Ctr Translat Canc Res, Inst Biosci & Technol, Houston, TX 77030 USA		Pan, HM; Han, WD (corresponding author), Zhejiang Univ, Coll Med, Dept Med Oncol, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China.; Pan, HM; Han, WD (corresponding author), Zhejiang Univ, Sch Med, Biomed Res Ctr, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China.	hongmingpan@gmail.com; hanwd@zju.edu.cn	Zhou, Yubin/D-4748-2011	Zhou, Yubin/0000-0001-7962-0517	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272593, 81572592, 81372621, 81572361]; Zhejiang Medicines and Health Platform Program [2014ZDA012]; National Health and Family Planning Commission Fund [2015112271]; Zhejiang Province Preeminence Youth Fund [LR16H160001]; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM112003] Funding Source: NIH RePORTER	This work was supported by the National Natural Science Foundation of China (81272593, 81572592), the Zhejiang Medicines and Health Platform Program (2014ZDA012), and the National Health and Family Planning Commission Fund (2015112271) to H. Pan, the National Natural Science Foundation of China (81372621, 81572361), and Zhejiang Province Preeminence Youth Fund (LR16H160001) to W. Han.	Balasubramaniam SL, 2015, J BIOL CHEM, V290, P12463, DOI 10.1074/jbc.M114.629519; Booth LA, 2014, CELL SIGNAL, V26, P549, DOI 10.1016/j.cellsig.2013.11.028; Cai R, 2009, INT J CANCER, V125, P2281, DOI 10.1002/ijc.24551; Chai SJ, 2015, ONCOTARGET, V6, P16069, DOI 10.18632/oncotarget.3866; Chai SJ, 2014, CANCER LETT, V344, P119, DOI 10.1016/j.canlet.2013.10.022; Elmore SP, 2001, FASEB J, V15, P2286, DOI 10.1096/fj.01-0206fje; Elmore SP, 2004, ARCH BIOCHEM BIOPHYS, V422, P145, DOI 10.1016/j.abb.2003.12.031; Fahrenholtz CD, 2014, ONCOTARGET, V5, P9007, DOI 10.18632/oncotarget.2346; Fedida-Metula S, 2012, CARCINOGENESIS, V33, P740, DOI 10.1093/carcin/bgs021; Feldman B, 2010, CELL CALCIUM, V47, P525, DOI 10.1016/j.ceca.2010.05.002; Gu Y, 2012, BLOOD, V120, P4829, DOI 10.1182/blood-2012-06-434894; Guthrie H. 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MAR 28	2016	372	2					226	238		10.1016/j.canlet.2016.01.006			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DE8RN	WOS:000370904500010	26803057	Green Accepted			2022-04-25	
J	Wei, JC; Yang, P; Li, WL; Hei, F; Zeng, SQ; Zhang, T; Zhong, JB; Huang, D; Chen, ZP; Wang, CX; Chen, HC; Hu, H; Cao, J				Wei, Jianchang; Yang, Ping; Li, Wanglin; Hei, Feng; Zeng, Shanqi; Zhang, Tong; Zhong, Junbin; Huang, Di; Chen, Zhuanpeng; Wang, Chengxing; Chen, Huacui; Hu, He; Cao, Jie			Gambogic acid potentiates the chemosensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting proliferation and inducing apoptosis	EXPERIMENTAL AND THERAPEUTIC MEDICINE			English	Article; Proceedings Paper	2nd Workshop on Paediatric Virology	OCT 08, 2016	Athens, GREECE			gambogic acid; 5-fluorouracil; colorectal cancer; chemosensitivity; apoptosis	THYMIDYLATE SYNTHASE; SURVIVIN EXPRESSION; IN-VITRO; P53; LEUCOVORIN; CARCINOMA; MODULATION; AUTOPHAGY; LYMPHOMA; PATHWAY	Chemotherapy using 5-fluorouracil (5-FU) for colorectal cancer (CRC) has low specificity and response rates, leading to severe side effects. Gambogic acid (GA), a traditional Chinese medicine, has multi-targeted anticancer effects, including growth inhibition and apoptosis induction. However, it is unclear whether a combination of 5-FU and GA has synergistic anticancer effects in CRC cells. In this study, SW480 and HCT116 human CRC cells and human intestinal epithelial cells (IECs) were treated with different concentrations of 5-FU, GA or 5-FU+GA. A Cell Counting kit-8 assay was conducted to quantify cell proliferation. The combination index (CI) was calculated and the median-effect principle was applied to analyze the interaction between 5-FU and GA. Flow cytometry was used to determine the percentage of cells undergoing apoptosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were applied to measure P53, survivin and thymidylate synthase (TS) mRNA and protein levels. It was found that 5-FU+GA more pronouncedly inhibited cell growth and induced apoptosis, compared with either monotherapy. CI values <1 indicated the synergistic effects of the drugs. 5-FU+GA further decreased P53, survivin and TS mRNA and protein levels in the two CRC cell lines compared with single drugs, whereas increased P53 protein levels were observed in HCT116 cells. Moreover, 5-FU+GA did not increase cytotoxicity to IECs. These results demonstrate that GA enhances the anticancer effects of 5-FU on CRC cells. Combined treatment with 5-FU and GA is effective and safe for CRC cells, and may become a promising chemotherapy treatment.	[Wei, Jianchang; Yang, Ping; Li, Wanglin; Hei, Feng; Zeng, Shanqi; Zhang, Tong; Zhong, Junbin; Huang, Di; Chen, Zhuanpeng; Wang, Chengxing; Chen, Huacui; Hu, He; Cao, Jie] Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Gen Surg, Guangzhou Digest Dis Ctr, 1 Panfu Rd, Guangzhou 510180, Guangdong, Peoples R China; [Wang, Chengxing] Sun Yat Sen Univ, Dept Gastrointestinal Surg, Affiliated Jiangmen Hosp, Jiangmen 529000, Guangdong, Peoples R China		Cao, J (corresponding author), Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Gen Surg, Guangzhou Digest Dis Ctr, 1 Panfu Rd, Guangzhou 510180, Guangdong, Peoples R China.	czhongt@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272556]	This study was supported by a grant from the National Natural Science Foundation of China (grant no. 81272556). The authors thank MedSci (Shanghai, China) for English editing.	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Ther. Med.	FEB	2017	13	2					662	668		10.3892/etm.2017.4021			7	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED); Conference Proceedings Citation Index - Science (CPCI-S)	Research & Experimental Medicine	EL9GH	WOS:000394927900047	28352348	gold, Green Published			2022-04-25	
J	Wang, Z; Chen, Q; Li, B; Xie, JM; Yang, XD; Zhao, K; Wu, Y; Ye, ZY; Chen, ZR; Qin, ZH; Xing, CG				Wang, Zhong; Chen, Qiang; Li, Bin; Xie, Jia-ming; Yang, Xiao-dong; Zhao, Kui; Wu, Yong; Ye, Zhen-yu; Chen, Zheng-rong; Qin, Zheng-hong; Xing, Chun-gen			Escin-induced DNA damage promotes escin-induced apoptosis in human colorectal cancer cells via p62 regulation of the ATM/gamma H2AX pathway	ACTA PHARMACOLOGICA SINICA			English	Article						escin, p62, DNA damage, ATM/gamma H2AX pathway; apoptosis, colorectal cancer; HCT116 cells; HCT8 cells	FACTOR-KAPPA-B; BETA-ESCIN; MULTIDRUG-RESISTANCE; IN-VITRO; LUNG ADENOCARCINOMA; P62/SEQUESTOSOME 1; DRUG-RESISTANCE; TUMOR-CELLS; AUTOPHAGY; PROLIFERATION	Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 mu g/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and gamma H2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escininduced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced an escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/gamma H2AX pathway-mediated escin-induced DNA damage and apoptosis.	[Wang, Zhong; Chen, Qiang; Xie, Jia-ming; Yang, Xiao-dong; Zhao, Kui; Wu, Yong; Ye, Zhen-yu; Chen, Zheng-rong; Xing, Chun-gen] Soochow Univ, Affiliated Hosp 2, Dept Gen Surg, Suzhou 215007, Peoples R China; [Li, Bin] First Peoples Hosp Wu Jiang, Dept Gen Surg, Suzhou 215200, Peoples R China; [Qin, Zheng-hong] Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Suzhou 215123, Peoples R China; [Qin, Zheng-hong] Soochow Univ, Lab Aging & Nervous Dis, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Jiangsu Key Lab Prevent & Translat Med Geriatr Di, Suzhou 215123, Peoples R China		Xing, CG (corresponding author), Soochow Univ, Affiliated Hosp 2, Dept Gen Surg, Suzhou 215007, Peoples R China.; Qin, ZH (corresponding author), Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Suzhou 215123, Peoples R China.; Qin, ZH (corresponding author), Soochow Univ, Lab Aging & Nervous Dis, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Jiangsu Key Lab Prevent & Translat Med Geriatr Di, Suzhou 215123, Peoples R China.	qinzhenhong@suda.edu.cn; xingcgchn@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672970]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20160338]; Suzhou Key Medical Center [LCZX201505]; Projects of Suzhou Technology Bureau [SS201753, SYS201552, SZS201618]; Second Affiliated Hospital of Soochow University Preponderant Clinic Discipline Group Project Funding; Invigorating Health Care through Science, Technology and Education (Jiangsu Provincial Medical Youth Talent) [QNRC2016249]; Graduate Student Scientific Research Innovation Projects of Jiangsu Province [KYCX17_1999]; National Natural Science Youth Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81602613]	This work was partially supported by the National Natural Science Foundation of China (No 81672970), the Natural Science Foundation of Jiangsu Province (No BK20160338), and supported by Suzhou Key Medical Center (No LCZX201505), the Projects of Suzhou Technology Bureau (No SS201753, SYS201552, SZS201618), the Second Affiliated Hospital of Soochow University Preponderant Clinic Discipline Group Project Funding, the Project of Invigorating Health Care through Science, Technology and Education (Jiangsu Provincial Medical Youth Talent, QNRC2016249) and Graduate Student Scientific Research Innovation Projects of Jiangsu Province (No KYCX17_1999), National Natural Science Youth Foundation of China (No 81602613).	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Sin.	OCT	2018	39	10					1645	1660		10.1038/aps.2017.192			16	Chemistry, Multidisciplinary; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	GY2RU	WOS:000448391500010	29849127	Bronze, Green Published			2022-04-25	
J	Wang, Y; Zhang, JY; Zheng, S				Wang, Yong; Zhang, Jingyu; Zheng, Shuang			The role of XBP-1-mediated unfolded protein response in colorectal cancer progression-a regulatory mechanism associated with lncRNA-miRNA-mRNA network	CANCER CELL INTERNATIONAL			English	Article						Colorectal cancer; XBP-1; Endoplasmic reticulum stress; KCNQ1OT1; XIST	ENDOPLASMIC-RETICULUM; XBP-1; STRESS; APOPTOSIS; AUTOPHAGY; XBP1S	Background We aim to identify the expression and analyze the molecular action of dysregulated lncRNA-miRNA mediated by XBP-1 in colorectal cancer (CRC). Methods Here, we identified XBP-1-mediated dysregulated lncRNAs and miRNAs in CRC by bioinformatics analysis. The expression level of lncRNAs and miRNA was measured using quantitative real time PCR, and the expression of XBP-1, as well as apoptosis-related proteins, were detected by western blot. CCK-8 and TUNEL assays were performed to determine cell proliferation and apoptosis, respectively. Luciferase reporter assay was conducted to verify the binding relationship among lncRNA-miRNA-XBP-1. BALB/c nude mice were inoculated subcutaneously with HCT116 cells to establish tumor-bearing mice model. Histological analysis was carried out by HE staining and immunohistochemical staining. Results Six downregulated lncRNAs (SLFNL1-AS1, KCNQ1OT1, NEAT1, XIST, AC016876.2, AC026362.1), four dysregulated miRNAs (miR-500a-3p, miR-370-3p, miR-2467-3p, miR-512-3p) and upregulated XBP-1 were identified in CRC cell lines. Gain- and loss-of-function experiments showed that overexpression of KCNQ1OT1/XIST promoted cell proliferation and suppressed cell apoptosis. In addition, overexpression of KCNQ1OT1/XIST partly abolished the inhibitory effects of XBP-1u knockdown or tunicamycin, an activator of endoplasmic reticulum stress, on CRC cell viability loss and apoptosis. Furthermore, KCNQ1OT1/XIST aggravated tumor growth in vivo by regulating endoplasmic reticulum stress and cell apoptosis. Conclusions This study has constructed lncRNA-miRNA-mRNA networks based on XBP-1 in CRC, and disclosed the regulatory mechanism of action, providing a set of pivotal biomarkers for future molecular investigation and targeted treatment of CRC.	[Wang, Yong] Nanjing Med Univ, Dept Colorectal Surg, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China; [Zhang, Jingyu] Second Peoples Hosp Lianyungang, Dept Gastrointestinal Oncol, Lianyungang 200023, Jiangsu, Peoples R China; [Zheng, Shuang] Wenzhou Med Univ, Taizhou Peoples Hosp 1, Dept Gen Surg, Huangyan Hosp, 218 Hengjie Rd, Taizhou City 318020, Zhejiang, Peoples R China		Zheng, S (corresponding author), Wenzhou Med Univ, Taizhou Peoples Hosp 1, Dept Gen Surg, Huangyan Hosp, 218 Hengjie Rd, Taizhou City 318020, Zhejiang, Peoples R China.	zszheng2021@163.com		, Shuang/0000-0003-0393-0505			Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Chen XX, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0962-6; Cheng CS, 2018, MED SCI MONITOR, V24, P6331, DOI 10.12659/MSM.908400; Cheng Y, 2019, DIS MARKERS, V2019, DOI 10.1155/2019/7636757; Day LW, 2015, GUT LIVER, V9, P143, DOI 10.5009/gnl14302; Dewal MB, 2015, CHEM BIOL, V22, P1301, DOI 10.1016/j.chembiol.2015.09.006; Dong XH, 2020, FRONT ONCOL, V10, DOI 10.3389/fonc.2020.00160; Fearnhead NS, 2002, BRIT MED BULL, V64, P27, DOI 10.1093/bmb/64.1.27; Feldman DE, 2005, MOL CANCER RES, V3, P597, DOI 10.1158/1541-7786.MCR-05-0221; Gao ZZ, 2019, TECHNOL CANCER RES T, V18, DOI 10.1177/1533033819853237; Hetz C, 2012, NAT REV MOL CELL BIO, V13, P89, DOI 10.1038/nrm3270; Hsu SK, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20102518; Huang C, 2017, SCI ADV, V3, DOI 10.1126/sciadv.1701383; Huang C, 2020, ONCOL REP, V44, P449, DOI 10.3892/or.2020.7639; Ji H, 2019, BIOCHEM BIOPH RES CO, V508, P203, DOI 10.1016/j.bbrc.2018.11.112; Koong AC, 2006, CANCER BIOL THER, V5, P756, DOI 10.4161/cbt.5.7.2973; Lee AH, 2003, MOL CELL BIOL, V23, P7448, DOI 10.1128/MCB.23.21.7448-7459.2003; Leung-Hagesteijn C, 2013, CANCER CELL, V24, P289, DOI 10.1016/j.ccr.2013.08.009; Li Y, 2020, INFLAMMATION, V43, P2264, DOI 10.1007/s10753-020-01295-w; Li ZC, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-018-1012-z; Lin LJ, 2020, DRUG DES DEV THER, V14, P1127, DOI 10.2147/DDDT.S238124; Liu Y, 2017, APOPTOSIS, V22, P544, DOI 10.1007/s10495-016-1334-2; Luo B, 2013, ONCOGENE, V32, P805, DOI 10.1038/onc.2012.130; Ma ZQ, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-08547-0; Mhaidat NM, 2015, J CHEMOTHERAPY, V27, P167, DOI 10.1179/1973947815Y.0000000006; Papaioannou A, 2018, CURR TOP MICROBIOL, V414, P159, DOI 10.1007/82_2017_36; Tirosh B, 2006, J BIOL CHEM, V281, P5852, DOI 10.1074/jbc.M509061200; Wang LY, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20225758; Wang M, 2016, NATURE, V529, P326, DOI 10.1038/nature17041; Wu SD, 2018, BIOCHEM BIOPH RES CO, V500, P530, DOI 10.1016/j.bbrc.2018.04.033; Xiao HQ, 2020, J CELL PHYSIOL, V235, P2881, DOI 10.1002/jcp.29193; Xu M, 2019, J HEMATOL ONCOL, V12, DOI 10.1186/s13045-018-0690-5; Yang L, 2020, J CELL PHYSIOL, DOI 10.1002/jcp.29484; Zhao Y, 2013, CELL RES, V23, P491, DOI 10.1038/cr.2013.2; Zhuang M, 2019, EBIOMEDICINE, V41, P286, DOI 10.1016/j.ebiom.2018.12.049	35	1	1	0	0	BMC	LONDON	CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND		1475-2867		CANCER CELL INT	Cancer Cell Int.	SEP 14	2021	21	1							488	10.1186/s12935-021-02167-5			14	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	UQ1RI	WOS:000695847800001	34521445	Green Published, gold			2022-04-25	
J	Sun, HZ; Wang, RR; Liu, Y; Mei, HT; Liu, XN; Peng, ZH				Sun, Hongze; Wang, Rangrang; Liu, Yuan; Mei, Haitao; Liu, Xueni; Peng, Zhihai			USP11 induce resistance to 5-Fluorouracil in Colorectal Cancer through activating autophagy by stabilizing VCP	JOURNAL OF CANCER			English	Article						USP11; VCP; colorectal cancer; 5-fluorouracil; chemotherapy resistance	SENSITIVITY; PROMOTES; SURVIVAL; THERAPY; VCP/P97; CELLS; CHEMOTHERAPY; MECHANISMS; APOPTOSIS; P53	Chemotherapy plays an important role in the treatment of patients with colorectal cancer (CRC). However, the resistance to chemotherapy severely affects the prognosis of CRC patients and the mechanisms are still poorly understood. Our study investigated the role of ubiquitin-specific protease 11 (USP11) in CRC chemotherapy and found that USP11 could induce resistance to 5-fluorouracil by activating autophagy. A series of in vitro and in vivo experiments revealed that USP11 promoted autophagy through AMPK/Akt/mTOR pathway via stabilizing valosin-containing protein (VCP). Overall, our study demonstrated that USP11 might be valuable to predict the chemotherapeutic sensitivity and improve the prognosis of CRC patients.	[Sun, Hongze; Wang, Rangrang; Liu, Yuan; Mei, Haitao; Liu, Xueni; Peng, Zhihai] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gen Surg, Shanghai, Peoples R China; [Sun, Hongze] Shandong Univ, Qilu Hosp, Dept Gen Surg, Jinan, Peoples R China; [Peng, Zhihai] Xiamen Univ, Sch Med, Xiangan Hosp, Dept Gen Surg, Xiamen, Peoples R China		Liu, XN; Peng, ZH (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gen Surg, Shanghai, Peoples R China.; Peng, ZH (corresponding author), Xiamen Univ, Sch Med, Xiangan Hosp, Dept Gen Surg, Xiamen, Peoples R China.	016543lxn@shgh.cn; pengzhihai1958@163.com		Liu, Yuan/0000-0001-6227-024X	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81530044, 81802343, 81972216]; Shanghai three-year action plan to promote clinical skills and clinical innovation capacity of municipal hospitals [16CR2008A]; Technology Major Project of China [2017ZX10203206]	This project was supported by the National Natural Science Foundation of China (81530044, 81802343, 81972216), Shanghai three-year action plan to promote clinical skills and clinical innovation capacity of municipal hospitals (No.16CR2008A) and Technology Major Project of China Grants (2017ZX10203206).	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Cancer		2021	12	8					2317	2325		10.7150/jca.52158			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	QP9EF	WOS:000624131100015	33758608	Green Published, gold			2022-04-25	
J	Zhang, D; Zhou, Q; Huang, DD; He, L; Zhang, H; Hu, B; Peng, H; Ren, DL				Zhang, Di; Zhou, Qian; Huang, Dandan; He, Lu; Zhang, Heng; Hu, Bang; Peng, Hui; Ren, Donglin			ROS/JNK/c-Jun axis is involved in oridonin-induced caspase-dependent apoptosis in human colorectal cancer cells	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Oridonin; Colorectal cancer; Apoptosis; Caspase; Reactive oxygen species; c-Jun N-Terminal kinase	DRUG-RESISTANCE; EFFECTIVELY REVERSES; REACTIVE OXYGEN; INHIBITION; INDUCTION; ACTIVATION; AUTOPHAGY; PATHWAYS; SURVIVAL; STRESS	Colorectal cancer (CRC) is one of the most common malignant neoplasms with high mortality worldwide. Oridonin, a diterpenoid isolated from the Chinese medicinal herb Rabdosia rubescens, has been proved to have anticancer effect on various types of cancer cells. However, the detailed mechanisms of oridonin in CRC cells remain unclear and if oridonin can overcome 5-FU resistance have not been investigated yet. In this study, we investigated the anticancer effect of oridonin in both 5-FU sensitive and resistant CRC cells and illuminated the underlying mechanisms. We showed that oridonin induced proliferation inhibition and caspase-dependent apoptosis in both 5-FU sensitive and resistant CRC cells. Oridonin induced reactive oxygen species (ROS) accumulation in both 5-FU sensitive and resistant CRC cells, which resulted in cell apoptosis as oridonin-induced apoptosis was almost abolished when cells were co-treated with the ROS scavenger N-acetyl-L-cysteine (NAC). Moreover, we found that oridonin induced CRC cell apoptosis via the c-Jun N-terminal kinase (JNK)/c-Jun pathway as oridonin activated JNK/c-Jun pathway and the JNK inhibitor SP600125 restored oridonin-induced apoptosis in CRC cells. Interestingly, when CRC cells were co-treated with NAC, the activation of JNK/c-Jun pathway induced by oridonin was nearly reversed, indicating that oridonin induced JNK/c-Jun pathway activation through the accumulation of ROS. Taken together, these data reveal that oridonin induces apoptosis through the ROS/JNK/c-Jun axis in both 5-FU sensitive and resistant CRC cells, suggesting that oridonin could be a potential agent for CRC treatment. (C) 2019 Elsevier Inc. All rights reserved.	[Zhang, Di; Zhou, Qian; Huang, Dandan; Zhang, Heng; Hu, Bang; Peng, Hui; Ren, Donglin] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Gastrointestinal Surg, Guangzhou, Guangdong, Peoples R China; [Zhang, Di; Zhou, Qian; Huang, Dandan; He, Lu; Zhang, Heng; Hu, Bang; Peng, Hui; Ren, Donglin] Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Inst Gastroenterol, Guangdong Prov Key Lab Colorectal & Pelv Floor Di, Guangzhou, Guangdong, Peoples R China; [He, Lu] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Neurol, Guangzhou, Guangdong, Peoples R China		Ren, DL (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 6, Guangzhou, Guangdong, Peoples R China.	rendl111@163.com			Science and Technology Program of Guangdong [Z20150108201706156]; Natural Science Foundation of GuangdongNational Natural Science Foundation of Guangdong Province [2015A030313165]	This study was supported by the Science and Technology Program of Guangdong (Z20150108201706156) and the Natural Science Foundation of Guangdong (2015A030313165).	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Biophys. Res. Commun.	JUN 4	2019	513	3					594	601		10.1016/j.bbrc.2019.04.011			8	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	HY6RW	WOS:000468258400010	30981511				2022-04-25	
J	Gholizadeh, M; Doustvandi, MA; Mohammadnejad, F; Shadbad, MA; Tajalli, H; Brunetti, O; Argentiero, A; Silvestris, N; Baradaran, B				Gholizadeh, Mahsa; Doustvandi, Mohammad Amin; Mohammadnejad, Fateme; Shadbad, Mahdi Abdoli; Tajalli, Habib; Brunetti, Oronzo; Argentiero, Antonella; Silvestris, Nicola; Baradaran, Behzad			Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?	MOLECULES			English	Article						photodynamic therapy; zinc phthalocyanine; cancer stem cell; colorectal cancer; stemness; prognosis; metastasis	CELLS; PHOTOSENSITIZER; APOPTOSIS	Photodynamic therapy (PDT) is a light-based cancer therapy approach that has shown promising results in treating various malignancies. Growing evidence indicates that cancer stem cells (CSCs) are implicated in tumor recurrence, metastasis, and cancer therapy resistance in colorectal cancer (CRC); thus, targeting these cells can ameliorate the prognosis of affected patients. Based on our bioinformatics results, SOX2 overexpression is significantly associated with inferior disease-specific survival and worsened the progression-free interval of CRC patients. Our results demonstrate that zinc phthalocyanine (ZnPc)-PDT with 12 J/cm(2) or 24 J/cm(2) irradiation can substantially decrease tumor migration via downregulating MMP9 and ROCK1 and inhibit the clonogenicity of SW480 cells via downregulating CD44 and SOX2. Despite inhibiting clonogenicity, ZnPc-PDT with 12 J/cm(2) irradiation fails to downregulate CD44 expression in SW480 cells. Our results indicate that ZnPc-PDT with 12 J/cm(2) or 24 J/cm(2) irradiation can substantially reduce the cell viability of SW480 cells and stimulate autophagy in the tumoral cells. Moreover, our results show that ZnPc-PDT with 12 J/cm(2) or 24 J/cm(2) irradiation can substantially arrest the cell cycle at the sub-G1 level, stimulate the intrinsic apoptosis pathway via upregulating caspase-3 and caspase-9 and downregulating Bcl-2. Indeed, our bioinformatics results show considerable interactions between the studied CSC-related genes with the studied migration- and apoptosis-related genes. Collectively, the current study highlights the potential role of ZnPc-PDT in inhibiting stemness and CRC development, which can ameliorate the prognosis of CRC patients.	[Gholizadeh, Mahsa; Doustvandi, Mohammad Amin; Mohammadnejad, Fateme; Shadbad, Mahdi Abdoli; Baradaran, Behzad] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz 5166614731, Iran; [Shadbad, Mahdi Abdoli] Tabriz Univ Med Sci, Student Res Comm, Tabriz 5166614731, Iran; [Tajalli, Habib] Islamic Azad Univ, Biophoton Res Ctr, Tabriz Branch, Tabriz 5157944533, Iran; [Tajalli, Habib] Univ Tabriz, Res Inst Appl Phys & Astron, Tabriz 5166616471, Iran; [Brunetti, Oronzo; Argentiero, Antonella; Silvestris, Nicola] Ist Nazl Tumori IRCCS, Ist Tumori BariGiovanni Paolo II, I-70124 Bari, Italy; [Silvestris, Nicola] Univ Bari Aldo Moro, Sch Med, Dept Biomed Sci & Human Oncol, I-70124 Bari, Italy; [Baradaran, Behzad] Tabriz Univ Med Sci, Neurosci Res Ctr, Tabriz 5166614731, Iran		Baradaran, B (corresponding author), Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz 5166614731, Iran.; Silvestris, N (corresponding author), Ist Nazl Tumori IRCCS, Ist Tumori BariGiovanni Paolo II, I-70124 Bari, Italy.; Silvestris, N (corresponding author), Univ Bari Aldo Moro, Sch Med, Dept Biomed Sci & Human Oncol, I-70124 Bari, Italy.; Baradaran, B (corresponding author), Tabriz Univ Med Sci, Neurosci Res Ctr, Tabriz 5166614731, Iran.	Gmahsa42@gmail.com; m.amin.dostvandi@gmail.com; fatememohamadnejad@gmail.com; abdoli.med99@gmail.com; habibtajalli@yahoo.com; dr.oronzo.brunetti1983@gmail.com; argentieroantonella@gmail.com; n.silvestris@oncologico.bari.it; baradaranb@tbzmed.ac.ir	Baradaran, Behzad/AAQ-5177-2020; Abdoli Shadbad, Mahdi/AAR-2537-2021	Baradaran, Behzad/0000-0002-8642-6795; Abdoli Shadbad, Mahdi/0000-0003-4865-8779; doustvandi, mohammad amin/0000-0002-3655-2515; Mohammadnejad, Fateme/0000-0002-4107-9689	Apulian Regional Project "Medicina di Precisione"Regione Puglia	This research was funded by the Apulian Regional Project "Medicina di Precisione" to N.S.	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J	Zheng, S; Zhong, YF; Tan, DM; Xu, Y; Chen, HX; Wang, D				Zheng, Sheng; Zhong, Yong-Fu; Tan, De-Ming; Xu, Yue; Chen, Huai-Xiang; Wang, Dan			miR-183-5p enhances the radioresistance of colorectal cancer by directly targeting ATG5	JOURNAL OF BIOSCIENCES			English	Review						ATG5; colorectal cancer; miR-183-5p; radiosensitivity	BREAST-CANCER; CELL-PROLIFERATION; MAMMALIAN TARGET; AUTOPHAGY; RADIOSENSITIVITY; INHIBITION; EXPRESSION; MICRORNAS; APOPTOSIS; ONCOGENE	Radioresistance is a material obstacle for effective treatment of colorectal cancer (CRC). Thus, the discovery of a novel biomarker for determining the CRC radiosensitivity is necessary. Recent studies have confirmed that miR-183-3p regulates cell phenotypes and tumor growth in various cancers. However, the role and mechanism of this micro-ribonucleic acid in CRC radiosensitivity remains unclear. Here, the abundances of miR-183-5p and ATG5 mRNA were detected by a real-time quantitative reverse transcription polymerase chain reaction. Kaplan-Meier survival analysis was carried out to explore the correlation between miR-183-5p and patient prognosis. Cell viability was evaluated by the MTT assay. Survival fraction analysis through colony formation was performed to assess the cell radiation response. Bioinformatic, luciferase and western blot assays were employed to verify the targeted interaction between miR-183-5p and ATG5. The results showed that an elevated abundance of miR-183-5p and a reduced ATG5 level in CRC were associated with the poor prognosis. The knockdown of miR-183-5p enhanced the sensitivity of CRC cells to radiation, inflected by the decreased cell viability and survival fraction. Mechanically, ATG5 was targeted by miR-183-5p. The addition of ATG5 conferred the radiosensitivity of the CRC cells, which was revered by miR-183-5p restoration. Furthermore, miR-183-5p knockdown hindered the tumor growth by repressing ATG5 in vivo after radiation treatment. In summary, the output data indicated that miR-183-5p heightened the radiation response of the CRC cells by targeting ATG5, promising a novel therapeutic target for CRC patients with radioresistance.	[Zheng, Sheng; Zhong, Yong-Fu; Tan, De-Ming; Xu, Yue; Chen, Huai-Xiang] Chongqing Three Gorges Cent Hosp, Dept Emergency Surg, Chongqing 404000, Peoples R China; [Wang, Dan] Chongqing Three Gorges Med Coll, Dept Publ Hlth & Management, Chongqing 404120, Peoples R China		Wang, D (corresponding author), Chongqing Three Gorges Med Coll, Dept Publ Hlth & Management, Chongqing 404120, Peoples R China.	xiaobaihau57@sina.com					An J, 2007, ONCOGENE, V26, P652, DOI 10.1038/sj.onc.1209830; Arora H, 2011, EXP MOL MED, V43, P298, DOI 10.3858/emm.2011.43.5.031; Baerga R, 2009, AUTOPHAGY, V5, P1118, DOI 10.4161/auto.5.8.9991; Banasiak D, 1999, RADIAT ONCOL INVESTI, V7, P77, DOI 10.1002/(SICI)1520-6823(1999)7:2<77::AID-ROI3>3.0.CO;2-M; Bartel DP, 2009, CELL, V136, P215, DOI 10.1016/j.cell.2009.01.002; Bi DP, 2016, ONCOL REP, V35, P2873, DOI 10.3892/or.2016.4631; Cao C, 2006, CANCER RES, V66, P10040, DOI 10.1158/0008-5472.CAN-06-0802; Cheng Y, 2016, REPROD BIOL, V16, P225, DOI 10.1016/j.repbio.2016.07.002; Falzone L, 2018, AGING-US, V10, P1000, DOI 10.18632/aging.101444; Fan HY, 2018, BIOMED PHARMACOTHER, V97, P1554, DOI 10.1016/j.biopha.2017.11.050; FARNIOK KE, 1994, CANCER-AM CANCER SOC, V74, P2154, DOI 10.1002/1097-0142(19941001)74:7+<2154::AID-CNCR2820741725>3.0.CO;2-G; Gao WY, 2019, ARCH BIOCHEM BIOPHYS, V665, P69, DOI 10.1016/j.abb.2018.01.013; He RQ, 2018, ONCOL REP, V40, P83, DOI 10.3892/or.2018.6429; Hu JL, 2018, ONCOGENESIS, V7, DOI 10.1038/s41389-018-0028-8; Iorio MV, 2012, CARCINOGENESIS, V33, P1126, DOI 10.1093/carcin/bgs140; Kim KW, 2006, J BIOL CHEM, V281, P36883, DOI 10.1074/jbc.M607094200; Kurrey NK, 2009, STEM CELLS, V27, P2059, DOI 10.1002/stem.154; Li F, 2010, BBA-REV CANCER, V1805, P167, DOI 10.1016/j.bbcan.2010.01.002; Lu YY, 2015, BIOMED PHARMACOTHER, V70, P151, DOI 10.1016/j.biopha.2015.01.016; Mo N, 2014, ONCOL REP, V32, P1905, DOI 10.3892/or.2014.3427; Pedroza-Torres A, 2014, MOLECULES, V19, P6263, DOI 10.3390/molecules19056263; Sarver AL, 2010, CANCER RES, V70, P9570, DOI 10.1158/0008-5472.CAN-10-2074; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; Sun QQ, 2015, INT J CANCER, V136, P1003, DOI 10.1002/ijc.29065; Sun Y, 2015, INT J ONCOL, V46, P750, DOI 10.3892/ijo.2014.2745; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; Toulany M, 2005, RADIOTHER ONCOL, V76, P143, DOI 10.1016/j.radonc.2005.06.024; Ueno K, 2013, BRIT J CANCER, V108, P1659, DOI 10.1038/bjc.2013.125; Volinia S, 2006, P NATL ACAD SCI USA, V103, P2257, DOI 10.1073/pnas.0510565103; Wang XJ, 2016, EUR REV MED PHARMACO, V20, P2020; Wang XF, 2016, ONCOTARGETS THER, V9, P1159, DOI 10.2147/OTT.S100427; Xu F, 2014, CLIN TRANSL ONCOL, V16, P980, DOI 10.1007/s12094-014-1183-9; Yan H, 2013, PHARMACOLOGY, V92, P167, DOI 10.1159/000354585; Yousefi S, 2006, NAT CELL BIOL, V8, P1124, DOI 10.1038/ncb1482; Yuan DW, 2015, CANCER BIOL THER, V16, P268, DOI 10.1080/15384047.2014.1002327; Yuan Y, 2018, INT J MOL MED, V42, P3562, DOI 10.3892/ijmm.2018.3871; Zhang XL, 2015, ONCOL REP, V34, P1557, DOI 10.3892/or.2015.4078; Zhang YQ, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0120884; Zhao ZJ, 2008, CELL HOST MICROBE, V4, P458, DOI 10.1016/j.chom.2008.10.003; Zheng L, 2015, J TRANSL MED, V13, DOI 10.1186/s12967-015-0592-z; Zhou ZR, 2017, ACTA PHARMACOL SIN, V38, P513, DOI 10.1038/aps.2016.136	41	19	19	1	6	INDIAN ACAD SCIENCES	BANGALORE	C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA	0250-5991	0973-7138		J BIOSCIENCES	J. Biosci.	SEP	2019	44	4							92	10.1007/s12038-019-9918-y			11	Biology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics	IN7WF	WOS:000478891800009	31502570				2022-04-25	
J	Peng, H; Zheng, J; Su, Q; Feng, XY; Peng, MS; Gong, L; Wu, H; Pan, X				Peng, Hong; Zheng, Jie; Su, Qiang; Feng, Xueya; Peng, Mingsha; Gong, Lei; Wu, Hong; Pan, Xue			VPS53 Suppresses Malignant Properties in Colorectal Cancer by Inducing the Autophagy Signaling Pathway	ONCOTARGETS AND THERAPY			English	Article						colorectal cancer; VPS53; autophagy; cell migration; cell invasion	STATISTICS; REGULATOR; CELLS	Background: Many studies found that VPS53, one of the subunits of the golgi-associated retrograde protein (GARP) complexes, was aberrantly expressed in human diseases. Aim: This study investigated the functions and molecular mechanisms of VPS53 in colorectal cancer (CRC). Methods: Expression and correlation of Beclin 1 and VPS53 were analyzed by RT-qPCR and Pearson's correlation in CRC tissues, and VPS53 expression was also determined in CRC cells. The changes of proliferation, migration, invasion, apoptosis, and autophagy of CRC cells were examined by a succession of functional experiments including CCK-8, flow cytometry, transwell assay, and electron microscopy. The levels of autophagy related proteins were evaluated by Western blotting analysis. Results: RT-qPCR results found that VPS53 was downregulated in CRC tissues and cells, and Beclin 1 expression was also decreased in CRC tissues. There was a positive correlation between VPS53 and Beclin 1. Functional results showed that overexpression of VPS53 could suppress proliferation, migration, and invasion, and accelerate apoptosis and autophagy of CRC cells. Also, VPS53 could upregulate Beclin 1 and LC3BII, suggesting the inductive effect of VPS53 on CRC cell autophagy. Furthermore, it was found that the autophagy inhibitor (Inhb) could attenuate the inhibition of VPS53 on CRC progression. Conclusion: VPS53 repressed CRC progression by regulating the autophagy signaling pathway, suggesting that VPS53 might be a promising therapeutic target for CRC.	[Peng, Hong; Feng, Xueya; Peng, Mingsha; Wu, Hong] Nanchong Cent Hosp, Clin Med Coll 2, North Sichuan Med Coll, Dept Anorectal Surg, Nanchong 637000, Sichuan, Peoples R China; [Zheng, Jie] Southwest Med Univ, Dept Anesthesiol, Affiliated Tradit Chinese Med Hosp, Luzhou 646000, Sichuan, Peoples R China; [Su, Qiang] Nanchong Cent Hosp, Nanchong Key Lab Individualized Drug Therapy Nanc, North Sichuan Med Coll, Dept Pharm,Clin Med Coll 2, Nanchong 637000, Sichuan, Peoples R China; [Gong, Lei] Nanchong Cent Hosp, Clin Med Coll 2, North Sichuan Med Coll, Dept Gastrointestinal Surg, Nanchong 637000, Sichuan, Peoples R China; [Pan, Xue] Chongqing Med Univ, Sci Res Dept, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China		Pan, X (corresponding author), Chongqing Med Univ, Sci Res Dept, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China.	panxue89012705@163.com			North Sichuan Medical College City school cooperation program [18SXHZ0364, 18SXHZ0408, 19SXHZ0297]; Science and Technology Research Project of Sichuan Province [2017JY0116]; School Grade Research Key Project of North Sichuan Medical College [CBY18-A-ZD13]; Basic Scientific and Technological Strategic Cooperation of Nanchong Municipal Schools [NSMC20170311]	This work was supported by North Sichuan Medical College City school cooperation program (18SXHZ0364, 18SXHZ0408, 19SXHZ0297); Science and Technology Research Project of Sichuan Province (2017JY0116); School Grade Research Key Project of North Sichuan Medical College (CBY18-A-ZD13), and Basic Scientific and Technological Strategic Cooperation of Nanchong Municipal Schools (NSMC20170311).	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J	Kong, FH; Zou, H; Liu, X; He, J; Zheng, YW; Xiong, L; Miao, XY				Kong, Fanhua; Zou, Heng; Liu, Xi; He, Jun; Zheng, Yanwen; Xiong, Li; Miao, Xiongying			miR-7112-3p targets PERK to regulate the endoplasmic reticulum stress pathway and apoptosis induced by photodynamic therapy in colorectal cancer CX-1 cells	PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY			English	Article						Colorectal cancer; miR-7112-3p; Photodynamic therapy; Endoplasmic reticulum stress; PERK; Apoptosis	ER STRESS; SINOPORPHYRIN SODIUM; AUTOPHAGY; EXPRESSION; SENSITIZER; HYPERICIN; MICRORNAS; DEATH; PDT	Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide. Photodynamic therapy (PDT) is an emerging modality for the treatment of solid tumors. Sinoporphyrin sodium (DVDMS) is a new photosensitizer with good therapeutic killing effects on cancer cells. Recent findings have shown that microRNAs play important roles in many biological processes. However, the functions of microRNAs in DVDMS-induced PDT remain largely unclear. Materials and Methods: Proteins involved in endoplasmic reticulum (ER) stress and apoptosis of CX-1 cells treated with DVDMS-PDT were examined by Western blotting and cell viability assays. 15 candidate miRNAs targeting RNA-dependent protein kinase-like ER kinase (PERK) were screened and verified using the TargetScan, miRWalk and miRDB databases. The downstream pathways of candidate miRNAs with high scores were studied by cell transfection, qRT-PCR, Western blotting and dual-luciferase reporter assays. The subcellular location of DVDMS was confirmed by laser confocal microscopy. Results: DVDMS-PDT induced apoptosis via elevated ER stress and activation of the PERK/ATF4/CHOP/caspase cascade pathway in CX-1 cells. The endoplasmic reticulum was involved in the subcellular accumulation of DVDMS in CX-1 cells. Dual-luciferase reporting experiment confirmed that a direct crosslinking between miR-7112-3p and PERK. In addition, miR-7112-3p was highly expressed in CRC tissues compared with peripheral tissues. Conclusion: Our work showed that miR-7112-3p directly targeted PERK and further regulated PERK/ATF4/CHOP/caspase cascade pathway, resulting in enhanced apoptosis in CX-1 cells treated with DVDMS-PDT.	[Kong, Fanhua; Zou, Heng; Liu, Xi; He, Jun; Zheng, Yanwen; Xiong, Li; Miao, Xiongying] Cent South Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha, Hunan, Peoples R China		Xiong, L; Miao, XY (corresponding author), Cent South Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha, Hunan, Peoples R China.	lixionghn@csu.edu.cn; miaoxiongying3016@csu.edu.cn			National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81773293, 31660266]; Natural Science Foundation of Hunan ProvinceNatural Science Foundation of Hunan Province [2015JJ4083,2018JJ3758,2019JJ50874]; Hunan provincial key research and development program [2017DK2011, 2017WK2060, 2015GK3117]; Hunan provincial traditional Chinese medicine research project [201869, 201951]	This study was supported by the National Natural Science Foundation (81773293, 31660266), Natural Science Foundation of Hunan Province (2015JJ4083,2018JJ3758,2019JJ50874), Hunan provincial key research and development program (2017DK2011, 2017WK2060, 2015GK3117), Hunan provincial traditional Chinese medicine research project (201869, 201951).	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Ther.	MAR	2020	29								101663	10.1016/j.pdpdt.2020.101663			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	LG2HV	WOS:000527929400048	31945549	hybrid			2022-04-25	
J	Park, SY; Lee, SJ; Cho, HJ; Kim, JT; Yoon, HR; Lee, KH; Kim, BY; Lee, Y; Lee, HG				Park, Sang Yoon; Lee, Seon-Jin; Cho, Hee Jun; Kim, Jong-Tae; Yoon, Hyang Ran; Lee, Kyung Ho; Kim, Bo Yeon; Lee, Younghee; Lee, Hee Gu			Epsilon-Globin HBE1 Enhances Radiotherapy Resistance by Down-Regulating BCL11A in Colorectal Cancer Cells	CANCERS			English	Article						ER stress; HBE1; BCL11A; JNK; radioresistant; oxidative stress; cell cycle arrest	DNA-DAMAGE RESPONSE; RADIATION-INDUCED AUTOPHAGY; STRAND BREAK REPAIR; IONIZING-RADIATION; STRESS; HEMOGLOBIN; APOPTOSIS; GENE; EXPRESSION; CONTRIBUTES	Resistance to radiotherapy is considered an important obstacle in the treatment of colorectal cancer. However, the mechanisms that enable tumor cells to tolerate the effects of radiation remain unclear. Moreover, radiotherapy causes accumulated mutations in transcription factors, which can lead to changes in gene expression and radiosensitivity. This phenomenon reduces the effectiveness of radiation therapy towards cancer cells. In the present study, radiation-resistant (RR) cancer cells were established by sequential radiation exposure, and hemoglobin subunit epsilon 1 (HBE1) was identified as a candidate radiation resistance-associated protein based on RNA-sequencing analysis. Then, compared to radiosensitive (RS) cell lines, the overexpression of HBE1 in RR cell lines was used to measure various forms of radiation-induced cellular damage. Consequently, HBE1-overexpressing cell lines were found to exhibit decreased radiation-induced intracellular reactive oxygen species (ROS) production and cell mortality. Conversely, HBE1 deficiency in RR cell lines increased intracellular ROS production, G2/M arrest, and apoptosis, and decreased clonogenic survival rate. These effects were reversed by the ROS scavenger N-acetyl cysteine. Moreover, HBE1 overexpression was found to attenuate radiation-induced endoplasmic reticulum stress and apoptosis via an inositol-requiring enzyme 1(IRE1)Jun amino-terminal kinase (JNK) signaling pathway. In addition, increased HBE1 expression induced by gamma-irradiation in RS cells attenuated expression of the transcriptional regulator BCL11A, whereas its depletion in RR cells increased BCL11A expression. Collectively, these observations indicate that the expression of HBE1 during radiotherapy might potentiate the survival of radiation-exposed colorectal cancer cells.	[Park, Sang Yoon; Cho, Hee Jun; Kim, Jong-Tae; Yoon, Hyang Ran; Lee, Kyung Ho; Kim, Bo Yeon; Lee, Hee Gu] Korea Res Inst Biosci & Biotechnol, Immunotherapy Convergence Res Ctr, Daejeon 34141, South Korea; [Park, Sang Yoon; Lee, Younghee] Chungbuk Natl Univ, Coll Nat Sci, Dept Biochem, Cheongju 28644, South Korea; [Lee, Seon-Jin] Korea Res Inst Biosci & Biotechnol, Environm Dis Res Ctr, Daejeon 34141, South Korea; [Lee, Seon-Jin; Lee, Hee Gu] Univ Sci & Technol, Dept Biomol Sci, Daejeon 34141, South Korea		Lee, HG (corresponding author), Korea Res Inst Biosci & Biotechnol, Immunotherapy Convergence Res Ctr, Daejeon 34141, South Korea.; Lee, HG (corresponding author), Univ Sci & Technol, Dept Biomol Sci, Daejeon 34141, South Korea.	psy478@kribb.re.kr; sjlee@kribb.re.kr; hjcho@kribb.re.kr; kjtdna@naver.com; yhr1205@kribb.re.kr; leekh@kribb.re.kr; bykim@kribb.re.kr; yh14177@chungbuk.ac.kr; hglee@kribb.re.kr	Lee, Seon-Jin/AAJ-8258-2020	Lee, Seon-Jin/0000-0001-7214-7536	R&D Convergence Program of the National Research Council of Science & Technology (NST) of the Republic of Korea [CAP-16-03-KRIBB]; National Research Foundation (NRF) - Korea government [2017R1A2B2005629]	This work was supported by the R&D Convergence Program (CAP-16-03-KRIBB) of the National Research Council of Science & Technology (NST) of the Republic of Korea and supported by the National Research Foundation (NRF) grant funded by the Korea government (No. 2017R1A2B2005629).	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J	Shao, BZ; Yao, Y; Li, JP; Chai, NL; Linghu, EQ				Shao, Bo-Zong; Yao, Yi; Li, Jin-Ping; Chai, Ning-Li; Linghu, En-Qiang			The Role of Neutrophil Extracellular Traps in Cancer	FRONTIERS IN ONCOLOGY			English	Review						neutrophil extracellular trap; cancer; neutrophil; immunity; inflammation	PROCOAGULANT ACTIVITY; EPITHELIAL-CELLS; BLOOD-CELLS; AUTOPHAGY; NETOSIS; TUMOR; RECEPTOR; RELEASE; GROWTH; MICE	Neutrophils are vital components of innate and adaptive immunity. It is widely acknowledged that in various pathological conditions, neutrophils are activated and release condensed DNA strands, triggering the formation of neutrophil extracellular traps (NETs). NETs have been shown to be effective in fighting against microbial infections and modulating the pathogenesis and progression of diseases, including malignant tumors. This review describes the current knowledge on the biological characteristics of NETs. Additionally, the mechanisms of NETs in cancer are discussed, including the involvement of signaling pathways and the crosstalk between other cancer-related mechanisms, including inflammasomes and autophagy. Finally, based on previous and current studies, the roles of NET formation and the potential therapeutic targets and strategies related to NETs in several well-studied types of cancers, including breast, lung, colorectal, pancreatic, blood, neurological, and cutaneous cancers, are separately reviewed and discussed.	[Shao, Bo-Zong; Yao, Yi; Li, Jin-Ping; Chai, Ning-Li; Linghu, En-Qiang] Gen Hosp Chinese Peoples Liberat Army, Dept Gastroenterol, Beijing, Peoples R China		Chai, NL; Linghu, EQ (corresponding author), Gen Hosp Chinese Peoples Liberat Army, Dept Gastroenterol, Beijing, Peoples R China.	csxlily@163.com; linghuenqiang@vip.sina.com			Ministry of Science and Technology of the Peoples Republic of ChinaMinistry of Science and Technology, China [2016YFC1303600]; General Hospital of the Chinese Peoples Liberation Army [2018ZD-006, 2018MS-012]	Funding This work was supported by a grant from Ministry of Science and Technology of the Peoples Republic of China (No. 2016YFC1303600) and grants from General Hospital of the Chinese Peoples Liberation Army (No. 2018ZD-006 and 2018MS-012).	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Oncol.	AUG 12	2021	11									10.3389/fonc.2021.714357			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	UN1NY	WOS:000693790100001	34476216	Green Published, gold			2022-04-25	
J	Kinsey, CG; Camolotto, SA; Boespflug, AM; Guillen, KP; Foth, M; Truong, A; Schuman, SS; Shea, JE; Seipp, MT; Yap, JT; Burrell, LD; Lum, DH; Whisenant, JR; Gilcrease, GW; Cavalieri, CC; Rehbein, KM; Cutler, SL; Affolter, KE; Welm, AL; Welm, BE; Scaife, CL; Snyder, EL; McMahon, M				Kinsey, Conan G.; Camolotto, Soledad A.; Boespflug, Amelie M.; Guillen, Katrin P.; Foth, Mona; Truong, Amanda; Schuman, Sophia S.; Shea, Jill E.; Seipp, Michael T.; Yap, Jeffrey T.; Burrell, Lance D.; Lum, David H.; Whisenant, Jonathan R.; Gilcrease, G. Weldon, III; Cavalieri, Courtney C.; Rehbein, Kaitrin M.; Cutler, Stephanie L.; Affolter, Kajsa E.; Welm, Alana L.; Welm, Bryan E.; Scaife, Courtney L.; Snyder, Eric L.; McMahon, Martin			Protective autophagy elicited by RAF -> MEK -> ERK inhibition suggests a treatment strategy for RAS-driven cancers	NATURE MEDICINE			English	Article							GROWTH; CELLS; BRAF; PHOSPHORYLATION; GEMCITABINE; COMBINATION; TRAMETINIB; RESISTANCE; PLATFORM; PROTEIN	Pancreatic ductal adenocarcinoma (PDA) was responsible for similar to 44,000 deaths in the United States in 2018 and is the epitome of a recalcitrant cancer driven by a pharmacologically intractable oncoprotein, KRAS(1-4). Downstream of KRAS, the RAF. MEK. ERK signaling pathway plays a central role in pancreatic carcinogenesis(5). However, paradoxically, inhibition of this pathway has provided no clinical benefit to patients with PDA(6). Here we show that inhibition of KRAS -> RAF -> MEK -> ERK signaling elicits autophagy, a process of cellular recycling that protects PDA cells from the cytotoxic effects of KRAS pathway inhibition. Mechanistically, inhibition of MEK1/2 leads to activation of the LKB1 -> AMPK -> ULK1 signaling axis, a key regulator of autophagy. Furthermore, combined inhibition of MEK1/2 plus autophagy displays synergistic anti-proliferative effects against PDA cell lines in vitro and promotes regression of xenografted patient-derived PDA tumors in mice. The observed effect of combination trametinib plus chloroquine was not restricted to PDA as other tumors, including patient-derived xenografts (PDX) of NRAS-mutated melanoma and BRAF-mutated colorectal cancer displayed similar responses. Finally, treatment of a patient with PDA with the combination of trametinib plus hydroxychloroquine resulted in a partial, but nonetheless striking disease response. These data suggest that this combination therapy may represent a novel strategy to target RAS-driven cancers.	[Kinsey, Conan G.; Camolotto, Soledad A.; Boespflug, Amelie M.; Guillen, Katrin P.; Foth, Mona; Truong, Amanda; Schuman, Sophia S.; Yap, Jeffrey T.; Burrell, Lance D.; Lum, David H.; Whisenant, Jonathan R.; Gilcrease, G. Weldon, III; Cavalieri, Courtney C.; Rehbein, Kaitrin M.; Cutler, Stephanie L.; Affolter, Kajsa E.; Welm, Alana L.; Welm, Bryan E.; Scaife, Courtney L.; Snyder, Eric L.; McMahon, Martin] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA; [Kinsey, Conan G.; Whisenant, Jonathan R.; Gilcrease, G. Weldon, III] Univ Utah, Sch Med, Dept Internal Med, Div Oncol, Salt Lake City, UT USA; [Boespflug, Amelie M.] Ctr Hosp Lyon Sud, Dept Dermatol, Pierre Benite, France; [Boespflug, Amelie M.] Claude Bernard Lyon 1 Univ, Canc Res Ctr Lyon, INSERM 1052, CNRS 5286, Villeurbanne, France; [Shea, Jill E.; Seipp, Michael T.; Welm, Bryan E.; Scaife, Courtney L.] Univ Utah, Sch Med, Dept Surg, Salt Lake City, UT USA; [Yap, Jeffrey T.] Univ Utah, Sch Med, Dept Radiol & Imaging Serv, Salt Lake City, UT USA; [Cavalieri, Courtney C.] Univ Utah, Huntsman Canc Inst, Dept Pharm Serv, Salt Lake City, UT USA; [Affolter, Kajsa E.; Snyder, Eric L.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA; [Welm, Alana L.] Univ Utah, Sch Med, Dept Oncol Sci, Salt Lake City, UT USA; [McMahon, Martin] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84132 USA		McMahon, M (corresponding author), Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.; McMahon, M (corresponding author), Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84132 USA.	martin.mcmahon@hci.utah.edu	Foth, Mona/AAU-5336-2021	Boespflug, Amelie/0000-0002-2656-5144; Foth, Mona/0000-0001-6507-8114; Yap, Jeffrey/0000-0001-5306-2860; Shea, Jill/0000-0002-8644-7772	National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01-CA176839, R01-CA131261, P30-CA042014]; Pancreatic Cancer Collective; Melanoma Research Alliance; Five for the Fight; Huntsman Cancer Foundation; Career Award for Medical Scientists from the Burroughs Wellcome FundBurroughs Wellcome Fund; V Scholar Award; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01CA212415]; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI); DoDUnited States Department of Defense [U54CA224076, W81XWH1410417]; Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale [FDM20150633361]; Societe Francaise de Dermatologie; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA176839, F30CA235964, R01CA131261, P30CA042014, U54CA224076, R01CA212415] Funding Source: NIH RePORTER	We dedicate this work to the memory of our patient and his family, whose courage continues to inspire us to further improve the diagnosis and treatment of pancreatic cancer. We thank the members of the McMahon Lab for their support, advice, guidance, comments and discussions during the course of this work. Additionally we thank I. Garrido-Laguna (HCI/Univ. of Utah), M. Tempero, E. Collisson and F. McCormick (U.C. San Francisco), E. White (Rutgers University), D. Tuveson (Cold Spring Harbor), and K. Olive (Columbia) for advice and guidance, J. Mulcahy-Levy and A. Thorburn (U.C. Denver) for inspiration, advice, guidance and reagents, H. Land (University of Rochester Medical Center) and K. Shokat (UCSF) for providing reagents, NCI Patient-Derived Models Repository for supplying the NCI-516677 NRAS-mutated melanoma PDX, K. Owings, D. Lum and the HCI Preclinical Research Resource for assistance with tumor xenografts and drug treatments and M. Silvis for assistance with drug dosing. C.K. & M.M. wish to acknowledge the collegiality of K. Bryant and C. Der (University of North Carolina, Chapel Hill) for ongoing discussions and for sharing data in advance of publication. M. M. acknowledges financial support from the National Cancer Institute (R01-CA176839, R01-CA131261 & P30-CA042014), the Pancreatic Cancer Collective, Melanoma Research Alliance, Five for the Fight, and the Huntsman Cancer Foundation. E.L.S. was supported in part by a Career Award for Medical Scientists from the Burroughs Wellcome Fund, a V Scholar Award, the Huntsman Cancer Foundation, and the NIH (R01CA212415). B.E.W. acknowledges support from the National Cancer Institute and DoD (U54CA224076 and W81XWH1410417). A.L.W. acknowledges support from the Huntsman Cancer Foundation. C.G.K acknowledges support from the Huntsman Cancer Foundation. A.M.B. acknowledges support from Fondation pour la Recherche Medicale (FDM20150633361) and Societe Francaise de Dermatologie.	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Med.	APR	2019	25	4					620	+		10.1038/s41591-019-0367-9			17	Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine	HR7OA	WOS:000463342800024	30833748	Green Accepted	Y	N	2022-04-25	
J	Liu, L; Ren, WH; Chen, KS				Liu, Liru; Ren, Weihua; Chen, Kuisheng			MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells	CELLULAR PHYSIOLOGY AND BIOCHEMISTRY			English	Article						miR-34a; HMGB1; Apoptosis; Autophagy; Acute myeloid leukemia	COLORECTAL-CANCER; GENE-EXPRESSION; MICRORNAS; GROWTH; P53; PROLIFERATION; MACROPHAGES; INDUCTION; INCREASES; SURVIVAL	Background: MiR-34a is identified as a tumor suppressor gene and involved in acute myeloid leukemia (AML) development. However, the regulatory mechanism of miR-34a in AML is unclear. Methods: The expression of miR-34a and HMGB1 in HL-60, THP-1 and HS-5 cells were detected by qRT-PCR and western blot. Lipofectamine 2000 was used to transfect with miR34a mimics, miR-34a inhibitor, si-HMGB1, pcDNA 3.1-HMGB1, and corresponding controls. The apoptosis and autophagy of transfected AML cells were assessed by flow cytometry and western blot, respectively. Bioinformatics software and dual luciferase reporter assay were applied to predict and verify the target of miR-34a. The effects of miR-34a mimics or si-HMGB1 on chemotherapy-induced autophagy were further explored in HL-60 cells treated with all-trans retinoic acid (ATRA) along with lysosomal protease inhibitors E64d and pepstatin A. Results: MiR-34a was lower expressed and HMGB1 mRNA and proteins were both higher expressed in HL-60 and THP-1 cells compared with that in HS-5 cells. Higher expression levels of MiR-34 and lower expression levels of HMGB1 both significantly promoted apoptosis and inhibited autophagy in HL-60 and THP-1 cells. Dual luciferase reporter system confirmed that HMGB1 was a potential target of miR-34a. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by higher expression level of miR-34a. Higher expression level of miR-34a and lower expression level of HMGB1 both inhibited chemotherapy-induced autophagy by stimulating the LC3 conversion. Conclusion: MiR-34a promoted cell apoptosis and inhibited autophagy by targeting HMGB1. Therefore, miR-34a may be a potential promising molecular target for AML therapy. (C) 2017 The Author(s). Published by S. Karger AG, Basel.	[Liu, Liru; Ren, Weihua] Zhengzhou Univ, Luoyang Cent Hosp, Dept Clin Lab, 288 Zhongzhou Rd, Xigong Dist 471000, Luoyang, Peoples R China; [Chen, Kuisheng] Zhengzhou Univ, Affiliated Hosp 1, Dept Pathol, Zhengzhou, Peoples R China		Liu, L (corresponding author), Zhengzhou Univ, Luoyang Cent Hosp, Dept Clin Lab, 288 Zhongzhou Rd, Xigong Dist 471000, Luoyang, Peoples R China.	klirucb@163.com					Aakula A, 2016, EUR UROL, V69, P1120, DOI 10.1016/j.eururo.2015.09.019; Adams BD, 2016, CANCER RES, V76, P927, DOI 10.1158/0008-5472.CAN-15-2321; Agostini M, 2014, ONCOTARGET, V5, P872, DOI 10.18632/oncotarget.1825; Ambros V, 2004, NATURE, V431, P350, DOI 10.1038/nature02871; Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; Chandrasekaran KS, 2016, TUMOR BIOL, V37, P13155, DOI 10.1007/s13277-016-5261-1; Chang TC, 2007, MOL CELL, V26, P745, DOI 10.1016/j.molcel.2007.05.010; Chen X, 2015, MOL MED REP, V12, P4462, DOI 10.3892/mmr.2015.3928; Cheng YJ, 2015, CELL PHYSIOL BIOCHEM, V36, P1577, DOI 10.1159/000430320; Chiu CF, 2016, INT J MOL SCI, V17, DOI 10.3390/ijms17081337; Farh KKH, 2005, SCIENCE, V310, P1817, DOI 10.1126/science.1121158; Favreau AJ, 2016, EXP HEMATOL ONCOL, V5, DOI 10.1186/s40164-016-0033-6; Han ZY, 2015, ONCOTARGET, V6, P13149, DOI 10.18632/oncotarget.3693; Huang KB, 2015, MOL MED REP, V12, P7830, DOI 10.3892/mmr.2015.4455; Huber R, 2016, SCI REP-UK, V6, DOI 10.1038/srep29914; Ichimura A, 2010, MOL PHARMACOL, V77, P1016, DOI 10.1124/mol.109.063321; JIANG HP, 1994, ONCOGENE, V9, P3397; Lewis BP, 2005, CELL, V120, P15, DOI 10.1016/j.cell.2004.12.035; Li GD, 2016, ADV MATER SCI ENG, V2016, DOI 10.1155/2016/8530574; Liu L, 2011, LEUKEMIA, V25, P23, DOI 10.1038/leu.2010.225; Lou GH, 2015, CELL PHYSIOL BIOCHEM, V35, P2192, DOI 10.1159/000374024; Lu F, 2014, INT J ONCOL, V45, P383, DOI 10.3892/ijo.2014.2390; Mehta A, 2015, IMMUNITY, V42, P1021, DOI 10.1016/j.immuni.2015.05.017; Ofran Y, 2014, ACTA HAEMATOL-BASEL, V132, P292, DOI 10.1159/000360200; Piletic K, 2016, ARCH TOXICOL, V90, P2405, DOI 10.1007/s00204-016-1815-7; Raver-Shapira N, 2007, MOL CELL, V26, P731, DOI 10.1016/j.molcel.2007.05.017; Rucker FG, 2013, LEUKEMIA, V27, P353, DOI 10.1038/leu.2012.208; Samuel N, 2016, ONCOTARGET, V7, P49611, DOI 10.18632/oncotarget.10417; Sengsayadeth S, 2015, HAEMATOLOGICA, V100, P859, DOI 10.3324/haematol.2015.123331; Song CS, 2017, BIOCHEM BIOPH RES CO, V482, P22, DOI 10.1016/j.bbrc.2016.11.037; SUGIMOTO K, 1992, BLOOD, V79, P2378, DOI 10.1182/blood.V79.9.2378.2378; Suren D, 2014, MED SCI MONITOR, V20, P530, DOI 10.12659/MSM.890531; Thiebes KP, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms8718; Traore K, 2005, LEUKEMIA RES, V29, P863, DOI 10.1016/j.leukres.2004.12.011; Wang JC, 2015, CELL PHYSIOL BIOCHEM, V35, P767, DOI 10.1159/000369736; Wang X, 2015, CELL SIGNAL, V27, P443, DOI 10.1016/j.cellsig.2014.12.003; WOLF D, 1985, P NATL ACAD SCI USA, V82, P790, DOI 10.1073/pnas.82.3.790; Xu Y, 2015, INT J CLIN EXP MED, V8, P6446; Yang DQ, 2017, INT J LAB HEMATOL, V39, P42, DOI 10.1111/ijlh.12566; Yu Yan, 2008, Ai Zheng, V27, P929; Zauli G, 2011, CLIN CANCER RES, V17, P2712, DOI 10.1158/1078-0432.CCR-10-3244; Zhao XD, 2015, J CELL BIOL, V210, P613, DOI 10.1083/jcb.201501073	42	75	80	0	9	KARGER	BASEL	ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND	1015-8987	1421-9778		CELL PHYSIOL BIOCHEM	Cell. Physiol. Biochem.		2017	41	5					1981	1992		10.1159/000475277			12	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	EY7LW	WOS:000404173800021	28478444	gold			2022-04-25	
J	Wang, Y; Lu, JH; Wu, QN; Jin, Y; Wang, DS; Chen, YX; Liu, J; Luo, XJ; Meng, Q; Pu, HY; Wang, YN; Hu, PS; Liu, ZX; Zeng, ZL; Zhao, Q; Deng, R; Zhu, XF; Ju, HQ; Xu, RH				Wang, Yun; Lu, Jia-Huan; Wu, Qi-Nian; Jin, Ying; Wang, De-Shen; Chen, Yan-Xing; Liu, Jia; Luo, Xiao-Jing; Meng, Qi; Pu, Heng-Ying; Wang, Ying-Nan; Hu, Pei-Shan; Liu, Ze-Xian; Zeng, Zhao-Lei; Zhao, Qi; Deng, Rong; Zhu, Xiao-Feng; Ju, Huai-Qiang; Xu, Rui-Hua			LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer	MOLECULAR CANCER			English	Article						Autophagy; CRC; IGF2BP2; LINRIS; MYC	LONG NONCODING RNA; MESSENGER-RNA; DNA METHYLATION; NUCLEAR-RNA; GROWTH; CELLS; GENE; MYC; METASTASIS; ACTIVATION	Background Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target. Methods We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo. Results LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N-6-methyladenosine (m(6)A) 'reader'. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models. Conclusion LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.	[Wang, Yun; Lu, Jia-Huan; Wu, Qi-Nian; Jin, Ying; Wang, De-Shen; Chen, Yan-Xing; Liu, Jia; Luo, Xiao-Jing; Meng, Qi; Pu, Heng-Ying; Wang, Ying-Nan; Hu, Pei-Shan; Liu, Ze-Xian; Zeng, Zhao-Lei; Zhao, Qi; Deng, Rong; Zhu, Xiao-Feng; Ju, Huai-Qiang; Xu, Rui-Hua] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Guangdong, Peoples R China; [Wang, Yun; Jin, Ying; Wang, De-Shen; Chen, Yan-Xing; Liu, Jia; Luo, Xiao-Jing; Meng, Qi; Xu, Rui-Hua] Sun Yat Sen Univ, Dept Med Oncol, Canc Ctr, Guangzhou, Guangdong, Peoples R China; [Lu, Jia-Huan] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anat & Cellular Pathol, State Key Lab Translat Oncol, Hong Kong, Peoples R China; [Wu, Qi-Nian] Sun Yat Sen Univ, Dept Pathol, Canc Ctr, Guangzhou, Guangdong, Peoples R China; [Ju, Huai-Qiang; Xu, Rui-Hua] Chinese Acad Med Sci, Precis Diag & Treatment Gastrointestinal Canc, Guangzhou, Guangdong, Peoples R China		Ju, HQ; Xu, RH (corresponding author), Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Guangdong, Peoples R China.; Xu, RH (corresponding author), Sun Yat Sen Univ, Dept Med Oncol, Canc Ctr, Guangzhou, Guangdong, Peoples R China.; Ju, HQ; Xu, RH (corresponding author), Chinese Acad Med Sci, Precis Diag & Treatment Gastrointestinal Canc, Guangzhou, Guangdong, Peoples R China.	juhq@sysucc.org.cn; xurh@sysucc.org.cn	Liu, Zexian/D-1153-2011; Zhao, Qi/X-7899-2019; Xu, Rui-Hua/AAW-4766-2021	Liu, Zexian/0000-0001-9698-0610; Zhao, Qi/0000-0002-8683-6145; Luo, Xiao-jing/0000-0001-9440-9189	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81930065, 81871951, 81802438]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2014A030312015]; Science and Technology Program of Guangdong [2019B020227002]; Science and Technology Program of Guangzhou [201904020046, 201803040019, 201704020228]; CAMS Innovation Fund for Medical Sciences [2019-I2M-5-036]; Pearl River S&T Nova Program of Guangzhou [201806010002]	This research was supported by National Natural Science Foundation of China (81930065, 81871951, 81802438); Natural Science Foundation of Guangdong Province (2014A030312015); Science and Technology Program of Guangdong (2019B020227002); Science and Technology Program of Guangzhou (201904020046, 201803040019, 201704020228); CAMS Innovation Fund for Medical Sciences (2019-I2M-5-036) and Pearl River S&T Nova Program of Guangzhou (201806010002).	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Cancer	DEC 2	2019	18	1							174	10.1186/s12943-019-1105-0			18	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	JT1RQ	WOS:000500775500001	31791342	gold, Green Published			2022-04-25	
J	Wang, YG; Liu, HH; Cao, YT; Zhang, LL; Huang, F; Yi, C				Wang, Yigang; Liu, Hui-Hui; Cao, Yu-Ting; Zhang, Lei-Lei; Huang, Fang; Yi, Cong			The Role of Mitochondrial Dynamics and Mitophagy in Carcinogenesis, Metastasis and Therapy	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY			English	Review						mitochondria; mitochondrial dynamics; mitophagy; carcinogenesis; therapy	HYPOXIA-INDUCED AUTOPHAGY; CELL-DEATH; BREAST-CANCER; DEPENDENT MITOPHAGY; COLORECTAL-CANCER; MAMMALIAN HOMOLOG; SIGNALING PATHWAY; TUMOR PROGRESSION; DRUG-RESISTANCE; PARKIN ISOFORMS	Mitochondria are key cellular organelles and play vital roles in energy metabolism, apoptosis regulation and cellular homeostasis. Mitochondrial dynamics refers to the varying balance between mitochondrial fission and mitochondrial fusion that plays an important part in maintaining mitochondrial homeostasis and quality. Mitochondrial malfunction is involved in aging, metabolic disease, neurodegenerative disorders, and cancers. Mitophagy, a selective autophagy of mitochondria, can efficiently degrade, remove and recycle the malfunctioning or damaged mitochondria, and is crucial for quality control. In past decades, numerous studies have identified a series of factors that regulate mitophagy and are also involved in carcinogenesis, cancer cell migration and death. Therefore, it has become critically important to analyze signal pathways that regulate mitophagy to identify potential therapeutic targets. Here, we review recent progresses in mitochondrial dynamics, the mechanisms of mitophagy regulation, and the implications for understanding carcinogenesis, metastasis, treatment, and drug resistance.	[Wang, Yigang; Liu, Hui-Hui; Cao, Yu-Ting; Zhang, Lei-Lei] Zhejiang Sci Tech Univ, Xinyuan Inst Med & Biotechnol, Sch Life Sci & Med, Hangzhou, Peoples R China; [Huang, Fang] Zhejiang Prov Peoples Hosp, Peoples Hosp, Dept Pathol, Hangzhou Med Coll, Hangzhou, Peoples R China; [Yi, Cong] Zhejiang Univ, Sch Med, Dept Biochem Hepatobiliary & Pancreat Surg, Affiliated Hosp 1, Hangzhou, Peoples R China		Huang, F (corresponding author), Zhejiang Prov Peoples Hosp, Peoples Hosp, Dept Pathol, Hangzhou Med Coll, Hangzhou, Peoples R China.; Yi, C (corresponding author), Zhejiang Univ, Sch Med, Dept Biochem Hepatobiliary & Pancreat Surg, Affiliated Hosp 1, Hangzhou, Peoples R China.	huangfang0794@163.com; yiconglab@zju.edu.cn			Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LY18C070002]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81803069, 91754107, 31771528]; Zhejiang Medical and Health Science and Technology project [2019337459]; Grant for 521 talent project of ZSTU	This work was supported by the Zhejiang Provincial Natural Science Foundation (No. LY18C070002), the National Natural Science Foundation of China (No. 81803069), Zhejiang Medical and Health Science and Technology project (No. 2019337459) and the Grant for 521 talent project of ZSTU to YW, and National Natural Science Foundation of China (Nos. 91754107 and 31771528) to CY.	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Cell. Dev. Biol.	JUN 10	2020	8								413	10.3389/fcell.2020.00413			12	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	MD3QA	WOS:000543884500001	32587855	gold, Green Published			2022-04-25	
J	Bobak, Y; Kurlishchuk, Y; Vynnytska-Myronovska, B; Grydzuk, O; Shuvayeva, G; Redowicz, MJ; Kunz-Schughart, LA; Stasyk, O				Bobak, Yaroslav; Kurlishchuk, Yuliya; Vynnytska-Myronovska, Bozhena; Grydzuk, Olesia; Shuvayeva, Galyna; Redowicz, Maria J.; Kunz-Schughart, Leoni A.; Stasyk, Oleh			Arginine deprivation induces endoplasmic reticulum stress in human solid cancer cells	INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY			English	Article						Arginine deprivation; ER stress; Canavanine; Metabolic anticancer therapy	UNFOLDED PROTEIN RESPONSE; ER STRESS; DEGRADING ENZYMES; IN-VITRO; ACID; APOPTOSIS; MECHANISMS; ORGANIZATION; AUTOPHAGY; PATHWAY	Deprivation for the single amino acid arginine is a rapidly developing metabolic anticancer therapy, which allows growth control in a number of highly malignant tumors. Here we report that one of the responses of human solid cancer cells to arginine starvation is the induction of prolonged endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). Systematic study of two colorectal carcinoma HCT-116 and HT29, glioblastoma U251 MG and ovarian carcinoma SKOV3 cell lines revealed, however, that the ER stress triggered by the absence of arginine does not result in massive apoptosis despite a profound upregulation of the proapoptotic gene CHOP. Instead, Akt- and MAPK-dependent pathways were activated which may counteract proapoptotic signaling. Treatment with DMSO as a disaggregating agent or with cycloheximide to block protein synthesis reduced ER stress evoked by arginine deprivation. On the other hand, ER stress and apoptosis induction in arginine-starved cells could be critically augmented by the arginine analog of plant origin canavanine, but not by the classic ER stress inducer tunicamycin. Our data suggest that canavanine treatment applied under the lack of arginine may enhance the efficacy of arginine deprivation -based anticancer therapy. (C) 2015 Elsevier Ltd. All rights reserved.	[Bobak, Yaroslav; Kurlishchuk, Yuliya; Vynnytska-Myronovska, Bozhena; Grydzuk, Olesia; Shuvayeva, Galyna; Stasyk, Oleh] Natl Acad Sci Ukraine, Inst Cell Biol, Dept Cell Signaling, Drahomanov Str 14-16, UA-79005 Lvov, Ukraine; [Kurlishchuk, Yuliya; Vynnytska-Myronovska, Bozhena; Kunz-Schughart, Leoni A.] Fac Med, OncoRay Natl Ctr Radiat Res Oncol, Fetscherstr 74, D-01307 Dresden, Germany; [Kurlishchuk, Yuliya; Vynnytska-Myronovska, Bozhena; Kunz-Schughart, Leoni A.] Univ Hosp Carl Gustav Carus, TU Dresden & Helmholtz Zentrum Dresden Rossendorf, Inst Radiooncol, Fetscherstr 74, D-01307 Dresden, Germany; [Redowicz, Maria J.] Polish Acad Sci, Nencki Inst Expt Biol, Lab Mol Basis Cell Motil, Pasteur Str 3, PL-02093 Warsaw, Poland; [Kunz-Schughart, Leoni A.] Dept Oncol, Old Rd,Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England; [Vynnytska-Myronovska, Bozhena] Univ Saarland, Clin Urol & Pediat Urol, Kirrberger Str, D-66421 Homburg, Germany		Stasyk, O (corresponding author), Natl Acad Sci Ukraine, Inst Cell Biol, Dept Cell Signaling, Drahomanov Str 14-16, UA-79005 Lvov, Ukraine.	bobakyaroslav@gmail.com; kurlishchukyuliya@gmail.com; b.vynnytskamyronovska@gmail.com; olesia.hr@gmail.com; galinash1977@mail.ru; jolanta@nencki.gov.pl; leoni.kunz-schughart@oncoray.de; stasyk@cellbiol.lviv.ua	Stasyk, Oleh/E-9496-2019; Shuvayeva, Galyna Yu/F-3863-2019; Bobak, Yaroslav P/F-4864-2019; Redowicz, Maria Jolanta/R-4083-2016; Redowicz, Maria Jolanta/AAM-8020-2020; Shuvayeva, Galyna/AAP-9669-2020	Stasyk, Oleh/0000-0001-8135-6102; Shuvayeva, Galyna Yu/0000-0001-7803-3900; Bobak, Yaroslav P/0000-0003-3399-1392; Redowicz, Maria Jolanta/0000-0001-5834-471X; Shuvayeva, Galyna/0000-0001-7803-3900; Kunz-Schughart, Leoni/0000-0003-3912-6594	Polish Ministry of Science and Higher EducationMinistry of Science and Higher Education, Poland [N303 3182 39]; statutory funds to the Nencki Institute; West-Ukrainian BioMedical Research Center; German Academic Exchange Service (DAAD)Deutscher Akademischer Austausch Dienst (DAAD)	The work has been supported by Polish Ministry of Science and Higher Education: grant N303 3182 39 to MJR, and the statutory funds to the Nencki Institute. YK and BVM were supported with fellowships granted by the West-Ukrainian BioMedical Research Center and the German Academic Exchange Service (DAAD).	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J. Biochem. Cell Biol.	JAN	2016	70						29	38		10.1016/j.biocel.2015.10.027			10	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	DB9WX	WOS:000368869500004	26546743				2022-04-25	
J	Wang, SH; Chong, ZZ; Shang, YC; Maiese, K				Wang, Shaohui; Chong, Zhao Zhong; Shang, Yan Chen; Maiese, Kenneth			WISP1 (CCN4) Autoregulates its Expression and Nuclear Trafficking of beta-Catenin during Oxidant Stress with Limited Effects upon Neuronal Autophagy	CURRENT NEUROVASCULAR RESEARCH			English	Article						Akt1; apoptosis; autophagy; beta-catenin; Beclin 1; CCN4; glycogen synthase kinase-3 beta; LC3; neurons; oxidative stress; p62; WISP; Wnt1	SIGNALING PATHWAY PROTEIN-1; INDUCED SECRETED PROTEIN-1; HUMAN COLORECTAL-CANCER; MICROGLIAL ACTIVATION; CELL-SURVIVAL; VASCULAR INTEGRITY; GENE-EXPRESSION; WNT PATHWAY; CROSS-TALK; KAPPA-B	Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4) is a CCN family member more broadly identified with development and tumorigenesis. However, recent studies have shed new light and enthusiasm on WISP1 as a novel target directed against toxic cell degeneration. Here we show WISP1 prevents apoptotic degeneration in primary neurons during oxidant stress through the activation of protein kinase B (Akt1), the post-translational maintenance of beta-catenin integrity that is consistent with inhibition of glycogen synthase kinase-3 beta (GSK-3 beta), and the subcellular trafficking of beta-catenin to foster its translocation to the nucleus. Interestingly, WISP1 autoregulates its expression through the promotion of beta-catenin activity and may employ beta-catenin to have a limited control over autophagy, but neuronal injury during oxidant stress as a result of autophagy appears portioned to a small population of neurons without significant impact upon overall cell survival. New strategies that target WISP1, its autoregulation, and the pathways responsible for neuronal cell injury may bring forth new insight for the treatment of neurodegenerative disorders.	[Maiese, Kenneth] New Jersey Hlth Sci Univ, Ctr Canc, Lab Cellular & Mol Signaling, Newark, NJ 07101 USA; [Maiese, Kenneth] New Jersey Hlth Sci Univ, Canc Inst New Jersey, Newark, NJ 07101 USA		Maiese, K (corresponding author), New Jersey Hlth Sci Univ, Ctr Canc, Lab Cellular & Mol Signaling, F 1220,205 S Orange Ave, Newark, NJ 07101 USA.	wntin75@yahoo.com	Wang, Shaohui/G-7247-2012		American Diabetes AssociationAmerican Diabetes Association; American Heart Association (National)American Heart Association; Bugher FoundationAmerican Heart Association; LEARN Foundation; NIH NIEHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS); NIH NIAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA); NIH NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS); NIH ARRAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS053946] Funding Source: NIH RePORTER	This research was supported by the following grants to Kenneth Maiese: American Diabetes Association, American Heart Association (National), Bugher Foundation Award, LEARN Foundation Award, NIH NIEHS, NIH NIA, NIH NINDS, and NIH ARRA.	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Neurovasc. Res.	MAY	2012	9	2					91	101		10.2174/156720212800410858			11	Clinical Neurology; Neurosciences	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology	934UR	WOS:000303472700003	22475393	Green Accepted			2022-04-25	
J	Wang, LH; Li, MM; Sha, BB; Hu, XY; Sun, YX; Zhu, MD; Xu, Y; Li, PP; Wang, YT; Guo, YN; Li, JF; Shi, JX; Li, P; Hu, T; Chen, P				Wang, Longhao; Li, Miaomiao; Sha, Beibei; Hu, Xuanyu; Sun, Yaxin; Zhu, Mingda; Xu, Yan; Li, Pingping; Wang, Yating; Guo, Yanyan; Li, Jiangfeng; Shi, Jianxiang; Li, Pei; Hu, Tao; Chen, Ping			Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma	CELL PROLIFERATION			English	Article						apoptosis; autophagy; ER stress; oesophageal squamous cell carcinoma; PR&#8208; 619	SMALL-MOLECULE INHIBITOR; ENDOPLASMIC-RETICULUM STRESS; COLORECTAL-CANCER; MULTIPLE-MYELOMA; OVARIAN-CANCER; ENZYME USP14; CAMKK-BETA; EXPRESSION; AMPK; PROLIFERATION	Objectives Targeting the deubiquitinases (DUBs) has become a promising avenue for anti-cancer drug development. However, the effect and mechanism of pan-DUB inhibitor, PR-619, on oesophageal squamous cell carcinoma (ESCC) cells remain to be investigated. Materials and Methods The effect of PR-619 on ESCC cell growth and cell cycle was evaluated by CCK-8 and PI staining. Annexin V-FITC/PI double staining was performed to detect apoptosis. LC3 immunofluorescence and acridine orange staining were applied to examine autophagy. Intercellular Ca2+ concentration was monitored by Fluo-3AM fluorescence. The accumulation of ubi-proteins and the expression of the endoplasmic reticulum (ER) stress-related protein and CaMKK beta-AMPK signalling were determined by immunoblotting. Results PR-619 could inhibit ESCC cell growth and induce G2/M cell cycle arrest by downregulating cyclin B1 and upregulating p21. Meanwhile, PR-619 led to the accumulation of ubiquitylated proteins, induced ER stress and triggered apoptosis by the ATF4-Noxa axis. Moreover, the ER stress increased cytoplasmic Ca2+ and then stimulated autophagy through Ca2+-CaMKK beta-AMPK signalling pathway. Ubiquitin E1 inhibitor, PYR-41, could reduce the accumulation of ubi-proteins and alleviate ER stress, G2/M cell cycle arrest, apoptosis and autophagy in PR-619-treated ESCC cells. Furthermore, blocking autophagy by chloroquine or bafilomycin A1 enhanced the cell growth inhibition effect and apoptosis induced by PR-619. Conclusions Our findings reveal an unrecognized mechanism for the cytotoxic effects of general DUBs inhibitor (PR-619) and imply that targeting DUBs may be a potential anti-ESCC strategy.	[Wang, Longhao; Li, Miaomiao; Sha, Beibei; Hu, Xuanyu; Sun, Yaxin; Zhu, Mingda; Xu, Yan; Li, Pingping; Wang, Yating; Guo, Yanyan; Li, Jiangfeng; Li, Pei; Hu, Tao; Chen, Ping] Zhengzhou Univ, Acad Med Sci, Sch Basic Med Sci, Zhengzhou, Peoples R China; [Shi, Jianxiang] Zhengzhou Univ, Henan Inst Med & Pharmaceut Sci, Precis Med Ctr, Zhengzhou, Peoples R China; [Shi, Jianxiang] Zhengzhou Univ, BGI Coll, Zhengzhou, Peoples R China; [Chen, Ping] Zhengzhou Univ, Henan Key Lab Precis Clin Pharm, Affiliated Hosp 1, Zhengzhou, Peoples R China		Hu, T; Chen, P (corresponding author), Zhengzhou Univ, Sch Basic Med Sci, Zhengzhou 450001, Peoples R China.	hnhutao@zzu.edu.cn; zzdx_chenping@zzu.edu.cn			Program for Innovation Research Team (in Science and Technology) in University of Henan Province [20IRTSTHN026]; National Natural Science Foundation Grant of ChinaNational Natural Science Foundation of China (NSFC) [81672421]; Program for Science&Technology Innovation Talents in Universities of Henan Province [18HASTIT046]; Outstanding Young Talent Research Fund of Zhengzhou University [51999223, 32210449]; Henan Key Laboratory of Precision Clinical Pharmacy	Program for Innovation Research Team (in Science and Technology) in University of Henan Province, Grant/Award Number: 20IRTSTHN026; National Natural Science Foundation Grant of China, Grant/Award Number: 81672421; Program for Science&Technology Innovation Talents in Universities of Henan Province, Grant/Award Number: 18HASTIT046; Outstanding Young Talent Research Fund of Zhengzhou University, Grant/Award Number: 51999223 and 32210449; Open Program of Henan Key Laboratory of Precision Clinical Pharmacy	Albert MC, 2014, MOL CELL ONCOL, V1, DOI 10.4161/mco.29906; Altun M, 2011, CHEM BIOL, V18, P1401, DOI 10.1016/j.chembiol.2011.08.018; An T, 2017, BIOCHEM PHARMACOL, V131, P29, DOI 10.1016/j.bcp.2017.02.011; Boutros R, 2007, NAT REV CANCER, V7, P495, DOI 10.1038/nrc2169; Cai JY, 2017, ONCOTARGET, V8, P63232, DOI 10.18632/oncotarget.18774; Chauhan D, 2012, CANCER CELL, V22, P345, DOI 10.1016/j.ccr.2012.08.007; 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JAN	2021	54	1							e12919	10.1111/cpr.12919		OCT 2020	17	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	PS9LS	WOS:000582979200001	33129231	gold, Green Published			2022-04-25	
J	Pan, SJ; Hong, F; Li, LT; Guo, Y; Qiao, XX; Zhang, J; Xu, PF; Zhai, YG				Pan, Shijia; Hong, Fan; Li, Letong; Guo, Yuan; Qiao, Xiaoxiao; Zhang, Jia; Xu, Pengfei; Zhai, Yonggong			Melatonin Attenuates Dextran Sodium Sulfate Induced Colitis in Obese Mice	PHARMACEUTICALS			English	Article						melatonin; obesity; colitis; lipolysis; autophagy	INFLAMMATORY-BOWEL-DISEASE; DIET-INDUCED OBESITY; OXIDATIVE STRESS; EPITHELIAL-CELLS; ANTIOXIDANT DEFENSES; COLORECTAL-CANCER; CROHNS-DISEASE; ADIPOSE-TISSUE; PPAR-GAMMA; TNF-ALPHA	Epidemiological studies have indicated that obesity is an independent risk factor for colitis and that a high-fat diet (HFD) increases the deterioration of colitis-related indicators in mice. Melatonin has multiple anti-inflammatory effects, including inhibiting tumor growth and regulating immune defense. However, the mechanism of its activity in ameliorating obesity-promoted colitis is still unclear. This study explored the possibility that melatonin has beneficial functions in HFD-induced dextran sodium sulfate (DSS)-induced colitis in mice. Here, we revealed that HFD-promoted obesity accelerated DSS-induced colitis, while melatonin intervention improved colitis. Melatonin significantly alleviated inflammation by increasing anti-inflammatory cytokine release and reducing the levels of proinflammatory cytokines in HFD- and DSS-treated mice. Furthermore, melatonin expressed antioxidant activities and reversed intestinal barrier integrity, resulting in improved colitis in DSS-treated obese mice. We also found that melatonin could reduce the ability of inflammatory cells to utilize fatty acids and decrease the growth-promoting effect of lipids by inhibiting autophagy. Taken together, our study indicates that the inhibitory effect of melatonin on autophagy weakens the lipid-mediated prosurvival advantage, which suggests that melatonin-targeted autophagy may provide an opportunity to prevent colitis in obese individuals.	[Pan, Shijia; Hong, Fan; Li, Letong; Guo, Yuan; Qiao, Xiaoxiao; Zhang, Jia; Xu, Pengfei; Zhai, Yonggong] Beijing Normal Univ, Coll Life Sci, Beijing Key Lab Gene Resource & Mol Dev, Beijing 100875, Peoples R China; [Pan, Shijia; Hong, Fan; Li, Letong; Guo, Yuan; Qiao, Xiaoxiao; Zhang, Jia; Zhai, Yonggong] Beijing Normal Univ, Coll Life Sci, State Educ Minist, Key Lab Cell Proliferat & Regulat Biol, Beijing 100875, Peoples R China; [Xu, Pengfei] Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA; [Xu, Pengfei] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA		Xu, PF; Zhai, YG (corresponding author), Beijing Normal Univ, Coll Life Sci, Beijing Key Lab Gene Resource & Mol Dev, Beijing 100875, Peoples R China.; Zhai, YG (corresponding author), Beijing Normal Univ, Coll Life Sci, State Educ Minist, Key Lab Cell Proliferat & Regulat Biol, Beijing 100875, Peoples R China.; Xu, PF (corresponding author), Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA.; Xu, PF (corresponding author), Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.	201931200003@mail.bnu.edu.cn; hongfanky@126.com; 201921200016@mail.bnu.edu.cn; gy5326@126.com; 201921200023@mail.bnu.edu.cn; 202021200029@mail.bnu.edu.cn; PEX9@pitt.edu; ygzhai@bnu.edu.cn		Xu, Pengfei/0000-0001-6854-6040	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31571164, 82070901]; BNU Interdisciplinary Research Foundation for First-Year Doctoral Candidates [BNUXKJC1924]	This research was funded by the National Natural Science Foundation of China (NO. 31571164 and NO. 82070901). This research was also supported by the BNU Interdisciplinary Research Foundation for First-Year Doctoral Candidates (Grant NO. BNUXKJC1924).	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J	He, J; Chen, YP; Cai, L; Li, ZL; Guo, XQ				He, Jing; Chen, Yuanping; Cai, Lu; Li, Zelei; Guo, Xiaoqing			UBAP2L silencing inhibits cell proliferation and G2/M phase transition in breast cancer	BREAST CANCER			English	Article						Breast cancer; CDK1; Cell proliferation; Cyclin B1; G2/M phase; UBAP2L	UBIQUITIN-PROTEASOME SYSTEM; PROTEIN 2-LIKE; CARCINOMA CELLS; DOWN-REGULATION; GROWTH; AUTOPHAGY; THERAPY	Ubiquitin-associated protein 2-like (UBAP2L) contains a ubiquitin-associated domain near its N-terminus, which has been demonstrated to be overexpressed in multiple tumors, including hepatocellular carcinoma and colorectal carcinoma but its role has not been well studied in breast cancer. Thus, this study was designed to evaluate whether UBAP2L can serve as a potential molecular target for breast cancer therapy. The expression of UBAP2L was determined in breast cancer tissues and cell lines by Western blotting and Oncomine database mining. Then the expression of UBAP2L was silenced using RNA interference and the effects of UBAP2L knockdown on breast cancer cell proliferation and cell cycle progression by MTT and colony formation assay, and Flow cytometry, respectively. We found the expression of UBAP2L was significantly up-regulated in breast cancer tissues and cell lines. Knockdown of UBAP2L suppressed cell proliferation, impaired colony formation ability and induced cell cycle arrest at G2/M phase. At molecular levels, knockdown of UBAP2L increased p21 expression, but decreased the expression of CDK1 and Cyclin B1 in breast cancer cells. Our findings suggest that UBAP2L plays an important role in breast cancer cell proliferation and might serve as a potential target for breast cancer treatment.	[He, Jing; Chen, Yuanping; Cai, Lu; Li, Zelei; Guo, Xiaoqing] Nanchang Univ, Dept Oncol, Affiliated Ganzhou Hosp, 17 Hongqi Ave, Ganzhou 341000, Jiangxi, Peoples R China		Guo, XQ (corresponding author), Nanchang Univ, Dept Oncol, Affiliated Ganzhou Hosp, 17 Hongqi Ave, Ganzhou 341000, Jiangxi, Peoples R China.	guoxiaoQ_0102@126.com					Al-Hajj M, 2003, P NATL ACAD SCI USA, V100, P3983, DOI 10.1073/pnas.0530291100; Baumgartner R, 2013, PLOS GENET, V9, DOI 10.1371/journal.pgen.1003598; Bordeleau ME, 2014, BLOOD, V124, P2362, DOI 10.1182/blood-2014-01-548651; Chai R, 2016, TUMOR BIOL, V37, P13225, DOI 10.1007/s13277-016-5159-y; Ciechanover A, 2003, NEURON, V40, P427, DOI 10.1016/S0896-6273(03)00606-8; Ford D, 1998, AM J HUM GENET, V62, P676, DOI 10.1086/301749; Huang WW, 2013, INT J ONCOL, V42, P2069, DOI 10.3892/ijo.2013.1909; Lee MJ, 2013, PROG NEUROBIOL, V105, P49, DOI 10.1016/j.pneurobio.2013.03.001; Li D, 2014, ONCOL REP, V32, P1578, DOI 10.3892/or.2014.3360; Liao YJ, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.66; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Ma XJ, 2009, BREAST CANCER RES, V11, DOI 10.1186/bcr2222; Maeda M, 2016, FASEB J, V30, P312, DOI 10.1096/fj.14-268987; Muller A, 2001, NATURE, V410, P50, DOI 10.1038/35065016; Prat A, 2015, BREAST, V24, pS26, DOI 10.1016/j.breast.2015.07.008; Rousseau D, 1999, ONCOGENE, V18, P4313, DOI 10.1038/sj.onc.1202686; Siegel R, 2014, CA-CANCER J CLIN, V64, P104, DOI 10.3322/caac.21220; Stockler M, 2000, CANCER TREAT REV, V26, P151, DOI 10.1053/ctrv.1999.0161; Wilde IB, 2011, J PROTEOME RES, V10, P1062, DOI 10.1021/pr1008543; Yang YL, 2009, CANCER SCI, V100, P24, DOI 10.1111/j.1349-7006.2008.01013.x; Ye T, 2017, CELL PHYSIOL BIOCHEM, V41, P1584, DOI 10.1159/000470824; Zhao B, 2015, INT J MOL MED, V36, P1012, DOI 10.3892/ijmm.2015.2323; Zhao HJ, 2004, MOL BIOL CELL, V15, P2523, DOI 10.1091/mbc.E03-11-0786	23	15	15	0	6	SPRINGER JAPAN KK	TOKYO	CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN	1340-6868	1880-4233		BREAST CANCER-TOKYO	Breast Cancer	MAR	2018	25	2					224	232		10.1007/s12282-017-0820-x			9	Oncology; Obstetrics & Gynecology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Obstetrics & Gynecology	FW8AJ	WOS:000425549100013	29196913	hybrid, Green Published			2022-04-25	
J	Lee, CS; Lee, LC; Yuan, TL; Chakka, S; Fellmann, C; Lowe, SW; Caplen, NJ; McCormick, F; Luo, J				Lee, Chih-Shia; Lee, Liam C.; Yuan, Tina L.; Chakka, Sirisha; Fellmann, Christof; Lowe, Scott W.; Caplen, Natasha J.; McCormick, Frank; Luo, Ji			MAP kinase and autophagy pathways cooperate to maintain RAS mutant cancer cell survival	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA			English	Article						KRAS; RAF; MAPK; autophagy; siRNA	INHIBITOR TRAMETINIB GSK1120212; SYNTHETIC LETHAL INTERACTIONS; IB DOSE-ESCALATION; LUNG-CANCER; K-RAS; C-RAF; TUMOR PROGRESSION; CYCLE ARREST; MOUSE MODEL; PHASE-I	Oncogenic mutations in the small GTPase KRAS are frequently found in human cancers, and, currently, there are no effective targeted therapies for these tumors. Using a combinatorial siRNA approach, we analyzed a panel of KRAS mutant colorectal and pancreatic cancer cell lines for their dependency on 28 gene nodes that represent canonical RAS effector pathways and selected stress response pathways. We found that RAF node knockdown best differentiated KRAS mutant and KRAS WT cancer cells, suggesting RAF kinases are key oncoeffectors for KRAS addiction. By analyzing all 376 pairwise combination of these gene nodes, we found that cotargeting the RAF, RAC, and autophagy pathways can improve the capture of KRAS dependency better than targeting RAF alone. In particular, codepletion of the oncoeffector kinases BRAF and CRAF, together with the autophagy E1 ligase ATG7, gives the best therapeutic window between KRAS mutant cells and normal, untransformed cells. Distinct patterns of RAS effector dependency were observed across KRAS mutant cell lines, indicative of heterogeneous utilization of effector and stress response pathways in supporting KRAS addiction. Our findings revealed previously unappreciated complexity in the signaling network downstream of the KRAS oncogene and suggest rational target combinations for more effective therapeutic intervention.	[Lee, Chih-Shia; Lee, Liam C.; Luo, Ji] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA; [Yuan, Tina L.; McCormick, Frank] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA; [Chakka, Sirisha; Caplen, Natasha J.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA; [Fellmann, Christof; Lowe, Scott W.] Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA; [Lowe, Scott W.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA; [Lowe, Scott W.] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10065 USA; [McCormick, Frank] Leidos Biomed Res, Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD 21702 USA; [Lee, Liam C.] Loxo Oncol, Med Affairs, Stamford, CT 06901 USA; [Yuan, Tina L.] Novartis Inst Biomed Res, Oncol Translat Res, Cambridge, MA 02139 USA; [Chakka, Sirisha] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA; [Fellmann, Christof] Gladstone Inst, Inst Data Sci & Biotechnol, San Francisco, CA 94158 USA		Luo, J (corresponding author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.; McCormick, F (corresponding author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.; McCormick, F (corresponding author), Leidos Biomed Res, Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD 21702 USA.	frank.mccormick@ucsf.edu; ji.luo@nih.gov	Caplen, Natasha J/H-2768-2016	Caplen, Natasha J/0000-0002-0001-9460; Fellmann, Christof/0000-0002-9545-5723	NCI Intramural Grant [ZIA BC 011437]; NCI Director's Innovation Award; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIABC011437] Funding Source: NIH RePORTER	We thank Drs. Eric Batchelor, Jayne Stommel, and Rosandra Kaplan for their constructive suggestions, and the Flow Cytometry Core Facility of the Center for Cancer Research at the National Cancer Institute (NCI) for the technical support. This work was supported by NCI Intramural Grant ZIA BC 011437 (to J.L.) and by an NCI Director's Innovation Award (to C.-S.L.).	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Natl. Acad. Sci. U. S. A.	MAR 5	2019	116	10					4508	4517		10.1073/pnas.1817494116			10	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	HN5RI	WOS:000460242100085	30709910	Bronze, Green Published			2022-04-25	
J	Tan, J; Wang, HL; Yang, J; Liu, QQ; Li, CM; Wang, YQ; Fu, LN; Gao, QY; Chen, YX; Fang, JY				Tan, Juan; Wang, Hao-Lian; Yang, Jie; Liu, Qian-Qian; Li, Chun-Min; Wang, Yun-Qian; Fu, Lin-Na; Gao, Qin-Yan; Chen, Ying-Xuan; Fang, Jing-Yuan			JMJD2B-induced amino acid alterations enhance the survival of colorectal cancer cells under glucose-deprivation via autophagy	THERANOSTICS			English	Article						JMJD2B; CRC; amino acids metabolism; autophagy; LC3B	HISTONE DEMETHYLASE JMJD2B; DNA-DAMAGE RESPONSE; EPIGENETIC REGULATION; NUTRIENT DEPRIVATION; PROTEIN-SYNTHESIS; CYCLE ARREST; IN-VITRO; PROLIFERATION; APOPTOSIS; MELANOMA	Rationale: Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation. Methods: Non-target metabolic profiling was used to evaluate the roles of JMJD2B in CRC cell metabolism under glucose starvation. The roles of amino acid alterations induced by JMJD2B on CRC cell survival were determined by cell viability, immunoblotting, and clonogenic assays, and flow cytometry. The underlying mechanisms by which JMJD2B affected CRC cell metabolism were assessed using immunofluorescence staining, chromatin immunoprecipitation assays, electron microscopy in CRC cell lines, and using xenograft models. The correlation between JMJD2B and LC3B expression in human CRC specimens was assessed using immunohistochemistry. Results: Profound metabolic reprogramming was detected in JMJD2B knockdown CRC cells under glucose deficiency, especially those involving amino acid metabolites. Silencing of JMJD2B reduced the levels of certain amino acids that were induced by glucose deficiency. Among these amino acids, asparagine (Asn), phenylalanine (Phe), and histidine (His) promoted CRC cell survival under glucose starvation when JMJD2B was knocked down. Mechanistically, downregulation of JMJD2B inhibited autophagy in CRC cells through epigenetic regulation of microtubule associated protein 1 light chain 3 beta (LC3B), and subsequently decreased intracellular amino acid (Asn, Phe, His) levels under glucose deprivation, thus suppressing the survival of CRC cells. Using a nude mouse xenograft model, we verified that inhibiting JMJD2B could decrease the levels of amino acids (Asn, Phe, His). In addition, the inhibitory effects of JMJD2B-knockdown on tumor growth and amino acids level were rescued by overexpression of LC3B. Furthermore, we observed that the high expression of LC3B was more likely detected in tissuses with high expression of JMJD2B (P < 0.001) in 60 human CRC tissues. Conclusion: These results indicated that JMJD2B sustained the intracellular amino acids derived from autophagy in CRC cells upon glucose deficiency, partly through epigenetic regulation of LC3B, thus driving the malignancy of CRC.	[Tan, Juan; Wang, Hao-Lian; Liu, Qian-Qian; Li, Chun-Min; Wang, Yun-Qian; Fu, Lin-Na; Gao, Qin-Yan; Chen, Ying-Xuan; Fang, Jing-Yuan] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Key Lab Gastroenterol & Hepatol,Minist Hlth, Renji Hosp,Sch Med,Div Gastroenterol & Hepatol, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China; [Tan, Juan; Wang, Hao-Lian; Liu, Qian-Qian; Li, Chun-Min; Wang, Yun-Qian; Fu, Lin-Na; Gao, Qin-Yan; Chen, Ying-Xuan; Fang, Jing-Yuan] Shanghai Inst Digest Dis, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China; [Yang, Jie] Shanghai Jiao Tong Univ, Educ Minist Cell Differentiat & Apoptosis, Dept Biochem & Mol Cell Biol, Sch Med,Inst Med Sci,Key Lab, 280 South Chongqing Rd, Shanghai 200025, Peoples R China		Chen, YX (corresponding author), 145 Middle Shandong Rd, Shanghai 200001, Peoples R China.	yingxuanchen71@sjtu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772506, 81530072]; Shanghai Shenkang Center [SHDC12018121]	This study was supported by the National Natural Science Foundation of China (No. 81772506, 81530072), the funds from Shanghai Shenkang Center (SHDC12018121).	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J	Zheng, XR; Wei, JL; Li, WJ; Li, XL; Wang, WY; Guo, JB; Fu, ZX				Zheng, Xiangru; Wei, Jinlai; Li, Wenjun; Li, Xiaoli; Wang, Wuyi; Guo, Jinbao; Fu, Zhongxue			PRDX2 removal inhibits the cell cycle and autophagy in colorectal cancer cells	AGING-US			English	Article						colorectal cancer; cell-cycle; autophagy; P38 pathway	PEROXIREDOXIN 2; SIGNALING PATHWAYS; MAPK; PROGRESSION; STATISTICS; SURVIVAL; GROWTH; CHINA; PI3K	Colorectal cancer (CRC) is a prevalent worldwide disease in which the antioxidant enzyme peroxiredoxin 2 (PRDX2) plays an important role. To investigate the molecular mechanism of PRDX2 in CRC, we performed bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets and Gene Expression Omnibus (GEO) DataSets (accession no. GSE81429). Our results suggest that PRDX2 is associated with cell-cycle progression and autophagy activated by the P38 MAPK/FOXO signaling pathway. Using a short-hairpin RNA vector, we verified that PRDX2 is essential for CRC cell proliferation and S-phase progression. Immunostaining, electron microscopy and western blotting assays verified the effect of PRDX2 knockdown on autophagy flux and p38 activation. The P38 activator dehydrocorydaline chloride partially rescued the effects of sh-PRDX2 on the expression of proteins related to cell-cycle progression and autophagy. We verified the correlation between PRDX2 expression and the expression of an array of cell-cycle and autophagy-related genes using data from an independent set of 222 CRC patient samples. A mouse xenoplast model was consistent with in vitro results. Our results suggest that PRDX2 promotes CRC cell-cycle progression via activation of the p38 MAPK pathway.	[Zheng, Xiangru; Wei, Jinlai; Wang, Wuyi; Fu, Zhongxue] Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Chongqing, Peoples R China; [Li, Wenjun] Chongqing Med Univ, Dept Pharm, Affiliated Hosp 3, Chongqing, Peoples R China; [Li, Xiaoli] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [Guo, Jinbao] Chongqing Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Chongqing, Peoples R China		Fu, ZX (corresponding author), Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 1, Chongqing, Peoples R China.	fzx@hospital.cqmu.edu.cn		Zheng, Xiangru/0000-0003-1170-943X; Fu, Zhongxue/0000-0003-2765-3469	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572319]; Chongqing Municipal Education Commission [KJ1702021]; Chongqing Science and Technology CommissionNatural Science Foundation Project of CQ CSTC [cstc2017jcyjAX0127]; Key Project of Prevention and Control of Priority Diseases in Chongqing [2019ZX003]	National Natural Science Foundation of China: 81572319, Chongqing Municipal Education Commission: KJ1702021, Chongqing Science and Technology Commission: cstc2017jcyjAX0127, Key Project of Prevention and Control of Priority Diseases in Chongqing: 2019ZX003.	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J	Colangelo, T; Polcaro, G; Ziccardi, P; Muccillo, L; Galgani, M; Pucci, B; Milone, MR; Budillon, A; Santopaolo, M; Mazzoccoli, G; Matarese, G; Sabatino, L; Colantuoni, V				Colangelo, T.; Polcaro, G.; Ziccardi, P.; Muccillo, L.; Galgani, M.; Pucci, B.; Milone, M. Rita; Budillon, A.; Santopaolo, M.; Mazzoccoli, G.; Matarese, G.; Sabatino, L.; Colantuoni, V.			The miR-27a-calreticulin axis affects drug-induced immunogenic cell death in human colorectal cancer cells	CELL DEATH & DISEASE			English	Article							CALRETICULIN EXPOSURE; ATP SECRETION; AUTOPHAGY; DAMPS; MECHANISMS; MICRORNAS; PROMOTES; PATHWAY; GROWTH	Immunogenic cell death (ICD) evoked by chemotherapeutic agents implies emission of selected damage-associated molecular patterns (DAMP) such as cell surface exposure of calreticulin, secretion of ATP and HMGB1. We sought to verify whether miR-27a is implicated in ICD, having demonstrated that it directly targets calreticulin. To this goal, we exposed colorectal cancer cell lines, genetically modified to express high or low miR-27a levels, to two bona fide ICD inducers (mitoxantrone and oxaliplatin). Low miR-27a-expressing cells displayed more ecto-calreticulin on the cell surface and increased ATP and HMGB1 secretion than high miR-27a-expressing ones in time-course experiments upon drug exposure. A calreticulin target protector counteracted the miR-27a effects while specific siRNAs mimicked them, confirming the results reported. In addition, miR-27a negatively influenced the PERK-mediated route and the late PI3K-dependent secretory step of the unfolded protein response to endoplasmic reticulum stress, suggesting that miR-27a modulates the entire ICD program. Interestingly, upon chemotherapeutic exposure, low miR-27a levels associated with an earlier and stronger induction of apoptosis and with morphological and molecular features of autophagy. Remarkably, in ex vivo setting, under the same chemotherapeutic induction, the conditioned media from high miR-27a-expressing cells impeded dendritic cell maturation while increased the secretion of specific cytokines (interleukin (IL)-4, IL-6, IL-8) and negatively influenced CD4(+) T-cell interferon. production and proliferation, all markers of a tumor immunoevasion strategy. In conclusion, we provide the first evidence that miR-27a impairs the cell response to drug-induced ICD through the regulatory axis with calreticulin.	[Colangelo, T.; Polcaro, G.; Ziccardi, P.; Muccillo, L.; Sabatino, L.; Colantuoni, V.] Univ Sannio, Dept Sci & Technol, Via PortArsa 11, I-82100 Benevento, Italy; [Galgani, M.; Matarese, G.] CNR, IEOS, I-80131 Naples, Italy; [Pucci, B.; Milone, M. Rita; Budillon, A.] Ist Nazl Tumori Fdn G Pascale IRCCS, Ctr Ric Oncol Mercogliano, I-83013 Mercogliano, AV, Italy; [Santopaolo, M.; Matarese, G.] Univ Naples Federico II, Dipartimento Med Mol & Biotecnol Med, I-80131 Naples, Italy; [Mazzoccoli, G.] IRCCS Casa Sollievo Sofferenza, Div Internal Med, I-71013 San Giovanni Rotondo, FG, Italy; [Mazzoccoli, G.] IRCCS Casa Sollievo Sofferenza, Chronobiol Unit, I-71013 San Giovanni Rotondo, FG, Italy		Colantuoni, V (corresponding author), Univ Sannio, Dept Sci & Technol, Via PortArsa 11, I-82100 Benevento, Italy.	colantuoni@unisannio.it	Pucci, Biagio/AAS-7502-2021; Polcaro, Giovanna/AAC-1810-2019; Matarese, Giuseppe/AAO-4077-2021; Mazzoccoli, Gianluigi/H-2447-2016; pucci, biagio/AAA-9268-2020; Galgani, Mario/AAC-3298-2022; Budillon, Alfredo/K-4763-2016; Colangelo, Tommaso/B-6119-2017	Polcaro, Giovanna/0000-0002-2329-3200; Matarese, Giuseppe/0000-0001-9429-0616; Mazzoccoli, Gianluigi/0000-0003-3535-7635; pucci, biagio/0000-0003-4502-1748; Budillon, Alfredo/0000-0002-6330-6053; Colangelo, Tommaso/0000-0002-6927-403X; Galgani, Mario/0000-0001-8414-1676	AIL (Associazione italiana per lo studio dei linfomi e plasmacitomi); Fondazione Italiana Sclerosi Multipla (FISM)Fondazione Italiana Sclerosi Multipla (FISM) [2012/R/11]; EU Ideas Programme; ERC-StG 'menTORingTregs' [310496]; FIRB MERIT Grant [RBNE08HWLZ_015]; CNR Medicina Personalizzata Grant; Juvenile Diabetes Research Foundation (JDRF)Juvenile Diabetes Research Foundation [1-PNF-2015-115-5-B]; PhD Program in Medicina Molecolare e Biotecnologie Mediche, Universita degli Studi di Napoli 'Federico ll'	This work was partially supported by a grant from AIL (Associazione italiana per lo studio dei linfomi e plasmacitomi) to VC, by grants from the Fondazione Italiana Sclerosi Multipla (FISM) n. 2012/R/11, EU Ideas Programme, ERC-StG 'menTORingTregs' n. 310496, FIRB MERIT Grant n. RBNE08HWLZ_015, and a CNR Medicina Personalizzata Grant to GM and by a grant from Juvenile Diabetes Research Foundation (JDRF) n. 1-PNF-2015-115-5-B to MG. MS is supported by the PhD Program in Medicina Molecolare e Biotecnologie Mediche, Universita degli Studi di Napoli 'Federico ll'. We are grateful to Prof Marco E Bianchi for generous gift of reagents, critical reading of the manuscript and discussion. We would like to thank Mariarosaria Montagna (DBBBM) for technical assistance.	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FEB	2016	7								e2108	10.1038/cddis.2016.29			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	DG5FU	WOS:000372102400013	26913599	Green Published, gold			2022-04-25	
J	Gallot, YS; Durieux, AC; Castells, J; Desgeorges, MM; Vernus, B; Plantureux, L; Remond, D; Jahnke, VE; Lefai, E; Dardevet, D; Nemoz, G; Schaeffer, L; Bonnieu, A; Freyssenet, DG				Gallot, Yann S.; Durieux, Anne-Cecile; Castells, Josiane; Desgeorges, Marine M.; Vernus, Barbara; Plantureux, Lea; Remond, Didier; Jahnke, Vanessa E.; Lefai, Etienne; Dardevet, Dominique; Nemoz, Georges; Schaeffer, Laurent; Bonnieu, Anne; Freyssenet, Damien G.			Myostatin Gene Inactivation Prevents Skeletal Muscle Wasting in Cancer	CANCER RESEARCH			English	Article							INHIBIN-DEFICIENT MICE; FOXO TRANSCRIPTION FACTORS; CACHEXIA-LIKE SYNDROME; ACTRIIB ANTAGONISM; TUMOR PROGRESSION; II RECEPTORS; IN-VIVO; ATROPHY; ACTIVIN; MASS	Cachexia is a muscle-wasting syndrome that contributes significantly to morbidity and mortality of many patients with advanced cancers. However, little is understood about how the severe loss of skeletal muscle characterizing this condition occurs. In the current study, we tested the hypothesis that the muscle protein myostatin is involved in mediating the pathogenesis of cachexia-induced muscle wasting in tumor-bearing mice. Myostatin gene inactivation prevented the severe loss of skeletal muscle mass induced in mice engrafted with Lewis lung carcinoma (LLC) cells or in Apc(Min/+) mice, an established model of colorectal cancer and cachexia. Mechanistically, myostatin loss attenuated the activation of muscle fiber proteolytic pathways by inhibiting the expression of atrophy-related genes, MuRF1 and MAFbx/Atrogin-1, along with autophagy-related genes. Notably, myostatin loss also impeded the growth of LLC tumors, the number and the size of intestinal polyps in Apc(Min/+) mice, thus strongly increasing survival in both models. Gene expression analysis in the LLC model showed this phenotype to be associated with reduced expression of genes involved in tumor metabolism, activin signaling, and apoptosis. Taken together, our results reveal an essential role for myostatin in the pathogenesis of cancer cachexia and link this condition to tumor growth, with implications for furthering understanding of cancer as a systemic disease. (C)2014 AACR.	[Gallot, Yann S.; Durieux, Anne-Cecile; Castells, Josiane; Desgeorges, Marine M.; Plantureux, Lea; Jahnke, Vanessa E.; Freyssenet, Damien G.] Univ Lyon, Lab Physiol Exercice, St Etienne, France; [Vernus, Barbara; Bonnieu, Anne] INRA, UMR Dynam Musculaire & Metab 866, F-34060 Montpellier, France; [Remond, Didier; Dardevet, Dominique] INRA, UMR 1019, Unite Nutr Humaine, Clermont Ferrand, France; [Lefai, Etienne; Nemoz, Georges] Univ Lyon, CarMeN Lab, INRA USC1235, INSERM U1060, Oullins, France; [Schaeffer, Laurent] Ecole Normale Super Lyon, Lab Biol Mol Cellule, CNRS UMR 5239, F-69364 Lyon, France		Freyssenet, DG (corresponding author), Fac Med, Lab Physiol Exercice, 15 Rue Ambroise Pare, F-42023 St Etienne 2, France.	damien.freyssenet@univ-st-etienne.fr	Lefai, Etienne/E-9615-2019; Lefai, Etienne/L-7961-2019; Gallot, Yann Simon/ABC-1826-2021; Bonnieu, Anne/ABA-7182-2020	Lefai, Etienne/0000-0002-3042-7801; Lefai, Etienne/0000-0002-3042-7801; Gallot, Yann Simon/0000-0003-4447-1448; schaeffer, laurent/0000-0001-6600-503X; Dardevet, Dominique/0000-0001-7320-9970; Remond, Didier/0000-0003-4430-0067	Ligue Contre le CancerLigue nationale contre le cancer; Institut National du Cancer (INCa)Institut National du Cancer (INCA) France	This work was supported by grants from the Ligue Contre le Cancer and the Institut National du Cancer (INCa).	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DEC 15	2014	74	24					7344	7356		10.1158/0008-5472.CAN-14-0057			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AW6FC	WOS:000346363900020	25336187	Bronze			2022-04-25	
J	Liu, YQ; Chen, XJ; Chen, XL; Liu, JQ; Gu, H; Fan, RT; Ge, H				Liu, Yingqiang; Chen, Xijuan; Chen, Xiling; Liu, Junqi; Gu, Hao; Fan, Ruitai; Ge, Hong			Long non-coding RNA HOTAIR knockdown enhances radiosensitivity through regulating microRNA-93/ATG12 axis in colorectal cancer	CELL DEATH & DISEASE			English	Article							AUTOPHAGY; RESISTANCE; MICRORNAS; ROLES; CERNA; CELLS	Colorectal cancer (CRC) is a global healthcare problem. Radioresistance is a huge setback for CRC radiotherapy. In this text, the roles and molecular mechanisms of long non-coding RNA HOTAIR in CRC tumorigenesis and radioresistance were further investigated. ATG12 mRNA, HOTAIR, and microRNA-93 (miR-93) levels were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. Protein levels of LC3 I, LC3 II, p62, ATG12, cleaved caspase 3, Bax, and Bcl-2 were detected by western blotting assay in cells and were examined by immunohistochemistry (IHC) assay in tissues. Cell survival fractions, viability, and apoptotic rates were determined by clonogenic survival assay, CCK-8 assay, and flow cytometry analysis, respectively. The relationships of HOTAIR, miR-93, and ATG12 were tested by bioinformatics analysis and luciferase reporter assay. Mouse xenograft tumor models were established to investigate the influence of HOTAIR knockdown on CRC radioresistance in vivo. We found that HOTAIR expression was markedly upregulated in plasma from CRC patients after radiotherapy and CRC cells after irradiation. HOTAIR knockdown, miR-93 overexpression, or ATG12 silencing weakened cell viability, induced cell apoptosis, inhibited cell autophagy, and enhanced cell radiosensitivity in CRC. HOTAIR exerted its functions by downregulating miR-93. Moreover, HOTAIR functioned as a molecular sponge of miR-93 to regulate ATG12 expression. ATG12 protein expression was markedly upregulated and associated with miR-93 and HOTAIR expression in CRC tissues. Furthermore, HOTAIR knockdown enhanced radiosensitivity of CRC xenograft tumors by regulating miR-93/ATG12 axis. In conclusion, HOTAIR knockdown potentiated radiosensitivity through regulating miR-93/ATG12 axis in CRC, further elucidating the roles and molecular basis of HOTAIR in CRC radioresistance.	[Liu, Yingqiang] Zhengzhou Univ, Affiliated Tumor Hosp, Dept Gen Surg, Zhengzhou, Henan, Peoples R China; [Chen, Xijuan; Ge, Hong] Zhengzhou Univ, Affiliated Tumor Hosp, Dept Radiat Oncol, Zhengzhou, Henan, Peoples R China; [Chen, Xiling] Zhengzhou Univ, Affiliated Hosp 2, Dept Geriatr Med, Zhengzhou, Henan, Peoples R China; [Liu, Junqi; Gu, Hao; Fan, Ruitai] Zhengzhou Univ, Affiliated Hosp 1, Dept Radiat Oncol, Zhengzhou, Henan, Peoples R China		Ge, H (corresponding author), Zhengzhou Univ, Affiliated Tumor Hosp, Dept Radiat Oncol, Zhengzhou, Henan, Peoples R China.	nihaoma22189@sina.com		Liu, Junqi/0000-0002-6015-1033	Subsidized Project of Henan Medical Science and Technology Research Program [201304060]	This work was supported by the Subsidized Project of Henan Medical Science and Technology Research Program (Grant Number 201304060).	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MAR 6	2020	11	3							175	10.1038/s41419-020-2268-8			14	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	KT8JV	WOS:000519258800003	32144238	Green Published, gold			2022-04-25	
J	Vangestel, C; Van de Wiele, C; Mees, G; Mertens, K; Staelens, S; Reutelingsperger, C; Pauwels, P; Van Damme, N; Peeters, M				Vangestel, Christel; Van de Wiele, Christophe; Mees, Gilles; Mertens, Koen; Staelens, Steven; Reutelingsperger, Chris; Pauwels, Patrick; Van Damme, Nancy; Peeters, Marc			Single-Photon Emission Computed Tomographic Imaging of the Early Time Course of Therapy-Induced Cell Death Using Technetium 99m Tricarbonyl His-Annexin A5 in a Colorectal Cancer Xenograft Model	MOLECULAR IMAGING			English	Article							APOPTOTIC TUMOR RESPONSE; IN-VIVO DETECTION; IONIZING-RADIATION; V SCINTIGRAPHY; CHEMOTHERAPY; PHOSPHATIDYLSERINE; AUTOPHAGY; PANITUMUMAB; INCREASES; EFFICACY	As apoptosis occurs over an interval of time after administration of apoptosis-inducing therapy in tumors, the changes in technetium 99m (Tc-99m)-tricarbonyl (CO)(3) His-annexin A5 (His-ann A5) accumulation over time were examined. Colo205-bearing mice were divided into six treatment groups: (1) control, (2) 5-fluorouracil (5-FU; 250 mg/kg), (3) irinotecan (100 mg/kg), (4) oxaliplatin (30 mg/kg), (5) bevacizumab (5 mg/kg), and (6) panitumumab (6 mg/kg). (99)mTc-(CO)(3) His-ann A5 was injected 4, 8, 12, 24, and 48 hours posttreatment, and micro-single-photon emission computed tomography was performed. Immunostaining of caspase-3 (apoptosis), survivin (antiapoptosis), and LC3-II (autophagy marker) was also performed. Different dynamics of (99)mTc-(CO)(3) His-ann A5 uptake were observed in this colorectal cancer xenograft model, in response to a single dose of three different chemotherapeutics (5-FU, irinotecan, and oxaliplatin). Bevacizumab-treated mice showed no increased uptake of the radiotracer, and a peak of (99)mTc-(CO)(3) HisannA5 uptake in panitumumab-treated mice was observed 24 hours posttreatment, as confirmed by caspase-3 immunostaining. For irinotecan-, oxaliplatin-, and bevacizumab-treated tumors, a significant correlation was established between the radiotracer uptake and caspase-3 immunostaining (r = .8, p < .05; r = .9, p < .001; r = .9, p < .001, respectively). For 5-FU- and panitumumab-treated mice, the correlation coefficients were r = .7 (p = .18) and r = .7 (p = .19), respectively. Optimal timing of annexin A5 imaging after the start of different treatments in the Colo205 model was determined.	[Vangestel, Christel] Ghent Univ Hosp, Dept Gastroenterol, B-9000 Ghent, Belgium; Ghent Univ Hosp, Dept Nucl Med & Radiol, B-9000 Ghent, Belgium; Ghent Univ Hosp, Dept Pathol, B-9000 Ghent, Belgium; Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, Groningen, Netherlands; Ghent Univ IBBT, Fac Engn, Dept Med Signal, Ghent, Belgium; Ghent Univ IBBT, Fac Engn, Image Proc Grp, Ghent, Belgium; Univ Maastricht, Cardiovasc Res Inst, Dept Biochem, Maastricht, Netherlands		Vangestel, C (corresponding author), Ghent Univ Hosp, Dept Gastroenterol, Pintelaan 185, B-9000 Ghent, Belgium.	christel.vangestel@uza.be	Peeters, Marc/C-5525-2013; Staelens, Steven/D-8385-2017	Peeters, Marc/0000-0003-4969-2303; Staelens, Steven/0000-0003-3376-0519	European Union through a Euregional PACT II grant from the Interreg IV program of Grensregio Vlaanderen-Nederland [IVA-VLANED-1.20]	Part of this work was financially supported by the European Union through a Euregional PACT II grant from the Interreg IV program of Grensregio Vlaanderen-Nederland (IVA-VLANED-1.20).	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Imaging	MAR-APR	2012	11	2					135	147		10.2310/7290.2011.00034			13	Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging	990QO	WOS:000307645900005	22469241	gold			2022-04-25	
J	Huang, Z; Liu, J; Luo, L; Sheng, P; Wang, B; Zhang, J; Peng, SS				Huang, Zhi; Liu, Jie; Luo, Liang; Sheng, Pan; Wang, Biao; Zhang, Jun; Peng, Sha-sha			Genome-Wide Identification of a Novel Autophagy-Related Signature for Colorectal Cancer	DOSE-RESPONSE			English	Article						colorectal cancer; autophagy-related genes; prognostic signature; RNA sequencing	NEUREGULIN-1 NRG1; PROLIFERATION; EXPRESSION; PROGRESSION; METASTASIS; RECURRENCE; SURVIVAL; INVASION; ISOFORM; THERAPY	Background: Plenty of evidence has suggested that autophagy plays a crucial role in the biological processes of cancers. This study aimed to screen autophagy-related genes (ARGs) and establish a novel a scoring system for colorectal cancer (CRC). Methods: Autophagy-related genes sequencing data and the corresponding clinical data of CRC in The Cancer Genome Atlas were used as training data set. The GSE39582 data set from the Gene Expression Omnibus was used as validation set. An autophagy-related signature was developed in training set using univariate Cox analysis followed by stepwise multivariate Cox analysis and assessed in the validation set. Then we analyzed the function and pathways of ARGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Finally, a prognostic nomogram combining the autophagy-related risk score and clinicopathological characteristics was developed according to multivariate Cox analysis. Results: After univariate and multivariate analysis, 3 ARGs were used to construct autophagy-related signature. The KEGG pathway analyses showed several significantly enriched oncological signatures, such as p53 signaling pathway, apoptosis, human cytomegalovirus infection, platinum drug resistance, necroptosis, and ErbB signaling pathway. Patients were divided into high- and low-risk groups, and patients with high risk had significantly shorter overall survival (OS) than low-risk patients in both training set and validation set. Furthermore, the nomogram for predicting 3- and 5-year OS was established based on autophagy-based risk score and clinicopathologic factors. The area under the curve and calibration curves indicated that the nomogram showed well accuracy of prediction. Conclusions: Our proposed autophagy-based signature has important prognostic value and may provide a promising tool for the development of personalized therapy.	[Huang, Zhi; Liu, Jie; Luo, Liang; Sheng, Pan; Wang, Biao; Zhang, Jun] Dazhou Cent Hosp, Dept Gen Surg, Dazhou, Sichuan, Peoples R China; [Peng, Sha-sha] Hubei Polytech Univ, Huangshi Cent Hosp, Dept Hepatobiliary & Pancreat Surg, Edong Healthcare Grp, 141 Tianjin Rd, Huangshi 435000, Hubei, Peoples R China; [Peng, Sha-sha] Wuhan Univ Sci & Technol, Hubei Prov Key Lab Occupat Hazard Identificat & C, 141 Tianjin Rd, Wuhan 435000, Hubei, Peoples R China		Peng, SS (corresponding author), Hubei Polytech Univ, Huangshi Cent Hosp, Dept Hepatobiliary & Pancreat Surg, Edong Healthcare Grp, 141 Tianjin Rd, Huangshi 435000, Hubei, Peoples R China.; Peng, SS (corresponding author), Wuhan Univ Sci & Technol, Hubei Prov Key Lab Occupat Hazard Identificat & C, 141 Tianjin Rd, Wuhan 435000, Hubei, Peoples R China.	drpengss@126.com			Health commission of Hubei Province Scientific Research Project [WJ2019H160]	The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Health commission of Hubei Province Scientific Research Project (WJ2019H160).	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J	Wanigasooriya, K; Tyler, R; Barros-Silva, JD; Sinha, Y; Ismail, T; Beggs, AD				Wanigasooriya, Kasun; Tyler, Robert; Barros-Silva, Joao D.; Sinha, Yashashwi; Ismail, Tariq; Beggs, Andrew D.			Radiosensitising Cancer Using Phosphatidylinositol-3-Kinase (PI3K), Protein Kinase B (AKT) or Mammalian Target of Rapamycin (mTOR) Inhibitors	CANCERS			English	Review						radiosensitiser; chemoradiotherapy; PI3K; AKT; mTOR inhibitors; rectal cancer; prostate cancer; glioblastoma multiforme; head and neck cancer; non-small cell lung cancer	DUAL PI3K/MTOR INHIBITOR; SQUAMOUS-CELL CARCINOMA; ESTRO-SIOG GUIDELINES; PHASE-I TRIAL; PROSTATE-CANCER; 3-KINASE/MAMMALIAN TARGET; RADIATION-THERAPY; LUNG-CANCER; DNA-REPAIR; NEOADJUVANT TREATMENT	Radiotherapy is routinely used as a neoadjuvant, adjuvant or palliative treatment in various cancers. There is significant variation in clinical response to radiotherapy with or without traditional chemotherapy. Patients with a good response to radiotherapy demonstrate better clinical outcomes universally across different cancers. The PI3K/AKT/mTOR pathway upregulation has been linked to radiotherapy resistance. We reviewed the current literature exploring the role of inhibiting targets along this pathway, in enhancing radiotherapy response. We identified several studies using in vitro cancer cell lines, in vivo tumour xenografts and a few Phase I/II clinical trials. Most of the current evidence in this area comes from glioblastoma multiforme, non-small cell lung cancer, head and neck cancer, colorectal cancer, and prostate cancer. The biological basis for radiosensitivity following pathway inhibition was through inhibited DNA double strand break repair, inhibited cell proliferation, enhanced apoptosis and autophagy as well as tumour microenvironment changes. Dual PI3K/mTOR inhibition consistently demonstrated radiosensitisation of all types of cancer cells. Single pathway component inhibitors and other inhibitor combinations yielded variable outcomes especially within early clinical trials. There is ample evidence from preclinical studies to suggest that direct pharmacological inhibition of the PI3K/AKT/mTOR pathway components can radiosensitise different types of cancer cells. We recommend that future in vitro and in vivo research in this field should focus on dual PI3K/mTOR inhibitors. Early clinical trials are needed to assess the feasibility and efficacy of these dual inhibitors in combination with radiotherapy in brain, lung, head and neck, breast, prostate and rectal cancer patients.	[Wanigasooriya, Kasun; Barros-Silva, Joao D.; Sinha, Yashashwi; Beggs, Andrew D.] Univ Birmingham, Inst Canc & Genom Sci, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England; [Wanigasooriya, Kasun; Tyler, Robert; Sinha, Yashashwi; Ismail, Tariq; Beggs, Andrew D.] Univ Hosp Birmingham NHS Fdn Trust, New Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England		Wanigasooriya, K (corresponding author), Univ Birmingham, Inst Canc & Genom Sci, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.; Wanigasooriya, K (corresponding author), Univ Hosp Birmingham NHS Fdn Trust, New Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England.	k.s.wanigasooriya@bham.ac.uk; r.tyler.2@bham.ac.uk; j.silva@bham.ac.uk; yashsinha1991@gmail.com; tariq.ismail@uhb.nhs.uk; a.beggs@bham.ac.uk	Beggs, Andrew/A-6912-2013	Beggs, Andrew/0000-0003-0784-2967; Wanigasooriya, Kasun/0000-0002-3683-1864; Barros Silva, Joao Diogo/0000-0002-6648-0217	Cancer Research UK, Advanced Clinician Scientist Award [C31641/A23923]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MR/M009157/1] Funding Source: UKRI	Cancer Research UK, Advanced Clinician Scientist Award (ref C31641/A23923).	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J	Draz, H; Goldberg, A; Guns, EST; Fazli, L; Safe, S; Sanderson, J				Draz, Hossam; Goldberg, Alexander A.; Guns, Emma S. Tomlinson; Fazli, Ladan; Safe, Stephen; Sanderson, J. Thomas			Autophagy inhibition improves the chemotherapeutic efficacy of cruciferous vegetable-derived diindolymethane in a murine prostate cancer xenograft model	INVESTIGATIONAL NEW DRUGS			English	Article						Prostate cancer; PC-3; CD-1 nude mice; Autophagy; Diindolylmethane; Ring-DIMs	IN-VIVO; 3,3'-DIINDOLYLMETHANE DIM; COLORECTAL-CANCER; CELLS; INDUCTION; APOPTOSIS; SURVIVAL; VITRO	Prostate cancer is the second leading cause of cancer-related deaths in men in North America and there is an urgent need for development of more effective therapeutic treatments against this disease. We have recently shown that diindolylmethane (DIM) and several of its halogenated derivatives (ring-DIMs) induce death and protective autophagy in human prostate cancer cells. However, the in vivo efficacy of ring-DIMs and the use of autophagy inhibitors as adjuvant therapy have not yet been studied in vivo. The objective of this study was to determine these effects on tumor growth in nude CD-1 mice bearing bioluminescent androgen-independent PC-3 human prostate cancer cells. We found that chloroquine (CQ) significantly sensitized PC-3 cells to death in the presence of sub-toxic concentrations of DIM or 4,4'-Br2DIM in vitro. Moreover, a combination of DIM (10 mg/kg) and CQ (60 mg/kg), 3x per week, significantly decreased PC-3 tumor growth in vivo after 3 and 4 weeks of treatment. Furthermore, 4,4'-Br2DIM at 10 mg/kg (3x per week) significantly inhibited tumour growth after 4 weeks of treatment. Tissues microarray analysis showed that DIM alone or combined with CQ induced apoptosis marker TUNEL; the combination also significantly inhibited the cell proliferation marker Ki67. In conclusion, we have confirmed that DIM and 4,4'-Br2DIM are effective agents against prostate cancer in vivo and shown that inhibition of autophagy with CQ enhances the anticancer efficacy of DIM. Our results suggest that including selective autophagy inhibitors as adjuvants may improve the efficacy of existing and novel drug therapies against prostate cancer.	[Draz, Hossam; Goldberg, Alexander A.; Sanderson, J. Thomas] INRS Inst Armand Frappier, 531 Blvd Prairies, Laval, PQ H7V 1B7, Canada; [Draz, Hossam] Natl Res Ctr, Dept Biochem, Cairo, Egypt; [Guns, Emma S. Tomlinson; Fazli, Ladan] Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC, Canada; [Safe, Stephen] Texas A&M Univ, Vet Physiol & Pharmacol, College Stn, TX USA		Sanderson, J (corresponding author), INRS Inst Armand Frappier, 531 Blvd Prairies, Laval, PQ H7V 1B7, Canada.	thomas.sanderson@iaf.inrs.ca	; Sanderson, Thomas/H-7272-2015	, Alexander/0000-0002-7471-8598; Sanderson, Thomas/0000-0002-3190-2811	Canadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR) [MOP-115019]; Fonds de Recherche du Quebec - Sante (FRQS)Fonds de la Recherche en Sante du Quebec	This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR grant no. MOP-115019) to Thomas Sanderson and Emma Guns. Hossam Draz received a scholarship from the Fonds de Recherche du Quebec - Sante (FRQS).	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New Drugs	AUG	2018	36	4					718	725		10.1007/s10637-018-0595-8			8	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	GO5CD	WOS:000440034600023	29607466				2022-04-25	
J	Biddle, A; Gammon, L; Liang, X; Costea, DE; Mackenzie, IC				Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C.			Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma	EBIOMEDICINE			English	Article						Cancer; Stem cell; CSC; EMT; Plasticity; Therapy; Resistance	EPITHELIAL-MESENCHYMAL TRANSITION; LARGE GENE LISTS; BREAST-CANCER; COLORECTAL-CANCER; RETINOIC ACID; TUMOR-GROWTH; METASTASIS; CHEMOTHERAPY; LINES; CD24	Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44(high)EpCAM(low)/-CD24(+) cell surface marker profile. Treatment with TGF beta and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum(ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).	[Biddle, Adrian; Gammon, Luke; Mackenzie, Ian C.] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England; [Liang, Xiao; Costea, Daniela Elena] Univ Bergen, Dept Clin Med, Gade Lab Pathol, N-5020 Bergen, Norway		Biddle, A (corresponding author), Blizard Inst, Ctr Cell Biol & Cutaneous Res, 4 Newark St, London E1 2AT, England.	a.biddle@qmul.ac.uk	Costea, Daniela Elena/AAB-9705-2020	Liang, Kristina Xiao/0000-0002-3586-4218; Biddle, Adrian/0000-0003-4371-9720; Costea, Daniela-Elena/0000-0001-7673-0358	National Centre for the Replacement [NC/L00061X/1, NC/K500495/1, G0900799/1] Funding Source: researchfish; National Centre for the Replacement, Refinement and Reduction of Animals in ResearchUK Research & Innovation (UKRI)National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) [G0900799/1, NC/K500495/1, NC/L00061X/1] Funding Source: Medline		Aigner S, 1997, BLOOD, V89, P3385, DOI 10.1182/blood.V89.9.3385; Al-Hajj M, 2003, P NATL ACAD SCI USA, V100, P3983, DOI 10.1073/pnas.0530291100; Azzam DJ, 2013, EMBO MOL MED, V5, P1502, DOI 10.1002/emmm.201302558; Biddle A, 2011, CANCER RES, V71, P5317, DOI 10.1158/0008-5472.CAN-11-1059; Brabletz T, 2012, CANCER CELL, V22, P699, DOI 10.1016/j.ccr.2012.11.009; Bretz N, 2012, CLIN EXP METASTAS, V29, P27, DOI 10.1007/s10585-011-9426-4; Buchberger A, 2010, MOL CELL, V40, P238, DOI 10.1016/j.molcel.2010.10.001; Chaffer CL, 2006, CANCER RES, V66, P11271, DOI 10.1158/0008-5472.CAN-06-2044; Chaffer CL, 2013, CELL, V154, P61, DOI 10.1016/j.cell.2013.06.005; Charafe-Jauffret E, 2010, CLIN CANCER RES, V16, P45, DOI 10.1158/1078-0432.CCR-09-1630; Chen F, 2007, DEVELOPMENT, V134, P2969, DOI 10.1242/dev.006221; Clarke Michael F, 2006, Cancer Res, V66, P9339, DOI 10.1158/0008-5472.CAN-06-3126; da Silva SD, 2012, FRONT PHARMACOL, V3, DOI 10.3389/fphar.2012.00149; Driessens G, 2012, NATURE, V488, P527, DOI 10.1038/nature11344; Drygin D, 2011, CANCER RES, V71, P1418, DOI 10.1158/0008-5472.CAN-10-1728; Ganley IG, 2011, MOL CELL, V42, P731, DOI 10.1016/j.molcel.2011.04.024; Gjerdrum C, 2010, P NATL ACAD SCI USA, V107, P1124, DOI 10.1073/pnas.0909333107; Goldman A, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms7139; Gupta PB, 2009, CELL, V138, P645, DOI 10.1016/j.cell.2009.06.034; Hay ED, 2005, DEV DYNAM, V233, P706, DOI 10.1002/dvdy.20345; Hermann PC, 2007, CELL STEM CELL, V1, P313, DOI 10.1016/j.stem.2007.06.002; Huang DW, 2009, NAT PROTOC, V4, P44, DOI 10.1038/nprot.2008.211; Huang DW, 2009, NUCLEIC ACIDS RES, V37, P1, DOI 10.1093/nar/gkn923; Jensen DH, 2015, J PATHOL, V236, P505, DOI 10.1002/path.4550; Ke XS, 2010, BMC GENOMICS, V11, DOI 10.1186/1471-2164-11-669; Kreso A, 2013, SCIENCE, V339, P543, DOI 10.1126/science.1227670; Kristiansen G, 2004, J MOL HISTOL, V35, P255; Kroemer G, 2010, MOL CELL, V40, P280, DOI 10.1016/j.molcel.2010.09.023; Lau AN, 2014, EMBO J, V33, P468, DOI 10.1002/embj.201386082; Li XX, 2008, J NATL CANCER I, V100, P672, DOI 10.1093/jnci/djn123; Lim J, 2014, ARCH BIOCHEM BIOPHYS, V558, P120, DOI 10.1016/j.abb.2014.06.022; Liu SL, 2014, STEM CELL REP, V2, P78, DOI 10.1016/j.stemcr.2013.11.009; Locke M, 2005, CANCER RES, V65, P8944, DOI 10.1158/0008-5472.CAN-05-0931; Martinsson H, 2005, EXP DERMATOL, V14, P161, DOI 10.1111/j.0906-6705.2005.00239.x; Metallo CM, 2008, STEM CELLS, V26, P372, DOI 10.1634/stemcells.2007-0501; Ocana OH, 2012, CANCER CELL, V22, P709, DOI 10.1016/j.ccr.2012.10.012; Prince ME, 2007, P NATL ACAD SCI USA, V104, P973, DOI 10.1073/pnas.0610117104; Sarrio D, 2012, STEM CELLS, V30, P292, DOI 10.1002/stem.791; Sharma SV, 2010, CELL, V141, P69, DOI 10.1016/j.cell.2010.02.027; Torre LA, 2015, CA CANC J CLIN; Tsai JH, 2012, CANCER CELL, V22, P725, DOI 10.1016/j.ccr.2012.09.022; Xu CY, 2005, J CLIN INVEST, V115, P2656, DOI 10.1172/JCI26373; Yamamoto A, 1998, CELL STRUCT FUNCT, V23, P33, DOI 10.1247/csf.23.33; Yang MH, 2008, NAT CELL BIOL, V10, P295, DOI 10.1038/ncb1691; Yeung TM, 2010, P NATL ACAD SCI USA, V107, P3722, DOI 10.1073/pnas.0915135107	45	70	75	0	8	ELSEVIER SCIENCE BV	AMSTERDAM	PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS	2352-3964			EBIOMEDICINE	EBioMedicine	FEB	2016	4						138	145		10.1016/j.ebiom.2016.01.007			8	Medicine, General & Internal; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine; Research & Experimental Medicine	DE7HL	WOS:000370806400024	26981578	Green Published, gold			2022-04-25	
J	Jo, YK; Park, NY; Shin, JH; Jo, DS; Bae, JE; Choi, ES; Maeng, S; Jeon, HB; Roh, SA; Chang, JW; Kim, JC; Cho, DH				Jo, Yoon Kyung; Park, Na Yeon; Shin, Ji Hyun; Jo, Doo Sin; Bae, Ji-Eun; Choi, Eun Sun; Maeng, Sungho; Jeon, Hong Bae; Roh, Seon Ae; Chang, Jong Wook; Kim, Jin Cheon; Cho, Dong-Hyung			Up-regulation of UVRAG by HDAC1 Inhibition Attenuates 5FU-induced Cell Death in HCT116 Colorectal Cancer Cells	ANTICANCER RESEARCH			English	Article						UVRAG; HDAC1; epigenetics; 5FU; colorectal cancer	TRANSCRIPTIONAL REGULATION; HISTONE DEACETYLASES; DUAL ROLE; AUTOPHAGY; GENE; MECHANISMS; APOPTOSIS; MUTATION; THERAPY	The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid. Down-regulation of HDAC1 enhanced UVRAG expression in colorectal cancer cells. In addition, both chemical and genetic inhibition of HDAC1 reduced the activation of caspase-3 and cytotoxicity in 5-fluorouracil (5FU)-treated cancer cells. In contrast, UVRAG overexpression inhibited caspase activation and cell death in 5FU-treated cells. Taken together, our findings suggest that up-regulation of UVRAG by HDAC1 inhibition potentiates DNA-damage-mediated cell death in colorectal cancer cells.	[Jo, Yoon Kyung; Park, Na Yeon; Shin, Ji Hyun; Jo, Doo Sin; Bae, Ji-Eun; Choi, Eun Sun; Maeng, Sungho; Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch East West Med Sci, Dept Gerontol, Seoul, South Korea; [Jeon, Hong Bae] MEDIPOST Corp, Biomed Res Inst, Seongnam, South Korea; [Roh, Seon Ae; Kim, Jin Cheon] Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea; [Chang, Jong Wook] Samsung Med Ctr, Stem Cell & Regenerat Med Inst, Seoul, South Korea; [Kim, Jin Cheon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul, South Korea		Kim, JC (corresponding author), Univ Ulsan, Coll Med, Asan Med Ctr 88, Dept Surg, Olymp Ro 43 Gil, Seoul 05505, South Korea.; Cho, DH (corresponding author), Kyung Hee Univ, Grad Sch East West Med Sci, 1732 Deogyeong Daero, Yongin 17014, Gyeonggi Do, South Korea.	jckim@amc.seoul.kr; dhcho@khu.ac.kr	Maeng, Sungho/N-2905-2018	Maeng, Sungho/0000-0002-9347-7902	National Research Foundation, Ministry of Science, ICT and Future Planning, Republic of Korea [NRF-2017R1A2B4005501, 2016R1E1A1A02919844]	This study was supported by grants from the National Research Foundation NRF-2017R1A2B4005501 and 2016R1E1A1A02919844), Ministry of Science, ICT and Future Planning, Republic of Korea	Boland CR, 2010, GASTROENTEROLOGY, V138, P2073, DOI [10.1053/j.gastro.2009.12.064, 10.1053/j.gastro.2010.04.024]; Choi AMK, 2013, NEW ENGL J MED, V368, P651, DOI [10.1056/NEJMra1205406, 10.1056/NEJMc1303158]; De Ruijter AJM, 2003, BIOCHEM J, V370, P737, DOI 10.1042/BJ20021321; Falkenberg KJ, 2014, NAT REV DRUG DISCOV, V13, P673, DOI 10.1038/nrd4360; Fullgrabe J, 2016, J CELL SCI, V129, P3059, DOI 10.1242/jcs.188920; He SS, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms8839; Huangfu LT, 2016, ONCOTARGET, V7, P4735, DOI 10.18632/oncotarget.6732; Kaur J, 2015, NAT REV MOL CELL BIO, V16, P461, DOI 10.1038/nrm4024; Kim MS, 2008, HUM PATHOL, V39, P1059, DOI 10.1016/j.humpath.2007.11.013; Kim Y, 2015, AUTOPHAGY, V11, P796, DOI 10.1080/15548627.2015.1035503; Klionsky DJ, 2016, AUTOPHAGY, V12, P1, DOI 10.1080/15548627.2015.1100356; Knaevelsrud H, 2010, AUTOPHAGY, V6, P863, DOI 10.4161/auto.6.7.13033; Lee JM, 2014, NATURE, V516, P112, DOI 10.1038/nature13961; Li ZM, 2014, INT J BIOL SCI, V10, P757, DOI 10.7150/ijbs.9067; Liang CY, 2007, AUTOPHAGY, V3, P69, DOI 10.4161/auto.3437; Liang C, 2006, NAT CELL BIOL, V8, P688, DOI 10.1038/ncb1426; Mottamal M, 2015, MOLECULES, V20, P3898, DOI 10.3390/molecules20033898; Santoro F, 2013, BLOOD, V121, P3459, DOI 10.1182/blood-2012-10-461988; Seok S, 2014, NATURE, V516, P108, DOI 10.1038/nature13949; Shin HJR, 2016, NATURE, V534, P553, DOI 10.1038/nature18014; Shin HJ, 2016, ONCOTARGET, V7, P39796; Wilson AJ, 2006, J BIOL CHEM, V281, P13548, DOI 10.1074/jbc.M510023200; Witt O, 2009, CANCER LETT, V280, P123, DOI 10.1016/j.canlet.2009.02.038; Xie YX, 2015, AUTOPHAGY, V11, P1934, DOI 10.1080/15548627.2015.1084460; Yang W, 2013, EXP CELL RES, V319, P122, DOI 10.1016/j.yexcr.2012.11.014; Yang YF, 2016, MOL CELL, V62, P507, DOI 10.1016/j.molcel.2016.04.014; Yin XC, 2011, EMBO REP, V12, P727, DOI 10.1038/embor.2011.79; Zhao Z, 2012, AUTOPHAGY, V8, P1392, DOI 10.4161/auto.21035; Zhao Z, 2012, DEV CELL, V22, P1001, DOI 10.1016/j.devcel.2011.12.027	29	15	16	1	9	INT INST ANTICANCER RESEARCH	ATHENS	EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE	0250-7005	1791-7530		ANTICANCER RES	Anticancer Res.	JAN	2018	38	1					271	277		10.21873/anticanres.12218			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FR5TW	WOS:000419130100035	29277783	Bronze			2022-04-25	
J	Long, HD; Ma, YS; Yang, HQ; Xue, SB; Liu, JB; Yu, F; Lv, ZW; Li, JY; Xie, RT; Chang, ZY; Lu, GX; Xie, WT; Fu, D; Pang, LJ				Long, Hui-Deng; Ma, Yu-Shui; Yang, Hui-Qiong; Xue, Shao-Bo; Liu, Ji-Bin; Yu, Fei; Lv, Zhong-Wei; Li, Ji-Yu; Xie, Ru-Ting; Chang, Zheng-Yan; Lu, Gai-Xia; Xie, Wen-Ting; Fu, Da; Pang, Li-Juan			Reduced hsa-miR-124-3p levels are associated with the poor survival of patients with hepatocellular carcinoma	MOLECULAR BIOLOGY REPORTS			English	Article						Hsa-miR-124-3p expression; HCC; OS; GEO; Biomarker	CANCER STEM-CELLS; COLORECTAL-CANCER; PROLIFERATION; MICRORNA-124A; MIR-124A; IDENTIFICATION; GLIOBLASTOMA; METASTASIS; AUTOPHAGY; ALTERS	Hsa-MicroRNA-124a-3p (hsa-miR-124-3p) is involved in tumor progression in certain malignant tumors. However, its function and clinical implication in hepatocellular carcinoma (HCC) have not yet been illustrated. In this study, we explored the expression and prognostic value of hsa-miR-124-3p in patients with HCC. Hsa-miR-124-3p expression in HCC was analyzed in silico, which was subsequently confirmed by quantitative PCR in 155 HCC biopsy samples. Overall survival (OS) and disease-free survival in HCC patients was evaluated by Kaplan-Meier survival analysis, and univariate and multivariate Cox proportional hazard models were used. The in silico results demonstrated that hsa-miR-124-3p was reduced in cell lines and tissues of HCC, and hsa-miR-124-3p expression was lower in HCC tumor samples than in normal liver tissues. Moreover, a decrease in hsa-miR-124-3p expression was closely correlated with tumor diameter (ae<yen> 5 cm) and number of lesions (multiple). Lower hsa-miR-124-3p expression was shown to be correlated with a shorter OS and poor prognosis in HCC. Our findings demonstrate that hsa-miR-124-3p might be a potential target for the diagnosis and prognosis of HCC.	[Long, Hui-Deng; Pang, Li-Juan] Shihezi Univ, Sch Med, Affiliated Hosp 1, Dept Pathol, Shihezi 832003, Xinjiang, Peoples R China; [Ma, Yu-Shui] East China Normal Univ, Coll Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Shanghai 200062, Peoples R China; [Ma, Yu-Shui; Yu, Fei; Lv, Zhong-Wei; Lu, Gai-Xia; Xie, Wen-Ting; Fu, Da] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Nucl Med, Shanghai 200072, Peoples R China; [Yang, Hui-Qiong; Xie, Ru-Ting; Chang, Zheng-Yan] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Pathol, Shanghai 200072, Peoples R China; [Xue, Shao-Bo; Li, Ji-Yu; Fu, Da] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Cent Lab Med Res, Shanghai 200072, Peoples R China; [Liu, Ji-Bin] Nantong Tumor Hosp, Inst Canc, Nantong 226631, Peoples R China		Pang, LJ (corresponding author), Shihezi Univ, Sch Med, Affiliated Hosp 1, Dept Pathol, Shihezi 832003, Xinjiang, Peoples R China.; Fu, D (corresponding author), Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Nucl Med, Shanghai 200072, Peoples R China.; Fu, D (corresponding author), Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Cent Lab Med Res, Shanghai 200072, Peoples R China.	fu800da900@126.com; ocean123456@163.com	Sui, Yanwei/AAH-9928-2021		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81560053, 81772932, 81201535, 81302065, 81472202, 81301993]; Youth Science and Technology Innovation Leading Talents Project of Corps [2017CB004]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [22120170212, 22120170117]; Shanghai Natural Science FoundationNatural Science Foundation of Shanghai [12ZR1436000]; Shanghai Municipal Commission of Health and Family Planning [201540228]; peak of six personnel Foundation in Jiangsu Province [WSW-009]; fifth phase of 333 talents Engineering Science and Technology Project of Jiangsu Province [BRA2017205]	This study was supported partly by grants from the National Natural Science Foundation of China (81560053, 81772932, 81201535, 81302065, 81472202 and 81301993), the Youth Science and Technology Innovation Leading Talents Project of Corps (2017CB004), The Fundamental Research Funds for the Central Universities (22120170212 and 22120170117), Shanghai Natural Science Foundation (12ZR1436000), Shanghai Municipal Commission of Health and Family Planning (201540228), The peak of six personnel Foundation in Jiangsu Province (WSW-009) and The fifth phase of 333 talents Engineering Science and Technology Project of Jiangsu Province (BRA2017205).	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Biol. Rep.	DEC	2018	45	6					2615	2623		10.1007/s11033-018-4431-1			9	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	HD5BS	WOS:000452543200102	30341691				2022-04-25	
J	Ji, E; Lee, H; Ahn, S; Jung, M; Lee, SH; Lee, JH; Lee, EK				Ji, Eunbyul; Lee, Heejin; Ahn, Sojin; Jung, Myeongwoo; Lee, Sung Hak; Lee, Jeong-Hwa; Lee, Eun Kyung			Heterogeneous nuclear ribonucleoprotein A1 promotes the expression of autophagy-related protein 6 in human colorectal cancer	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Heterogeneous nuclear ribonucleoprotein A1; Autophagy-related gene 6; Colorectal cancer; Post-transcriptional regulation	RNA-BINDING PROTEIN; BECLIN 1; POOR-PROGNOSIS; GENE; PHOSPHORYLATION; TRANSCRIPTION; MECHANISM; PATTERNS; SWITCH; CELLS	Autophagy, a lysosomal self-degradative process of cellular components, is essential for cellular homeostasis to response cellular stress and is tightly controlled by autophagy-related genes (ATGs). Autophagy-related gene 6 (ATG6, also known as Beclin-1 in human) is an essential factor regulating autophagy and apoptosis. RNA binding proteins (RBPs) regulate gene expression at the post-transcriptional level and their differential expression is linked to the pathogenesis of several human diseases. Here, we demonstrate the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) as a novel factor regulating ATG6 expression. hnRNPA1 associates with the 3' untranslated region (3'UTR) of ATG6 mRNA and promotes its expression without significant changes at the mRNA level. Knockdown of hnRNPA1 decreases ATG6 expression, which is enhanced by the overexpression of hnRNPA1. Also, we show augmented expression of both hnRNPA1 and ATG6 in the colorectal cancer (CRC) tissues obtained from patients and demonstrate a positive correlation of their expression in CRC tissues. Our results suggest the potential role of hnRNPA1-mediated ATG6 regulation in the pathogenesis of CRC. (C) 2019 Elsevier Inc. All rights reserved.	[Ji, Eunbyul; Lee, Heejin; Ahn, Sojin; Jung, Myeongwoo; Lee, Jeong-Hwa; Lee, Eun Kyung] Catholic Univ, Korea Coll Med, Dept Biochem, Seoul 06591, South Korea; [Lee, Jeong-Hwa; Lee, Eun Kyung] Catholic Univ, Korea Coll Med, Inst Aging & Metab Dis, Seoul 06591, South Korea; [Lee, Sung Hak] Catholic Univ, Korea Coll Med, Dept Hosp Pathol, Seoul 06591, South Korea		Lee, EK (corresponding author), 222 Banpodae Ro, Seoul 06591, South Korea.	leeek@catholic.ac.kr		Lee, Eun Kyung/0000-0003-4207-2080	National Research Foundation of Korea - Korea governmentNational Research Foundation of KoreaKorean Government [2017R1A2B2009381, 2017R1A2B2005508]	This work is supported by the National Research Foundation of Korea grant funded by the Korea government (2017R1A2B2009381 and 2017R1A2B2005508).	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J	Li, X; Hu, ZH; Shi, HR; Wang, C; Lei, J; Cheng, Y				Li, Xia; Hu, Zhenhua; Shi, Huirong; Wang, Cong; Lei, Jia; Cheng, Yan			Inhibition of VEGFA Increases the Sensitivity of Ovarian Cancer Cells to Chemotherapy by Suppressing VEGFA-Mediated Autophagy	ONCOTARGETS AND THERAPY			English	Article						ovarian cancer; VEGFA; chemotherapy; autophagy	COLORECTAL-CANCER; 1ST-LINE CHEMOTHERAPY; DOWN-REGULATION; ANGIOGENESIS; EXPRESSION; PROLIFERATION; PROGRESSION; RESISTANT; APOPTOSIS; MIGRATION	Background: Ovarian cancer (OvCa) is the leading cause of death of gynecological malignancies worldwide. Vascular endothelial growth factor A (VEGFA), the most potent angiogenic factor, is responsible for tumor growth and angiogenesis, but its role in OvCa chemotherapy resistance remains unclear. Methods: RT-PCR and Western blot were used to detect VEGFA expression in tumor cells and normal ovarian surface epithelial cells. Gene Ontology (GO) enrichment analysis was used to analyze GO terms correlated with VEGFA. In in vitro experiments, we knockdown VEGFA in tumor cells and detected the tumor cell viability and apoptosis after chemotherapy drug treatment by MTT assay and flow cytometry. Western blot was used to detect autophagy and apoptosis related proteins. Results: We proved that VEGFA was highly expressed in tumor cells comparted with normal ovarian surface epithelial cells, and enriched GO analysis of VEGFA showed that VEGFA was involved in anti-apoptotic process. Further in vitro experiments confirmed that expression of VEGFA was correlated with chemotherapy resistance and this effect was mediated by autophagy. Meanwhile tumor cells treated with chemotherapy drugs also promoted the expression of VEGFA. Knockdown VEGFA inhibited autophagy of tumor cells and thus potents the killing efficiency in DDP resistant tumor cells and this effect could be reversed by the addition of recombinant VEGFA. Conclusion: Taken together, our study demonstrates that VEGFA is involved in antiapoptosis of tumor cells to chemotherapy, killing partly through autophagy, indicating that VEGFA may serve as a potential target to improve chemotherapy treatment.	[Li, Xia; Wang, Cong; Lei, Jia; Cheng, Yan] Zhengzhou Univ, Affiliated Hosp 1, Gynecol Oncol Radiotherapy Ward, Zhengzhou, Henan, Peoples R China; [Hu, Zhenhua; Shi, Huirong] Zhengzhou Univ, Dept Gynecol & Obstet, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China		Cheng, Y (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China.	djzdyfy@163.com			Basic and Advanced Technology Research Foundation from Science and Technology Department of Henan Province [172102310008]	This work was supported by the Basic and Advanced Technology Research Foundation from Science and Technology Department of Henan Province (Grant No.172102310008).	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J	Abu el Maaty, MA; Strassburger, W; Qaiser, T; Dabiri, Y; Wolfl, S				Abu el Maaty, Mohamed A.; Strassburger, Wendy; Qaiser, Tooba; Dabiri, Yasamin; Woelfl, Stefan			Differences in p53 status significantly influence the cellular response and cell survival to 1,25-dihydroxyvitamin D3-metformin cotreatment in colorectal cancer cells	MOLECULAR CARCINOGENESIS			English	Article						1,25-dihydroxyvitamin D3; AMPK; metformin; p53	VITAMIN-D; DIRECT TARGET; METFORMIN; APOPTOSIS; AUTOPHAGY; FAMILY; AMPK; FAK	Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Previous studies have demonstrated additive/synergistic anti-cancer effects of the 1,25D3-metformin combination in different models, however, the influence of p53 status on the efficacy of this regimen has not been investigated. The CRC colorectal cancer (CRC) cell lines HCT116 wild-type (wt), HCT116 p53-/-, and HT-29 (mutant; R273H) were employed, covering three different p53 variations. Synergistic effects of the combination were confirmed in all cell lines using MTT assay. Detailed evaluation of the combination's effects was performed, including on-line measurements of cellular metabolism (glycolysis/respiration) using a biosensor chip system, analyses of mitochondrial activity (membrane potential and ATP/ROS production), mRNA expression analysis of WNT/-catenin pathway players, and a comprehensive proteomic screen using immunoblotting and ELISA microarrays. AMPK signaling was found to be more strongly induced in response to all treatments in HCT116wt cells compared to other cell lines, an observation that was coupled to a stronger accumulation of intracellular ROS in response to metformin/combination, and finally an induction in autophagy, depicted by an increase in LC3II:LC3I ratio in combination-treated cells compared to mono-treatments. An induction in apoptotic signaling was observed in the other cell lines in response to the combination, illustrated by a decrease in expression of pro-survival Bcl2 family members. P53 status impacts cellular responses to the combination but does not hamper its anti-proliferative synergy.	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Carcinog.	NOV	2017	56	11					2486	2498		10.1002/mc.22696			13	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	FJ2NK	WOS:000412565500012	28618116				2022-04-25	
J	Tang, CT; Yang, J; Liu, ZD; Chen, YX; Zeng, CY				Tang, Chao-Tao; Yang, Jing; Liu, Zi-De; Chen, Youxiang; Zeng, Chunyan			Taraxasterol acetate targets RNF31 to inhibit RNF31/p53 axis-driven cell proliferation in colorectal cancer	CELL DEATH DISCOVERY			English	Article							PHARMACOLOGY-BASED IDENTIFICATION; LINEAR UBIQUITINATION; MICE; INFLAMMATION; RESPONSES	Colorectal cancer (CRC) is the third most common cancer worldwide. Several studies have suggested that taraxasterol acetate (TA) can inhibit the growth of tumor cells. However, to date, it remains unclear how TA inhibits cell growth and how RNF31 functions as an oncogene. We examined the expression of RNF31 in CRC tissue samples via immunohistochemistry and elucidated the function of RNF31 in CRC cells by constructing a cell model with RNF31 depletion. A cycloheximide (CHX)-chase analysis and immunofluorescence assays were conducted to demonstrate that TA can promote RNF31 degradation by activating autophagy. We used the PharmMapper website to predict targets of TA and identified RNF31. CHX-chase experiments showed that TA could facilitate RNF31 degradation, which was inhibited by the administration of chloroquine. Immunofluorescence assays showed that RNF31 protein was colocalized with LC3I/II and p62, suggesting that TA promoted RNF31 degradation by activating autophagy. We also found that CRC patients with RNF31 overexpression had poorer survival than those with low RNF31 expression. The results of the CHX-chase experiment showed that depletion of RNF31 alleviated p53 degradation, which was inhibited by MG132. A series of co-immunoprecipitation (Co-IP) assays revealed that RNF31 interacts with p53 and promotes p53 ubiquitination and degradation. A Co-IP assay performed with a truncated RNF31 plasmid showed that the PUB domain interacts with p53. Moreover, the PUB domain is the key structure in the induction of p53 ubiquitination. Our findings reveal a key role of RNF31 in CRC cell growth and indicate a mechanism through which TA inhibits cell growth.	[Tang, Chao-Tao; Yang, Jing; Liu, Zi-De; Chen, Youxiang; Zeng, Chunyan] Nanchang Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanchang, Jiangxi, Peoples R China		Chen, YX; Zeng, CY (corresponding author), Nanchang Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanchang, Jiangxi, Peoples R China.	chenyx102@ncu.edu.cn; zengcy896@ncu.edu.cn			Foundation of Jiangxi provincial department of Science and Technology [20201ZDG02007]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81660404, 82060448, 81560398]; Special fund for innovation of Postgraduates in Jiangxi Province [YC2020-B058]	The Foundation of Jiangxi provincial department of Science and Technology (Grant No. 20201ZDG02007, PI: Y.X.C.); This study was supported by grants from the National Natural Science Foundation of China (Grant No. 81660404 and 82060448, PI: C.Y.Z.); the National Natural Science Foundation of China (Grant No. 81560398, PI: Y.X.C.). Special fund for innovation of Postgraduates in Jiangxi Province (YC2020-B058).	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APR 6	2021	7	1							66	10.1038/s41420-021-00449-5			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	WN1BU	WOS:000711511200003	33824292	gold, Green Published			2022-04-25	
J	Sueda, T; Sakai, D; Kawamoto, K; Konno, M; Nishida, N; Koseki, J; Colvin, H; Takahashi, H; Haraguchi, N; Nishimura, J; Hata, T; Takemasa, I; Mizushima, T; Yamamoto, H; Satoh, T; Doki, Y; Mori, M; Ishii, H				Sueda, Toshinori; Sakai, Daisuke; Kawamoto, Koichi; Konno, Masamitsu; Nishida, Naohiro; Koseki, Jun; Colvin, Hugh; Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Yamamoto, Hirofumi; Satoh, Taroh; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi			BRAF(V600E) inhibition stimulates AMP-activated protein kinase-mediated autophagy in colorectal cancer cells	SCIENTIFIC REPORTS			English	Article							ENERGY SENSOR; BRAF; PHOSPHORYLATION; RESISTANCE; PATHWAY; NUTRIENT; GROWTH; TARGET; LKB1	Although BRAF(V600E) mutation is associated with adverse clinical outcomes in patients with colorectal cancer (CRC), response and resistance mechanisms for therapeutic BRAF(V600E) inhibitors remains poorly understood. In the present study, we demonstrate that selective BRAF(V600E) inhibition activates AMP-activated protein kinase (AMPK), which induces autophagy as a mechanism of therapeutic resistance in human cancers. The present data show AMPK-dependent cytoprotective roles of autophagy under conditions of therapeutic BRAF(V600E) inhibition, and AMPK was negatively correlated with BRAF(V600E) dependent activation of MEK-ERK-RSK signaling and positively correlated with unc-51-like kinase 1 (ULK1), a key initiator of autophagy. Furthermore, selective BRAF(V600E) inhibition and concomitant suppression of autophagy led to the induction of apoptosis. Taken together, present experiments indicate that AMPK plays a role in the survival of BRAF(V600E) CRC cells by selective inhibition and suggest that the control of autophagy contributes to overcome the chemoresistance of BRAF(V600E) CRC cells.	[Sueda, Toshinori; Sakai, Daisuke; Konno, Masamitsu; Nishida, Naohiro; Colvin, Hugh; Satoh, Taroh; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi] Osaka Univ, Grad Sch Med, Dept Frontier Sci Canc & Chemotherapy, Suita, Osaka 5650871, Japan; [Sueda, Toshinori; Kawamoto, Koichi; Colvin, Hugh; Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Masaki] Osaka Univ, Grad Sch Med, Dept Gastrointestinal Surg, Suita, Osaka 5650871, Japan; [Koseki, Jun; Colvin, Hugh; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi] Osaka Univ, Grad Sch Med, Dept Canc Profiling Discovery, Suita, Osaka 5650871, Japan; [Yamamoto, Hirofumi] Osaka Univ, Grad Sch Med & Hlth Sci, Dept Mol Pathol, Suita, Osaka 5650871, Japan		Mori, M (corresponding author), Osaka Univ, Grad Sch Med, Dept Frontier Sci Canc & Chemotherapy, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.	mmori@gesurg.med.osaka-u.ac.jp; hishii@gesurg.med.osaka-u.ac.jp	Satoh, Taroh/AAF-5193-2021; Satoh, Taroh/AAF-7913-2020; Koseki, Jun/ABH-7420-2020; Ishii, Hideshi/AAV-5317-2020	Satoh, Taroh/0000-0002-4615-2638; 	Ministry of Education, Culture, Sports, Science, and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT); P-DIRECT; Ministry of Health, Labour and WelfareMinistry of Health, Labour and Welfare, Japan; Taiho Pharmaceutical Co., Ltd.; Evidence Based Medical (EBM) Research Center, Chugai Co., Ltd.; Yakult Honsha Co., Ltd.	We thank the members of our laboratories for their helpful discussions. In particular, we thank H. Yoshimori, M. Hamasaki, and the members of The Yoshimori Lab of the Department of Genetics, Osaka University Graduate school of Medicine. This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology; P-DIRECT; Ministry of Health, Labour and Welfare. Partial support was received as institutional endowments from Taiho Pharmaceutical Co., Ltd., the Evidence Based Medical (EBM) Research Center, Chugai Co., Ltd., and Yakult Honsha Co., Ltd. No funding bodies were involved in data collection or analysis, the decision to publish, or preparation of the manuscript.	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J	Lee, NR; Meng, RY; Rah, SY; Jin, H; Ray, N; Kim, SH; Park, BH; Kim, SM				Lee, Na-Ri; Meng, Ruo Yu; Rah, So-Young; Jin, Hua; Ray, Navin; Kim, Seong-Hun; Park, Byung Hyun; Kim, Soo Mi			Reactive Oxygen Species-Mediated Autophagy by Ursolic Acid Inhibits Growth and Metastasis of Esophageal Cancer Cells	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						ursolic acid; esophageal squamous cell carcinoma; anticancer; autophagy; reactive oxygen species; cell death	COLORECTAL-CANCER; INDUCED APOPTOSIS; ACTIVATION; DEATH; PATHWAY; AKT; PROLIFERATION; PROMOTES; SUPPRESSION; METABOLISM	Ursolic acid (UA) possesses various pharmacological activities, such as antitumorigenic and anti-inflammatory effects. In the present study, we investigated the mechanisms underlying the effects of UA against esophageal squamous cell carcinoma (ESCC) (TE-8 cells and TE-12 cells). The cell viability assay showed that UA decreased the viability of ESCC in a dose-dependent manner. In the soft agar colony formation assay, the colony numbers and size were reduced in a dose-dependent manner after UA treatment. UA caused the accumulation of vacuoles and LC3 puncta, a marker of autophagosome, in a dose-dependent manner. Autophagy induction was confirmed by measuring the expression levels of LC3 and p62 protein in ESCC cells. UA increased LC3-II protein levels and decreased p62 levels in ESCC cells. When autophagy was hampered using 3-methyladenine (3-MA), the effect of UA on cell viability was reversed. UA also significantly inhibited protein kinase B (Akt) activation and increased p-Akt expression in a dose-dependent manner in ESCC cells. Accumulated LC3 puncta by UA was reversed after wortmannin treatment. LC3-II protein levels were also decreased after treatment with Akt inhibitor and wortmannin. Moreover, UA treatment increased cellular reactive oxygen species (ROS) levels in ESCC in a time- and dose-dependent manner. Diphenyleneiodonium (an ROS production inhibitor) blocked the ROS and UA induced accumulation of LC3-II levels in ESCC cells, suggesting that UA-induced cell death and autophagy are mediated by ROS. Therefore, our data indicate that UA inhibits the growth of ESCC cells by inducing ROS-dependent autophagy.	[Lee, Na-Ri] Jeonbuk Natl Univ, Div Hematol & Oncol, Med Sch, Jeonju 54907, South Korea; [Lee, Na-Ri; Kim, Seong-Hun] Jeonbuk Natl Univ, Dept Internal Med, Med Sch, Jeonju 54907, South Korea; [Lee, Na-Ri] Jeonbuk Natl Univ, Res Inst Clin Med, Biomed Res Inst, Med Sch, Jeonju 54907, South Korea; [Meng, Ruo Yu; Ray, Navin; Kim, Soo Mi] Jeonbuk Natl Univ, Dept Physiol, Med Sch, Jeonju 54907, South Korea; [Meng, Ruo Yu; Ray, Navin; Kim, Soo Mi] Jeonbuk Natl Univ, Inst Med Sci, Med Sch, Jeonju 54907, South Korea; [Rah, So-Young; Park, Byung Hyun] Jeonbuk Natl Univ, Dept Biochem, Med Sch, Jeonju 54907, South Korea; [Jin, Hua] Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China		Kim, SM (corresponding author), Jeonbuk Natl Univ, Dept Physiol, Med Sch, Jeonju 54907, South Korea.; Kim, SM (corresponding author), Jeonbuk Natl Univ, Inst Med Sci, Med Sch, Jeonju 54907, South Korea.	nariflower@jbnu.ac.kr; kathymeng1216@gmail.com; syrah1004@hanmail.net; jinhuaxy@126.com; navin.ray@gmail.com; shkimgi@jbnu.ac.kr; bhpark@jbnu.ac.kr; soomikim@jbnu.ac.kr		Rah, So-Young/0000-0002-0255-1960	Basic Science Research Program [2018R1D1A1B07048569]; Medical Research Center Program through the National Research Foundation - Korean government (MSIP) [NRF-2017R1A5A2015061]; Chonbuk National University in 2019	This paper was supported by research funds for newly appointed professors of Chonbuk National University in 2019, by the Basic Science Research Program (2018R1D1A1B07048569), and by grants from the Medical Research Center Program (NRF-2017R1A5A2015061) through the National Research Foundation, which is funded by the Korean government (MSIP).	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J. Mol. Sci.	DEC	2020	21	24							9409	10.3390/ijms21249409			16	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	PL8TB	WOS:000603385900001	33321911	gold, Green Published			2022-04-25	
J	Huang, S; Zhao, SM; Shan, LH; Zhou, XL				Huang Shuai; Zhao Shuang-Mei; Shan Lian-Hai; Zhou Xian-Li			Antitumor activity of nervosine VII, and the crosstalk between apoptosis and autophagy in HCT116 human colorectal cancer cells	CHINESE JOURNAL OF NATURAL MEDICINES			English	Article						Liparis nervosa; Pyrrolizidine alkaloids; Nervosine VII; Autophagy; Apoptosis; HCT116 cells	NERVOGENIC ACID-DERIVATIVES; PYRROLIZIDINE ALKALOIDS; MODULATION; PATHWAYS	Nervosine VII is one of the known saturated pyrrolizidine alkaloids isolated from the plant of Liparis nervosa. This is first study to investigate the antitumor activity of nervosine VII in vitro, and the results indicated that nervosine VII induced autophagy and apoptosis in HCT116 human colorectal cancer cells. Mechanistic studies showed that nervosine VII-induced apoptosis was associated with the intrinsic pathway by the activation of caspase-9, -3 and -7. Autophagy induced by nervosine VII was characteristic with the regulation of autophagic markers including the increase of LC3-II and beclin 1 proteins, and the decrease of p62 protein. Nervosine VII simultaneously induced autophagy and apoptosis by activated MAPKs signaling pathway including JNK, ERK1/2 and p38, suppressing the p53 signaling pathway.	[Huang Shuai; Zhao Shuang-Mei; Shan Lian-Hai; Zhou Xian-Li] Southwest Jiaotong Univ, Sch Life Sci & Engn, Chengdu 610031, Peoples R China		Huang, S; Zhou, XL (corresponding author), Southwest Jiaotong Univ, Sch Life Sci & Engn, Chengdu 610031, Peoples R China.	shuaih@swjtu.edu.cn; zhouxl@swjtu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402803]	This work was supported by the National Natural Science Foundation of China (No. 81402803).	Amaravadi RK, 2007, J CLIN INVEST, V117, P326, DOI 10.1172/JCI28833; BUSH LP, 1993, AGR ECOSYST ENVIRON, V44, P81, DOI 10.1016/0167-8809(93)90040-V; Castells E, 2014, PHYTOCHEMISTRY, V108, P137, DOI 10.1016/j.phytochem.2014.09.006; Chen L, 2013, PHYTOCHEMISTRY, V93, P154; Debatin KM, 2004, CANCER IMMUNOL IMMUN, V53, P153, DOI 10.1007/s00262-003-0474-8; Editorial Committee of the Flora of China of Chinese Academy of Science, 1999, FLORA CHINA, V18, P71; Feng ZH, 2005, P NATL ACAD SCI USA, V102, P8204, DOI 10.1073/pnas.0502857102; Hartmann T, 1999, PLANTA, V207, P483, DOI 10.1007/s004250050508; Hua YX, 1999, CHINESE HERBAL, V12, P997; Huang S, 2016, CHINESE CHEM LETT, V27, P757, DOI 10.1016/j.cclet.2016.01.003; Huang S, 2013, CHINESE CHEM LETT, V24, P734, DOI 10.1016/j.cclet.2013.04.043; Huang S, 2013, PHYTOCHEMISTRY, V93, P154, DOI 10.1016/j.phytochem.2013.03.009; Huang S, 2013, PLANTA MED, V79, P281, DOI 10.1055/s-0032-1328109; Kim WK, 2016, J NAT PROD, V79, P1097, DOI 10.1021/acs.jnatprod.6b00006; Liu XJ, 2017, PHYTOCHEMISTRY, V138, P93, DOI 10.1016/j.phytochem.2017.02.027; Pliyev BK, 2012, APOPTOSIS, V17, P1050, DOI 10.1007/s10495-012-0738-x; Siciliano T, 2005, PHYTOCHEMISTRY, V66, P1593, DOI 10.1016/j.phytochem.2005.05.002; Sun YJ, 2013, FOOD CHEM TOXICOL, V51, P53, DOI 10.1016/j.fct.2012.09.012; Thornberry NA, 1998, SCIENCE, V281, P1312, DOI 10.1126/science.281.5381.1312; Wang G, 2017, BIOORG CHEM, V72, P64, DOI 10.1016/j.bioorg.2017.03.011; White E, 2009, CLIN CANCER RES, V15, P5308, DOI 10.1158/1078-0432.CCR-07-5023; Xu MY, 2014, J NAT PROD, V77, P370, DOI 10.1021/np401022g; Zhang L, 2015, FITOTERAPIA, V103, P46, DOI 10.1016/j.fitote.2015.03.010	23	3	3	0	6	CHINESE JOURNAL NATURAL MEDICINES	NANJING	24, TONGJIA XIANG, NANJING, 210009, PEOPLES R CHINA	2095-6975	1875-5364		CHIN J NAT MEDICINES	Chin. J. Nat. Med.	FEB	2020	18	2					81	89		10.1016/S1875-5364(20)30009-1			9	Integrative & Complementary Medicine; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine; Pharmacology & Pharmacy	KU3CI	WOS:000519585300001	32172951				2022-04-25	
J	Chang, CL; Chen, KH; Sung, PH; Chiang, JY; Huang, CR; Chen, HH; Yip, HK				Chang, Chia-Lo; Chen, Kuan-Hung; Sung, Pei-Hsun; Chiang, John Y.; Huang, Chi-Ruei; Chen, Hong-Hwa; Yip, Hon-Kan			Combined high energy of extracorporeal shock wave and 5-FU effectively suppressed the proliferation and growth of tongue squamous cell carcinoma	BIOMEDICINE & PHARMACOTHERAPY			English	Article						Cancer cells; Tumor growth; Extracorporeal shock wave; Anti-cancer drug	HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; INDUCED CHRONIC CYSTITIS; PERITONEAL CARCINOMATOSIS; CANCER STATISTICS; THERAPY; CYTOREDUCTION; PATHWAY; ISCHEMIA; COLON	Background: We tested the hypothesis that extracorporeal shock wave (ECSW)-assisted 5-FU therapy effectively suppressed human tongue squamous carcinoma cell line SAS (i.e., SAS cells) proliferation and tumor growth. Methods and results: In vitro study showed that as compared with lower ECSW energy (<= 0.12 mJ/mm(2)), higher ECSW energy (>= 0.25-035 mJ/mm(2)) significantly suppressed the SAS cell proliferation and upregulated tumor cell apoptosis/DNA-damage/oxidative-stress, whereas combined higher ECSW energy (0.35 mJ/mm(2)) and 5-FU (20uM) further significantly altered the expressions of these parameters (all p < 0.001). Adult male nude mice (NM) (n = 36) were equally categorized into group 1 (2.0 x 10(5) SAS cells were implanted into NM back), group 2 [SAS in NM back + stepwise-increased ECSW energy (from 0.05/0.1/0.3/to 0.5 mJ/mm(2))/500 impulses which applied to the tumor at days 9/12/15/21], group 3 (SAS in NM back + 5-FU/i.p./7 mg/kg/every 3-day) and group 4 (SAS in NM back + ECSW + 5-FU) and tumors were removed from each animal by day-28. The result showed that tumor volume and tumor weight were significantly progressively reduced from group 1 to group 4 (all p < 0.0001). The protein expressions of apoptotic (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cyclophyllin-D), autophagic (ratio of LC3B-II/LC3B-I) and oxidative-stress (NOX-1/NOX-2) biomarkers displayed an opposite pattern of tumor mass among the groups, whereas the cell-stress signaling (p-PI3K/p-Akt/p-m-TOR, and ASK1/MKK4/MKK7/p38/p-JNK/p-c-JUN), MAP kinase family members (RAS/cRAF/KRAS/BRAF/p-ERK1/2), tumor protein (p53) and cellular levels of angiogenesis/DNA-damage (alpha-SMA+/VEGF+/gamma-H2AX+) exhibited an identical pattern of tumor mass among the groups (all p < 0.0001). Conclusion: Combined high-energy ECSW and 5-FU offers an additional benefit for suppressing the cancer cell proliferation and tumor growth.	[Chang, Chia-Lo; Chen, Hong-Hwa] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Div Colorectal Surg, Kaohsiung, Taiwan; [Chang, Chia-Lo; Chen, Kuan-Hung; Sung, Pei-Hsun; Huang, Chi-Ruei; Chen, Hong-Hwa; Yip, Hon-Kan] Chang Gung Univ, Coll Med, 123 Dapi Rd, Kaohsiung 83301, Taiwan; [Chen, Kuan-Hung] Kaohsiung Chang Gung Mem Hosp, Dept Anesthesiol, Kaohsiung, Taiwan; [Sung, Pei-Hsun; Huang, Chi-Ruei; Yip, Hon-Kan] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Cardiol, 123 Dapi Rd, Kaohsiung 83301, Taiwan; [Chiang, John Y.] Natl Sun Yat Sen Univ, Dept Comp Sci & Engn, Kaohsiung 80424, Taiwan; [Sung, Pei-Hsun; Yip, Hon-Kan] Kaohsiung Chang Gung Mem Hosp, Inst Translat Res Biomed, Kaohsiung 83301, Taiwan; [Sung, Pei-Hsun; Yip, Hon-Kan] Kaohsiung Chang Gung Mem Hosp, Ctr Shockwave Med & Tissue Engn, Kaohsiung 83301, Taiwan; [Yip, Hon-Kan] China Med Univ Hosp, China Med Univ, Dept Med Res, Taichung 40402, Taiwan; [Yip, Hon-Kan] Asia Univ, Dept Nursing, Taichung 41354, Taiwan; [Yip, Hon-Kan] Xiamen Chang Gung Hosp, Div Cardiol, Dept Internal Med, Xiamen 361028, Fujian, Peoples R China		Chen, HH; Yip, HK (corresponding author), Chang Gung Univ, Coll Med, 123 Dapi Rd, Kaohsiung 83301, Taiwan.; Yip, HK (corresponding author), Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Cardiol, 123 Dapi Rd, Kaohsiung 83301, Taiwan.	ma2561@adm.cgmh.org.tw; han.gung@msa.hinet.net		Sung, Pei-Hsun/0000-0002-1989-9752	Chang Gung Memorial Hospital, Chang Gung UniversityChang Gung Memorial Hospital [CRRPG8J0121(1/3), CRRPG8J0122(2/3), CRRPG8J0123(3/3)]	This study was supported by a program grant from Chang Gung Memorial Hospital, Chang Gung University [Grant number: CRRPG8J0121(1/3), CRRPG8J0122(2/3), CRRPG8J0123(3/3)].	Chen YT, 2020, AM J TRANSL RES, V12, P999; Chen YT, 2019, J PINEAL RES, V66, DOI 10.1111/jpi.12536; Chen YT, 2018, AM J TRANSL RES, V10, P1036; Delaloge S, 2017, LANCET ONCOL, V18, P1293, DOI 10.1016/S1470-2045(17)30514-4; Fu M, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0024342; Hilger RA, 2002, ONKOLOGIE, V25, P511, DOI 10.1159/000068621; Huang TH, 2016, MOL MED, V22, P850, DOI 10.2119/molmed.2016.00108; Lee FY, 2017, AM J TRANSL RES, V9, P1603; Lin KC, 2018, MEDIAT INFLAMM, V2018, DOI 10.1155/2018/5425346; LoRusso PM, 2016, J CLIN ONCOL, V34, P3803, DOI 10.1200/JCO.2014.59.0018; Lu T, 2019, CANCER MANAG RES, V11, P943, DOI 10.2147/CMAR.S187317; Ma FY, 2014, AM J PHYSIOL-RENAL, V307, pF1263, DOI 10.1152/ajprenal.00211.2014; Meloche S, 2007, ONCOGENE, V26, P3227, DOI 10.1038/sj.onc.1210414; Nadler A, 2015, CLIN COLON RECT SURG, V28, P234, DOI 10.1055/s-0035-1564431; Naghavi M, 2017, LANCET, V390, P1151, DOI 10.1016/S0140-6736(17)32152-9; Nishida T, 2004, CIRCULATION, V110, P3055, DOI 10.1161/01.CIR.0000148849.51177.97; Noguti J, 2012, CANCER GENOM PROTEOM, V9, P329; Ogden JA, 2001, CLIN ORTHOP RELAT R, P8; Ogier JM, 2020, J MOL MED, V98, P335, DOI 10.1007/s00109-020-01878-y; Ramalingam SS, 2011, CA-CANCER J CLIN, V61, P91, DOI 10.3322/caac.20102; Rawla P, 2019, GASTROENTEROL REV, V14, P89, DOI 10.5114/pg.2018.81072; Rompe JD, 2003, AM J SPORT MED, V31, P268, DOI 10.1177/03635465030310021901; Rompe JD, 2001, CLIN ORTHOP RELAT R, P72; Sheu JJ, 2017, ONCOTARGET, V8, P54747, DOI 10.18632/oncotarget.18287; Siegel R, 2014, CA-CANCER J CLIN, V64, P104, DOI 10.3322/caac.21220; Sundling KE, 2016, CANCER TREAT RES, V168, P309, DOI 10.1007/978-3-319-34244-3_15; Sung PH, 2018, OXID MED CELL LONGEV, V2018, DOI 10.1155/2018/7518920; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; Vaira M, 2010, IN VIVO, V24, P79; Verwaal VJ, 2008, ANN SURG ONCOL, V15, P2426, DOI 10.1245/s10434-008-9966-2; Wang L, 2008, AM J SPORT MED, V36, P340, DOI 10.1177/0363546507307402; Yang CH, 2019, NEUROCHEM RES, V44, P796, DOI 10.1007/s11064-018-02713-0; Yeh KH, 2012, CRIT CARE MED, V40, P169, DOI 10.1097/CCM.0b013e31822d74d0; Yin TC, 2019, VASC PHARMACOL, V113, P57, DOI 10.1016/j.vph.2018.12.003; Yuen CM, 2015, AM J TRANSL RES, V7, P976	35	0	0	1	2	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER	ISSY-LES-MOULINEAUX	65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE	0753-3322	1950-6007		BIOMED PHARMACOTHER	Biomed. Pharmacother.	OCT	2021	142								112036	10.1016/j.biopha.2021.112036		AUG 2021	13	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	UR6ZH	WOS:000696894400004	34411913	gold			2022-04-25	
J	Wu, WB; Dong, JY; Gou, H; Geng, RM; Yang, XL; Chen, D; Xiang, B; Zhang, ZK; Ren, SC; Chen, LH; Liu, J				Wu, Wenbing; Dong, Jingying; Gou, Hui; Geng, Ruiman; Yang, Xiaolong; Chen, Dan; Xiang, Bing; Zhang, Zhengkun; Ren, Sichong; Chen, Lihong; Liu, Ji			EGCG synergizes the therapeutic effect of irinotecan through enhanced DNA damage in human colorectal cancer cells	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						apoptosis; autophagy; colorectal cancer; DNA damage; EGCG; irinotecan	GREEN TEA; EPIGALLOCATECHIN-3-GALLATE EGCG; AUTOPHAGY; DEATH; APOPTOSIS; ATM; INACTIVATION; CONSTITUENT	Irinotecan is a kind of alkaloid with antitumour activity, but its low solubility and high toxicity limit its application. Epigallocatechin-3-gallate (EGCG) is one of the main bioactive components in tea. The epidemiological investigation and animal and cell experiments show that EGCG has a preventive and therapeutic effect on many kinds of tumours. Here, colorectal cancer cells RKO and HCT116 were employed, and the CCK8 proliferation test was used to screen the appropriate concentration of EGCG and irinotecan, and the effects of single and/or combined drugs on migration, invasion, DNA damage, cell cycle and autophagy of tumour cells were investigated. The results showed that EGCG combined with irinotecan (0.5 mu mol L-) not only had a stronger inhibitory effect on tumour cells than EGCG or irinotecan alone but also prevented tumour cell migration and invasion. EGCG alone did not cause DNA damage in colorectal cancer cells, but its combination with irinotecan could induce S or G2 phase arrest by inhibiting topoisomerase I to cause more extensive DNA damage. EGCG also induced apoptosis by promoting autophagy with irinotecan synergistically. These results indicated that EGCG in combination with irinotecan could be a promising strategy for colorectal cancer.	[Wu, Wenbing; Dong, Jingying; Geng, Ruiman; Yang, Xiaolong; Chen, Dan; Xiang, Bing; Zhang, Zhengkun; Chen, Lihong; Liu, Ji] Sichuan Univ, Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, Chengdu, Peoples R China; [Wu, Wenbing] Southwest Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Luzhou, Peoples R China; [Gou, Hui] Southwest Med Univ, Dept Pharm, Affiliated Hosp, Luzhou, Peoples R China; [Ren, Sichong] Sichuan Acad Tradit Chinese Med, State Key Lab Qual Evaluat Tradit Chinese Med, Chengdu, Peoples R China		Chen, LH; Liu, J (corresponding author), Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, Chengdu 610041, Peoples R China.	chenlih_bioch@126.com; liuji6103@163.com		wenbing, wu/0000-0002-8132-5100; Xiang, Bin/0000-0002-9261-8347; Geng, Ruiman/0000-0002-9253-9171	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81803967]	National Natural Science Foundation of China, Grant/Award Number: 81803967	Abe O, 2018, EUR J CLIN PHARMACOL, V74, P775, DOI 10.1007/s00228-018-2436-2; Abedin MJ, 2007, CELL DEATH DIFFER, V14, P500, DOI 10.1038/sj.cdd.4402039; Alexander A, 2010, AUTOPHAGY, V6, P672, DOI 10.4161/auto.6.5.12509; Alshatwi AA, 2016, CHEM-BIOL INTERACT, V247, P1, DOI 10.1016/j.cbi.2016.01.012; Berger SJ, 2001, BIOCHEM BIOPH RES CO, V288, P101, DOI 10.1006/bbrc.2001.5736; Bhat KPL, 2002, ANN NY ACAD SCI, V957, P210, DOI 10.1111/j.1749-6632.2002.tb02918.x; Blackford AN, 2017, MOL CELL, V66, P801, DOI 10.1016/j.molcel.2017.05.015; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Brewer JR, 2016, GYNECOL ONCOL, V140, P176, DOI 10.1016/j.ygyno.2015.11.011; Calgarotto AK, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-21516-5; Campbell JM, 2017, PHARMACOGENOMICS J, V17, P21, DOI 10.1038/tpj.2016.58; Filippini T, 2020, COCHRANE DB SYST REV, DOI 10.1002/14651858.CD005004.pub3; Fujiki H, 2018, MOL CELLS, V41, P73, DOI 10.14348/molcells.2018.2227; Guole L., 2019, CHINESE GEN PRACTICE, V22, P4031; Haller DG, 2005, J CLIN ONCOL, V23, P8671, DOI 10.1200/JCO.2004.00.5686; HSIANG YH, 1985, J BIOL CHEM, V260, P4873; Inoue M, 1998, CANCER CAUSE CONTROL, V9, P209, DOI 10.1023/A:1008890529261; Kang KB, 2009, MOL CANCER, V8, DOI 10.1186/1476-4598-8-66; Katayama M, 2007, CELL DEATH DIFFER, V14, P548, DOI 10.1038/sj.cdd.4402030; Lecumberri E, 2013, CLIN NUTR, V32, P894, DOI 10.1016/j.clnu.2013.03.008; Lu LDY, 2013, SCI REP-UK, V3, DOI 10.1038/srep03169; Masuda M, 2001, CLIN CANCER RES, V7, P4220; Meschini S, 2008, AUTOPHAGY, V4, P1020, DOI 10.4161/auto.6952; Rieber M, 2008, CANCER BIOL THER, V7, P1561, DOI 10.4161/cbt.7.10.6540; Shunichiro K., 2013, CANCER CELL INT, V13, P1; Singh BN, 2011, BIOCHEM PHARMACOL, V82, P1807, DOI 10.1016/j.bcp.2011.07.093; Smith GCM, 1999, MOL CELL BIOL, V19, P6076; Song X, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.463; Staker BL, 2002, P NATL ACAD SCI USA, V99, P15387, DOI 10.1073/pnas.242259599; Stearns ME, 2011, TRANSL ONCOL, V4, P147, DOI 10.1593/tlo.10286; Takacs-Vellai K, 2005, CURR BIOL, V15, P1513, DOI 10.1016/j.cub.2005.07.035; Wang JZ, 2006, AM J PHYSIOL-RENAL, V291, pF1300, DOI 10.1152/ajprenal.00509.2005; Wenzel ES, 2018, IN VIVO, V32, P1, DOI 10.21873/invivo.11197; Yang CS., 2006, CANCER RES, V66, P1150; Zhang FL, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0081815; [朱虹 ZHU Hong], 2007, [生命科学, Chinese Bulletin of Life Sciences], V19, P139	36	2	2	4	7	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1582-1838	1582-4934		J CELL MOL MED	J. Cell. Mol. Med.	AUG	2021	25	16					7913	7921		10.1111/jcmm.16718		JUN 2021	9	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	TZ1DR	WOS:000661840800001	34132471	Green Published, gold			2022-04-25	
J	Zhao, DY; Sun, XZ; Long, SD; Yao, SK				Zhao, Dongyan; Sun, Xizhen; Long, Sidan; Yao, Shukun			An autophagy-related long non-coding RNA signature for patients with colorectal cancer	PHYSIOLOGY INTERNATIONAL			English	Article						autophagy; long non-coding RNA; prognostic signature; colorectal cancer; TCGA	GROWTH	Aim: Long non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients. Methods: LncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms. Results: We obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients' overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-beta p53, mTOR and WNT signaling pathway. Conclusions: Our study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.	[Zhao, Dongyan; Sun, Xizhen; Yao, Shukun] Peking Union Med Coll & Chinese Acad Med Sci, Grad Sch, Beijing 100730, Peoples R China; [Long, Sidan] Beijing Univ Chinese Med, Beijing 100029, Peoples R China; [Yao, Shukun] China Japan Friendship Hosp, Dept Gastroenterol, 2nd Yinghua East Rd, Beijing 100029, Peoples R China		Yao, SK (corresponding author), China Japan Friendship Hosp, Dept Gastroenterol, 2nd Yinghua East Rd, Beijing 100029, Peoples R China.	shukunyao@126.com			National Key Development Plan for Precision Medicine Research [2017YFC0910002]	The authors thank the TCGA project for providing invaluable datasets for statistical analyses. This work was supported by the National Key Development Plan for Precision Medicine Research (2017YFC0910002).	Amaravadi RK, 2011, CLIN CANCER RES, V17, P654, DOI 10.1158/1078-0432.CCR-10-2634; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Broz DK, 2013, GENE DEV, V27, P1016, DOI 10.1101/gad.212282.112; Devenport SN, 2019, CELLS-BASEL, V8, DOI 10.3390/cells8111349; Fan YF, 2020, BIOSCIENCE REP, V40, DOI 10.1042/BSR20193309; Filfan M, 2017, ROM J MORPHOL EMBRYO, V58, P27; Guinney J, 2015, NAT MED, V21, P1350, DOI 10.1038/nm.3967; Janku F, 2011, NAT REV CLIN ONCOL, V8, P384, DOI 10.1038/nrclinonc.2011.82; Johansson I, 2012, BREAST CANCER RES, V14, DOI 10.1186/bcr3116; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Li D, 2019, IN VITRO CELL DEV-AN, V55, P577, DOI 10.1007/s11626-019-00376-x; Li J, 2017, DNA CELL BIOL, V36, P1117, DOI 10.1089/dna.2017.3888; Li XY, 2019, AGING-US, V11, P5646, DOI 10.18632/aging.102149; Li Y, 2019, FRONT PHARMACOL, V10, DOI 10.3389/fphar.2019.00139; Liu LK, 2020, J ORAL PATHOL MED, V49, P243, DOI 10.1111/jop.12989; Liu PF, 2014, AUTOPHAGY, V10, P1454, DOI 10.4161/auto.29556; Markle B, 2010, CANCER METAST REV, V29, P395, DOI 10.1007/s10555-010-9234-3; Marmol I, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18010197; Morris KV, 2014, NAT REV GENET, V15, P423, DOI 10.1038/nrg3722; Mowers EE, 2017, ONCOGENE, V36, P1619, DOI 10.1038/onc.2016.333; Muzny DM, 2012, NATURE, V487, P330, DOI 10.1038/nature11252; Newton PT, 2019, BIOCHEM J, V476, P779, DOI 10.1042/BCJ20190020; Niklaus M, 2017, ONCOTARGET, V8, P54604, DOI 10.18632/oncotarget.17554; Roychowdhury A, 2020, GENOMICS, V112, P961, DOI 10.1016/j.ygeno.2019.06.012; Ruan ZH, 2019, ONCOL LETT, V18, P1107, DOI 10.3892/ol.2019.10435; Saxton RA, 2017, CELL, V168, P960, DOI [10.1016/j.cell.2017.02.004, 10.1016/j.cell.2017.03.035]; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Subramanian A, 2005, P NATL ACAD SCI USA, V102, P15545, DOI 10.1073/pnas.0506580102; Sui X, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.350; Tasdemir E, 2008, NAT CELL BIOL, V10, P676, DOI 10.1038/ncb1730; Wang Y, 2019, BIOMED PHARMACOTHER, V111, P1297, DOI 10.1016/j.biopha.2018.12.134; Weiser MR, 2011, J CLIN ONCOL, V29, P4796, DOI 10.1200/JCO.2011.36.5080; Yu H, 2015, J THORAC ONCOL, V10, P645, DOI 10.1097/JTO.0000000000000470; Zhang J, 2017, AUTOPHAGY, V13, P1004, DOI 10.1080/15548627.2017.1312041; Zheng YS, 2019, J CELL BIOCHEM, V120, P3922, DOI 10.1002/jcb.27676; Zhu Z, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20030728	36	0	0	0	1	AKADEMIAI KIADO ZRT	BUDAPEST	BUDAFOKI UT 187-189-A-3, H-1117 BUDAPEST, HUNGARY	2498-602X			PHYSIOL INT	Physiol. Int.	JUN	2021	108	2					202	220		10.1556/2060.2021.00125			19	Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Physiology	TZ0QL	WOS:000684181000004	34224393	Green Accepted			2022-04-25	
J	Wu, XL; Feng, XF; Zhao, XQ; Ma, FT; Liu, N; Guo, HM; Li, CN; Du, H; Zhang, BX				Wu, Xiaoli; Feng, Xuefeng; Zhao, Xiaoqing; Ma, Futian; Liu, Na; Guo, Hongming; Li, Chaonan; Du, Huan; Zhang, Baoxi			Role of Beclin-1-Mediated Autophagy in the Survival of Pediatric Leukemia Cells	CELLULAR PHYSIOLOGY AND BIOCHEMISTRY			English	Article						Pediatric leukemia (PL); Oxidative stress; Autophagy; Apoptosis; Beclin-1; miR-93	ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; INHIBITS TUMOR-GROWTH; PATHWAY IN-VITRO; CANCER-CELLS; COLORECTAL-CANCER; INDUCED APOPTOSIS; GASTRIC-CANCER; BREAST-CANCER	Background/Aims: Acute and chronic leukemia are severe malignant cancers worldwide, and can occur in pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia (PL) remains challenging. Autophagy is essential for the regulation of cell survival in the harsh environment. However, the role of autophagy in the survival of PL cells under the oxidative stress, e.g. chemotherapy, remain ill-defined. In the current study, we addressed these questions. Methods: We analyzed the effects of oxidative stress on the cell viability of PL cells in vitro, using a CCK-8 assay. We analyzed the effects of oxidative stress on the apoptosis and autophagy of PL cells. We analyzed the levels of Beclin-1 and microRNA-93 (miR-93) in PL cells. Prediction of binding between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The relationship between levels of miR-93 and patients' survival was analyzed in PL patients. Results: We found that oxidative stress dose-dependently increased autophagy in PL cells. While low-level oxidative stress did not increase apoptosis, high-level oxidative stress increased apoptosis, seemingly from failure of autophagy-mediated cell survival. High-level oxidative stress appeared to suppress the protein levels of an autophagy protein Beclin-1 in PL cells, possibly through induction of miR-93, which inhibited the translation of Beclin-1 mRNA via 3'-UTR binding. Conclusion: Beclin-1-mediated autophagy plays a key role in the survival of PL cells against oxidative stress. Induction of miR-93 may increase the sensitivity of PL cells to oxidative stress during chemotherapy to improve therapeutic outcome. (C) 2016 The Author(s) Published by S. Karger AG, Basel	[Wu, Xiaoli; Zhao, Xiaoqing; Ma, Futian; Liu, Na; Guo, Hongming; Li, Chaonan; Du, Huan; Zhang, Baoxi] Hebei Med Univ, Hosp 2, Dept Pediat Hematol Oncol, 215 Heping West Rd, Shijiazhuang 050000, Peoples R China; [Feng, Xuefeng] Hebei Med Univ, Hosp 2, Dept Hematol, Shijiazhuang, Peoples R China		Zhang, BX (corresponding author), Hebei Med Univ, Hosp 2, Dept Pediat Hematol Oncol, 215 Heping West Rd, Shijiazhuang 050000, Peoples R China.	zbx_238@yeah.net			Science and Technology Department of Hebei Province [152777206]	This work is supported by Science and Technology Department of Hebei Province (NO: 152777206).	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Physiol. Biochem.		2016	39	5					1827	1836		10.1159/000447882			10	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	EC9ZT	WOS:000388503500015	27744427	gold			2022-04-25	
J	Jiffry, J; Thavornwatanayong, T; Rao, D; Fogel, EJ; Saytoo, D; Nahata, R; Guzik, H; Chaudhary, I; Augustine, T; Goel, S; Maitra, R				Jiffry, Jeeshan; Thavornwatanayong, Thongthai; Rao, Devika; Fogel, Elisha J.; Saytoo, Durvanand; Nahata, Rishika; Guzik, Hillary; Chaudhary, Imran; Augustine, Titto; Goel, Sanjay; Maitra, Radhashree			Oncolytic Reovirus (pelareorep) Induces Autophagy in KRAS-mutated Colorectal Cancer	CLINICAL CANCER RESEARCH			English	Article							DOUBLE-EDGED-SWORD; BECLIN 1; APOPTOSIS; EXPRESSION; MUTATIONS; NECROSIS	Purpose: To explore the effects of pelareorep on autophagy in multiple models of colorectal cancer, including patient-derived peripheral blood mononuclear cells (PBMCs). Experimental Design: HCT116 [KRAS mutant (mut)] and Hke3 [KRAS wild-type (WT)] cells were treated with pelareorep (multiplicity of infection, 5) and harvested at 6 and 9 hours. LC3 A/B expression was determined by immunofluorescence and flow cytometry; five autophagic proteins were analyzed by Western blotting. The expression of 88 autophagy genes was determined by qRT-PCR. Syngeneic mouse models, CT26/Balb-C (KRAS mut) and MC38/C57B6 (KRAS WT), were developed and treated with pelareorep (10 x 10(6) plaque-forming unit/day) intraperitoneally. Protein and RNA were extracted from harvested tumor tissues. PBMCs from five experimental and three control patients were sampled at 0 (pre) and 48 hours, and on days 8 and 15. The gene expression normalized to "pre" was determined using 2(-Delta Delta Ct) method. Results: Pelareorep induced significant upregulation of LC3 A/B in HCT116 as compared with Hke3 cells by immunofluorescence (3.24 x and 8.67 x), flow cytometry (2.37 x and 2.58 x), and autophagosome formation (2.02 x and 1.57 x), at 6 and 9 hours, respectively; all P < 0.05. Western blot analysis showed an increase in LC3 A/B (2.38 x and 6.82 x) and Beclin1 ( 1.17 x and 1.24 x) at 6 and 9 hours, ATG5 (2.4 x) and P-62 (1.52 x) at 6 hours, and VPS-34 (1.39 x) at 9 hours (all P < 0.05). Induction of 13 transcripts in cell lines (>4 x; 6 and 9 hours; P < 0.05), 12 transcripts in CT26 (qRT-PCR), and 14 transcripts in human PBMCs (P < 0.05) was observed. LC3 A/B, RICTOR, and RASD1 expression was upregulated in all three model systems. Conclusions: Pelareorep hijacks host autophagic machinery in KRAS-mut conditions to augment its propagation and preferential oncolysis of the cancer cells.	[Jiffry, Jeeshan; Thavornwatanayong, Thongthai; Saytoo, Durvanand; Nahata, Rishika; Guzik, Hillary; Augustine, Titto; Goel, Sanjay; Maitra, Radhashree] Albert Einstein Coll Med, Bronx, NY 10467 USA; [Rao, Devika; Chaudhary, Imran; Goel, Sanjay; Maitra, Radhashree] Montefiore Med Ctr, 1695 Eastchester Rd, Bronx, NY 10461 USA; [Fogel, Elisha J.; Maitra, Radhashree] Yeshiva Univ, Dept Biol, New York, NY 10033 USA		Goel, S (corresponding author), Montefiore Med Ctr, 1695 Eastchester Rd, Bronx, NY 10461 USA.; Maitra, R (corresponding author), Yeshiva Univ, 500 West 185th St,BH 1404, New York, NY 10033 USA.	sgoel@montefiore.org; radhashree.maitra@yu.edu	Rao, Devika/AAZ-5201-2020	GOEL, SANJAY/0000-0002-2798-7568; Fogel, Elisha/0000-0002-0190-6934; Augustine, Titto/0000-0002-0539-864X	NIH/AG1R21 NIH grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AG 1R21AG058027-01]; Yeshiva University [2A4108]; NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA013330]	S. Goel was supported by NIH/AG1R21 NIH grant AG 1R21AG058027-01. R. Maitra was supported by Yeshiva University startup fund 2A4108. We gratefully acknowledge the Genomic Facility, Flow Cytometry Core Facility, and the Analytical Imaging Facility of Albert Einstein College of Medicine (Bronx, NY) along with the NCI cancer center support grant (P30CA013330), which partially supports all morphometric work conducted with 3D Histech P250 High Capacity Slide Scanner SIG #1S10OD019961-01 of the shared facilities. We also thankfully acknowledge Prof. Xingxing Zang (Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY) for kind gift of two transplantable (syngeneic) models of murine tumor cell lines, CT26 and MC38. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.	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Cancer Res.	FEB 1	2021	27	3					865	876		10.1158/1078-0432.CCR-20-2385			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	QG1CK	WOS:000617323900021	33168658	Green Accepted			2022-04-25	
J	Gu, W; Wan, DW; Qian, QY; Yi, B; He, ZL; Gu, YL; Wang, L; He, SB				Gu, Wen; Wan, Daiwei; Qian, Qinyi; Yi, Bin; He, Zhilong; Gu, Yilin; Wang, Liang; He, Songbing			Ambra1 Is an Essential Regulator of Autophagy and Apoptosis in SW620 Cells: Pro-Survival Role of Ambra1	PLOS ONE			English	Article							CALPAIN-MEDIATED CLEAVAGE; COLORECTAL-CANCER CELLS; MOLECULAR-MECHANISMS; MONITORING AUTOPHAGY; BECLIN-1; INHIBITION; EXPRESSION; THERAPY; PROTEIN	Recent research has revealed a role for Ambra1, an autophagy-related gene-related (ATG) protein, in the autophagic pro-survival response, and Ambra1 has been shown to regulate Beclin1 and Beclin1-dependent autophagy in embryonic stem cells. However, whether Ambra1 plays an important role in the autophagy pathway in colorectal cancer cells is unknown. In this study, we hypothesized that Ambra1 is an important regulator of autophagy and apoptosis in CRC cell lines. To test this hypothesis, we confirmed autophagic activity in serum-starved SW620 CRC cells by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3) localization, the presence of autophagosomes (transmission electron microscopy) and LC3 protein levels (Western blotting). Ambra1 expression was detected by Western blot in SW620 cells treated with staurosporine or etoposide. Calpain and caspase inhibitors were employed to verify whether calpains and caspases were responsible for Ambra1 cleavage. To examine the role of Ambra1 in apoptosis, Ambra1 knockdown cells were treated with staurosporine and etoposide. Cell apoptosis and viability were measured by annexin-V and PI staining and MTT assays. We determined that serum deprivation-induced autophagy was associated with Ambra1 upregulation in colorectal cancer cell lines. Ambra1 expression decreased during staurosporine- or etoposide-induced apoptosis. Calpains and caspases may be responsible for Ambra1 degradation. When Ambra1 expression was reduced by siRNA, SW620 cells were more sensitive to staurosporine-or etoposide-induced apoptosis. In addition, starvation-induced autophagy decreased. Finally, Co-immunoprecipitation of Ambra1 and Beclin1 demonstrated that Ambra1 and Beclin1 interact in serum-starved or rapamycin-treated SW620 cells, suggesting that Ambra1 regulates autophagy in CRC cells by interacting with Beclin1. In conclusion, Ambra1 is a crucial regulator of autophagy and apoptosis in CRC cells that maintains the balance between autophagy and apoptosis.	[Gu, Wen; Yi, Bin; Wang, Liang; He, Songbing] Soochow Univ, Affiliated Hosp 1, Dept Gen Surg, Suzhou, Peoples R China; [Wan, Daiwei] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Guangzhou 510275, Guangdong, Peoples R China; [He, Songbing] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China; [He, Songbing] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Immunol, Shanghai, Peoples R China; [He, Songbing] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China; [Qian, Qinyi] Changshu 2 Peoples Hosp, Dept Ultrasonog, Changshu, Peoples R China; [Gu, Yilin] Soochow Univ, Affiliated Hosp 1, Dept Operating Rooms, Suzhou, Peoples R China; [He, Zhilong] Soochow Univ, Affiliated Hosp 1, Dept Gastroenterol, Suzhou, Peoples R China; [He, Songbing] Washington Univ, Sch Med, St Louis, MO USA		Wang, L (corresponding author), Soochow Univ, Affiliated Hosp 1, Dept Gen Surg, Suzhou, Peoples R China.	wangliangsuda@163.com; hesongbing1979@163.com			Nature Science Foundation of P.R. China [81201905]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2013M540374]; Shanghai Postdoctoral Scientific Program of P.R. China [13R21415200]; Nature Science Research Grants of the University of Jiangsu Province of P.R. China [12KJB320009]; Research Project of the Science and Technology Bureau of Suzhou City of P.R. China [SYS201220]; Government Overseas Scholarship from the Department of Education of Jiangsu Province	This work was supported by the Project of the Nature Science Foundation of P.R. China (81201905), the China Postdoctoral Science Foundation (2013M540374), the Shanghai Postdoctoral Scientific Program of P.R. China (13R21415200), Nature Science Research Grants of the University of Jiangsu Province of P.R. China (12KJB320009), and the Research Project of the Science and Technology Bureau of Suzhou City of P.R. China (SYS201220), and sponsored by a Government Overseas Scholarship from the Department of Education of Jiangsu Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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J	Kaliszczak, M; van Hechanova, E; Li, YQ; Alsadah, H; Parzych, K; Auner, HW; Aboagye, EO				Kaliszczak, Maciej; van Hechanova, Erich; Li, Yunqing; Alsadah, Hibah; Parzych, Katarzyna; Auner, Holger W.; Aboagye, Eric O.			The HDAC6 inhibitor C1A modulates autophagy substrates in diverse cancer cells and induces cell death	BRITISH JOURNAL OF CANCER			English	Article							HISTONE DEACETYLASE 6; REGULATES AGGRESOME FORMATION; KINASE INHIBITOR; ANTITUMOR-ACTIVITY; N-MYC; COMBINATION; BORTEZOMIB; MECHANISMS; PROTEIN; DRUG	BACKGROUND: Cytosolic deacetylase histone deacetylase 6 (HDAC6) is involved in the autophagy degradation pathway of malformed proteins, an important survival mechanism in cancer cells. We evaluated modulation of autophagy-related proteins and cell death by the HDAC6-selective inhibitor C1A. METHODS: Autophagy substrates (light chain-3 (LC-3) and p62 proteins) and endoplasmic reticulum (ER) stress phenotype were determined. Caspase-3/7 activation and cellular proliferation assays were used to assess consequences of autophagy modulation. RESULTS: C1A potently resolved autophagy substrates induced by 3-methyladenine and chloroquine. The mechanism of autophagy inhibition by HDAC6 genetic knockout or C1A treatment was consistent with abrogation of autophagosome-lysosome fusion, and decrease of Myc protein. CIA alone or combined with the proteasome inhibitor, bortezomib, enhanced cell death in malignant cells, demonstrating the complementary roles of the proteasome and autophagy pathways for clearing malformed proteins. Myc-positive neuroblastoma, KRAS-positive colorectal cancer and multiple myeloma cells showed marked cell growth inhibition in response to HDAC6 inhibitors. Finally, growth of neuroblastoma xenografts was arrested in vivo by single agent C1A, while combination with bortezomib slowed the growth of colorectal cancer xenografts. CONCLUSIONS: C1A resolves autophagy substrates in malignant cells and induces cell death, warranting its use for in vivo preclinical autophagy research.	[Kaliszczak, Maciej; van Hechanova, Erich; Li, Yunqing; Aboagye, Eric O.] Imperial Coll London, Hammersmith Hosp, Canc Imaging Ctr, Dept Surg & Canc, Du Cane Rd, London W12 0NN, England; [Alsadah, Hibah; Parzych, Katarzyna; Auner, Holger W.] Imperial Coll London, Hammersmith Hosp, Dept Med, Canc Cell Prot Metab Grp, Du Cane Rd, London W12 0NN, England; [Kaliszczak, Maciej] Biogen, Preclin Imaging & Pharmacol, 125 Broadway St, Cambridge, MA 02142 USA; [van Hechanova, Erich] UCL, UCL Great Ormond St Inst Child Hlth, Dev Biol Birth Defects Sect, 30 Guilford St, London WC1N 1EH, England		Aboagye, EO (corresponding author), Imperial Coll London, Hammersmith Hosp, Canc Imaging Ctr, Dept Surg & Canc, Du Cane Rd, London W12 0NN, England.	eric.aboagye@imperial.ac.uk		Auner, Holger/0000-0003-4040-0642; ABOAGYE, Eric/0000-0003-2276-6771	Cancer Research UKCancer Research UK [C2536/A10337] Funding Source: Medline; Cancer Research UK (CRUK)Cancer Research UK [C2536/A16584] Funding Source: Medline		Auner HW, 2015, BRIT J HAEMATOL, V168, P14, DOI 10.1111/bjh.13172; BARONE MV, 1995, NATURE, V378, P509, DOI 10.1038/378509a0; Belounis A, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2906-9; Blake RA, 2000, MOL CELL BIOL, V20, P9018, DOI 10.1128/MCB.20.23.9018-9027.2000; Boone BA, 2015, ANN SURG ONCOL, V22, P4402, DOI 10.1245/s10434-015-4566-4; Chesler L, 2008, NEOPLASIA, V10, P1268, DOI 10.1593/neo.08778; Chesler L, 2006, CANCER RES, V66, P8139, DOI 10.1158/0008-5472.CAN-05-2769; Dimopoulos M, 2013, LANCET ONCOL, V14, P1129, DOI 10.1016/S1470-2045(13)70398-X; Dolman MEM, 2015, CLIN CANCER RES, V21, P5100, DOI 10.1158/1078-0432.CCR-15-0313; Dong LH, 2013, J HEMATOL ONCOL, V6, DOI 10.1186/1756-8722-6-53; Furstoss O, 2002, EMBO J, V21, P514, DOI 10.1093/emboj/21.4.514; Ganley IG, 2011, MOL CELL, V42, P731, DOI 10.1016/j.molcel.2011.04.024; Gillet JP, 2011, P NATL ACAD SCI USA, V108, P18708, DOI 10.1073/pnas.1111840108; Grandori C, 2000, ANNU REV CELL DEV BI, V16, P653, DOI 10.1146/annurev.cellbio.16.1.653; Graves JA, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0037699; He CC, 2009, ANNU REV GENET, V43, P67, DOI 10.1146/annurev-genet-102808-114910; Hideshima T, 2005, P NATL ACAD SCI USA, V102, P8567, DOI 10.1073/pnas.0503221102; Hideshima T, 2016, P NATL ACAD SCI USA, V113, P13162, DOI 10.1073/pnas.1608067113; Huang R, 2011, FASEB J, V25, P4138, DOI 10.1096/fj.11-185033; Iwata A, 2005, J BIOL CHEM, V280, P40282, DOI 10.1074/jbc.M508786200; Kaliszczak M, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2016.180; Kaliszczak M, 2013, BRIT J CANCER, V109, P2356, DOI 10.1038/bjc.2013.584; Kaliszczak M, 2013, BRIT J CANCER, V108, P342, DOI 10.1038/bjc.2012.576; Kaliszczak M, 2010, AAPS J, V12, P617, DOI 10.1208/s12248-010-9225-x; Kamada Y, 2003, CURR TOP MICROBIOL, V279, P73; Kawaguchi Y, 2003, CELL, V115, P727, DOI 10.1016/S0092-8674(03)00939-5; Krypuy M, 2006, BMC CANCER, V6, DOI 10.1186/1471-2407-6-295; Lambert LA, 2008, CANCER RES, V68, P7966, DOI 10.1158/0008-5472.CAN-08-1333; Lee JH, 2013, P NATL ACAD SCI USA, V110, P15704, DOI 10.1073/pnas.1313893110; Luscher B, 2012, EUR J CELL BIOL, V91, P506, DOI 10.1016/j.ejcb.2011.07.005; Lutz W, 1996, ONCOGENE, V13, P803; Lwin T, 2013, J CLIN INVEST, V123, P4612, DOI 10.1172/JCI64210; Mathew R, 2007, NAT REV CANCER, V7, P961, DOI 10.1038/nrc2254; Mizushima N, 2010, CELL, V140, P313, DOI 10.1016/j.cell.2010.01.028; Nakaso K, 2004, BRAIN RES, V1012, P42, DOI 10.1016/j.brainres.2004.03.029; Nawrocki ST, 2008, BLOOD, V112, P2917, DOI 10.1182/blood-2007-12-130823; Nesbit CE, 1999, ONCOGENE, V18, P3004, DOI 10.1038/sj.onc.1202746; Ouyang H, 2012, J BIOL CHEM, V287, P2317, DOI 10.1074/jbc.M111.273730; Parzych K, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.373; Pitts TM, 2009, MOL CANCER THER, V8, P342, DOI 10.1158/1535-7163.MCT-08-0534; Poklepovic A, 2014, AUTOPHAGY, V10, P1478, DOI 10.4161/auto.29428; Rosenfeld MR, 2014, AUTOPHAGY, V10, P1359, DOI 10.4161/auto.28984; Santo L, 2012, BLOOD, V119, P2579, DOI 10.1182/blood-2011-10-387365; SCHWAB M, 1985, NATURE, V316, P160, DOI 10.1038/316160a0; Simi L, 2008, AM J CLIN PATHOL, V130, P247, DOI 10.1309/LWDY1AXHXUULNVHQ; Sui X, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.350; Verfaillie T., 2010, INT J CELL BIOL, V2010, DOI [10.1155/2010/93050920145727, DOI 10.1155/2010/930509]; Vichai V, 2006, NAT PROTOC, V1, P1112, DOI 10.1038/nprot.2006.179; Vogl DT, 2017, CLIN CANCER RES, V23, P3307, DOI 10.1158/1078-0432.CCR-16-2526; Watanabe Y, 2011, J CELL SCI, V124, P2692, DOI 10.1242/jcs.081232; White E, 2012, NAT REV CANCER, V12, P401, DOI 10.1038/nrc3262; Workman P, 2010, BRIT J CANCER, V102, P1555, DOI 10.1038/sj.bjc.6605642; Wu YY, 2013, AUTOPHAGY, V9, P595, DOI 10.4161/auto.23641; Yao Tso-Pang, 2010, Genes Cancer, V1, P779; Zhang XJ, 2013, ACTA PHARMACOL SIN, V34, P595, DOI 10.1038/aps.2012.184	55	33	34	0	6	NATURE PUBLISHING GROUP	LONDON	MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	0007-0920	1532-1827		BRIT J CANCER	Br. J. Cancer	NOV 13	2018	119	10					1278	1287		10.1038/s41416-018-0232-5			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HA8TK	WOS:000450566200013	30318510	Green Published, hybrid			2022-04-25	
J	Gong, J; Lin, YY; Zhang, HQ; Liu, CQ; Cheng, Z; Yang, XW; Zhang, JM; Xiao, YY; Sang, N; Qian, XY; Wang, L; Cen, XB; Du, X; Zhao, YL				Gong, Jin; Lin, Yiyun; Zhang, Huaqin; Liu, Chunqi; Cheng, Zhong; Yang, Xiaowei; Zhang, Jiamei; Xiao, Yuanyuan; Sang, Na; Qian, Xinying; Wang, Liang; Cen, Xiaobo; Du, Xiao; Zhao, Yinglan			Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells	CELL DEATH & DISEASE			English	Article							TUMOR-STROMA; FATTY-ACIDS; GROWTH; METASTASIS; INHIBITION; APOPTOSIS; AUTOPHAGY; INVASION; BINDING; MARKER	Metabolic interaction between cancer-associated fibroblasts (CAFs) and colorectal cancer (CRC) cells plays a major role in CRC progression. However, little is known about lipid alternations in CAFs and how these metabolic reprogramming affect CRC cells metastasis. Here, we uncover CAFs conditioned medium (CM) promote the migration of CRC cells compared with normal fibroblasts CM. CAFs undergo a lipidomic reprogramming, and accumulate more fatty acids and phospholipids. CAFs CM after protein deprivation still increase the CRC cells migration, which suggests small molecular metabolites in CAFs CM are responsible for CRC cells migration. Then, we confirm that CRC cells take up the lipids metabolites that are secreted from CAFs. Fatty acids synthase (FASN), a crucial enzyme in fatty acids synthesis, is significantly increased in CAFs. CAF-induced CRC cell migration is abolished by knockdown of FASN by siRNA or reducing the uptake of fatty acids by CRC cells by sulfo-N-succinimidyloleate sodium in vitro and CD36 monoclonal antibody in vivo. To conclude, our results provide a new insight into the mechanism of CRC metastasis and suggest FASN of CAFs or CD36 of CRC cells may be potential targets for anti-metastasis treatment in the future.	[Gong, Jin; Lin, Yiyun; Zhang, Huaqin; Liu, Chunqi; Yang, Xiaowei; Sang, Na; Qian, Xinying; Zhao, Yinglan] Sichuan Univ, West China Hosp, State Key Lab Biotherapy & Canc Ctr, Chengdu 610041, Peoples R China; [Gong, Jin; Lin, Yiyun; Zhang, Huaqin; Liu, Chunqi; Yang, Xiaowei; Zhang, Jiamei; Xiao, Yuanyuan; Sang, Na; Qian, Xinying; Wang, Liang; Cen, Xiaobo; Zhao, Yinglan] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China; [Cheng, Zhong; Du, Xiao] Sichuan Univ, West China Hosp, Dept Gastrointestinal Surg, Chengdu 610041, Peoples R China; [Zhang, Jiamei; Xiao, Yuanyuan; Wang, Liang; Cen, Xiaobo] Sichuan Univ, Natl Chengdu Ctr Safety Evaluat Drugs, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China; [Du, Xiao] Ya An Peoples Hosp, Dept Gen Surg, Yaan 625000, Peoples R China		Zhao, YL (corresponding author), Sichuan Univ, West China Hosp, State Key Lab Biotherapy & Canc Ctr, Chengdu 610041, Peoples R China.; Zhao, YL (corresponding author), Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China.; Du, X (corresponding author), Sichuan Univ, West China Hosp, Dept Gastrointestinal Surg, Chengdu 610041, Peoples R China.; Du, X (corresponding author), Ya An Peoples Hosp, Dept Gen Surg, Yaan 625000, Peoples R China.	Duxiao_home@163.com; zhaoyinglan@scu.edu.cn		Lin, Yiyun/0000-0002-9277-3048	Project of the National keypoint research and invention program of China Ministry of Science and Technology [MOST-2016YFC1303200]; National ST Major project [2018ZX09201018]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773198]	This work was supported by Project of the National keypoint research and invention program of China Ministry of Science and Technology (MOST-2016YFC1303200) and National S&T Major project (2018ZX09201018), National Natural Science Foundation of China (81773198).	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APR 23	2020	11	4								10.1038/s41419-020-2434-z			15	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	LJ6KX	WOS:000530273000005	32327627	Green Published, gold			2022-04-25	
J	Bao, YJ; Tang, JY; Qian, Y; Sun, TT; Chen, HM; Chen, ZF; Sun, DF; Zhong, M; Chen, HY; Hong, J; Chen, YX; Fang, JY				Bao, Yujie; Tang, Jiayin; Qian, Yun; Sun, Tiantian; Chen, Huimin; Chen, Zhaofei; Sun, Danfeng; Zhong, Ming; Chen, Haoyan; Hong, Jie; Chen, Yingxuan; Fang, Jing-Yuan			Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway	CELL DEATH & DISEASE			English	Article							MICROBIOTA; AUTOPHAGY; DIFFERENTIATION; EXPRESSION; NETWORK; GROWTH; CELLS	Long noncoding RNAs (lncRNAs) contribute to many steps in carcinogenesis and often serve as biomarkers or therapeutic targets for tumor diagnosis and therapy. Although the role of lncRNAs in tumor formation is becoming clear, whether lncRNAs mediate gut microbiota-induced colorectal cancer (CRC) is largely unknown. Enterotoxigenic Bacteroides fragilis (ETBF) is a well-known tumor-inducing bacterium in the human gut; however, its tumorigenic effect remains to be explored. In the present study, we revealed the mechanism by which a lncRNA participates in gut bacteria-induced carcinogenesis: Bacteroides fragilis-associated lncRNA1 (BFAL1) in CRC tissues mediates ETBF carcinogenesis. BFAL1 was highly expressed in CRC tissues compared with that in adjacent normal tissues. In vitro, BFAL1 was upregulated in ETBF-treated CRC cells. Mechanistically, ETBF promoted tumor growth via BFAL1 by activating the Ras homolog, which is the MTORC1 binding/mammalian target of the rapamycin (RHEB/mTOR) pathway. Furthermore, BFAL1 regulated RHEB expression by competitively sponging microRNAs miR-155-5p and miR-200a-3p. Clinically, both high expression of BFAL1 and high abundance of ETBF in CRC tissues predicted poor outcomes for patients with CRC. Thus, BFAL1 is a mediator of ETBF-induced carcinogenesis and may be a potential therapeutic target for ETBF-induced CRC.	[Bao, Yujie; Tang, Jiayin; Qian, Yun; Sun, Tiantian; Chen, Huimin; Chen, Zhaofei; Sun, Danfeng; Chen, Haoyan; Hong, Jie; Chen, Yingxuan; Fang, Jing-Yuan] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, State Key Lab Oncogenes & Related Genes, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China; [Bao, Yujie; Tang, Jiayin; Qian, Yun; Sun, Tiantian; Chen, Huimin; Chen, Zhaofei; Sun, Danfeng; Chen, Haoyan; Hong, Jie; Chen, Yingxuan; Fang, Jing-Yuan] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Key Lab Gastroenterol & Hepatol,Minist Hlth, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China; [Bao, Yujie; Tang, Jiayin; Qian, Yun; Sun, Tiantian; Chen, Huimin; Chen, Zhaofei; Sun, Danfeng; Chen, Haoyan; Hong, Jie; Chen, Yingxuan; Fang, Jing-Yuan] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Div Gastroenterol & Hepatol, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China; [Bao, Yujie; Tang, Jiayin; Qian, Yun; Sun, Tiantian; Chen, Huimin; Chen, Zhaofei; Sun, Danfeng; Chen, Haoyan; Hong, Jie; Chen, Yingxuan; Fang, Jing-Yuan] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Inst Digest Dis, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China; [Bao, Yujie] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Dept Infect Dis, 639 Zhizhaoju Rd, Shanghai 200001, Peoples R China; [Tang, Jiayin; Zhong, Ming] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Gastrointestinal Surg, Shanghai 200001, Peoples R China		Fang, JY (corresponding author), Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, State Key Lab Oncogenes & Related Genes, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China.; Fang, JY (corresponding author), Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Key Lab Gastroenterol & Hepatol,Minist Hlth, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China.; Fang, JY (corresponding author), Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Div Gastroenterol & Hepatol, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China.; Fang, JY (corresponding author), Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Inst Digest Dis, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China.	jingyuanfang@sjtu.edu.cn	Tang, Jiayin/AAJ-5473-2021	Tang, Jiayin/0000-0002-2510-6448	Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine; Shanghai Jiao Tong University; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81421001, 81530072, 81871901, 81874159, 81790632]	This work was supported by the Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, and Shanghai Jiao Tong University. 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J	Qi, JJ; Zhou, NN; Li, LY; Mo, SY; Zhou, YD; Deng, Y; Chen, T; Shan, CL; Chen, Q; Lu, B				Qi, Jianjun; Zhou, Ningning; Li, Liyi; Mo, Shouyong; Zhou, Yidan; Deng, Yao; Chen, Ting; Shan, Changliang; Chen, Qin; Lu, Bin			Ciclopirox activates PERK-dependent endoplasmic reticulum stress to drive cell death in colorectal cancer	CELL DEATH & DISEASE			English	Article							UNFOLDED PROTEIN RESPONSE; FUNGICIDE CICLOPIROX; ER; AUTOPHAGY	Ciclopirox (CPX) modulates multiple cellular pathways involved in the growth of a variety of tumor cell types. However, the effects of CPX on colorectal cancer (CRC) and the underlying mechanisms for its antitumor activity remain unclear. Herein, we report that CPX exhibited strong antitumorigenic properties in CRC by inducing cell cycle arrest, repressing cell migration, and invasion by affecting N-cadherin, Snail, E-cadherin, MMP-2, and MMP-9 expression, and disruption of cellular bioenergetics contributed to CPX-associated inhibition of cell growth, migration, and invasion. Interestingly, CPX-induced reactive oxygen species (ROS) production and impaired mitochondrial respiration, whereas the capacity of glycolysis was increased. CPX (20mg/kg, intraperitoneally) substantially inhibited CRC xenograft growth in vivo. Mechanistic studies revealed that the antitumor activity of CPX relies on apoptosis induced by ROS-mediated endoplasmic reticulum (ER) stress in both 5-FU-sensitive and -resistant CRC cells. Our data reveal a novel mechanism for CPX through the disruption of cellular bioenergetics and activating protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent ER stress to drive cell death and overcome drug resistance in CRC, indicating that CPX could potentially be a novel chemotherapeutic for the treatment of CRC.	[Qi, Jianjun; Zhou, Ningning; Zhou, Yidan; Deng, Yao; Chen, Ting; Lu, Bin] Wenzhou Med Univ, Sch Lab Med & Life Sci, Prot Qual Control & Dis Lab, Wenzhou 325035, Zhejiang, Peoples R China; [Qi, Jianjun; Chen, Qin] Wenzhou Med Univ, Dept Intens Care, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China; [Li, Liyi] Wenzhou Med Univ, Dept Surg, Affiliated Hosp 2, Wenzhou 325000, Zhejiang, Peoples R China; [Mo, Shouyong] Wenzhou Med Univ, Dept Lab Med, Affiliated Hosp 5, Lishui 32300, Zhejiang, Peoples R China; [Shan, Changliang] Nankai Univ, Coll Pharm, State Key Lab Med Chem Biol, Tianjin 300350, Peoples R China; [Shan, Changliang; Chen, Qin; Lu, Bin] Nankai Univ, Tianjin Key Lab Mol Drug Res, Tianjin 300350, Peoples R China		Lu, B (corresponding author), Wenzhou Med Univ, Sch Lab Med & Life Sci, Prot Qual Control & Dis Lab, Wenzhou 325035, Zhejiang, Peoples R China.; Chen, Q (corresponding author), Wenzhou Med Univ, Dept Intens Care, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China.	chenqin@wmu.edu.cn; lubmito@wmu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31570772, 31771534]; Key Discipline of Zhejiang Province in Medical Technology (First Class, Category A)	The authors thank Prof. Michael B. Mathews (Rutgers New Jersey Medical School) and Prof. Jianhong Zhu (Wenzhou Medical University) for the critical reading and editing of the paper. This research was supported by the National Natural Science Foundation of China (31570772 and 31771534 to B.L.), and the Key Discipline of Zhejiang Province in Medical Technology (First Class, Category A).	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JUL 27	2020	11	7							582	10.1038/s41419-020-02779-1			16	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	MV9XZ	WOS:000556702900001	32719342	gold, Green Published			2022-04-25	
J	Maiese, K				Maiese, Kenneth			Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer	CURRENT NEUROVASCULAR RESEARCH			English	Review						Aging; aging-related disorders; Alzheimer's disease; AMP activated protein kinase (AMPK); angiogenesis; apoptosis; autophagy; BMAL1; cardiovascular disease; beta-catenin; circadian rhythm; CLOCK; clock genes; Cryptochrome; diabetes mellitus; hamartin (tuberous sclerosis 1)/tuberin (tuberous sclerosis 2) (TSC1/TSC2); Huntington's disease; mechanistic target of rapamycin (mTOR); mTOR Complex 1 (mTORC1); mTOR Complex 2 (mTORC2); metabolism; nerve growth factor; nicotinamide; nicotinamide adenine dinucleotide (NAD(+)); Parkinson's disease; period (PER); oxidative stress; programmed cell death; REV-ERB alpha; ROR alpha; RORE; shift work; silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1); sirtuin; space travel; stem cells; suprachiasmatic nucleus; wingless; Wnt	CATENIN SIGNALING PATHWAY; MAMMALIAN TARGET; ALZHEIMERS-DISEASE; STEM-CELLS; CARDIOVASCULAR-DISEASE; NEURODEGENERATIVE DISEASES; THERAPEUTIC STRATEGIES; INDUCED NEUROTOXICITY; CALORIC RESTRICTION; MECHANISTIC TARGET	Background: The mammalian circadian clock and its associated clock genes are increasingly been recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. Methods: In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis. Results: In experimental models, lifespan is significantly reduced with the introduction of arrhythmic mutants and leads to an increase in oxidative stress exposure. Interestingly, patients with Alzheimer's disease and Parkinson's disease may suffer disease onset or progression as a result of alterations in the DNA methylation of clock genes as well as prolonged pharmacological treatment for these disorders that may lead to impairment of circadian rhythm function. Tumorigenesis also can occur with the loss of a maintained circadian rhythm and lead to an increased risk for nasopharyngeal carcinoma, breast cancer, and metastatic colorectal cancer. Interestingly, the circadian clock system relies upon the regulation of the critical pathways of autophagy, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) as well as proliferative mechanisms that involve the wingless pathway of Wnt/beta-catenin pathway to foster cell survival during injury and block tumor cell growth. Conclusion: Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm may hold the key for the development of novel and effective therapies against aging-related disorders, neurodegenerative disease, and tumorigenesis.	[Maiese, Kenneth] Cellular & Mol Signaling, Newark, NJ 07101 USA		Maiese, K (corresponding author), Cellular & Mol Signaling, Newark, NJ 07101 USA.	wntin75@yahoo.com			American Diabetes AssociationAmerican Diabetes Association; American Heart AssociationAmerican Heart Association; NIH NIEHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS); NIH NIAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA); NIH NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS); NIH ARRAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS053946] Funding Source: NIH RePORTER	This research was supported by the following grants to Kenneth Maiese: American Diabetes Association, American Heart Association, NIH NIEHS, NIH NIA, NIH NINDS, and NIH ARRA.	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Neurovasc. Res.		2017	14	3					299	304		10.2174/1567202614666170718092010			6	Clinical Neurology; Neurosciences	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology	FF1MP	WOS:000408663900013	28721811	Green Accepted			2022-04-25	
J	Espinoza, JA; Zisi, A; Kanellis, DC; Carreras-Puigvert, J; Henriksson, M; Huhn, D; Watanabe, K; Helleday, T; Lindstrom, MS; Bartek, J				Espinoza, Jaime A.; Zisi, Asimina; Kanellis, Dimitris C.; Carreras-Puigvert, Jordi; Henriksson, Martin; Huhn, Daniela; Watanabe, Kenji; Helleday, Thomas; Lindstrom, Mikael S.; Bartek, Jiri			The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity	CELL DEATH AND DIFFERENTIATION			English	Article							RNA-POLYMERASE-I; TRANSCRIPTION; CANCER; ACTIVATION; NUCLEOLUS; CELLS; CHLOROQUINE; METABOLISM; INITIATION; COMPLEX	Pharmacological inhibition of ribosome biogenesis is a promising avenue for cancer therapy. Herein, we report a novel activity of the FDA-approved antimalarial drug amodiaquine which inhibits rRNA transcription, a rate-limiting step for ribosome biogenesis, in a dose-dependent manner. Amodiaquine triggers degradation of the catalytic subunit of RNA polymerase I (Pol I), with ensuing RPL5/RPL11-dependent stabilization of p53. Pol I shutdown occurs in the absence of DNA damage and without the subsequent ATM-dependent inhibition of rRNA transcription. RNAseq analysis revealed mechanistic similarities of amodiaquine with BMH-21, the first-in-class Pol I inhibitor, and with chloroquine, the antimalarial analog of amodiaquine, with well-established autophagy-inhibitory activity. Interestingly, autophagy inhibition caused by amodiaquine is not involved in the inhibition of rRNA transcription, suggesting two independent anticancer mechanisms. In vitro, amodiaquine is more efficient than chloroquine in restraining the proliferation of human cell lines derived from colorectal carcinomas, a cancer type with predicted susceptibility to ribosome biogenesis stress. Taken together, our data reveal an unsuspected activity of a drug approved and used in the clinics for over 30 years, and provide rationale for repurposing amodiaquine in cancer therapy.	[Espinoza, Jaime A.; Zisi, Asimina; Kanellis, Dimitris C.; Carreras-Puigvert, Jordi; Huhn, Daniela; Lindstrom, Mikael S.; Bartek, Jiri] Karolinska Inst, Dept Med Biochem & Biophys, Div Genome Biol, Sci Life Lab, S-17121 Stockholm, Sweden; [Henriksson, Martin; Helleday, Thomas] Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, S-17176 Stockholm, Sweden; [Watanabe, Kenji; Bartek, Jiri] Danish Canc Soc, Res Ctr, DK-2100 Copenhagen, Denmark; [Helleday, Thomas] Univ Sheffield, Dept Oncol & Metab, Weston Pk Canc Ctr, Sheffield S10 2RX, S Yorkshire, England		Lindstrom, MS; Bartek, J (corresponding author), Karolinska Inst, Dept Med Biochem & Biophys, Div Genome Biol, Sci Life Lab, S-17121 Stockholm, Sweden.; Bartek, J (corresponding author), Danish Canc Soc, Res Ctr, DK-2100 Copenhagen, Denmark.	mikael.lindstrom@ki.se; jb@cancer.dk	Carreras-Puigvert, Jordi/AAN-3020-2021; Zisi, Asimina P/Q-5796-2017; Lindström, Mikael S/AAA-1451-2019	Zisi, Asimina P/0000-0002-4253-0275; Lindström, Mikael S/0000-0003-1148-8497; 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FEB	2020	27	2					773	789		10.1038/s41418-019-0387-5			17	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	KH8YO	WOS:000510936500025	31285544	Green Published, hybrid, Green Accepted			2022-04-25	
J	Cho, HS; Han, TS; Hur, K; Ban, HS				Cho, Hyun-Soo; Han, Tae-Su; Hur, Keun; Ban, Hyun Seung			The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer	GENES			English	Review						hypoxia; non-coding RNA; microRNA; hypoxia-inducible factor; gastrointestinal cancer	GASTRIC-CANCER; COLORECTAL-CANCER; INDUCED AUTOPHAGY; CELL-PROLIFERATION; PROMOTES; METASTASIS; EXPRESSION; INVASION; HIF-1-ALPHA; OVEREXPRESSION	Hypoxia-inducible factors (HIFs) are transcription factors that play central roles in cellular responses against hypoxia. In most cancers, HIFs are closely associated with tumorigenesis by regulating cell survival, angiogenesis, metastasis, and adaptation to the hypoxic tumor microenvironment. Recently, non-coding RNAs (ncRNAs) have been reported to play critical roles in the hypoxic response in various cancers. Here, we review the roles of hypoxia-response ncRNAs in gastrointestinal cancer, with a particular focus on microRNAs and long ncRNAs, and discuss the functional relationships and regulatory mechanisms between HIFs and ncRNAs.	[Cho, Hyun-Soo; Han, Tae-Su; Ban, Hyun Seung] Korea Res Inst Biosci & Biotechnol, Daejeon 34141, South Korea; [Hur, Keun] Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Daegu 41944, South Korea		Ban, HS (corresponding author), Korea Res Inst Biosci & Biotechnol, Daejeon 34141, South Korea.; Hur, K (corresponding author), Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Daegu 41944, South Korea.	chohs@kribb.re.kr; tshan@kribb.re.kr; KeunHur@knu.ac.kr; banhs@kribb.re.kr	; Ban, Hyun Seung/F-9526-2014	cho, Hyun-soo/0000-0002-8242-9390; Ban, Hyun Seung/0000-0002-2698-6037; Hur, Keun/0000-0002-6944-2718	National Research Foundation of Korea (NRF) - Ministry of Science and ICT [NRF-2017R1C1B2012268, 2018M3A9H3023077, 2019R1A2C1083892, 2019R1I1A2A01060951]; KRIBB Research Initiative Program	This study supported by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017R1C1B2012268, 2018M3A9H3023077, 2019R1A2C1083892, 2019R1I1A2A01060951) and the KRIBB Research Initiative Program.	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