﻿PT	AU	BA	BE	GP	AF	BF	CA	TI	SO	SE	BS	LA	DT	CT	CY	CL	SP	HO	DE	ID	AB	C1	C3	RP	EM	RI	OI	FU	FX	CR	NR	TC	Z9	U1	U2	PU	PI	PA	SN	EI	BN	J9	JI	PD	PY	VL	IS	PN	SU	SI	MA	BP	EP	AR	DI	D2	EA	PG	WC	WE	SC	GA	UT	PM	OA	HC	HP	DA
J	Yan, T; Seo, Y; Kinsella, TJ				Yan, Tao; Seo, Yuji; Kinsella, Timothy J.			Differential Cellular Responses to Prolonged LDR-IR in MLH1-Proficient and MLH1-Deficient Colorectal Cancer HCT116 Cells	CLINICAL CANCER RESEARCH			English	Article							DNA MISMATCH REPAIR; STRAND BREAK REPAIR; HOMOLOGOUS RECOMBINATION; REPLICATION FIDELITY; S-PHASE; ARREST; GENES; RAD51; IRRADIATION; MECHANISMS	Purpose: MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining genomic stability by participating in the repair of endogenous and exogenous mispairs in the daughter strands during S phase. Exogenous mispairs can result following treatment with several classes of chemotherapeutic drugs, as well as with ionizing radiation. In this study, we investigated the role of the MLH1 protein in determining the cellular and molecular responses to prolonged low-dose rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer brachytherapy. Experimental Design: An isogenic pair of MMR+ (MLH1(+)) and MMR- (MLH1(-)) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR (1.3-17 cGy/h x 24-96 h). The clonogenic survival and gene mutation rates were examined. Cell cycle distribution was analyzed with flow cytometry. Changes in selected DNA damage repair proteins, DNA damage response proteins, and cell death marker proteins were examined with Western blotting. Results: MLH1(+) HCT116 cells showed greater radiosensitivity with enhanced expression of apoptotic and autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell cycle alterations (increased late-S population and a G(2)/M arrest) following LDR-IR compared with MLH1(-) HCT116 cells. Importantly, a progressive increase in MLH1 protein levels was found in MLH1(+) cells during prolonged LDR-IR, which was temporally correlated with a progressive decrease in Rad51 protein (involved in homologous recombination) levels. Conclusions: MLH1 status significantly affects cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to prolonged LDR-IR through inhibition of homologous recombination (through inhibition of Rad51). (Clin Cancer Res 2009;15(22):6912-20)	Univ Hosp Cleveland, Case Med Ctr, Dept Radiat Oncol, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA; Univ Hosp Cleveland, Case Med Ctr, Case Integrat Canc Biol Program, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA; Case Western Reserve Univ, Sch Med, Cleveland, OH USA		Kinsella, TJ (corresponding author), SUNY Stony Brook, Ctr Canc, 3 Edmund Pellegrino Rd, Stony Brook, NY 11794 USA.	tkinsella@notes.cc.sunysb.edu			National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [U56 CA112963]; NASANational Aeronautics & Space Administration (NASA) [G1072]; DBJ; University Radiation Medicine foundations; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [U56CA112963] Funding Source: NIH RePORTER	National Cancer Institute grant (U56 CA112963), NASA grant (G1072), and the DBJ and University Radiation Medicine foundations. 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.	NOV 15	2009	15	22					6912	6920		10.1158/1078-0432.CCR-09-1698			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	520EJ	WOS:000271822600020	19861440	Green Accepted			2022-04-25	
J	Malami, I; Muhammad, A; Abubakar, IB; Etti, IC; Waziri, PM; Abubakar, RM; Mshelia, HE				Malami, Ibrahim; Muhammad, Aliyu; Abubakar, Ibrahim B.; Etti, Imaobong C.; Waziri, Peter M.; Abubakar, Ramadan M.; Mshelia, Halilu E.			5,6-dehydrokawain from the rhizome of Alpinia mutica Roxb. induced proangiogenic tumour-derived VEGF of HT-29 colorectal cancer	NATURAL PRODUCT RESEARCH			English	Article						5,6-dehydrokawain; VEGF; angiogenesis, HT-29 cells	ANGIOGENESIS; AUTOPHAGY	Vascular endothelial growth factor (VEGF) is a glycoprotein vital to the regulation of vascular endothelial cells proliferation, migration and angiogenesis. The expression of VEGF is required for the formation of new blood vessels critical in supplying oxygen and nutrition in the course of tumorigenesis. The present study investigated the effect of 5,6-dehydrokawain isolated from the rhizomes of Alpinia mutica on VEGF expression in vitro using HT-29 cell line. The results revealed that 5,6-dehydrokawain induced the expression of proangiogenic tumour-derived VEGF of HT-29 cells, which may explain the inability of 5,6-dehydrokawain in suppressing cancer cells proliferation. [GRAPHICS] .	[Malami, Ibrahim; Mshelia, Halilu E.] Usmanu Danfodiyo Univ, Dept Pharmacognosy & Ethnopharm, Fac Pharmaceut Sci, Sokoto, Nigeria; [Muhammad, Aliyu] Ahmadu Bello Univ, Dept Biochem, Fac Life Sci, Zaria, Nigeria; [Abubakar, Ibrahim B.] Kebbi State Univ, Dept Biochem, Aliero, Nigeria; [Etti, Imaobong C.] Univ Uyo, Dept Pharmacol & Toxicol, Uyo, Nigeria; [Waziri, Peter M.] Kaduna State Univ, Dept Biochem, Kaduna, Nigeria; [Abubakar, Ramadan M.] Usmanu Danfodiyo Univ, Dept Pharmacol & Toxicol, Fac Pharmaceut Sci, Sokoto, Nigeria		Malami, I (corresponding author), Usmanu Danfodiyo Univ, Dept Pharmacognosy & Ethnopharm, Fac Pharmaceut Sci, Sokoto, Nigeria.	Ibrahim.malami@udusok.edu.ng	Malami, Ibrahim/AAZ-3430-2021; Malami, Ibrahim/C-4513-2019; Abubakar, Ibrahim Babangida/X-5713-2019; Etti, Imaobong/AAE-4969-2022; Muhammad, Aliyu/AAC-6717-2019	Malami, Ibrahim/0000-0001-9271-6927; Malami, Ibrahim/0000-0001-9271-6927; Abubakar, Ibrahim Babangida/0000-0002-9359-8982; Muhammad, Aliyu/0000-0002-4167-7793			Ashton AW, 2004, CIRC RES, V95, P372, DOI 10.1161/01.RES.0000138300.41642.15; Dharmaratne HRW, 2002, PHYTOCHEMISTRY, V59, P429; Du JH, 2012, AM J PHYSIOL-CELL PH, V302, pC383, DOI 10.1152/ajpcell.00164.2011; Fu ZP, 2015, ONCOTARGET, V6, P19469, DOI 10.18632/oncotarget.3625; Jantan I, 2004, PHYTOTHER RES, V18, P1005, DOI 10.1002/ptr.1608; Kumagai M, 2016, BIOSCI BIOTECH BIOCH, V80, P1425, DOI 10.1080/09168451.2016.1153959; Liu ZB, 2017, J BIOMED RES, V31, P408, DOI 10.7555/JBR.31.20160160; Malek NA, 2011, MOLECULES, V16, P583, DOI 10.3390/molecules16010583; Olsson AK, 2006, NAT REV MOL CELL BIO, V7, P359, DOI 10.1038/nrm1911; Sirat HM, 2013, NAT PROD RES, V27, P1468, DOI 10.1080/14786419.2012.718772; Tanaka A, 2010, BIOORGAN MED CHEM, V18, P3133, DOI 10.1016/j.bmc.2010.03.034; Teng C M, 1990, Chin J Physiol, V33, P41; Xiao H, 2017, NAT PROD RES, V31, P2053, DOI 10.1080/14786419.2016.1269094	13	1	1	1	6	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.	DEC 17	2018	32	24					2964	2967		10.1080/14786419.2017.1392954			4	Chemistry, Applied; Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	HN0NE	WOS:000459884600017	29052437				2022-04-25	
J	Chen, LM; Song, TJ; Xiao, JH; Huang, ZH; Li, Y; Lin, TY				Chen, Li-Min; Song, Tian-Jiao; Xiao, Jian-Hong; Huang, Zheng-Hui; Li, Yong; Lin, Ting-Yan			Tripchlorolide induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR pathway and improves cisplatin sensitivity in A549/DDP cells	ONCOTARGET			English	Article						tripchlorolide; autophagy; lung cancer; PI3K/AKT/mTOR; MDR1	COLORECTAL-CANCER; DOWN-REGULATION; APOPTOSIS; RESISTANCE; DEATH; KINASE; LIVER	Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT. Expression of LC3II increased in parallel to the increase of the T4 concentration in both A549 and A549/DDP cells and was repressed by overexpression of AKT. The expression levels of PI3-K, PI3-P, AKT, TSC2, mTOR, p70S6K and 4E-BP1 were minimally affected by the wortmannin, perifosine, or rapamycin plus T4 treatments, but their phosphorylated products were greatly affected in A549 lung cancer cells and slightly affected in A549/DDP lung cancer cells. These results indicate that T4 induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway. We further found that T4 decreased expression of MDR1 and improved cisplatin sensitivity of A549/DDP cells. Altogether, these results have meaningful implications for tumor therapy in the future.	[Chen, Li-Min; Song, Tian-Jiao; Huang, Zheng-Hui; Li, Yong; Lin, Ting-Yan] Fujian Med Univ, Union Hosp, Dept Resp Med, Fuzhou 350001, Fujian, Peoples R China; [Chen, Li-Min; Song, Tian-Jiao] Fujian Med Univ, Union Hosp, Dept Geriatr, Fuzhou 350001, Fujian, Peoples R China; [Chen, Li-Min; Song, Tian-Jiao] Fujian Med Univ, Union Hosp, Fujian Inst Geriatr, Fuzhou 350001, Fujian, Peoples R China; [Xiao, Jian-Hong] Mindong Hosp Ningde City, Dept Resp Med, Fuan 355000, Fujian, Peoples R China		Chen, LM; Lin, TY (corresponding author), Fujian Med Univ, Union Hosp, Dept Resp Med, Fuzhou 350001, Fujian, Peoples R China.; Chen, LM (corresponding author), Fujian Med Univ, Union Hosp, Dept Geriatr, Fuzhou 350001, Fujian, Peoples R China.; Chen, LM (corresponding author), Fujian Med Univ, Union Hosp, Fujian Inst Geriatr, Fuzhou 350001, Fujian, Peoples R China.	13599438522@163.com; tingyanlin58@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472848]; Key Clinical Specialty Discipline Construction Program of Fujian and Nation, P.R.; Key Clinical Specialty Discipline Construction Program of Fujian and Nation, P.R. [2011J01176, 2016J01454]	This work was supported by the National Natural Science Foundation of China (grant number 81472848) Key Clinical Specialty Discipline Construction Program of Fujian and Nation, P.R. and the Fujian Provincial Natural Science Foundation (grant number 2011J01176 and grant number 2016J01454).	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J	Ma, ZH; Bao, XB; Gu, JB				Ma, Zhao; Bao, Xuebin; Gu, Junbao			Furowanin A-induced autophagy alleviates apoptosis and promotes cell cycle arrest via inactivation STAT3/Mcl-1 axis in colorectal cancer	LIFE SCIENCES			English	Article						Furowanin A; Colorectal cancer; Autophagy; Apoptosis; Cell cycle arrest; STAT3	PROTECTIVE AUTOPHAGY; OVARIAN-CANCER; METASTASIS; KINASES; PATHWAY; GROWTH; DEATH; MCL-1; LIFE	Aim Furowanin A (Fur A) is a flavonoid isolated from Millettia pachycarpa Benth. Studies show its potent antineoplastic effects against leukemia cells. The aim of the present study was to determine the potential therapeutic effect of Fur A against colorectal cancer (CRC), and elucidate the underlying mechanism. Material and methods: Cell Counting Kit-8 (CCK-8) assay was used to determine cell, and TUNEL and Annexin-V/PI staining was used to detect apoptosis and the cell cycle distribution. The expression levels of specific proteins in the CRC cells were analyzed by Western blotting. A xenograft model was also established to evaluate the therapeutic effect of Fur A in vivo. Key findings: Fur A suppressed proliferation, blocked cell cycle progression, induced apoptosis and promoted autophagy in CRC cells. Interestingly, Fur A-induced autophagy functioned not only as a survival mechanism against apoptosis but also intensified the cell cycle arrest in CRC cells. In addition, Fur A mediated its effects via the inactivation of the STAT3/Mcl-1 axis. Significance: Fur A is a promising drug candidate for the treatment and prevention of CRC.	[Ma, Zhao; Bao, Xuebin; Gu, Junbao] Zhengzhou Univ, Peoples Hosp Henan Prov, Peoples Hosp, Gastrointestinal Surg Dept, Zhengzhou, Henan, Peoples R China		Bao, XB (corresponding author), 7 Weiwu Rd, Zhengzhou 450003, Henan, Peoples R China.	xuebinbaozz@126.com			Basic Frontier Project of Science and Technology Department in Henan Province [132300410367]	This study was supported by the Basic Frontier Project of Science and Technology Department in Henan Province (No. 132300410367).	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FEB 1	2019	218						47	57		10.1016/j.lfs.2018.12.027			11	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	HH4WO	WOS:000455727100007	30562490				2022-04-25	
J	Zhu, HT; Diao, S; Lim, V; Hu, LN; Hu, JG				Zhu, Hongtao; Diao, Shuai; Lim, Vincent; Hu, Lina; Hu, Jianguo			FAM83D inhibits autophagy and promotes proliferation and invasion of ovarian cancer cells via PI3K/AKT/mTOR pathway	ACTA BIOCHIMICA ET BIOPHYSICA SINICA			English	Article						FAM83D; ovarian cancer; autophagy; mTOR	COLORECTAL-CANCER; SIGNALING PATHWAY; UP-REGULATION; MIGRATION; RESISTANCE; APOPTOSIS; MTOR	Ovarian cancer is one of the most lethal malignant tumors in women. The family with sequence similarity 83, member D (FAM83D) plays an important role in several cancers, but its function and underlying mechanism in ovarian cancer remain unknown. To investigate the role of FAM83D in ovarian cancer, the expression of FAM83D was determined by immunohistochemistry in tissue microarray slide. Cellular proliferation and invasion were detected by 5-Ethynyl-2-deoxyuridine assays and transwell invasion assays. The correlations between FAM83D and autophagy were detected by western blot analysis and confocal microscopy. Western blot analysis was used to identify the protein expression of FAM83D, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) and Sequestosome 1 (P62). Tumorigenesis in nude mice was used to explore the function of FAM83D in vivo. We found high expression level of FAM83D in ovarian cancer tissues as compared to the normal ovarian tissues. Knockdown of FAM83D in SKOV3 cells enhanced autophagy and inhibited the proliferation and invasion in vitro, whereas ectopic expression of FAM83D in A2780 cells exerted an opposite effect. Mechanistically, overexpression of FAM83D activated the PI3K/AKT/mTOR pathway, and Torin1 could suppress FAM83D-induced cell proliferation and invasion. In vivo, overexpression FAM83D promoted tumor growth. Overall, FAM83D promoted ovarian cancer cell invasion and proliferation, while inhibited autophagy via the PI3K/AKT/mTOR signaling pathway. Our results suggest that FAM83D may be a candidate oncogene in ovarian cancer, which provides a fresh perspective of FAM83D in ovarian cancer.	[Zhu, Hongtao; Diao, Shuai; Lim, Vincent; Hu, Lina; Hu, Jianguo] Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China		Hu, LN; Hu, JG (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China.	461374248@qq.com; cqhulina@126.com; angeljianguo@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81702557]	This work was supported by the grant from the National Natural Science Foundation of China (No. 81702557).	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Biophys. Sin.	MAY	2019	51	5					509	516		10.1093/abbs/gmz028			8	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	IA2ZA	WOS:000469431000007	30939187				2022-04-25	
J	Booth, L; Cruickshanks, N; Tavallai, S; Roberts, JL; Peery, M; Poklepovic, A; Dent, P				Booth, Laurence; Cruickshanks, Nichola; Tavallai, Seyedmehrad; Roberts, Jane L.; Peery, Matthew; Poklepovic, Andrew; Dent, Paul			Regulation of dimethyl-fumarate toxicity by proteasome inhibitors	CANCER BIOLOGY & THERAPY			English	Article							ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; NF-KAPPA-B; MITOCHONDRIAL DYSFUNCTION; CELLS; APOPTOSIS; CARFILZOMIB; ACID; GENERATION; BORTEZOMIB	The present studies examined the biology of the multiple sclerosis drug dimethyl-fumarate (DMF) or its in vivo breakdown product and active metabolite mono-methyl-fumarate (MMF), alone or in combination with proteasome inhibitors, in primary human glioblastoma (GBM) cells. MMF enhanced velcade and carfilzomib toxicity in multiple primary GBM isolates. Similar data were obtained in breast and colon cancer cells. MMF reduced the invasiveness of GBM cells, and enhanced the toxicity of ionizing radiation and temozolomide. MMF killed freshly isolated activated microglia which was associated with reduced IL-6, TGF and TNF production. The combination of MMF and the multiple sclerosis drug Gilenya further reduced both GBM and activated microglia viability and cytokine production. Over-expression of c-FLIP-s or BCL-XL protected GBM cells from MMF and velcade toxicity. MMF and velcade increased plasma membrane localization of CD95, and knock down of CD95 or FADD blocked the drug interaction. The drug combination inactivated AKT, ERK1/2 and mTOR. Molecular inhibition of AKT/ERK/mTOR signaling enhanced drug combination toxicity whereas molecular activation of these pathways suppressed killing. MMF and velcade increased the levels of autophagosomes and autolysosomes and knock down of ATG5 or Beclin1 protected cells. Inhibition of the eIF2/ATF4 arm or the IRE1/XBP1 arm of the ER stress response enhanced drug combination lethality. This was associated with greater production of reactive oxygen species and quenching of ROS suppressed cell killing.	[Booth, Laurence; Cruickshanks, Nichola; Tavallai, Seyedmehrad; Roberts, Jane L.; Peery, Matthew; Dent, Paul] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23284 USA; [Poklepovic, Andrew] Virginia Commonwealth Univ, Richmond, VA USA		Dent, P (corresponding author), Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23284 USA.	pdent@vcu.edu			PHS grants from the National Institutes of Health [R01-CA141704, R01-CA150214, R01-DK52825]; Department of DefenseUnited States Department of Defense [W81XWH-10-1-0009]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA150214] 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) [R01DK052825] Funding Source: NIH RePORTER	Support for the present study was funded from PHS grants from the National Institutes of Health [R01-CA141704, R01-CA150214, R01-DK52825]; the Department of Defense [W81XWH-10-1-0009]. PD is the holder of the Universal Inc. Chair in Signal Transduction Research.	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Ther.		2014	15	12					1646	1657		10.4161/15384047.2014.967992			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AZ7EP	WOS:000348382100009	25482938	Bronze, Green Published			2022-04-25	
J	Schmidt, LS; Linehan, WM				Schmidt, Laura S.; Linehan, W. Marston			FLCN: The causative gene for Birt-Hogg-Dube syndrome	GENE			English	Review						FLCN; Folliculin; FNIP1; FNIP2; Birt-Hogg-Dube syndrome; Kidney tumor; DENN domain; mTOR; AMPK; PGC1 alpha	RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; AMINO-ACID PERMEASE; NIHON RAT MODEL; SPONTANEOUS PNEUMOTHORAX; BHD GENE; PRIMARY CILIUM; INTRAGENIC DELETIONS; EMBRYONIC LETHALITY; COLORECTAL-CANCER	Germline mutations in the novel tumor suppressor gene FLCN are responsible for the autosomal dominant inherited disorder Birt-Hogg-Dube (BHD) syndrome that predisposes to fibrofolliculomas, lung cysts and spontaneous pneumothorax, and an increased risk for developing kidney tumors. Although the encoded protein, folliculin (FLCN), has no sequence homology to known functional domains, x-ray crystallographic studies have shown that the C-terminus of FLCN has structural similarity to DENN (differentially expressed in normal cells and neoplasia) domain proteins that act as guanine nucleotide exchange factors (GEFs) for small Rab GTPases. FLCN forms a complex with folliculin interacting proteins 1 and 2 (FNIP1, FNIP2) and with 5' AMP-activated protein kinase (AMPK). This review summarizes FLCN functional studies which support a role for FLCN in diverse metabolic pathways and cellular processes that include modulation of the mTOR pathway, regulation of PGC1 alpha a and mitochondrial biogenesis, cell-cell adhesion and RhoA signaling, control of TFE3/TFEB transcriptional activity, amino acid-dependent activation of mTORC1 on lysosomes through Rag GTPases, and regulation of autophagy. Ongoing research efforts are focused on clarifying the primary FLCN-associated pathway(s) that drives the development of fibrofolliculomas, lung cysts and kidney tumors in BHD patients carrying germline FLCN mutations.	[Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA; [Schmidt, Laura S.] Leidos Biomed Res Inc, Basic Sci Program, Frederick Lab Canc Res, Frederick, MD 21702 USA		Schmidt, LS; Linehan, WM (corresponding author), NCI, NIH, Bldg10 CRC 1W-5940,10 Ctr Dr, Bethesda, MD 20892 USA.	schmidtl@mail.nih.gov; wml@nih.gov			National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM089820]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer ResearchUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIA BC011028, ZIA BC011043, ZO1BC011044-01]; Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001E]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZICBC011044, ZIABC011043, Z01BC011043, ZIABC011028, Z01BC011028, ZIABC011038, ZIDBC011089] 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) [R01GM089820] Funding Source: NIH RePORTER	This review and the corresponding Gene Wiki article are written as part of the GeneWiki Review series-a series resulting from a collaboration between the journal GENE and the Gene Wiki Initiative. The Gene Wiki Initiative is supported by the National Institutes of Health (GM089820). Additional support for Gene Wiki Reviews is provided by Elsevier, the publisher of GENE. This work was supported by the Intramural Research Program of the NIH, National Cancer Institute (ZIA BC011028, ZIA BC011043, ZO1BC011044-01), Center for Cancer Research. This project has been funded in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH, under Contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. The corresponding Gene Wiki entry for this review can be found here: http://en.wikipedia.org/wiki/Folliculin.	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J	Liu, WB; Yu, XF; Zhou, L; Li, JG; Li, M; Li, W; Gao, F				Liu, Wenbin; Yu, Xinfang; Zhou, Li; Li, Jigang; Li, Ming; Li, Wei; Gao, Feng			Sinomenine Inhibits Non-Small Cell Lung Cancer via Downregulation of Hexokinases II-Mediated Aerobic Glycolysis	ONCOTARGETS AND THERAPY			English	Article						sinomenine; non-small cell lung cancer; glycolysis; hexokinase 2	COLORECTAL-CANCER; CARCINOMA-CELLS; PROLIFERATION; MIGRATION; SUPPRESSION; AUTOPHAGY; INVASION; GROWTH	Background: Addiction to aerobic glycolysis is a common metabolic phenotype in human non-small cell lung cancer (NSCLC). The natural product Sinomenine (Sin) exhibits significant anti-tumor effects in various human cancers. However, the underlying mechanism remains elusive. Methods: The inhibitory effect of Sin on NSCLC cells was determined by MTS and soft agar assays. The glycolysis efficacy of NSCLC cells was examined by glucose uptake and lactate production. The activation of Akt signaling and the protein level of hexokinases II (HK2) were examined by immunoblot (IB), qRT-PCR, and immunohistochemical staining (IHC). The in vivo anti-tumor effect of Sin was validated by the xenograft mouse model. Results: We showed that HK2 is highly expressed in NSCLC tissues and cell lines. Depletion of HK2 suppressed cell viability, anchorage-independent colony formation, and xenograft tumor growth. Sinomenine exhibited a profound inhibitory effect on NSCLC cells by reducing HK2-mediated glycolysis both in vitro and in vivo. Ectopic overexpression of HK2 compromised these anti-tumor efficacies in sinomenine-treated NSCLC cells. Moreover, we revealed that sinomenine decreased Akt activity, which caused the down-regulation of HK2-mediated glycolysis. Knockdown of Akt reduced HK2 protein level and impaired glycolysis. In contrast, overexpression of constitutively activated Akt1 reversed this phenotype. Conclusion: This study suggests that targeting HK2-mediated aerobic glycolysis is required for sinomenine-mediated anti-tumor activity.	[Liu, Wenbin; Li, Jigang] Cent South Univ, Xiangya Sch Med, Affiliated Canc Hosp, Dept Pathol, Changsha 410006, Hunan, Peoples R China; [Yu, Xinfang] Cleveland Clin, Dept Canc Biol, Lerner Res Inst, Cleveland, OH 44195 USA; [Zhou, Li] Cent South Univ, Xiangya Hosp, Dept Pathol, Changsha 410008, Hunan, Peoples R China; [Li, Ming] Hunan Univ Chinese Med, Sch Stomatol, Changsha 410208, Hunan, Peoples R China; [Li, Ming] Hunan Univ Chinese Med, Changsha Stomatol Hosp, Changsha 410004, Hunan, Peoples R China; [Li, Wei] Cent South Univ, Xiangya Hosp 3, Dept Radiol, Changsha 410013, Hunan, Peoples R China; [Gao, Feng] Cent South Univ, Xiangya Hosp 3, Dept Ultrasonog, Changsha 410013, Hunan, Peoples R China		Li, W (corresponding author), Cent South Univ, Xiangya Hosp 3, Dept Radiol, Changsha 410013, Hunan, Peoples R China.; Gao, F (corresponding author), Cent South Univ, Xiangya Hosp 3, Dept Ultrasonog, Changsha 410013, Hunan, Peoples R China.	weililx@csu.edu.cn; gf0731@csu.edu.cn		li, wei/0000-0002-7267-6494	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81904262, 81972,837]; Natural Science Foundation of Hunan ProvinceNatural Science Foundation of Hunan Province [2018JJ3787, 2018JJ2604, 2019JJ50682]; Natural Science Foundation of Changsha Science and Technology Bureau [kq1701018]	This work was supported by the National Natural Science Foundation of China (No. 81904262, 81972,837), the Natural Science Foundation of Hunan Province (2018JJ3787, 2018JJ2604, 2019JJ50682), and the Natural Science Foundation of Changsha Science and Technology Bureau (kq1701018).	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J	Tang, ZY; Li, Y; Tang, YT; Ma, XD; Tang, ZY				Tang, Zhong-Yuan; Li, Yang; Tang, Yu-Ting; Ma, Xiao-Dong; Tang, Ze-Yao			Anticancer activity of oleanolic acid and its derivatives: Recent advances in evidence, target profiling and mechanisms of action	BIOMEDICINE & PHARMACOTHERAPY			English	Review						Oleanolic acid; Derivatives; Apoptotic pathways; Angiogenesis; Metastasis; Systematic-analysis review	NF-KAPPA-B; CELL-CYCLE ARREST; COLORECTAL-CANCER ANGIOGENESIS; HEPATOCELLULAR-CARCINOMA CELLS; FAMILY 1B10 AKR1B10; IN-VITRO; PROSTATE-CANCER; SAIKOSAPONIN-D; URSOLIC ACID; CDDO-ME	Oleanolic acid (OA, 3 13 - hydroxyoleanolic acid-12-en-28-oic acid) is a pentacyclic triterpenoid present in many plants. As a new framework for development of semi synthetic triterpenoids, OA is of great significance in the discovery of anticancer drugs. Some of these derivatives, such as CDDO (2-cyano-3,12-dioxooleana-1, 9 (11)dien-28-oic acid) have been verified in clinical trials, while other derivatives studied previously, such as SZC014, SZC015 and SZC017 (OA derivatives respectively), are also candidate drugs for cancer treatment. This paper reviews the preclinical studies, literature evidence, target analysis and anticancer mechanism of OA and its derivatives. The mechanism of action of its derivatives mainly includes anti-cancer cell proliferation, inducing tumor cell apoptosis, inducing autophagy, regulating cell cycle regulatory proteins, inhibiting vascular endothelial growth, anti angiogenesis, inhibiting tumor cell migration and invasion. In recent years, the molecular mechanism of OA and its derivatives has been elucidated. These effects seem to be mediated by the alterations in a variety of signaling pathways induced by OA and its derivatives. In conclusion, OA and its derivatives are considered as important candidate drugs for the treatment of cancer, indicating that OA and its derivatives have the potential to be used as anticancer drugs in practice.	[Li, Yang; Tang, Yu-Ting; Ma, Xiao-Dong; Tang, Ze-Yao] Dalian Med Univ, Pharmacol Dept, 9 West Sect,South Rd Lvshun, Dalian 116044, Liaoning, Peoples R China; [Tang, Zhong-Yuan] Jilin Univ, Sch Stornatol, Dept Orthodont, 1500 Qinghua Rd, Changchun 130021, Jilin, Peoples R China		Tang, ZY (corresponding author), Dalian Med Univ, Pharmacol Dept, 9 West Sect,South Rd Lvshun, Dalian 116044, Liaoning, Peoples R China.	tangzeyao411@dmu.edu.cn					Adamska A, 2019, MOLECULES, V24, DOI 10.3390/molecules24162958; Akl MR, 2014, EUR J PHARMACOL, V740, P209, DOI 10.1016/j.ejphar.2014.07.011; Bao YM, 2020, MOL PHARMACEUT, V17, P1343, DOI 10.1021/acs.molpharmaceut.0c00044; Bian M., 2020, CHEMISTRY, V26; Borella R, 2019, MOLECULES, V24, DOI 10.3390/molecules24224097; Chakravarti B, 2012, J ETHNOPHARMACOL, V142, P72, DOI 10.1016/j.jep.2012.04.015; Chang Q, 2013, NEOPLASIA, V15, P848, DOI 10.1593/neo.13706; Chen D, 2020, ACS OMEGA, V5, P995, DOI 10.1021/acsomega.9b02261; Chen X, 2016, PHYTOMEDICINE, V23, P1555, DOI 10.1016/j.phymed.2016.09.002; 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Pharmacother.	JAN	2022	145								112397	10.1016/j.biopha.2021.112397		NOV 2021	21	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	XG8AZ	WOS:000724971900004	34798468	gold			2022-04-25	
J	Mahli, A; Saugspier, M; Koch, A; Sommer, J; Dietrich, P; Lee, S; Thasler, R; Schulze-Luehrmann, J; Luehrmann, A; Thasler, WE; Muller, M; Bosserhoff, A; Hellerbrand, C				Mahli, Abdo; Saugspier, Michael; Koch, Andreas; Sommer, Judith; Dietrich, Peter; Lee, Seren; Thasler, Reinhard; Schulze-Luehrmann, Jan; Luehrmann, Anja; Thasler, Wolfgang Erwin; Mueller, Martina; Bosserhoff, Anja; Hellerbrand, Claus			ERK activation and autophagy impairment are central mediators of irinotecan-induced steatohepatitis	GUT			English	Article							COLORECTAL LIVER METASTASES; CHEMOTHERAPY-ASSOCIATED HEPATOTOXICITY; HEPATOCELLULAR-CARCINOMA CELLS; SORAFENIB; CANCER; MITOCHONDRIA; CHLOROQUINE; RESISTANCE; THERAPY; STRESS	Objective Preoperative chemotherapy with irinotecan is associated with the development of steatohepatitis, which increases the risk of perioperative morbidity and mortality for liver surgery. The molecular mechanisms of this chemotherapeutic complication are widely unknown. Design Mechanisms of irinotecan-induced steatohepatitis were studied in primary human hepatocytes in vitro, in mice treated with irinotecan and in liver specimens from irinotecan-treated compared with control patients. Results Irinotecan dose-dependently induced lipid accumulation and pro-inflammatory gene expression in hepatocytes. This was accompanied by an impairment of mitochondrial function with reduced expression of carnitine palmitoyltransferase I and an induction of acylcoenzyme A oxidase-1 (ACOX1), oxidative stress and extracellular signal-regulated kinase (ERK) activation. ERK inhibition prevented irinotecan-induced pro-inflammatory gene expression but had only a slight effect on lipid accumulation. However, irinotecan also induced an impairment of the autophagic flux mediated by alkalisation of lysosomal pH. Re-acidification of lysosomal pH abolished irinotecan-induced autophagy impairment and lipid accumulation. Also in mice, irinotecan treatment induced hepatic ACOX1 expression, ERK phosphorylation and inflammation, as well as impairment of autophagy and significant steatosis. Furthermore, irinotecan-treated patients revealed higher hepatic ERK activity, expression of pro-inflammatory genes and markers indicative for a shift to peroxisomal fatty acid oxidation and an impaired autophagic flux. Pretreatment with the multityrosine kinase inhibitor sorafenib did not affect autophagy impairment and steatosis but significantly reduced ERK phosphorylation and inflammatory response in irinotecan-treated hepatocytes and murine livers. Conclusions Irinotecan induces hepatic steatosis via autophagy impairment and inflammation via ERK activation. Sorafenib appears as a novel therapeutic option for the prevention and treatment of irinotecan-induced inflammation.	[Mahli, Abdo; Saugspier, Michael; Koch, Andreas; Sommer, Judith; Mueller, Martina; Hellerbrand, Claus] Univ Hosp Regensburg, Dept Internal Med 1, Regensburg, Germany; [Mahli, Abdo; Koch, Andreas; Sommer, Judith; Dietrich, Peter; Bosserhoff, Anja; Hellerbrand, Claus] Friedrich Alexander Univ Erlangen Nurnberg, Inst Biochem, Emil Fischer Zentrum, Erlangen, Germany; [Lee, Seren; Thasler, Reinhard; Thasler, Wolfgang Erwin] Ludwig Maximilians Univ Munchen, Dept Gen Visceral & Transplantat Surg, Biobank Ob HTCR, Munich, Germany; [Schulze-Luehrmann, Jan; Luehrmann, Anja] Friedrich Alexander Univ FAU Erlangen Nurnberg, Univ Klinikum Erlangen, Klin Mikrobiol Immunol & Hyg, Mikrobiol Inst, Erlangen, Germany; [Bosserhoff, Anja] CCC Erlangen EMN, Comprehens Canc Ctr Erlangen, Erlangen, Germany		Hellerbrand, C (corresponding author), Friedrich Alexander Univ Erlangen Nurnberg, Inst Biochem, D-91054 Erlangen, Germany.	claus.hellerbrand@fau.de	Mahli, Abdo/AAD-4744-2019	Mahli, Abdo/0000-0002-8333-7551; Bosserhoff, Anja/0000-0001-8147-394X; Lee, Serene/0000-0001-5231-0607	German Research Association (DFG)German Research Foundation (DFG) [FOR 2127, Bo1573, He2458, KFO262]; Interdisciplinary Center for Clinical Research (IZKF) Erlangen [J55, D24]	This work was supported by grants from the German Research Association (DFG) to AB and CH (FOR 2127; Bo1573 and He2458) and CH (KFO262; He2458) and by the Interdisciplinary Center for Clinical Research (IZKF) Erlangen to PD (J55) and AB (D24).	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J	Ferraresi, A; Phadngam, S; Morani, F; Galetto, A; Alabiso, O; Chiorino, G; Isidoro, C				Ferraresi, Alessandra; Phadngam, Suratchanee; Morani, Federica; Galetto, Alessandra; Alabiso, Oscar; Chiorino, Giovanna; Isidoro, Ciro			Resveratrol inhibits IL-6-induced ovarian cancer cell migration through epigenetic up-regulation of autophagy	MOLECULAR CARCINOGENESIS			English	Article						Resveratrol; ovarian cancer; autophagy; microRNA; cell migration	TUMOR-SUPPRESSOR GENE; EPITHELIAL-MESENCHYMAL TRANSITION; INDUCIBLE FACTOR-1-ALPHA EXPRESSION; EPHRIN-A1 MESSENGER-RNA; ARHI DIRAS3; IN-VITRO; MICRORNA-21 PROMOTES; COLORECTAL-CANCER; POOR-PROGNOSIS; INTERLEUKIN-6	Interleukin-6 (IL-6), a pro-inflammatory cytokine released by cancer-associated fibroblasts, has been linked to the invasive and metastatic behavior of ovarian cancer cells. Resveratrol is a naturally occurring polyphenol with the potential to inhibit cancer cell migration. Here we show that Resveratrol and IL-6 affect in an opposite manner the expression of RNA messengers and of microRNAs involved in cell locomotion and extracellular matrix remodeling associated with the invasive properties of ovarian cancer cells. Among the several potential candidates responsible for the anti-invasive effect promoted by Resveratrol, here we focused our attention on ARH-I (DIRAS3), that encodes a Ras homolog GTPase of 26-kDa. This protein is known to inhibit cell motility, and it has been shown to regulate autophagy by interacting with BECLIN 1. IL-6 down-regulated the expression of ARH-I and inhibited the formation of LC3-positive autophagic vacuoles, while promoting cell migration. On opposite, Resveratrol could counteract the IL-6 induction of cell migration in ovarian cancer cells through induction of autophagy in the cells at the migration front, which was paralleled by up-regulation of ARH-I and down-regulation of STAT3 expression. Spautin 1-mediated disruption of BECLIN 1-dependent autophagy abrogated the effects of Resveratrol, while promoting cell migration. The present data indicate that Resveratrol elicits its anti-tumor effect through epigenetic mechanisms and support its inclusion in the chemotherapy regimen for highly aggressive ovarian cancers. (C) 2016 Wiley Periodicals, Inc.	[Ferraresi, Alessandra; Phadngam, Suratchanee; Morani, Federica; Isidoro, Ciro] Univ Piemonte Orientale, Dept Hlth Sci, Lab Mol Pathol & Nanobioimaging, Novara, Italy; [Galetto, Alessandra; Alabiso, Oscar] Univ Piemonte Orientale, Dept Translat Med, Unit Oncol, Novara, Italy; [Chiorino, Giovanna] Fdn Edo & Elvo Tempia, Canc Genom Lab, Biella, Italy		Isidoro, C (corresponding author), Univ A Avogadro, Dipartimento Sci Salute, Via P Solaroli 17, I-28100 Novara, Italy.		Morani, Federica/D-2365-2018; Ferraresi, Alessandra/H-1518-2017; Isidoro, Ciro/J-6063-2016; Chiorino, Giovanna/K-5037-2016	Morani, Federica/0000-0002-4903-6878; Ferraresi, Alessandra/0000-0002-7192-9672; Isidoro, Ciro/0000-0002-5494-3034; Chiorino, Giovanna/0000-0002-9502-6400	Ministry of Education,Universities and Research (MIUR);ItalyMinistry of Education, Universities and Research (MIUR); Comoli,Ferrari C.SpA	A.F. and S.P. are PhD students supported by the Ministry of Education, Universities and Research (MIUR; Italy).The financial support of Comoli, Ferrari &C.SpA is fully acknowledged.The technical assistance for artwork by Roberto Serra is fully acknowledged.	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J	Li, L; Li, G; Chen, MB; Cai, RZ				Li, Liang; Li, Gao; Chen, Minbiao; Cai, Renzhong			Astragaloside IV enhances the sensibility of lung adenocarcinoma cells to bevacizumab by inhibiting autophagy	DRUG DEVELOPMENT RESEARCH			English	Article; Early Access						apoptosis; astragaloside; autophagy; bevacizumab; proliferation	CISPLATIN CHEMOSENSITIVITY; ACTIVATION PROMOTES; COLORECTAL-CANCER; INDUCED APOPTOSIS; EXPRESSION; RESISTANCE; GLIOBLASTOMA; BCL-2; PROLIFERATION; CASPASE-3	Bevacizumab (BV) has an inhibitory effect on tumor growth including lung adenocarcinoma. However, its efficacy is greatly affected by drug resistance. Astragaloside IV (AST-IV) is effective in combination with other drugs is effective to treat cancer. This study aimed to investigate the effect of AST-IV on enhancing the sensibility of lung adenocarcinoma cells to BV. A549 cells were treated by different concentrations of BV and AST-IV. Cell viability, cell cycle, and apoptosis were detected by thiazolyl blue tetrazolium bromide (MTT) and flow cytometry, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to detect the expression levels of autophagy- and apoptosis-related proteins, protein kinase B (AKT), and mammalian target of rapamycin (mTOR). The results showed that BV or AST-IV could inhibit the viability and promote the apoptosis of A549 cells in a concentration-dependent manner. Moreover, BV or AST-IV inhibited Bcl-2 expression and increased the expressions of Bax and Cleaved caspase-3, and promoted apoptosis. BV and AST-IV in combination acted synergistically on viability and apoptosis of A549 cells. However, BV alone down-regulated P62 expression, LC3I/LC3II level, the number of cells arrested at S phase and the phosphorylation levels of AKT and mTOR, but upregulated the number of cells arrested at G0/G1 phase and Beclin1 expression, whereas AST-IV alone could reverse the effect of BV on autophagy-related proteins, the phosphorylation levels of AKT and mTOR. This paper demonstrates that AST-IV enhances the effect of BV on inhibiting proliferation and promoting apoptosis of lung adenocarcinoma cells through inhibiting autophagy pathway.	[Li, Liang; Li, Gao; Chen, Minbiao; Cai, Renzhong] Hainan Gen Hosp, Dept Thorac Surg, 19 Xiuhua Rd, Haikou 570311, Hainan, Peoples R China		Cai, RZ (corresponding author), Hainan Gen Hosp, Dept Thorac Surg, 19 Xiuhua Rd, Haikou 570311, Hainan, Peoples R China.	cairenzhong_crz@163.com					Bade BC, 2020, CLIN CHEST MED, V41, P1, DOI 10.1016/j.ccm.2019.10.001; Cao ZJ, 2017, CELL PHYSIOL BIOCHEM, V43, P1803, DOI 10.1159/000484066; Chen J, 2017, BIOMED PHARMACOTHER, V87, P118, DOI 10.1016/j.biopha.2016.12.093; Chen Y, 2020, BIOMED PHARMACOTHER, V125, DOI 10.1016/j.biopha.2020.109958; Dolka I, 2016, RES VET SCI, V105, P124, DOI 10.1016/j.rvsc.2016.02.004; Domagala A, 2018, BMC CANCER, V18, DOI 10.1186/s12885-018-4126-y; Du SX, 2017, LIPIDS HEALTH DIS, V16, DOI 10.1186/s12944-017-0468-8; Gao ML, 2016, ACTA HISTOCHEM, V118, P63, DOI 10.1016/j.acthis.2015.11.002; He CS, 2016, CELL PHYSIOL BIOCHEM, V40, P1221, DOI 10.1159/000453175; Huang F, 2018, WORLD J GASTROENTERO, V24, P4643, DOI 10.3748/wjg.v24.i41.4643; Huang H, 2018, ONCOL LETT, V15, P1487, DOI 10.3892/ol.2017.7446; Huo RC, 2016, MOL MED REP, V14, P3013, DOI 10.3892/mmr.2016.5648; Jiang YF, 2018, BIOCHEM BIOPH RES CO, V506, P266, DOI 10.1016/j.bbrc.2018.10.089; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Li W, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0805-4; Li YJ, 2017, CHIN J CANCER, V52, DOI 10.1186/s40880-017-0219-2; Lian X, 2018, BIOCHEM BIOPH RES CO, V496, P70, DOI 10.1016/j.bbrc.2017.12.168; Liang J, 2015, ONCOTARGET, V6, P31479, DOI 10.18632/oncotarget.5491; Lin HY, 2019, COLORECTAL DIS, V21, P123, DOI 10.1111/codi.14477; Liu GB, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18020367; Liu WJ, 2016, CELL MOL BIOL LETT, V21, DOI 10.1186/s11658-016-0031-z; Ma MJ, 2018, J THORAC DIS, V10, P5384, DOI 10.21037/jtd.2018.08.64; Mathews ES, 2016, J NEUROSCI, V36, P7628, DOI 10.1523/JNEUROSCI.0726-16.2016; Meher JG, 2018, ARTIF CELL NANOMED B, V46, pS344, DOI 10.1080/21691401.2018.1492933; Mindell JA, 2012, ANNU REV PHYSIOL, V74, P69, DOI 10.1146/annurev-physiol-012110-142317; Ming J, 2019, MOL CARCINOGEN, V58, P358, DOI 10.1002/mc.22933; Muller-Greven G, 2017, CLIN CANCER RES, V23, P7059, DOI 10.1158/1078-0432.CCR-17-0249; Nazim UMD, 2017, ONCOTARGET, V8, P100021, DOI 10.18632/oncotarget.21754; Palladino G, 2016, ENDOCR-RELAT CANCER, V23, P699, DOI 10.1530/ERC-16-0063; Ramezani S, 2019, CANCER BIOTHER RADIO, V34, P345, DOI 10.1089/cbr.2018.2651; Rossi L, 2017, ONCOTARGET, V8, P12389, DOI 10.18632/oncotarget.13310; Schlafli AM, 2016, ONCOTARGET, V7, P39544, DOI 10.18632/oncotarget.9647; Shan YL, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-1832-6; Somers J, 2013, INT J BIOCHEM CELL B, V45, P1690, DOI 10.1016/j.biocel.2013.04.020; Song P, 2017, CANCER MED-US, V6, P1154, DOI 10.1002/cam4.1047; Tamura R, 2017, BRAIN TUMOR PATHOL, V34, P62, DOI 10.1007/s10014-017-0284-x; Tian WG, 2018, DRUG DES DEV THER, V12, P3563, DOI 10.2147/DDDT.S163157; Toyokawa G, 2018, ANN THORAC SURG, V105, P1655, DOI 10.1016/j.athoracsur.2018.01.037; Wang L, 2020, FOOD SCI NUTR, V8, P6357, DOI 10.1002/fsn3.1751; Wang Q, 2018, PHYTOMEDICINE, V39, P160, DOI 10.1016/j.phymed.2017.12.029; Wu HB, 2017, AUTOPHAGY, V13, P1528, DOI 10.1080/15548627.2017.1336277; Xie T, 2016, ONCOL RES, V24, P447, DOI 10.3727/096504016X14685034103590; Xu HD, 2019, ADV EXP MED BIOL, V1206, P109, DOI 10.1007/978-981-15-0602-4_5; Xu W, 2021, CANCER CELL INT, V21, DOI 10.1186/s12935-020-01688-9; Yang RF, 2018, BRAZ J MED BIOL RES, V51, DOI [10.1590/1414-431X20176073, 10.1590/1414-431x20176073]; Zhang S, 2017, ANTICANCER RES, V37, P464, DOI 10.21873/anticanres.11338; Zhao Z, 2018, J CANCER, V9, P3407, DOI 10.7150/jca.24201; Zheng YF, 2019, J CELL PHYSIOL, V234, P4277, DOI 10.1002/jcp.27196; Zhou J, 2013, CELL RES, V23, P508, DOI 10.1038/cr.2013.11	50	0	0	5	5	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0272-4391	1098-2299		DRUG DEVELOP RES	Drug Dev. Res.												10.1002/ddr.21878		SEP 2021	9	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	UO4CI	WOS:000694642800001	34499759				2022-04-25	
J	Peng, ZH; Yuan, L; XuHong, JC; Tian, H; Zhang, Y; Deng, J; Qi, XW				Peng, Zaihui; Yuan, Long; XuHong, Juncheng; Tian, Hao; Zhang, Yi; Deng, Jun; Qi, Xiaowei			Chiral nanomaterials for tumor therapy: autophagy, apoptosis, and photothermal ablation	JOURNAL OF NANOBIOTECHNOLOGY			English	Review						Chirality; Nanomedicine; Biomaterials; Tumor therapy	QUANTUM DOTS; GOLD NANOPARTICLES; COLORECTAL-CANCER; BREAST-CANCER; SURFACE; PROTEIN; DIAGNOSIS; DESIGN; CYTOTOXICITY; BIOINTERFACE	Chirality is a fundamental characteristic of natural molecules and a crucial factor in the biochemical reactions of living cells and organisms. Recently, researchers have successfully introduced chiral molecules to the surfaces of nanomaterials, creating chiral nanomaterials that exhibit an upscaling of chiral behavior from the molecular scale to the nanoscale. These chiral nanomaterials can selectively induce autophagy, apoptosis, and photothermal ablation in tumor cells based on their chirality, making them promising for application in anti-tumor therapy. However, these interesting and important phenomena have hitherto received little attention. Accordingly, we herein present a review of recent research progress in the field of chiral nanomaterials for tumor therapy along with brief looks at the mechanistic details of their actions. Finally, the current challenges and future perspectives of chiral nanomaterials in terms of maximizing their potential in tumor therapy are discussed. Thus, this review provides a helpful introduction to the design of chiral nanomaterials and will hopefully highlight the importance of chirality in tumor therapy.	[Peng, Zaihui; Yuan, Long; XuHong, Juncheng; Tian, Hao; Zhang, Yi; Qi, Xiaowei] Army Med Univ, Southwest Hosp, Dept Breast Surg, Chongqing 400038, Peoples R China; [Deng, Jun] Army Med Univ, Southwest Hosp, State Key Lab Trauma Burn & Combined Injury, Inst Burn Res, Chongqing 400038, Peoples R China		Zhang, Y; Qi, XW (corresponding author), Army Med Univ, Southwest Hosp, Dept Breast Surg, Chongqing 400038, Peoples R China.; Deng, J (corresponding author), Army Med Univ, Southwest Hosp, State Key Lab Trauma Burn & Combined Injury, Inst Burn Res, Chongqing 400038, Peoples R China.	ZY53810@163.com; djun.123@163.com; qxw9908@foxmail.com	; Qi, Xiaowei/O-1338-2018	Deng, Jun/0000-0002-9951-2393; Qi, Xiaowei/0000-0002-5876-4957	National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [51703243]; Chongqing Basic Research and Frontier Exploration Project [cstc2018jcyjA0137]; Program of National Key Clinical Specialist Construction [413F1Z113]; Military Medical Staff Innovation Plan of Southwest Hospital [SWH2018BJLC-04]; Army Medical University [XZ-2019-505-042]	This work was supported in National Natural Science Foundation of China (NSFC) (No. 51703243), Chongqing Basic Research and Frontier Exploration Project (No. cstc2018jcyjA0137), Program of National Key Clinical Specialist Construction (No. 413F1Z113), Military Medical Staff Innovation Plan of Southwest Hospital (No. SWH2018BJLC-04) and Army Medical University (No. XZ-2019-505-042).	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Nanobiotechnol.	JUL 22	2021	19	1							220	10.1186/s12951-021-00965-7			13	Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Science & Technology - Other Topics	TR3DQ	WOS:000678849800001	34294083	Green Published, gold			2022-04-25	
J	Como, C; Perego, P				Como, Cristina; Perego, Paola			KiSS1 in regulation of metastasis and response to antitumor drugs	DRUG RESISTANCE UPDATES			English	Review						KiSS1; GPR54; Cancer; Metastasis; Drug response	RENAL-CELL CARCINOMA; BREAST-CANCER CELL; SUPPRESSOR GENE; TRANSCRIPTIONAL REGULATION; COLORECTAL-CANCER; KISSPEPTIN/GPR54 SYSTEM; EXPRESSION; RESISTANCE; GPR54; MELANOMA	Metastatic dissemination of tumor cells represents a major obstacle towards cancer cure. Tumor cells with metastatic capacity are often resistant to chemotherapy. Experimental efforts revealed that the metastatic cascade is a complex process that involves multiple positive and negative regulators. In this respect, several metastasis suppressor genes have been described. Here, we review the role of the metastasis suppressor KiSS1 in regulation of metastasis and in response to antitumor agents. Physiologically, KiSS1 plays a key role in the activation of the hypothalamic-pituitary-gonadal axis regulating puberty and reproductive functions. KiSS1derived peptides i.e., kisspeptins, signal through the G-protein coupled receptor GPR54. In cancer, KiSS1 signaling suppresses metastases and maintains dormancy of disseminated malignant cells, by interfering with cell migratory and invasive abilities. Besides, KiSS1 modulates glucose and lipid metabolism, by reprogramming energy production towards oxidative phosphorylation and beta-oxidation. Loss or reduced expression of KiSS1, in part through promoter hypermethylation, is related to the development of metastases in various cancer types, with some conflicting reports. The poorly understood role of KiSS1 in response to chemotherapeutic agents appears to be linked to stimulation of the intrinsic apoptotic pathway and inhibition of cell defense factors (e.g., glutathione S-transferase-pi) as well as autophagy modulation. Deciphering the molecular basis underlying regulation of the metastatic potential is crucial for the establishment of novel treatment strategies.	[Como, Cristina; Perego, Paola] Fdn IRCCS Ist Nazl Tumori, Mol Pharmacol Unit, Dept Appl Res & Technol Dev, Via Amadeo 42,Via Venezian 1, I-20133 Milan, Italy		Perego, P (corresponding author), Fdn IRCCS Ist Nazl Tumori, Mol Pharmacol Unit, Dept Appl Res & Technol Dev, Via Amadeo 42,Via Venezian 1, I-20133 Milan, Italy.	paola.perego@istitutotumori.mi.it	Perego, Paola/J-7647-2016; Corno, Cristina/J-2937-2018	Perego, Paola/0000-0003-2806-7269; Corno, Cristina/0000-0003-3529-0805	Fondazione CARIPLO-Regione LombardiaFondazione CariploRegione Lombardia [2016-1019]	This work was in part supported by a grant by Fondazione CARIPLO-Regione Lombardia to PP (grant 2016-1019).	Akkaya H, 2017, J BIOCHEM MOL TOXIC, V31, DOI 10.1002/jbt.21881; Albers-Wolthers CHJ, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0179156; Altorki N. 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Update	JAN	2019	42						12	21		10.1016/j.drup.2019.02.001			10	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	HW1PI	WOS:000466454400002	30776659				2022-04-25	
J	Xu, J; Pan, YX; Liu, YY; Na, S; Zhou, H; Li, L; Chen, FY; Song, H				Xu, Jing; Pan, Yunxia; Liu, Yanyan; Na, Sha; Zhou, Hui; Li, Lu; Chen, Fengyuan; Song, Hang			A review of anti-tumour effects of ginsenoside in gastrointestinal cancer	JOURNAL OF PHARMACY AND PHARMACOLOGY			English	Review						ginsenoside; gastrointestinal cancer; autophagy; apoptosis; natural product	EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL TUMOR-GROWTH; GASTRIC-CANCER; INHIBITS PROLIFERATION; 20(S)-GINSENOSIDE RG3; ANTICANCER ACTIVITY; DOWN-REGULATION; RED GINSENG; COMPOUND K; CELL-DEATH	Objectives: Gastrointestinal cancer, one of the major causes of cancer-related deaths in the world, refers to malignant conditions of the gastrointestinal (GI) tract and other organs. Although conventional therapy has been successful to some extent in cancer treatment, drug resistance and cancer recurrence still limit the therapeutic efficacy. There is increasing evidence indicating that ginsenoside, as a kind of high nutritional value and widely used traditional Chinese medicine, could contribute to the promotion of treatment in GI cancer, which deserves further investigation. Key findings: Based on previous studies, the possible mechanisms mainly include regulation of autophagy, apoptosis, proliferation, migration and angiogenesis. However, no studies recently have conducted a more in-depth review of the anti-cancer effects of ginsenoside in GI cancer. Summary: Therefore, this review will summarise and analyse the latest developments in the anti-tumour effects of ginsenosides in GI cancer, thus may promote further research of the anti-tumour efficacy of ginsenoside.	[Xu, Jing; Pan, Yunxia; Chen, Fengyuan; Song, Hang] Anhui Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Hefei, Peoples R China; [Liu, Yanyan; Na, Sha; Zhou, Hui; Li, Lu; Song, Hang] Anhui Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Dept Biochem & Mol Biol, Hefei, Peoples R China; [Liu, Yanyan; Na, Sha; Zhou, Hui; Li, Lu; Chen, Fengyuan; Song, Hang] Anhui Acad Chinese Med, Inst Integrat Med, Hefei, Peoples R China; [Liu, Yanyan; Na, Sha; Zhou, Hui; Li, Lu; Chen, Fengyuan; Song, Hang] Key Lab Chinese Med Formula Anhui Prov, Hefei, Peoples R China		Chen, FY; Song, H (corresponding author), Anhui Univ Tradit Chinese Med, 1 Qianjiang Rd, Hefei, Peoples R China.	isobellachen@163.com			Project of High-Level Talents in Anhui University of Chinese Medicine [2019rcZD001, DT19200015]; Innovation Foundation for the Returned Overseas Chinese Scholars, Anhui ProvinceScientific Research Foundation for the Returned Overseas Chinese Scholars [2020LCX009]	This work was supported by the Project of High-Level Talents in Anhui University of Chinese Medicine (Project code: 2019rcZD001 and DT19200015) and the Innovation Foundation for the Returned Overseas Chinese Scholars, Anhui Province (Project code: 2020LCX009).	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Pharm. Pharmacol.	OCT	2021	73	10					1292	1301		10.1093/jpp/rgab048		APR 2021	10	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	UR2JX	WOS:000696581500002	33836068				2022-04-25	
J	Liu, ZQ; Li, Q; Zhao, X; Cui, B; Zhang, LB; Wang, Q				Liu, Zhiqiang; Li, Qiang; Zhao, Xin; Cui, Bin; Zhang, Libo; Wang, Qiang			MicroRNA-935 Inhibits Proliferation and Invasion of Osteosarcoma Cells by Directly Targeting High Mobility Group Box 1	ONCOLOGY RESEARCH			English	Article						MicroRNA-935; Osteosarcoma (OS); Proliferation; Invasion; High-mobility group box 1 (HMGB1)	TUMOR-SUPPRESSOR; HMGB1-MEDIATED AUTOPHAGY; COLORECTAL-CANCER; HMGB1 EXPRESSION; CERVICAL-CANCER; POOR-PROGNOSIS; GASTRIC-CANCER; PROMOTES; MIGRATION; PROTEIN	Numerous studies have suggested that microRNAs (miRNAs) are dysregulated in osteosarcoma (OS), implicating miRNAs in OS initiation and progression. Therefore, knowledge of aberrantly expressed miRNAs in OS may provide novel mechanistic insights into the tumorigenesis and tumor development of OS and facilitate therapeutic methods for patients with this aggressive bone neoplasm. In this study, data obtained from reverse transcription quantitative polymerase chain reaction (RT-qPCR) revealed that miR-935 was significantly decreased in OS tissues and cell lines. Restoration expression of miR-935 obviously restricted proliferation and invasion of OS cells. In addition, high-mobility group box 1 (HMGB1) was predicted to be a putative target of miR-935. Subsequent dual-luciferase reporter assay, RT-qPCR, and Western blot analysis confirmed that miR-935 could directly target the 3'-untranslated region of HMGB1 and negatively regulated HMGB1 expression in OS cells. Furthermore, a significant negative association was found between miR-935 and HMGB1 mRNA expression in OS tissues. Rescue experiments showed that recovery of HMGB1 expression partially rescued miR-935-induced suppression of cell proliferation and invasion in OS. These results provide the first evidence for the suppressive roles of miR-935 in OS by directly targeting HMGB1, suggesting that miR-935 may be a potential candidate for the treatment of patients with this disease.	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Res.		2018	26	9					1439	1446		10.3727/096504018X15189093975640			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GX3KP	WOS:000447623200015	29471892	Green Published, hybrid			2022-04-25	
J	Sainz, J; Garcia-Verdejo, FJ; Martinez-Bueno, M; Kumar, A; Sanchez-Maldonado, JM; Diez-Villanueva, A; Vodickova, L; Vymetalkova, V; Sanchez, VM; Da Silva, MI; Sampaio-Marques, B; Brezina, S; Butterbach, K; ter Horst, R; Hoffmeister, M; Ludovico, P; Jurado, M; Li, Y; Sanchez-Rovira, P; Netea, MG; Gsur, A; Vodicka, P; Moreno, V; Hemminki, K; Brenner, H; Chang-Claude, J; Forsti, A				Sainz, Juan; Garcia-Verdejo, Francisco Jose; Martinez-Bueno, Manuel; Kumar, Abhishek; Sanchez-Maldonado, Jose Manuel; Diez-Villanueva, Anna; Vodickova, Ludmila; Vymetalkova, Veronika; Martin Sanchez, Vicente; Da Silva Filho, Miguel Inacio; Sampaio-Marques, Belem; Brezina, Stefanie; Butterbach, Katja; ter Horst, Rob; Hoffmeister, Michael; Ludovico, Paula; Jurado, Manuel; Li, Yang; Sanchez-Rovira, Pedro; Netea, Mihai G.; Gsur, Andrea; Vodicka, Pavel; Moreno, Victor; Hemminki, Kari; Brenner, Hermann; Chang-Claude, Jenny; Foersti, Asta			Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts	CANCERS			English	Article						colorectal cancer; autophagy; genetic variants; susceptibility		Simple Summary We investigated the influence of autophagy-related variants in modulating colorectal cancer (CRC) risk through a meta-analysis of genome-wide association study (GWAS) data from four large European cohorts. We found that genetic variants within the DAPK2 and ATG5 loci were associated with CRC risk. This study also shed some light onto the functional mechanisms behind the observed associations and demonstrated the impact of DAPK2(rs11631973) and ATG5(rs546456) polymorphisms on the modulation of host immune responses, blood derived-cell counts and serum inflammatory protein levels, which might be involved in promoting cancer development. No effect of the DAPK2 and ATG5 polymorphisms on the autophagy flux was observed. The role of genetic variation in autophagy-related genes in modulating autophagy and cancer is poorly understood. Here, we comprehensively investigated the association of autophagy-related variants with colorectal cancer (CRC) risk and provide new insights about the molecular mechanisms underlying the associations. After meta-analysis of the genome-wide association study (GWAS) data from four independent European cohorts (8006 CRC cases and 7070 controls), two loci, DAPK2 (p = 2.19 x 10(-5)) and ATG5 (p = 6.28 x 10(-4)) were associated with the risk of CRC. Mechanistically, the DAPK2(rs11631973G) allele was associated with IL1 beta levels after the stimulation of peripheral blood mononuclear cells (PBMCs) with Staphylococcus aureus (p = 0.002), CD24 + CD38 + CD27 + IgM + B cell levels in blood (p = 0.0038) and serum levels of en-RAGE (p = 0.0068). ATG5(rs546456T) allele was associated with TNF alpha and IL1 beta levels after the stimulation of PBMCs with LPS (p = 0.0088 and p = 0.0076, respectively), CD14+CD16- cell levels in blood (p = 0.0068) and serum levels of CCL19 and cortisol (p = 0.0052 and p = 0.0074, respectively). Interestingly, no association with autophagy flux was observed. These results suggested an effect of the DAPK2 and ATG5 loci in the pathogenesis of CRC, likely through the modulation of host immune responses.	[Sainz, Juan; Sanchez-Maldonado, Jose Manuel; Jurado, Manuel] Univ Granada, Andalusian Reg Govt, Ctr Genom & Oncol Res Pfizer, Genom Oncol Area,GENYO, Granada 18016, Spain; [Sainz, Juan; Sanchez-Maldonado, Jose Manuel; Jurado, Manuel] Virgen Nieves Univ Hosp, Hematol Dept, Granada 18012, Spain; [Sainz, Juan; Sanchez-Maldonado, Jose Manuel; Jurado, Manuel] Inst Invest Biosanataria IBs Granada, Granada 18012, Spain; [Sainz, Juan] Univ Granada, Dept Med, Granada 18016, Spain; [Garcia-Verdejo, Francisco Jose; Sanchez-Rovira, Pedro] Complejo Hosp Jaen, Dept Med Oncol, Jaen 23007, Spain; [Martinez-Bueno, Manuel] Univ Granada, Andalusian Reg Govt, Ctr Genom & Oncol Res Pfizer, Area Genom Med,GENYO, Granada 18016, Spain; [Kumar, Abhishek; Da Silva Filho, Miguel Inacio; Hemminki, Kari; Foersti, Asta] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany; [Kumar, Abhishek] Int Technol Pk, Inst Bioinformat, Bangalore 560066, Karnataka, India; [Kumar, Abhishek] Manipal Acad Higher Educ MAHE, Manipal 576104, Karnataka, India; [Diez-Villanueva, Anna; Moreno, Victor] Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Catalan Inst Oncol, Bellvitge Biomed Res Inst IDIBELL, Barcelona 08908, Spain; [Diez-Villanueva, Anna; Moreno, Victor] Univ Barcelona, Barcelona 08908, Spain; [Vodickova, Ludmila; Vymetalkova, Veronika; Vodicka, Pavel] Acad Sci Czech Republ, Inst Expt Med, Dept Mol Biol Canc, Prague 14200, Czech Republic; [Vodickova, Ludmila; Vymetalkova, Veronika; Vodicka, Pavel] Charles Univ Prague, Inst Biol & Med Genet, Med Fac 1, Prague 12800, Czech Republic; [Vodickova, Ludmila; Vymetalkova, Veronika; Vodicka, Pavel] Charles Univ Prague, Fac Med Pilsen, Biomed Ctr, Plzen 32300, Czech Republic; [Martin Sanchez, Vicente] Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Madrid 28029, Spain; [Martin Sanchez, Vicente] Univers Leon, Inst Biomed IBIOMED, Leon 24071, Spain; [Sampaio-Marques, Belem; Ludovico, Paula] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, P-4710057 Braga, Portugal; [Sampaio-Marques, Belem; Ludovico, Paula] ICVS 3BsPT Govt Associate Lab, Braga, Guimaraes, Portugal; [Brezina, Stefanie; Gsur, Andrea] Med Univ Vienna, Inst Canc Res, Dept Med 1, Borschkegasse 8a, A-1090 Vienna, Austria; [Butterbach, Katja; Brenner, Hermann] Heidelberg Univ, Network Aging Res, D-69115 Heidelberg, Germany; [ter Horst, Rob; Li, Yang; Netea, Mihai G.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands; [ter Horst, Rob; Li, Yang; Netea, Mihai G.] Radboud Univ Nijmegen, Radboud Ctr Infect Dis, Med Ctr, NL-6525 GA Nijmegen, Netherlands; [Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Neuenheimer Feld 280, D-69120 Heidelberg, Germany; [Li, Yang] Helmholtz Ctr Infect Res HZI, Ctr Individualised Infect Med CiiM, D-30625 Hannover, Germany; [Li, Yang] Helmholtz Ctr Infect Res HZI, TWINCORE, D-30625 Hannover, Germany; [Li, Yang] Hannover Med Sch MHH, D-30625 Hannover, Germany; [Netea, Mihai G.] Univ Bonn, Life & Med Sci Inst LIMES, Dept Immunol & Metab, D-53115 Bonn, Germany; [Hemminki, Kari] German Canc Res Ctr, Div Canc Epidemiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany; [Hemminki, Kari] Charles Univ Prague, Fac Med, Plzen 30605, Czech Republic; [Hemminki, Kari] Charles Univ Prague, Biomed Ctr Pilsen, Plzen 30605, Czech Republic; [Brenner, Hermann] Natl Ctr Tumour Dis NCT, German Canc Res Ctr DKFZ, Div Prevent Oncol, D-69120 Heidelberg, Germany; [Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, D-69120 Heidelberg, Germany; [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany; [Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr, Genet Tumour Epidemiol Grp, D-20246 Hamburg, Germany; [Foersti, Asta] German Canc Consortium DKTK, German Canc Res Ctr DKFZ, Div Pediat Neurooncol, D-69120 Heidelberg, Germany; [Foersti, Asta] Hopp Childrens Canc Ctr KiTZ, D-69120 Heidelberg, Germany		Sainz, J (corresponding author), Univ Granada, Andalusian Reg Govt, Ctr Genom & Oncol Res Pfizer, Genom Oncol Area,GENYO, Granada 18016, Spain.; Sainz, J (corresponding author), Virgen Nieves Univ Hosp, Hematol Dept, Granada 18012, Spain.; Sainz, J (corresponding author), Inst Invest Biosanataria IBs Granada, Granada 18012, Spain.; Sainz, J (corresponding author), Univ Granada, Dept Med, Granada 18016, Spain.; Forsti, A (corresponding author), German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany.; Forsti, A (corresponding author), German Canc Consortium DKTK, German Canc Res Ctr DKFZ, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.; Forsti, A (corresponding author), Hopp Childrens Canc Ctr KiTZ, D-69120 Heidelberg, Germany.	juan.sainz@genyo.es; francisco.garcia.verdejo.sspa@juntadeandalucia.es; manuel.martinez@genyo.es; abhishek@ibioinformatics.org; josemanuel.sanchez@genyo.es; adiez@iconcologia.net; ludmila.vodickova@iem.cas.cz; veronika.vymetalkova@iem.cas.cz; vicente.martin@unileon.es; m.daSilvaFilho@dkfz.de; mbmarques@med.uminho.pt; stefanie.brezina@meduniwien.ac.at; k.butterbach@dkfz.de; RterHorst@cemm.oeaw.ac.at; m.hoffmeister@dkfz.de; pludovico@med.uminho.pt; manuel.jurado.sspa@juntadeandalucia.es; Yang.Li@helmholtz-hzi.de; oncopsr@yahoo.es; mihai.netea@radboudumc.nl; andrea.gsur@meduniwien.ac.at; pavel.vodicka@iem.cas.cz; v.moreno@iconcologia.net; k.hemminki@dkfz-heidelberg.de; h.brenner@dkfz-heidelberg.de; j.chang-claude@dkfz.de; a.foersti@kitz-heidelberg.de	Hoffmeister, Michael/T-7187-2019; Martin, Vicente/A-1597-2008; Brenner, Hermann/B-4627-2017; Hoffmeister, Michael/AAB-2321-2022; Martin, Vicente/ABF-2276-2021; Brenner, Hermann/ABE-6383-2020; Vymetalkova, Veronika/H-3167-2014; Ludovico, Paula/B-4338-2011; Kumar, Abhishek/A-8727-2012; Sampaio-Marques, Belem/M-4758-2013	Hoffmeister, Michael/0000-0002-8307-3197; Martin, Vicente/0000-0003-0552-2804; Brenner, Hermann/0000-0002-6129-1572; Hoffmeister, Michael/0000-0002-8307-3197; Martin, Vicente/0000-0003-0552-2804; Brenner, Hermann/0000-0002-6129-1572; Martinez Bueno, Manuel/0000-0002-4333-4487; Sanchez Maldonado, Jose Manuel/0000-0002-4651-3675; Forsti, Asta/0000-0002-9857-4728; Li, Yang/0000-0003-4022-7341; Vymetalkova, Veronika/0000-0001-6870-6788; Gsur, Andrea/0000-0002-9795-1528; Ludovico, Paula/0000-0003-4130-7167; ter Horst, Rob/0000-0003-0576-5873; Kumar, Abhishek/0000-0003-4172-4059; Sampaio-Marques, Belem/0000-0001-6580-0971	Instituto de Salud Carlos III (Madrid, Spain)Instituto de Salud Carlos III [PI12/02688, PI17/02256]; Austrian Research Promotion Agency (FFG) BRIDGE grant [829675]; Herzfelder'sche Familienstiftung; GACRGrant Agency of the Czech Republic [18-09709S, 19-10543S, 20-03997S]; COST (European Cooperation in Science and Technology)European Cooperation in Science and Technology (COST) [CA17118]; Ramalingaswami Re-Retry Faculty Fellowship from the Department of Biotechnology (DBT), Government of India (GOI) [BT/RLF/Re-entry/38/2017]; Agency for Management of University and Research Grants (AGAUR) of the Catalan Government [2017SGR723]; Instituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Commission; FEDER funds-a way to build Europe [PI14-00613, PI17-00092]; Spanish Association Against Cancer (AECC) Scientific Foundation [GCTRA18022MORE]; European Union Horizon 2020 [856620];  [ProgresQ28/1.LF];  [UNCE/MED/006]	This work was partially supported by grants from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688 and PI17/02256). CORSA was funded by the Austrian Research Promotion Agency (FFG) BRIDGE grant (no. 829675, to Andrea Gsur), the "Herzfelder'sche Familienstiftung" (grant to Andrea Gsur). Czech Republic CCS was funded by GACR grants (18-09709S, 19-10543S and 20-03997S), ProgresQ28/1.LF and UNCE/MED/006 grants. This article is based upon work from COST Action CA17118, supported by COST (European Cooperation in Science and Technology). A.K. is a recipient of a Ramalingaswami Re-Retry Faculty Fellowship (Grant; BT/RLF/Re-entry/38/2017) from the Department of Biotechnology (DBT), Government of India (GOI). V.M. received funding from the Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723, the Instituto de Salud Carlos III, co-funded by FEDER funds-a way to build Europe-grants PI14-00613, PI17-00092 and the Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE. K.H. was supported by European Union Horizon 2020 grant No. 856620. We thank the CERCA Programme, Generalitat de Catalunya for institutional support.	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J	Li, XL; Zhou, JB; Xia, CJ; Min, H; Lu, ZK; Chen, ZR				Li, Xiao-Lan; Zhou, Jianbiao; Xia, Chen-Jing; Min, Han; Lu, Zhong-Kai; Chen, Zhi-Rong			PRIMA-1(met) induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK-ULK1-Vps34 signaling cascade	ONCOLOGY REPORTS			English	Article						p53-reactivation and induction of massive apoptosis-1(methylated); autophagy; oncotherapy; p53; colorectal cancer		p53-reactivation and induction of massive apoptosis-1, APR-017 methylated (PRIMA-1(met); APR246) targets mutant p53 to restore its wild-type structure and function. It was previously demonstrated that PRIMA-1(met) effectively inhibited the growth of colorectal cancer (CRC) cells in a p53-independent manner, and distinctly induced apoptosis by upregulating Noxa in p53-mutant cell lines. The present study including experiments of western blotting, acridine orange staining and transmission electron microscopy revealed that PRIMA-1(met) induced autophagy in CRC cells independently of p53 status. Importantly, PRIMA-1(met) not only promoted autophagic vesicle (AV) formation and AV-lysosome fusion, but also increased lysosomal degradation. Furthermore, Cell Counting Kit-8 assay, colony formation assay and small interfering RNA transfection were performed to investigate the underling mechanisms. The study indicated that activation of the mTOR/AMPK-ULK1-Vps34 autophagic signaling cascade was key for PRIMA-1(met)-induced autophagy. Additionally, autophagy served a crucial role in the inhibitory effect of PRIMA-1(met) in cells harboring wild-type p53, which was closely associated with the increased expression of Noxa. Taken together, the results determined the effect of PRIMA-1(met) on autophagy, and further revealed mechanistic insights into different CRC cell lines. It was concluded that PRIMA-1(met)-based therapy may be an effective strategy for CRC treatment.	[Li, Xiao-Lan; Min, Han; Lu, Zhong-Kai; Chen, Zhi-Rong] Nanjing Med Univ, Affiliated Suzhou Hosp, Dept Gastroenterol, 16 Baita St West, Suzhou 215001, Jiangsu, Peoples R China; [Zhou, Jianbiao] Natl Univ Singapore, Canc Sci Inst Singapore, Ctr Translat Med, Singapore 117599, Singapore; [Xia, Chen-Jing] Tradit Chinese Med Hosp Kunshan, Dept Gastroenterol, Suzhou 215300, Jiangsu, Peoples R China		Chen, ZR (corresponding author), Nanjing Med Univ, Affiliated Suzhou Hosp, Dept Gastroenterol, 16 Baita St West, Suzhou 215001, Jiangsu, Peoples R China.	czr88188@163.com			National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81603128]; Gusu Health Layer Training Program for Young Top Talent [GSWS2019059]; Science and Technology Project of Suzhou [SYSD2018136, SS201717]	The current study was supported by a grant from the National Natural Science Foundation of China (NSFC; grant no. 81603128), which funded the design of the study, experiments, data analysis and writingof the manuscript. The current study was also supported by the Gusu Health Layer Training Program for Young Top Talent (grant no. GSWS2019059) and the Science and Technology Project of Suzhou (grant nos. SYSD2018136 and SS201717), which contributed to completion of the experiments.	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J	Du, HL; Chen, L; Luo, FX; Chen, XY; Li, Y; Cheng, QJ				Du, Hailei; Chen, Ling; Luo, Fangxiu; Chen, Xueyu; Li, Yong; Cheng, Qijian			Beclin-1 expression is associated with prognosis in a Bcl-2-dependent manner in non-small cell lung cancer	ONCOLOGY LETTERS			English	Article						autophagy; Beclin-1; Bcl-2; prognosis; non-small cell lung cancer	COLORECTAL-CANCER; BCL-2; ADENOCARCINOMA; DISCOVERY; CARCINOMA	Beclin-1 and Bcl-2 expression abnormalities have been confirmed in different types of cancer. As important regulators of autophagy and apoptosis, respectively, these molecules serve a complex role in tumorigenesis. However, limited information is currently available regarding the association between Beclin-1 and Bcl-2 in (NSCLC). In the present study, the expression levels of Beclin-1 and Bcl-2 were detected in lung cancer tissues, and their prognostic significance was analyzed for NSCLC. A total of 120 patients with lung cancer who underwent surgical resection were included in the present study. Beclin-1 and Bcl-2 expression was assessed using immunohistochemistry and their associations with the overall survival (OS) in patients with NSCLC was examined. The expression rate of Beclin-1 was significantly lower in NSCLC tissues compared with that in adjacent tissues, whereas the expression rate of Bcl-2 was significantly higher in lung cancer tissues compared with that in adjacent tissues. Additionally, Beclin-1 and Bcl-2 protein expression was strongly associated (P<0.05) in NSCLC. Patients with NSCLC with low Beclin-1 expression were in more advanced stages, with more lymph node metastasis and more poorly differentiated tumors. Similarly, patients with NSCLC with high Bcl-2 expression were also in a more advanced stage and had more lymph node metastasis. Cox regression analysis revealed that the association between Bcl-2 expression and survival was not significant, while a multivariate analysis revealed that Beclin-1 expression was significantly associated with OS. Notably, Beclin-1 expression was significantly associated with OS only in patients with high Bcl-2 expression. In conclusion, the present data indicated that the autophagy activity is decreased in NSCLC. Beclin-1 expression was downregulated, while Bcl-2 expression was upregulated in NSCLC tissues compared with that in adjacent tissues. Additionally, these two proteins were associated with the occurrence and progression of NSCLC. Beclin-1 may be a promising prognostic marker for patients with NSCLC with high Bcl-2 expression. The present findings provided a more accurate prognostic assessment for patients with NSCLC. Furthermore, they may be used to actively follow-up and promptly treat patients with a poor prognosis, which may benefit a greater number of patients with NSCLC.	[Du, Hailei; Chen, Xueyu] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Thorac Surg, Sch Med, Shanghai 200025, Peoples R China; [Chen, Ling; Li, Yong; Cheng, Qijian] Shanghai Jiao Tong Univ, Ruijin Hosp North, Sch Med, Dept Resp & Crit Care Med, Shanghai 201821, Peoples R China; [Luo, Fangxiu] Shanghai Jiao Tong Univ, Ruijin Hosp North, Sch Med, Dept Pathol, Shanghai 201821, Peoples R China		Cheng, QJ (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Dept Resp & Crit Care Med, Ruijin Hosp North,Jiading New Town Ctr, Shanghai 201821, Peoples R China.	chengqijian@aliyun.com			project of the Shanghai Jiading District Health Committee [2017KY02]	The present study was partly supported by a grant from a project of the Shanghai Jiading District Health Committee (grant no. 2017KY02)	Baspinar S, 2014, PATHOL RES PRACT, V210, P412, DOI 10.1016/j.prp.2014.02.008; Callagy GM, 2008, BMC CANCER, V8, DOI 10.1186/1471-2407-8-153; Cao MM, 2019, THORAC CANCER, V10, P3, DOI 10.1111/1759-7714.12916; Chen LX, 2019, J CANCER, V10, P6207, DOI 10.7150/jca.37335; Chen Y, 2017, MOL BIOSYST, V13, P991, DOI 10.1039/c6mb00653a; Chi XX, 2018, J VET MED SCI, V80, P1348, DOI 10.1292/jvms.17-0001; Cotzomi-Ortega I, 2018, MEDIAT INFLAMM, V2018, DOI 10.1155/2018/4231591; D'Arcy MS, 2019, CELL BIOL INT, V43, P582, DOI 10.1002/cbin.11137; Goldstraw P, 2016, J THORAC ONCOL, V11, P39, DOI 10.1016/j.jtho.2015.09.009; Guadagno E, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20164066; Han Y, 2014, ASIAN PAC J CANCER P, V15, P4583, DOI 10.7314/APJCP.2014.15.11.4583; Hoy H, 2019, CRIT CARE NURS CLIN, V31, P303, DOI 10.1016/j.cnc.2019.05.002; Huang Q, 2017, WORLD J GASTROENTERO, V23, P5018, DOI 10.3748/wjg.v23.i27.5018; Jiang LC, 2014, BRAZ J MED BIOL RES, V47, P252, DOI 10.1590/1414-431X20133231; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Liu XW, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0029670; Mao YS, 2016, SURG ONCOL CLIN N AM, V25, P439, DOI 10.1016/j.soc.2016.02.001; Nasim F, 2019, MED CLIN N AM, V103, P463, DOI 10.1016/j.mcna.2018.12.006; Qiu DM, 2014, BMC CANCER, V14, DOI 10.1186/1471-2407-14-327; Qiu XG, 2019, DNA CELL BIOL, V38, P85, DOI 10.1089/dna.2018.4318; Rahman MA, 2016, BIOCHEM PHARMACOL, V117, P97, DOI 10.1016/j.bcp.2016.08.006; Schenk RL, 2017, BIOCHEM BIOPH RES CO, V482, P459, DOI 10.1016/j.bbrc.2016.10.100; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Song SS, 2017, ONCOL LETT, V14, P7849, DOI 10.3892/ol.2017.7218; Sun HY, 2019, J BUON, V24, P634; Won KY, 2010, HUM PATHOL, V41, P107, DOI 10.1016/j.humpath.2009.07.006; Xu HD, 2019, ADV EXP MED BIOL, V1206, P109, DOI 10.1007/978-981-15-0602-4_5; Yang ZL, 2015, CLIN RES HEPATOL GAS, V39, P98, DOI 10.1016/j.clinre.2014.06.014; Yu Y, 2018, MOL MED REP, V18, P2124, DOI 10.3892/mmr.2018.9209; Zheng TL, 2018, ONCOTARGETS THER, V11, P4167, DOI 10.2147/OTT.S164987	30	3	3	1	5	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	OCT	2020	20	4							9	10.3892/ol.2020.11870			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NN6JV	WOS:000568893300072	32802158	gold, Green Published			2022-04-25	
J	Xia, Y; Lei, Q; Zhu, YX; Ye, TH; Wang, NY; Li, GB; Shi, XH; Liu, YT; Shao, B; Yin, T; Zhao, LF; Wu, WS; Song, XJ; Xiong, Y; Wei, YQ; Yu, LT				Xia, Yong; Lei, Qian; Zhu, Yongxia; Ye, Tinghong; Wang, Ningyu; Li, Guobo; Shi, Xuanhong; Liu, Yantong; Shao, Bin; Yin, Tao; Zhao, Lifeng; Wu, Wenshuang; Song, Xuejiao; Xiong, Ying; Wei, Yuquan; Yu, Luoting			SKLB316, a novel small-molecule inhibitor of cell-cycle progression, induces G2/M phase arrest and apoptosis in vitro and inhibits tumor growth in vivo	CANCER LETTERS			English	Article						SKLB316; Anti-cancer; Cell cycle arrest; Apoptosis; Drug discovery	BIOLOGICAL EVALUATION; EXPRESSION; AUTOPHAGY; DERIVATIVES; CHECKPOINT; STRATEGY; KINASES; PATHWAY; TARGETS; ROLES	Benzothiazole derivatives have received considerable attentions for their potencies in cancer therapy. In the present study, we reported that SKLB316, a novel synthesized benzothiazole derivative, exhibits activities to inhibit colorectal and pancreatic cancer in vitro and in vivo by inducing G2/M cell cycle arrest and apoptosis. In vitro, it exhibited significant anti-proliferative activities against human cancer cells derived from different histotypes including the colorectal cancer cell line HCT116 and pancreatic cancer cell line CFPAC-1. We chose these cell lines to study the possible anti-tumor mechanism because they are sensitive to SKLB316 treatment. Flow cytometry assays showed that SKLB316 could induce G2/M cell cycle arrest. Mechanistically, SKLB316 could decrease the activities of cdc2/cyclin B1 complex, including decreasing the synthesis of cyclin B1, cdc2 and cdc25c, while accumulating the levels of phosphorylated cdc2 (Tyr15) and checkpoint kinase 2. SKLB316 could also decrease the level of cyclin E and A2. Moreover, SKLB316 could induce cancer cell apoptosis, which was associated with activation of caspase 9, downregulation of Bcl-2 and upregulation of Bax. SKLB316 could also decrease the mitochondrial membrane potential and induce the generation of reactive oxygen species in cells. The results implied that SKLB316 may induce apoptosis via the mitochondria-mediated apoptotic pathway. Moreover, SKLB316 could suppress the growth of established colorectal and pancreatic cancer tumors in nude mice without causing obvious side effects. TUNEL assays confirmed that SKLB316 could also induce tumor cell apoptosis in vivo. Taken together, these findings demonstrate the potential value of SKLB316 as a novel anti-tumor drug candidate. (C) 2014 Elsevier Ireland Ltd. All rights reserved.	[Xia, Yong; Lei, Qian; Zhu, Yongxia; Ye, Tinghong; Wang, Ningyu; Li, Guobo; Shi, Xuanhong; Liu, Yantong; Shao, Bin; Yin, Tao; Zhao, Lifeng; Wu, Wenshuang; Song, Xuejiao; Xiong, Ying; Wei, Yuquan; Yu, Luoting] Sichuan Univ, State Key Lab Biotherapy, Collaborat Innovat Ctr Biotherapy, West China Hosp,West China Med Sch, Chengdu 610041, Peoples R China; [Xiong, Ying] Third Mil Med Univ, Xinqiao Hosp, Dept Pharm, Chongqing 400037, Peoples R China		Yu, LT (corresponding author), Sichuan Univ, State Key Lab Biotherapy, Collaborat Innovat Ctr Biotherapy, West China Hosp,West China Med Sch, Chengdu 610041, Peoples R China.	yuluot@scu.edu.cn		Wang, Ning-Yu/0000-0003-3571-4903; Li, Guo-Bo/0000-0002-4915-6677	Shijiazhuang Pharmaceutical Group Co., Ltd [11H0684]	This work was financially supported by Shijiazhuang Pharmaceutical Group Co., Ltd (11H0684).	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J	Zhuo, JW; Wang, XY				Zhuo, Jingwei; Wang, Xinying			Combination of targeting CD24 and inhibiting autophagy suppresses the proliferation and enhances the apoptosis of colorectal cancer cells	MOLECULAR MEDICINE REPORTS			English	Article						CD24; autophagy; proliferation; apoptosis; colorectal cancer	NF-KAPPA-B; SIGNALING PATHWAYS; ACTIVATION; CHEMOTHERAPY; EXPRESSION; CONTRIBUTES; PROGRESSION; SURVIVAL; THERAPY; DISEASE	CD24 can regulate angiogenesis, drug sensitivity and the progression of colorectal cancer (CRC). However, whether CD24 regulates autophagy and apoptosis in CRC cells remains to be fully elucidated. The present study investigated the functional role of the altered expression of CD24 in the autophagy and apoptosis of HCT116 and HT29 human CRC cells. The results revealed lower expression levels of CD24 in HCT116 cells but higher levels in HT29 cells. Inducing the overexpression or the knockdown of CD24 did not affect the viability or spontaneous apoptosis of HCT116 and HT29 cells, respectively. Induction of the overexpression of CD24 significantly decreased the relative expression levels of Beclin-1, autophagy-related (Atg)3 and Atg5, and the numbers of microtubule-associated protein-1 light chain-3 (LC3)-positive puncta, but increased the expression of p62 in HCT116 cells. By contrast, CD24 silencing increased the expression of Beclin-1, Atg3 and Atg5, and the numbers of LC3-positive puncta, but decreased the expression of p62 in HT29 cells. Treatment with 3-methyladenine, or the knockdown of Atg5 by specific small interfering RNA to attenuate autophagy significantly enhanced the viability of CD24-overexpressing HCT116 cells, but reduced the viability of CD24-silenced HT29 cells, relative to their controls. As a result, the attenuation of autophagy significantly decreased the frequency of apoptotic CD24-overexpressing HCT116 cells, but increased the percentages of apoptotic CD24-silenced HT29 cells. The overexpression of CD24 promoted the activation of nuclear factor (NF)-kappa Bp65, whereas CD24 silencing attenuated its activation in CRC cells. Inhibition of the activation of NF-kappa B enhanced the CD24 overexpression-induced decrease in autophagy, but attenuated the CD24 silencing-induced increase in autophagy in CRC cells. Therefore, CD24 inhibited the autophagy of CRC cells, and the combination of targeting CD24 and inhibiting autophagy promoted the apoptosis of CRC cells. Conceivably, these findings may aid in the design of novel therapies for the intervention of CRC.	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Med. Rep.	JUL	2019	20	1					539	548		10.3892/mmr.2019.10288			10	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	II0DR	WOS:000474876100057	31180548	Green Published, hybrid, Green Submitted			2022-04-25	
J	Enkhbat, T; Nishi, M; Yoshikawa, K; Jun, H; Tokunaga, T; Takasu, C; Kashihara, H; Ishikawa, D; Tominaga, M; Shimada, M				Enkhbat, Tumenjin; Nishi, Masaaki; Yoshikawa, Kozo; Jun, Higashijima; Tokunaga, Takuya; Takasu, Chie; Kashihara, Hideya; Ishikawa, Daichi; Tominaga, Masahide; Shimada, Mitsuo			Epigallocatechin-3-gallate Enhances Radiation Sensitivity in Colorectal Cancer Cells Through Nrf2 Activation and Autophagy	ANTICANCER RESEARCH			English	Article						EGCG; radiation; colorectal cancer; Nrf2; autophagy	GREEN TEA CATECHIN; GALLATE; MECHANISMS; APOPTOSIS; INDUCTION; ROLES; EGCG	Background/Aim: Epigallocatechin-3-gallate (EGCG) is a major polyphenolic component of green tea. EGCG plays a potential role in radio-sensitizing cancer cells. The combined effect of EGCG and radiation was investigated in a colorectal cancer cell line, focusing on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) autophagy signalling. Materials and Methods: HCT-116 cells were treated with 12.5 ,uM EGCG for different periods of time, 2 Gy radiation, or both. Cell viability was determined with the WST-8 assay. The number of colonies was determined with the colony formation assay. mRNA expression of LC3 and caspase-9 was analyzed with quantitative real-time polymerase chain reaction. Results: Combination treatment with EGCG and radiation significantly decreased the growth of HCT-116 cells. The number of colonies was reduced to 34.2% compared to the control group. Immunofluorescence microscopy images showed that nuclear translocation of Nrf2 was significantly increased when cells were treated with the combination of EGCG and radiation compared to the control and single-treatment groups. Combined treatment with EGCG and radiation significantly induced LC3 and caspase-9 mRNA expression. Conclusion: EGCG increased the sensitivity of colorectal cancer cells to radiation by inhibiting cell proliferation and inducing Nrf2 nuclear translocation and autophagy.	[Enkhbat, Tumenjin; Nishi, Masaaki; Yoshikawa, Kozo; Jun, Higashijima; Tokunaga, Takuya; Takasu, Chie; Kashihara, Hideya; Ishikawa, Daichi; Shimada, Mitsuo] Tokushima Univ, Inst Biomed Sci, Dept Surg, Grad Sch, Tokushima, Japan; [Tominaga, Masahide] Univ Tokushima, Dept Therapeut Radiol, Inst Biomed Sci, Grad Sch, Tokushima, Japan		Shimada, M (corresponding author), Univ Tokushima, Inst Hlth Biosci, Dept Surg, Grad Sch, 3-18-15 Kuramoto Cho, Tokushima 7708503, Japan.	mitsuo.shimada@tokushima-u.ac.jp		Enkhbat, Tumenjin/0000-0002-9463-0622			Baatout S, 2005, INT J MOL MED, V15, P337; Chen HHW, 2017, ONCOTARGET, V8, P62742, DOI 10.18632/oncotarget.18409; De Nicola GM, 2011, NATURE, V475, P106, DOI 10.1038/nature10189; Ding WX, 2012, BIOL CHEM, V393, P547, DOI 10.1515/hsz-2012-0119; Gonzalez-Donquiles C, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0177549; Haraldsdottir S, 2014, LAEKNABLADID, V100, P75, DOI 10.17992/lbl.2014.02.531; Ichimura Y, 2013, MOL CELL, V51, P618, DOI 10.1016/j.molcel.2013.08.003; Lee SLO, 2016, OXID MED CELL LONGEV, V2016, DOI 10.1155/2016/6823471; Masuda M, 2001, CLIN CANCER RES, V7, P4220; Menegon S, 2016, TRENDS MOL MED, V22, P578, DOI 10.1016/j.molmed.2016.05.002; Paschka AG, 1998, CANCER LETT, V130, P1, DOI 10.1016/S0304-3835(98)00084-6; Saito Y, 2014, J GASTROENTEROL, V49, P692, DOI 10.1007/s00535-013-0799-9; Singh BN, 2011, BIOCHEM PHARMACOL, V82, P1807, DOI 10.1016/j.bcp.2011.07.093; Suganuma M, 2011, CANCER SCI, V102, P317, DOI 10.1111/j.1349-7006.2010.01805.x; Sun WX, 2017, FREE RADICAL BIO MED, V108, P840, DOI 10.1016/j.freeradbiomed.2017.04.365; Tan XH, 2000, CANCER LETT, V158, P1, DOI 10.1016/S0304-3835(00)00445-6; Vyas S, 2016, CELL, V166, P555, DOI 10.1016/j.cell.2016.07.002; Wang HN, 2018, CHEM-BIOL INTERACT, V281, P11, DOI 10.1016/j.cbi.2017.12.017; Wubetu GY, 2016, J GASTROEN HEPATOL, V31, P256, DOI 10.1111/jgh.13069; Yang CS, 2011, PHARMACOL RES, V64, P113, DOI 10.1016/j.phrs.2011.03.001; Zhang G, 2012, CURR MOL MED, V12, P163, DOI 10.2174/156652412798889063; Zhao HX, 2016, BRIT J RADIOL, V89, DOI 10.1259/bjr.20150665; Zhao HX, 2015, RADIOTHER ONCOL, V114, P351, DOI 10.1016/j.radonc.2015.02.014	23	26	27	0	14	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.	NOV	2018	38	11					6247	6252		10.21873/anticanres.12980			6	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HA1KY	WOS:000449973000064	30396944	Bronze			2022-04-25	
J	Shi, DH; Niu, PG; Heng, XJ; Chen, LJ; Zhu, YT; Zhou, JT				Shi, Daohua; Niu, Peiguang; Heng, Xiaojie; Chen, Lijun; Zhu, Yanting; Zhou, Jintuo			Autophagy induced by cardamonin is associated with mTORC1 inhibition in SKOV3 cells	PHARMACOLOGICAL REPORTS			English	Article						Autophagy; Cardamonin; mTOR; Ovarian cancer; Raptor	NF-KAPPA-B; PI3K/AKT/MTOR SIGNALING PATHWAY; COLORECTAL-CARCINOMA HCT116; OVARIAN-CANCER; MULTIPLE-MYELOMA; DOWN-REGULATION; APOPTOSIS; CISPLATIN; ACTIVATION; ANTIPROLIFERATION	Background: The mammalian target of rapamycin (mTOR) integrates energy level to modulate cell proliferation and autophagy. Cardamonin exhibits anti-proliferative activity through inhibiting mTOR. In this study, the effect of cardamonin on autophagy and its mechanism on mTOR inhibition were investigated. Methods: Cell viability and proliferation were measured by MTT assay and BrdU incorporation, respectively. Cell apoptosis was assayed by flow cytometry and cell autophagy was detected by electron microscopy and GFP-LC3 fluorescence. The mechanism of cardamonin on mTORC1 inhibition was investigated by Raptor siRNA and Raptor over-expression. Results: The cell viability and proliferation were inhibited by cardamonin. The autophagosomes and the protein level of LC3-II were increased by cardamonin. Cell apoptosis and the levels of cleaved PARP and Caspase-3 were increased by cardamonin. Cardamonin inhibited the phosphorylation of mTOR and ribosome S6 protein kinase 1 (S6K1) as well as the protein level of regulatory associated protein of mTOR (Raptor). However, cardamonin had no effect on the component of mTORC2 and its downstream substrate Akt. The inhibitory effect of cardamonin on the phosphorylation of mTOR and S6K1 was eliminated by Raptor knockdown with siRNA, whereas this effect of cardamonin was stronger than that of rapamycin and AZD8055 in Raptor over-expression cells. Cell viability was inhibited by cardamonin in both Raptor knockdown and Raptor over-expression cells, which was consistent with the inhibitory effect of cardamonin on mTOR. Conclusion: These findings demonstrated that the autophagy induced by cardamonin was associated with mTORC1 inhibition through decreasing the protein level of Raptor in SKOV3 cells. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.	[Shi, Daohua; Niu, Peiguang; Heng, Xiaojie; Chen, Lijun; Zhu, Yanting; Zhou, Jintuo] Fujian Med Univ, Affiliated Hosp, Fujian Prov Matern & Childrens Hosp, Dept Pharm, Fuzhou, Fujian, Peoples R China		Shi, DH (corresponding author), Fujian Med Univ, Affiliated Hosp, Fujian Prov Matern & Childrens Hosp, Dept Pharm, Fuzhou, Fujian, Peoples R China.	shidh@yeah.net	Daohua, Shi/C-3952-2011	Daohua, Shi/0000-0002-3383-5640	Natural Science Foundation of Fujian Province, ChinaNatural Science Foundation of Fujian Province [2015J01368, 2016J01492, 2017J01234]; Innovative Medical Foundation of Fujian Provincial Health and Family Planning Commission, China [2016-CX-13]	This work was supported by the Natural Science Foundation of Fujian Province, China (grant numbers: 2015J01368, 2016J01492, 2017J01234) and Innovative Medical Foundation of Fujian Provincial Health and Family Planning Commission, China (grant number: 2016-CX-13).	Bahrami F, 2014, AM J CANCER RES, V4, P558; Chude CI, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18061279; Crazzolara R, 2009, AUTOPHAGY, V5, P727, DOI 10.4161/auto.5.5.8507; Dennis MD, 2013, J BIOL CHEM, V288, P10, DOI 10.1074/jbc.M112.402461; Dibble CC, 2009, MOL CELL BIOL, V29, P5657, DOI 10.1128/MCB.00735-09; El-Khattouti Abdelouahid, 2013, J Cell Death, V6, P37, DOI 10.4137/JCD.S11034; El-Naga RN, 2014, TOXICOL APPL PHARM, V274, P87, DOI 10.1016/j.taap.2013.10.031; Feng N, 2016, MOL MED REP, V13, P3243, DOI 10.3892/mmr.2016.4887; Frey JW, 2014, CELL SIGNAL, V26, P313, DOI 10.1016/j.cellsig.2013.11.009; Fulda S, 2017, FRONT ONCOL, V7, DOI 10.3389/fonc.2017.00128; Goncalves LM, 2014, J MED FOOD, V17, P633, DOI 10.1089/jmf.2013.0061; Gozuacik D, 2004, ONCOGENE, V23, P2891, DOI 10.1038/sj.onc.1207521; Harder LM, 2014, AUTOPHAGY, V10, P339, DOI 10.4161/auto.26863; Kim YJ, 2015, BIOORG MED CHEM LETT, V25, P2559, DOI 10.1016/j.bmcl.2015.04.054; Ko H, 2011, J CELL BIOCHEM, V112, P2471, DOI 10.1002/jcb.23171; Kumar D, 2014, CANCER LETT, V343, P179, DOI 10.1016/j.canlet.2013.10.003; Kumar S, 2015, J CELL BIOCHEM, V116, P985, DOI 10.1002/jcb.25053; Lee DH, 2016, EUR J PHARMACOL, V784, P164, DOI 10.1016/j.ejphar.2016.05.025; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Li YY, 2015, INT IMMUNOPHARMACOL, V25, P332, DOI 10.1016/j.intimp.2015.02.002; Li YT, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.407; Liao Q, 2010, EUR J PHARMACOL, V641, P179, DOI 10.1016/j.ejphar.2010.05.024; Lou M, 2016, BIOMED PHARMACOTHER, V84, P1, DOI 10.1016/j.biopha.2016.08.055; Mabuchi S, 2007, CLIN CANCER RES, V13, P4261, DOI 10.1158/1078-0432.CCR-06-2770; Mabuchi S, 2011, CLIN CANCER RES, V17, P4462, DOI 10.1158/1078-0432.CCR-10-2987; Mabuchi S, 2009, CLIN CANCER RES, V15, P5404, DOI 10.1158/1078-0432.CCR-09-0365; Matsumoto K, 2015, JPN J CLIN ONCOL, V45, P408, DOI 10.1093/jjco/hyv014; Niu PG, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0127778; Niu PG, 2018, ONCOL LETT, V15, P3991, DOI 10.3892/ol.2018.7743; Prieto-Dominguez N, 2016, FRONT PHARMACOL, V7, DOI 10.3389/fphar.2016.00151; Qin Y, 2012, LEUKEMIA RES, V36, P514, DOI 10.1016/j.leukres.2011.11.014; Saxton RA, 2017, CELL, V168, P960, DOI [10.1016/j.cell.2017.02.004, 10.1016/j.cell.2017.03.035]; Shrivastava S, 2017, BIOFACTORS, V43, P152, DOI 10.1002/biof.1315; Sini P, 2010, AUTOPHAGY, V6, P553, DOI 10.4161/auto.6.4.11671; Tang Y, 2014, LIFE SCI, V99, P44, DOI 10.1016/j.lfs.2014.01.066; Veverka V, 2008, ONCOGENE, V27, P585, DOI 10.1038/sj.onc.1210693; Xu Dong-Wei, 2015, Asian Pac J Cancer Prev, V16, P2167; Xue ZG, 2016, PLANTA MED, V82, P70, DOI 10.1055/s-0035-1557901; Zhang DM, 2013, CARCINOGENESIS, V34, P1331, DOI 10.1093/carcin/bgt060; Zhang SL, 2017, MOL IMMUNOL, V85, P214, DOI 10.1016/j.molimm.2017.02.020; Zhang XJ, 2016, BIOMED PHARMACOTHER, V83, P1164, DOI 10.1016/j.biopha.2016.08.035; Zheng Wei, 2010, Zhongguo Zhong Yao Za Zhi, V35, P2318	42	12	14	0	8	POLISH ACAD SCIENCES INST PHARMACOLOGY	KRAKOW	SMETNA 12, 31-343 KRAKOW, POLAND	1734-1140			PHARMACOL REP	Pharmacol. Rep.	OCT	2018	70	5					908	916		10.1016/j.pharep.2018.04.005			9	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	GV2JK	WOS:000445914400012					2022-04-25	
J	Xu, YC; Huang, YS; Pan, GF; Li, ZX; Lin, LW; Chen, J; Wu, JH				Xu, Yanchang; Huang, Yisen; Pan, Guofeng; Li, Zhixiong; Lin, Linwen; Chen, Jian; Wu, Jihuang			Expression of autophagy-related proteins is associated with the clinical outcome of patients with advanced gastric cancer receiving fluoropyrimidine/platinum chemotherapy	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY			English	Article						Gastric cancer; autophagy; unc-51-like kinase 1; beclin 1; prognosis	SQUAMOUS-CELL CARCINOMA; HEDGEHOG SIGNALING PATHWAY; UNC-51-LIKE KINASE 1; COLORECTAL-CANCER; INDUCED APOPTOSIS; POOR-PROGNOSIS; OVARIAN-CANCER; BECLIN-1; RESISTANCE; MTOR	The precise prediction of the clinical outcome of cancer patients is crucial for determining therapeutic options and providing optimal cancer care. Although targeted therapy is widely used in cancer treatment, chemotherapy remains the first-line treatment for patients with advanced gastric cancer. This study aimed to investigate the expression of autophagy-related proteins, unc-51-like kinase 1 (ULK1) and beclin 1 (BECN1), in advanced gastric cancer to clarify their clinical significance in the prognosis assessment of patients receiving fluoropyrimidine/platinum chemotherapy. The expression levels of ULK1 and BECN1 in gastric cancer tissues from 149 patients with TNM stages III and IV were measured by immunohistochemical staining. Both ULK1 and BECN1 were upregulated in gastric cancer. High expression of ULK1 and BECN1 were associated with older age and poor differentiation, respectively. In the univariate survival analysis, ULK1 and BECN1 expression were identified as predictors of poor prognosis. Only BECN1 expression was independently associated with poor prognosis in multivariate analysis. This association was significantly evident in cases who were older than 65 years, male, never smokers, drinkers, and those with poor differentiation or TNM stage III. Furthermore, the combined analysis revealed a significant cumulative effect on overall survival. Taken together, the expression levels of autophagy-related proteins could predict clinical benefit of fluoropyrimidine/platinum chemotherapy in patients with advanced gastric cancer.	[Xu, Yanchang; Pan, Guofeng; Li, Zhixiong; Lin, Linwen; Chen, Jian; Wu, Jihuang] Fujian Med Univ, Hosp Putian City 1, Dept Gastrointestinal Surg, Putian, Fujian, Peoples R China; [Huang, Yisen] Fujian Med Univ, Hosp Quanzhou 1, Dept Gastroenterol, Putian, Fujian, Peoples R China		Xu, YC (corresponding author), Fujian Med Univ, Hosp Putian City 1, Dept Gastrointestinal Surg, Putian, Fujian, Peoples R China.	cccxyc@163.com			Putian Science and Technology Agency, Fujian, China [2012 S01 (2)]	This study was supported by Research Fund of the Putian Science and Technology Agency, Fujian, China [grant No. 2012 S01 (2)].	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J. Clin. Exp. Pathol.		2016	9	3					3735	3742					8	Oncology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pathology	DO2FA	WOS:000377594100118					2022-04-25	
J	Han, Y; Zhou, SF; Wang, XY; Mao, EQ; Huang, L				Han, Yi; Zhou, Shaofei; Wang, Xiaoyan; Mao, Enqiang; Huang, Liang			SNHG14 stimulates cell autophagy to facilitate cisplatin resistance of colorectal cancer by regulating miR-186/ATG14 axis	BIOMEDICINE & PHARMACOTHERAPY			English	Article						CRC; SNHG14; miR-186; ATG14; Autophagy; Cisplatin resistance	LONG NONCODING RNA; PROLIFERATION; PROGRESSION; INVASION; PROMOTES	Colorectal cancer (CRC) is a malignant tumor with a high incidence and death rate in the world. Molecular interactions inside cells or tissues during tumor occurrence, development, and drug resistance are important for disease prevention and treatment. The long non-coding RNA SNHG14 has been proven to exert its oncogenic function in multiple cancers. However, there is no study regarding the role of SNHG14 in CRC research. In the present study, we applied RT-qPCR and western blot to determine the gene expression levels. MTT and TUNEL assays were used to detect cell proliferation and apoptosis rate. Cell migration and invasion abilities were determined by wound healing and transwell assays, respectively. StarBase was used to predict the potential binding sites and luciferase reporter assay was applied to confirm the direct interactions. Besides, we conducted a xenograft experiment to detect tumor growth rate in vivo. Our results showed that SNHG14 and ATG14 were both significantly higher in CRC tumor tissues than the normal ones, while miR-186 was decreased. The similar results were also observed in CRC cell lines. We confirmed that SNHG14 could directly interact with miR-186 and inhibited its expression. Meanwhile, miR-186 could directly bind ATG14 to inhibit its expression level. In vitro experiments showed that higher expression of SNHG14 led to higher cell proliferation, migration and invasion, while miR-186 significantly inhibited these tumor phenotypes. Furthermore, overexpression of ATG14 could strongly recover the CRC phenotypes attenuated by shSNHG14 or miR-186 mimics. Interestingly, we constructed cisplatin-resistant CRC cells and found that overexpression of ATG14 significantly enhanced the cell proliferation rate and inhibited cell apoptosis. Our research indicated that the novel axis of SNHG14/miR-186/ATG14 could play a vital role in regulating CRC cell progression. Moreover, this axis showed its clinical potential in regulating cisplatin resistance during CRC treatment.	[Han, Yi; Wang, Xiaoyan; Huang, Liang] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Traumatol, 197 RuiJin Second Rd, Shanghai 200025, Peoples R China; [Zhou, Shaofei] Qingdao Municipal Hosp, Dept Gen Surg, Qingdao, Shandong, Peoples R China; [Mao, Enqiang] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Emergency, Shanghai, Peoples R China		Huang, L (corresponding author), Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Traumatol, 197 RuiJin Second Rd, Shanghai 200025, Peoples R China.	liangh6522@126.com					Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Chen Y, 2014, CELL PROLIFERAT, V47, P105, DOI 10.1111/cpr.12095; Dong HY, 2018, INT J ONCOL, V53, P1013, DOI 10.3892/ijo.2018.4467; Dueland S, 2015, ANN SURG, V261, P956, DOI 10.1097/SLA.0000000000000786; Dyczynski M, 2018, CANCER LETT, V435, P32, DOI 10.1016/j.canlet.2018.07.028; Fang CY, 2017, CANCER LETT, V410, P50, DOI 10.1016/j.canlet.2017.09.012; Gonzalez R, 2005, SURG ENDOSC, V19, P43, DOI 10.1007/s00464-003-8207-9; Ji NN, 2019, PATHOL RES PRACT, V215, P668, DOI 10.1016/j.prp.2018.12.026; Kramer N, 2013, MUTAT RES-REV MUTAT, V752, P10, DOI 10.1016/j.mrrev.2012.08.001; Lambert JM, 2018, ANNU REV MED, V69, P191, DOI 10.1146/annurev-med-061516-121357; Li B, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0439-7; Li CF, 2017, BIOCHEM BIOPH RES CO, V491, P552, DOI 10.1016/j.bbrc.2017.03.042; Li G, 2018, J CELL MOL MED, V22, P5565, DOI 10.1111/jcmm.13830; Li JL, 2018, ARCH BIOCHEM BIOPHYS, V640, P53, DOI 10.1016/j.abb.2018.01.002; Liao R, 2018, J GASTROINTEST SURG, V22, P1679, DOI 10.1007/s11605-018-3810-1; Liu Z, 2018, J CELL BIOCHEM, V119, P6905, DOI 10.1002/jcb.26889; Lu DF, 2018, CELL PHYSIOL BIOCHEM, V48, P2517, DOI 10.1159/000492690; Ma T, 2018, CANCER LETT, V436, P129, DOI 10.1016/j.canlet.2018.08.010; Ouyang L, 2012, CELL PROLIFERAT, V45, P487, DOI 10.1111/j.1365-2184.2012.00845.x; Riss T. L., 2016, CELL VIABILITY ASSAY; Shenouda SK, 2009, CANCER METAST REV, V28, P369, DOI 10.1007/s10555-009-9188-5; Song H, 2017, J BUON, V22, P696; Sui X, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.350; Wild AT, 2017, VISC MED, V33, P54, DOI 10.1159/000454685; Wu K, 2019, BIOMED PHARMACOTHER, V116, DOI 10.1016/j.biopha.2019.108995; Xi ZW, 2019, INT J ONCOL, V54, P239, DOI 10.3892/ijo.2018.4609; Xie SD, 2019, EUR REV MED PHARMACO, V23, P2461, DOI 10.26355/eurrev_201903_17393; Yang GD, 2014, BBA-GENE REGUL MECH, V1839, P1097, DOI 10.1016/j.bbagrm.2014.08.012; Yin QQ, 2018, BIOSCIENCE REP, V38, DOI 10.1042/BSR20180516; Zhang JJ, 2019, J HIGH ENERGY PHYS, DOI 10.1007/JHEP02(2019)007; Zhang XF, 2019, BIOCHEM BIOPH RES CO, V510, P508, DOI 10.1016/j.bbrc.2019.01.109; Zhang Y, 2018, ONCOL LETT, V15, P6336, DOI 10.3892/ol.2018.8127; Zhang Zhiqiang, 2019, Cell Physiol Biochem, V52, P553, DOI 10.33594/000000039; Zhou JJ, 2017, MOL MED REP, V16, P4980, DOI 10.3892/mmr.2017.7162	34	20	20	1	8	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.	JAN	2020	121								109580	10.1016/j.biopha.2019.109580			8	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	JT1GJ	WOS:000500746200044	31704614	gold			2022-04-25	
J	Zhao, GT; Wang, YJ; Yang, CQ; Zhao, L; Guo, LL; Li, LM; Wei, ZB				Zhao, Ganting; Wang, Yanjing; Yang, Changqing; Zhao, Li; Guo, Lili; Li, Lingmin; Wei, Zibai			Interplay Between Autophagy and Apoptosis in Lycorine Hydrochloride-Induced Cytotoxicity of HCT116 Cells	NATURAL PRODUCT COMMUNICATIONS			English	Article						lycorine hydrochloride; apoptosis; autophagy; colorectal cancer; interplay	CANCER	The aim of this study was to investigate the antitumor effect of lycorine hydrochloride (LH) and discuss the correlation between LH-induced apoptosis and autophagy in the human colorectal cancer cell line HCT116. Here the results by the Cell Counting Kit-8 and colony formation assays showed that LH concentration-dependently decreased cell viability and colony formation in HCT116 cells, suggesting inhibition of cell proliferation by LH. By flow cytometry, LH was found to increase apoptotic rate in HCT116 cells. Mechanistically, Western blot results revealed that LH increased the expression of the protein of Bax and Caspase-3, and decreased Bcl-2 proteins expression. Moreover, the reverse transcriptase quantitative polymerase chain reaction and Western blot analysis also showed that LH increased the expression of Beclin-1 and LC3B-II/LC3B-I ratio, indicating that autophagy was induced by LH. LH induced autophagy via downregulating phospho-mammalian target of rapamycin and upregulating phospho-AMPK (5 ' adenosine monophosphate-activated protein kinase). Furthermore, to understand the role of LH-induced autophagy and its association with apoptosis, cells were analyzed after Beclin-1 small interfering RNA transfection. The results indicated that the proapoptotic ability of LH was increased by inhibition of autophagy. In conclusion, the present investigation suggested that LH induced apoptosis and autophagy in HCT116 cells via the mitochondrial and AMPK/mTOR pathways. The suppression of autophagy promoted LH-induced apoptosis by modulating Beclin-1 and Bcl-2.	[Zhao, Ganting; Yang, Changqing; Zhao, Li; Guo, Lili; Wei, Zibai] Changzhi Med Coll, Heping Hosp, Dept Gastroenterol & Hepatol, 100 South Yanan Rd, Changzhi 046000, Peoples R China; [Wang, Yanjing] Capital Med Univ, Beijing Anzhen Hosp, Dept Ultrasound, Beijing, Peoples R China; [Li, Lingmin] Shanxi Med Univ, Dept Pathol, Taiyuan, Shanxi, Peoples R China		Wei, ZB (corresponding author), Changzhi Med Coll, Heping Hosp, Dept Gastroenterol & Hepatol, 100 South Yanan Rd, Changzhi 046000, Peoples R China.	15914308560@163.com					Booth LA, 2014, CELL SIGNAL, V26, P549, DOI 10.1016/j.cellsig.2013.11.028; Cerella C, 2014, BIOTECHNOL ADV, V32, P1111, DOI 10.1016/j.biotechadv.2014.03.006; Cimmino A, 2017, CHIRALITY, V29, P486, DOI 10.1002/chir.22719; Cui YQ, 2018, BIOCHEM BIOPH RES CO, V497, P916, DOI 10.1016/j.bbrc.2017.12.144; Ji YB, 2017, SAUDI PHARM J, V25, P633, DOI 10.1016/j.jsps.2017.04.036; Jiang HB, 2010, BIOCHEM BIOPH RES CO, V395, P471, DOI 10.1016/j.bbrc.2010.04.030; Lamoral-Theys D, 2009, J MED CHEM, V52, P6244, DOI 10.1021/jm901031h; Li BW, 2017, CANCER LETT, V410, P212, DOI 10.1016/j.canlet.2017.09.035; Li JZ, 2016, SCI REP-UK, V6, DOI 10.1038/srep23975; Ludmir EB, 2017, CANCER-AM CANCER SOC, V123, P1497, DOI 10.1002/cncr.30600; Mukhopadhyay S, 2014, APOPTOSIS, V19, P555, DOI 10.1007/s10495-014-0967-2; Nair JJ, 2014, NAT PROD COMMUN, V9, P1193; Roy M, 2016, THERANOSTICS, V6, P2209, DOI 10.7150/thno.15584; Sui X, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.350; Wang CS, 2017, BIOCHEM BIOPH RES CO, V483, P197, DOI 10.1016/j.bbrc.2016.12.168; Wang Q, 2018, TOXICOL LETT, V289, P28, DOI 10.1016/j.toxlet.2018.03.002; White E, 2015, CLIN CANCER RES, V21, P5037, DOI 10.1158/1078-0432.CCR-15-0490; Ying XX, 2017, SCI CHINA LIFE SCI, V60, P417, DOI 10.1007/s11427-016-0368-y; Yu HY, 2017, MOL CANCER THER, V16, P2711, DOI 10.1158/1535-7163.MCT-17-0498; Zeng H, 2017, MED SCI MONITOR, V23, P2035, DOI 10.12659/MSM.900742; Zerillo JA, 2017, JAMA ONCOL, V3, P686, DOI 10.1001/jamaoncol.2017.0417; Zhang XY, 2018, APPL MICROBIOL BIOT, V102, P6503, DOI 10.1007/s00253-018-9069-3	22	1	1	0	2	SAGE PUBLICATIONS INC	THOUSAND OAKS	2455 TELLER RD, THOUSAND OAKS, CA 91320 USA	1934-578X	1555-9475		NAT PROD COMMUN	Nat. Prod. Commun.	JUL	2019	14	7								10.1177/1934578X19862100			7	Chemistry, Medicinal; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy; Food Science & Technology	IM5OZ	WOS:000478044500023		hybrid			2022-04-25	
J	Wang, YH; Feng, L; Piao, BK; Zhang, PT				Wang, Yaohan; Feng, Li; Piao, Bingkui; Zhang, Peitong			Review on Research about Traditional Chinese Medicine in Cancer Stem Cell	EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE			English	Review							BUFALIN-INDUCED APOPTOSIS; ACUTE MYELOID-LEUKEMIA; TZE HUANG SUPPRESSES; COLORECTAL-CANCER; PROLIFERATION; AUTOPHAGY; ACTIVATION; MECHANISMS; STAT3; MODEL	Cancer stem cells (CSCs) are small subpopulations of neoplastic cells within a tumor, which have self-renewal and differentiation abilities and could generate new tumors with few cells. Researches have showed that CSCs are considered the most likely reason for cancer recurrence and metastasis. Accumulating evidences have showed that traditional Chinese medicine (TCM) has significant effect on CSCs. It could inhibit the proliferation, self-renew, and multidifferentiation of CSCs. We aimed to summarize the theories of CSCs in TCM, the inhibitory effect, and the pathway on CSCs of TCM. This review will provide potential new strategies and alternative perspectives for CSCs treatments and basic research into complementary and alternative medicine.	[Wang, Yaohan; Piao, Bingkui; Zhang, Peitong] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, 5 Beixiange, Beijing 100053, Peoples R China; [Feng, Li] Chinese Acad Med Sci, Canc Hosp, Natl Canc Ctr, Tradit Chinese Med Dept, Beijing 100021, Peoples R China; [Feng, Li] Peking Union Med Coll, Beijing 100021, Peoples R China		Piao, BK; Zhang, PT (corresponding author), China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, 5 Beixiange, Beijing 100053, Peoples R China.; Feng, L (corresponding author), Chinese Acad Med Sci, Canc Hosp, Natl Canc Ctr, Tradit Chinese Med Dept, Beijing 100021, Peoples R China.; Feng, L (corresponding author), Peking Union Med Coll, Beijing 100021, Peoples R China.	fengli663@126.com; piaobingkui123@163.com; drzhangpeitong@hotmail.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81173450]	This work was supported by National Natural Science Foundation of China (no. 81173450).	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T., 2012, STUDY EFFECT 5 KINDS; Zhang Y., 2009, CHINA ACAD CHINESE M, V4; Zhang Y. R., 2014, BEIJING U CHINESE TR; Zheng J., 2011, CELLULAR MOL BIOL CA, P150; Zhou BBS, 2009, NAT REV DRUG DISCOV, V8, P806, DOI 10.1038/nrd2137; Zhou QM, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0136694; Zhuang QC, 2012, INT J ONCOL, V40, P1569, DOI 10.3892/ijo.2012.1326; 颜兵, 2012, [中国中医药信息杂志, Chinese Journal of Information on Traditional Chinese Medicine], V19, P93	92	2	2	0	12	HINDAWI LTD	LONDON	ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, W1T 5HF, ENGLAND	1741-427X	1741-4288		EVID-BASED COMPL ALT	Evid.-based Complement Altern. Med.		2017	2017								4505194	10.1155/2017/4505194			10	Integrative & Complementary Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine	FI7AT	WOS:000412148700001	29234398	Green Published, gold			2022-04-25	
J	Zhou, Z; Mo, SB; Dai, WX; Ying, Z; Zhang, L; Xiang, WA; Han, LY; Wang, ZM; Li, QG; Wang, RJ; Cai, GX				Zhou, Zheng; Mo, Shaobo; Dai, Weixing; Ying, Zhen; Zhang, Long; Xiang, Wengiang; Han, Lingyu; Wang, Zhimin; Li, Qingguo; Wang, Renjie; Cai, Guoxiang			Development and Validation of an Autophagy Score Signature for the Prediction of Post-operative Survival in Colorectal Cancer	FRONTIERS IN ONCOLOGY			English	Article						colorectal cancer; early relapse; autophagy; signature; nomogram	EARLY RELAPSE; GENE SIGNATURE; STAGES II; STATISTICS; POLYMORPHISMS	Background: Survival rates for Colorectal cancer (CRC) patients who experienced early relapse have usually been relatively low. Our study aims at developing an autophagy signature that could help to detect early relapse cases in CRC. Methods: Propensity score matching analysis was carried out between patients from the early relapse group and the long-term survival group from GSE39582. For both groups, respectively, global autophagy expression changes were then analyzed to identify the differentially expressed prognostic autophagy related genes by conducting Linear Models for Microarray data method analysis. Then, the multi-gene signature was validated in TCGA and Fudan University Shanghai Cancer Center (FUSCC) cohorts. Time-dependent ROC were used to test the efficiency of this signature feature in predicting the prognosis of CRC patients. Results: 5 autophagy genes were finally identified to build an early relapse classifier. With specific risk score formula, patients were classified into low- or high-risk group. Time-dependent ROC analyses proved its prognostic accuracy, with AUC 0.841 and 0.803 at 1 and 3 years, respectively. Then, we validated its prognostic value in two external validation series (GSE17538 and GSE33113) and proved that the result is indeed significant irrespective of datasets in two external independent validation cohorts (TCGA and FUSCC cohorts). A nomogram was constructed to guide individualized treatment of patients with CRC. Conclusions: The identification of robust autophagy-related features can effectively classify CRC patients into groups with low and high risk of early relapse. This signature may be used to help select high-risk CRC patients who require more aggressive treatment interventions.	[Zhou, Zheng; Mo, Shaobo; Dai, Weixing; Ying, Zhen; Zhang, Long; Xiang, Wengiang; Han, Lingyu; Li, Qingguo; Wang, Renjie; Cai, Guoxiang] Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai, Peoples R China; [Zhou, Zheng; Mo, Shaobo; Dai, Weixing; Ying, Zhen; Xiang, Wengiang; Han, Lingyu; Li, Qingguo; Wang, Renjie; Cai, Guoxiang] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China; [Zhang, Long] Fudan Univ, Dept Canc Inst, Shanghai Canc Ctr, Shanghai, Peoples R China; [Wang, Zhimin] Shanghai Ind Technol Inst, Shanghai MOST Key Lab Hlth & Dis Genom, Chinese Natl Human Genome Ctr, Shanghai, Peoples R China		Li, QG; Wang, RJ; Cai, GX (corresponding author), Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai, Peoples R China.; Li, QG; Wang, RJ; Cai, GX (corresponding author), Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China.	oncosurgeonli@sohu.com; wangbladejay@sina.com; gxcaifuscc@163.com			National Key R&D Program of China [2016YFC0905300, 2016YFC0905301]; Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [16401970502]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572351]; Shanghai Shenkang Program [SHDC12014206]; development fund for Shanghai talents [2017120]; FDUROP (Fudan's Undergraduate Research Opportunities Program) [18097]	The present study was supported by the National Key R&D Program of China (Nos. 2016YFC0905300 and 2016YFC0905301), the Grant of Science and Technology Commission of Shanghai Municipality (No. 16401970502), the Grant of National Natural Science Foundation of China (No. 81572351), Shanghai Shenkang Program (No. SHDC12014206), the development fund for Shanghai talents (No. 2017120), and FDUROP (Fudan's Undergraduate Research Opportunities Program) (No. 18097).	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J	Ito, C; Matsui, T; Takano, M; Wu, TS; Itoigawa, M				Ito, Chihiro; Matsui, Takuya; Takano, Makiko; Wu, Tian-Shung; Itoigawa, Masataka			Anti-cell proliferation effect of naphthoquinone dimers isolated from Plumbago zeylanica	NATURAL PRODUCT RESEARCH			English	Article						Plumbago zeylanica; Plumbaginaceae; naphthoquinones; cell proliferation; cell cycle	CANCER CELLS; APOPTOSIS; AUTOPHAGY; CONSTITUENTS; PATHWAYS; ARREST; CYCLE	Study of the chemical constituents of the roots of Plumbago zeylanica L. collected in Taiwan led to the isolation and identification of a new naphthoquinone dimer, plumzeylanone (1), along with eight known compounds (2-9). Nine naphthoquinones isolated from this plant were assayed for cell growth inhibition activity using NALM-6 (human B cell precursor leukaemia), A549 (human lung adenocarcinoma), Colo205 (human colorectal adenocarcinoma) and KB (human epidermoid carcinoma). Plumzeylanone (1), a novel plumbagin dimer, suppressed cell proliferation in only NALM-6 cells (IC50 3.98M). However, maritinone (9) showed strong inhibition of cell growth in all cell lines tested (0.12<IC50<9.06M). This compound appeared to affect the cell cycle. [GRAPHICS] .	[Ito, Chihiro; Matsui, Takuya; Takano, Makiko] Meijo Univ, Fac Pharm, Tempaku, Japan; [Matsui, Takuya] Aichi Med Univ, Dept Physiol, Nagakute, Aichi, Japan; [Wu, Tian-Shung] Natl Cheng Kung Univ, Dept Chem, Tainan, Taiwan; [Itoigawa, Masataka] Tokai Gakuen Univ, Sch Sport & Hlth Sci, Miyoshi, Japan		Matsui, T (corresponding author), Meijo Univ, Fac Pharm, Tempaku, Japan.; Matsui, T (corresponding author), Aichi Med Univ, Dept Physiol, Nagakute, Aichi, Japan.	tmatsui@aichi-med-u.ac.jp			JSPS KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [17K08353]	This work was supported by JSPS KAKENHI [grant number 17K08353].	Bae KJ, 2016, BIOCHEM BIOPH RES CO, V473, P272, DOI 10.1016/j.bbrc.2016.03.092; BINDER RG, 1989, PHYTOCHEMISTRY, V28, P2799, DOI 10.1016/S0031-9422(00)98092-0; Bringmann G, 1999, PHYTOCHEMISTRY, V51, P693, DOI 10.1016/S0031-9422(99)00080-1; Demma J, 2009, TOXICOL IN VITRO, V23, P266, DOI 10.1016/j.tiv.2008.12.007; Feng S, 2016, NAT PROD RES, P1; Gu JQ, 2004, J NAT PROD, V67, P1156, DOI 10.1021/np040027m; GUNAHERATH GMKB, 1983, PHYTOCHEMISTRY, V22, P1245, DOI 10.1016/0031-9422(83)80232-5; Kawamura F, 2010, BIOL PHARM BULL, V33, P881, DOI 10.1248/bpb.33.881; Li YC, 2014, CANCER LETT, V344, P239, DOI 10.1016/j.canlet.2013.11.001; Maruo S, 2013, ORG LETT, V15, P1556, DOI 10.1021/ol400335s; Mishra BB, 2013, NAT PROD RES, V27, P480, DOI 10.1080/14786419.2012.696254; Pan ST, 2015, DRUG DES DEV THER, V9, P1601, DOI 10.2147/DDDT.S76057; Qiu JX, 2015, DRUG DES DEV THER, V9, P349, DOI 10.2147/DDDT.S71677; Reshma RS, 2016, PHARMACOL RES, V105, P134, DOI 10.1016/j.phrs.2016.01.012; SANKARAM AVB, 1979, TETRAHEDRON, V35, P1777, DOI 10.1016/0040-4020(79)88008-4; Sunil C, 2012, FOOD CHEM TOXICOL, V50, P4356, DOI 10.1016/j.fct.2012.08.046; Wang F, 2015, DRUG DES DEV THER, V9, P537, DOI 10.2147/DDDT.S73689; Xue YL, 2016, ONCOL LETT, V12, P1095, DOI 10.3892/ol.2016.4725	18	2	3	1	15	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	18					2127	2132		10.1080/14786419.2017.1366476			6	Chemistry, Applied; Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	GP7EW	WOS:000441057100001	28823173				2022-04-25	
J	Vania, L; Morris, G; Ferreira, E; Weiss, SFT				Vania, Leila; Morris, Gavin; Ferreira, Eloise; Weiss, Stefan F. T.			Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells	BMC CANCER			English	Article						Colorectal cancer; Small interfering RNAs; Apoptosis; 37 kDa/67 kDa laminin receptor; LRP/LR; Telomerase; Proteomics; Therapeutics		Background The 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in several tumourigenic-promoting processes including cellular viability maintenance and apoptotic evasion. Thus, the aim of this study was to assess the molecular mechanism of LRP/LR on apoptotic pathways in late stage (DLD-1) colorectal cancer cells upon siRNA-mediated down-regulation of LRP/LR. Methods siRNAs were used to down-regulate the expression of LRP/LR in DLD-1 cells which was assessed using western blotting and qPCR. To evaluate the mechanistic role of LRP/LR, proteomic analysis of pathways involved in proliferation and apoptosis were investigated. The data from the study was analysed using a one-way ANOVA, followed by a two-tailed student's t-test with a confidence interval of 95%. Results Here we show that knock-down of LRP/LR led to significant changes in the proteome of DLD-1 cells, exposing new roles of the protein. Moreover, analysis showed that LRP/LR may alter components of the MAPK, p53-apoptotic and autophagic signalling pathways to aid colorectal cancer cells in continuous growth and survival. Knock-down of LRP/LR also resulted in significant decreases in telomerase activity and telomerase-related proteins in the DLD-1 cells. Conclusions These findings show that LRP/LR is critically implicated in apoptosis and cell viability maintenance and suggest that siRNA-mediated knock-down of LRP/LR may be a possible therapeutic strategy for the treatment of colorectal cancer.	[Vania, Leila; Morris, Gavin; Ferreira, Eloise; Weiss, Stefan F. T.] Univ Witwatersrand, Sch Mol & Cell Biol, Private Bag 3, ZA-2050 Johannesburg, South Africa		Weiss, SFT (corresponding author), Univ Witwatersrand, Sch Mol & Cell Biol, Private Bag 3, ZA-2050 Johannesburg, South Africa.	stefan.weiss@wits.ac.za			National Research Foundation (NRF), the Republic of South Africa (RSA) [99061, 92745, 109298]; South African Medical Research Council (MRC) under the Wits Common Epithelial Cancer Research Centre (CECRC) grant; Cancer Association of South Africa (CANSA)	This work is based upon research supported by the National Research Foundation (NRF), the Republic of South Africa (RSA). Grant Numbers 99061, 92745 and 109298. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s), and therefore, the National Research Foundation does not accept any liability in this regard thereto. Financial support was received from the South African Medical Research Council (MRC) under the Wits Common Epithelial Cancer Research Centre (CECRC) grant. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s), and therefore, the MRC does not accept any liability in this regard thereto. Financial support was further received from the Cancer Association of South Africa (CANSA). Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s), and therefore, CANSA does not accept any liability in this regard thereto.	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J	Zhu, QY; Meng, YX; Li, SW; Xin, JY; Du, ML; Wang, ML; Cheng, G				Zhu, Qiuyuan; Meng, Yixuan; Li, Shuwei; Xin, Junyi; Du, Mulong; Wang, Meilin; Cheng, Gong			Association of genetic variants in autophagy-lysosome pathway genes with susceptibility and survival to prostate cancer	GENE			English	Article						SLC11A1; Single nucleotide polymorphism; Risk; Prognosis	ACTIVE SURVEILLANCE; RISK; SLC11A1; POLYMORPHISMS; BIOMARKERS; TRANSPORT; MANGANESE; DISEASE	Background: Previous studies have indicated the connections between autophagy-lysosome pathway genes dysfunction and prostate cancer, but few studies have investigated whether single nucleotide polymorphisms (SNPs) in autophagy-lysosome pathway genes are implicated in prostate cancer risk and survival. Materials and methods: Logistic regression analysis and stepwise Cox regression analysis were conducted in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The false positive rate probability (FPRP) method was applied to correct for multiple comparisons. Gene-based analysis was calculated by versatile gene-based association study approach. Results: We found that SLC11A1 rs7573065 significantly increased the risk of prostate cancer [adjusted odds ratio (OR) = 1.24, 95% confidence interval (CI) = 1.06-1.46, P = 7.02 x 10(-3), FPRP = 0.082]. Furthermore, rs7573065 was confirmed as the independent predicator of overall survival (OS) for prostate cancer patients [Hazard ratio (HR) = 1.30, 95% CI = 1.01-1.66, P = 0.041]. The significant association between SLC11A1 and prostate cancer risk was calculated by gene-based analysis (P = 0.030). We also observed that the mRNA of SLC11A1 in prostate tumor tissues was significantly over-expressed than that in normal tissues. Conclusion: This study suggested that rs7573065 in SLC11A1 was associated with an increased risk and poor OS of prostate cancer. Our findings may provide evidence for genetic variants in autophagy-lysosome pathway as the risk and prognostic biomarkers for prostate cancer.	[Zhu, Qiuyuan; Cheng, Gong] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing, Peoples R China; [Zhu, Qiuyuan; Meng, Yixuan; Li, Shuwei; Xin, Junyi; Wang, Meilin] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Genet Toxicol,Key Lab Modern Toxicol,Minist, Nanjing, Peoples R China; [Du, Mulong] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, Nanjing, Peoples R China		Cheng, G (corresponding author), Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing, Peoples R China.	gcheng@njmu.edu.cn					Ballabio A, 2020, NAT REV MOL CELL BIO, V21, P101, DOI 10.1038/s41580-019-0185-4; Blessing AM, 2017, AUTOPHAGY, V13, P506, DOI 10.1080/15548627.2016.1268300; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Cao DL, 2020, CANCER MED-US, V9, P9462, DOI 10.1002/cam4.3538; Chistiakov DA, 2018, SEMIN CANCER BIOL, V52, P9, DOI 10.1016/j.semcancer.2018.01.012; Cucchiara V, 2018, EUR UROL, V73, P572, DOI 10.1016/j.eururo.2017.10.036; Culp MB, 2020, EUR UROL, V77, P38, DOI 10.1016/j.eururo.2019.08.005; Cuzick J, 2014, LANCET ONCOL, V15, pE484, DOI 10.1016/S1470-2045(14)70211-6; de la Rosa J, 2017, NAT GENET, V49, P730, DOI 10.1038/ng.3817; Farrow JM, 2014, NAT REV UROL, V11, P508, DOI 10.1038/nrurol.2014.196; Fenton JJ, 2018, JAMA-J AM MED ASSOC, V319, P1914, DOI 10.1001/jama.2018.3712; Forbes JR, 2003, BLOOD, V102, P1884, DOI 10.1182/blood-2003-02-0425; Forbes JR, 2001, TRENDS MICROBIOL, V9, P397, DOI 10.1016/S0966-842X(01)02098-4; Galluzzi L, 2014, CELL, V159, P1263, DOI 10.1016/j.cell.2014.11.006; GAO X, 1995, CANCER RES, V55, P1002; Gohagan JK, 2015, REV RECENT CLIN TRIA, V10, P173, DOI 10.2174/1574887110666150730123004; Hu DX, 2020, J TRANSL MED, V18, DOI 10.1186/s12967-020-02323-x; Huang CY, 2015, SCI REP-UK, V5, DOI 10.1038/srep14045; Islami F, 2014, EUR UROL, V66, P1054, DOI 10.1016/j.eururo.2014.08.059; Jabado N, 2000, J EXP MED, V192, P1237, DOI 10.1084/jem.192.9.1237; Jiang PD, 2014, CELL RES, V24, P69, DOI 10.1038/cr.2013.161; Klotz L, 2014, CURR OPIN UROL, V24, P270, DOI 10.1097/MOU.0000000000000055; Leongamornlert DA, 2019, EUR UROL, V76, P329, DOI 10.1016/j.eururo.2019.01.050; Levine B, 2019, CELL, V176, P11, DOI 10.1016/j.cell.2018.09.048; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Li WQ, 2018, EUR UROL, V74, P710, DOI 10.1016/j.eururo.2018.06.021; Liu JZ, 2010, AM J HUM GENET, V87, P139, DOI 10.1016/j.ajhg.2010.06.009; Loeb S, 2015, EUR UROL, V67, P619, DOI 10.1016/j.eururo.2014.10.010; Perera R, 2015, NATURE, V524, P361, DOI 10.1038/nature14587; Pernar CH, 2018, CSH PERSPECT MED, V8, DOI 10.1101/cshperspect.a030361; Romero-Gomez M, 2004, GUT, V53, P446, DOI 10.1136/gut.2003.028274; Schumacher FR, 2018, NAT GENET, V50, P928, DOI 10.1038/s41588-018-0142-8; Shui IM, 2014, EUR UROL, V65, P1069, DOI 10.1016/j.eururo.2013.12.058; Siegel RL, 2016, CA-CANCER J CLIN, V66, P7, DOI 10.3322/caac.21332; Tan J, 2018, INT J CANCER, V143, P80, DOI 10.1002/ijc.31288; Tangen CM, 2016, J CLIN ONCOL, V34, P4338, DOI 10.1200/JCO.2016.68.1965; Tryka KA, 2014, NUCLEIC ACIDS RES, V42, pD975, DOI 10.1093/nar/gkt1211; Wacholder S, 2004, J NATL CANCER I, V96, P434, DOI 10.1093/jnci/djh075; Yang JHM, 2011, BMC MED GENET, V12, DOI 10.1186/1471-2350-12-59; Yang L, 2016, J CLIN ONCOL, V34, P4231, DOI 10.1200/JCO.2016.68.4837; Yeager M, 2007, NAT GENET, V39, P645, DOI 10.1038/ng2022; Yu L, 2018, ONCOL LETT, V15, P9413, DOI 10.3892/ol.2018.8504; Zaahl MG, 2005, CANCER GENET CYTOGEN, V159, P48, DOI 10.1016/j.cancergencyto.2004.09.017; Zaahl MG, 2004, BLOOD CELL MOL DIS, V33, P45, DOI 10.1016/j.bcmd.2004.04.003; Zaahl MG, 2006, INT J COLORECTAL DIS, V21, P402, DOI 10.1007/s00384-005-0019-z; Zhu XY, 2012, EUR UROL, V61, P652, DOI 10.1016/j.eururo.2011.11.029	46	0	0	9	9	ELSEVIER	AMSTERDAM	RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS	0378-1119	1879-0038		GENE	Gene	JAN 15	2022	808								145953	10.1016/j.gene.2021.145953		OCT 2021	8	Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Genetics & Heredity	WG2VH	WOS:000706854800001	34500048				2022-04-25	
J	Zhang, HS; Xu, G; Wu, SH; Gong, L; Zhou, YY; Li, XM				Zhang, Haosheng; Xu, Gang; Wu, Shihai; Gong, Long; Zhou, Yayan; Li, Xianming			THE MECHANISM OF CAIX IN TUMOR THERAPY AND ITS INFLUENCE ON PATIENT PROGNOSIS	ACTA MEDICA MEDITERRANEA			English	Article						Carbonic anhydrase IX (CAIX); PH; radiosensitivity; chemotherapy sensitivity	CARBONIC-ANHYDRASE IX; CARCINOMA-CELL LINE; ENHANCES RADIOSENSITIVITY; CANCER-THERAPY; AUTOPHAGY; HYPOXIA; ACIDITY; TARGET	The carbonic anhydrase IX (CAIX) family (originally named MN/G250) is a type of zinc-containing metalloenzyme family of cell surface transmembrane protein v. Many studies worldwide have demonstrated that CAIX is a protease that rapidly converts CO2 and H2O into H+ and HCO3-. its main mechanism in cells is to act as a "proton pump" in similar cells to maintain the weak alkalinity and extracelltdar acidic microenvironment of tumour cells. The positive expression of CAIX protein can be detected in trimly tumours such as nasopharyngeal carcinoma, cervical cancer, breast cancer, rectal cancer and gastric cancer, and is related to the occurrence and development of the tumour as well as the therapeutic effect and prognosis of patients. Therefore, the mechanism of CAIX in rumour cells is described in this paper, and the relationship between the expression of CAIX in cells and tumour treatment and prognosis is also discussed.	[Zhang, Haosheng; Xu, Gang; Wu, Shihai; Gong, Long; Zhou, Yayan; Li, Xianming] Southern Univ Sci & Technol, Affiliated Hosp 1, Clin Med Coll 2, Dept Radiat Oncol,Shenzhen Peoples Hosp,Jinan Uni, Shenzhen 518020, Guangdong, Peoples R China		Li, XM (corresponding author), Southern Univ Sci & Technol, Affiliated Hosp 1, Clin Med Coll 2, Dept Radiat Oncol,Shenzhen Peoples Hosp,Jinan Uni, Shenzhen 518020, Guangdong, Peoples R China.	lxm1828@hotmail.com					Andersen CJ, 2018, NUTRIENTS, V10, DOI 10.3390/nu10060764; Aspatwar A, 2018, J ENZYM INHIB MED CH, V33, P1064, DOI 10.1080/14756366.2018.1482285; Chen Xinwei, 2016, Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, V30, P42; Chen YH, 2014, MED ONCOL, V31, DOI 10.1007/s12032-014-0304-1; Denoyer D, 2015, METALLOMICS, V7, P1459, DOI 10.1039/c5mt00149h; Huber V, 2017, SEMIN CANCER BIOL, V43, P74, DOI 10.1016/j.semcancer.2017.03.001; Huizing FJ, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-54824-5; Hussein EM, 2019, BMC CHEM, V13, DOI 10.1186/s13065-019-0603-x; Jan YH, 2019, J HEMATOL ONCOL, V12, DOI 10.1186/s13045-019-0698-5; Jiang LJ, 2017, ONCOTARGETS THER, V10, P4701, DOI 10.2147/OTT.S144756; Khoshinani HM, 2016, CANCER INVEST, V34, P536, DOI 10.1080/07357907.2016.1245317; Kim BR, 2012, CELL SIGNAL, V24, P1406, DOI 10.1016/j.cellsig.2012.03.002; Kim SR, 2016, INT J RADIAT BIOL, V92, P502, DOI 10.1080/09553002.2016.1206222; Kopecka J, 2016, ONCOTARGET, V7, P85861, DOI 10.18632/oncotarget.13040; Lacroix R, 2018, CANCER IMMUNOL IMMUN, V67, P1331, DOI 10.1007/s00262-018-2195-z; Lai E, 2019, CANCER TREAT REV, V81, DOI 10.1016/j.ctrv.2019.101926; Lee CT, 2014, ANTIOXID REDOX SIGN, V21, P313, DOI 10.1089/ars.2013.5759; Luo YT, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-11500-6; McDonald PC, 2019, GASTROENTEROLOGY, V157, P823, DOI 10.1053/j.gastro.2019.05.004; Najy AJ, 2016, AM J PHYSIOL-CELL PH, V310, pC293, DOI 10.1152/ajpcell.00043.2015; Pastorek J, 2015, SEMIN CANCER BIOL, V31, P52, DOI 10.1016/j.semcancer.2014.08.002; Pellegrini P, 2016, ONCOTARGET, V7, P35703, DOI 10.18632/oncotarget.9601; Pilon-Thomas S, 2016, CANCER RES, V76, P1381, DOI 10.1158/0008-5472.CAN-15-1743; Rabiee S, 2019, J CELL PHYSIOL, V234, P12061, DOI 10.1002/jcp.27876; Ren JL, 2018, DIAGN PATHOL, V13, DOI 10.1186/s13000-018-0708-x; Rzepakowska A, 2019, EUR ARCH OTO-RHINO-L, V276, P1; Salaroglio IC, 2018, MOL CANCER THER, V17, P2598, DOI 10.1158/1535-7163.MCT-18-0533; Song JR, 2017, CELL DEATH DISCOV, V3, DOI 10.1038/cddiscovery.2017.68; Suresh PK, 2017, ACTA CYTOL, V61, P199, DOI 10.1159/000471916; Takacova M, 2013, ONCOL LETT, V5, P191, DOI 10.3892/ol.2012.1001; Tang M, 2020, ARTIF CELL NANOMED B, V48, P159, DOI 10.1080/21691401.2019.1699822; Taylor MA, 2018, APOPTOSIS, V23, P563, DOI 10.1007/s10495-018-1480-9; Tsai MM, 2014, WORLD J GASTROENTERO, V20, P13791, DOI 10.3748/wjg.v20.i38.13791; von Neubeck B, 2018, INT J CANCER, V143, P2065, DOI 10.1002/ijc.31607; Wachters JE, 2013, LARYNGOSCOPE, V123, P2154, DOI 10.1002/lary.23831; Waheed A, 2017, GENE, V623, P33, DOI 10.1016/j.gene.2017.04.027; Wang F, 2018, CELL PHYSIOL BIOCHEM, V45, P54, DOI 10.1159/000486222; Wang W, 2016, EUR REV MED PHARMACO, V20, P92; Wang YS, 2014, ACTA OTO-LARYNGOL, V134, P105, DOI 10.3109/00016489.2013.844365; Ward C, 2018, METABOLITES, V8, DOI 10.3390/metabo8010013; Webb BA, 2011, NAT REV CANCER, V11, P671, DOI 10.1038/nrc3110; Wu T, 2017, CANCER LETT, V387, P61, DOI 10.1016/j.canlet.2016.01.043; Xin Y, 2017, J CANCER RES CLIN, V143, P2147, DOI 10.1007/s00432-017-2487-2; Xu H, 2018, COMPR PHYSIOL, V8, P555, DOI 10.1002/cphy.c170027; Zhou H, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-017-19069-0	45	0	0	3	4	CARBONE EDITORE	PALERMO	VIA QUINTINO SELLA, 68, PALERMO, 90139, ITALY	0393-6384	2283-9720		ACTA MEDICA MEDITERR	Acta Medica Mediterr.		2020	36	6					3661	3667		10.19193/0393-6384_2020_6_580			7	Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine	PE6WK	WOS:000598504300079					2022-04-25	
J	Huang, YY; Du, J; Mi, Y; Li, TY; Gong, Y; Ouyang, HS; Hou, Y				Huang, Yongye; Du, Juan; Mi, Yan; Li, Tianye; Gong, Ying; Ouyang, Hongsheng; Hou, Yue			Long Non-coding RNAs Contribute to the Inhibition of Proliferation and EMT by Pterostilbene in Human Breast Cancer	FRONTIERS IN ONCOLOGY			English	Article						pterostilbene; lncRNAs; cancer; autophagy; epithelial-to-mesenchymal transition	EPITHELIAL-MESENCHYMAL TRANSITION; ENDOPLASMIC-RETICULUM STRESS; COLORECTAL-CANCER; E-CADHERIN; CELLS; AUTOPHAGY; PROMOTES; METASTASIS; LNCRNA; MICROENVIRONMENT	Background: There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in the process of carcinogenesis and treatment using chemotherapy. Pterostilbene, a phytochemical agent with natural antioxidant and anti-inflammatory properties, has been shown to modulate oncogenic processes in many cancers. However, there has been limited research on the association between pterostilbene and the expression of lncRNAs. Methods: MCF7 breast cancer cells were treated with various concentrations of pterostilbene and their gene expression profile was analyzed by quantitative real-time PCR, Western blotting and immunofluorescence. Results: Treatment with pterostilbene inhibited cell proliferation and epithelial-to-mesenchymal transition (EMT), and increased cell apoptosis, autophagy and ER stress. The Akt/mTOR pathway was downregulated, but p38 MAPK/Erk signaling was activated in cells following treatment with pterostilbene. Pterostilbene increased the expression of the lncRNAs MEG3, TUG1, H19, and DICER1-AS1 whereas the expression of LINC01121, PTTG3P, and HOTAIR declined. Knockdown of lncRNA H19 resulted in a reduction of the cell invasion, with the cells becoming more sensitive to pterostilbene therapy. Conclusions: These results suggest that efficient optimum disruption of lncRNA expression might possibly improve the anti-tumor effects of phytochemical agents, thus serving as a potential therapy for breast cancer.	[Huang, Yongye; Du, Juan; Mi, Yan; Li, Tianye; Gong, Ying; Hou, Yue] Northeastern Univ, Coll Life & Hlth Sci, Shenyang, Liaoning, Peoples R China; [Ouyang, Hongsheng] Jilin Univ, Coll Anim Sci, Jilin Prov Key Lab Anim Embryo Engn, Changchun, Jilin, Peoples R China		Hou, Y (corresponding author), Northeastern Univ, Coll Life & Hlth Sci, Shenyang, Liaoning, Peoples R China.; Ouyang, HS (corresponding author), Jilin Univ, Coll Anim Sci, Jilin Prov Key Lab Anim Embryo Engn, Changchun, Jilin, Peoples R China.	ouyh@jlu.edu.cn; houyue@mail.neu.edu.cn		Huang, Yongye/0000-0002-9083-250X	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81502582, 81473330, U1603125]; Program for JLU Science and Technology Innovative Research Team [2017TD-28]; Fundamental Research Funds for the Central Universities of ChinaFundamental Research Funds for the Central Universities [N162004003]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities	This work was supported by the National Natural Science Foundation of China (No. 81502582, No. 81473330 and U1603125). This work was also financially supported by the Program for JLU Science and Technology Innovative Research Team (2017TD-28), Fundamental Research Funds for the Central Universities of China (N162004003), and Fundamental Research Funds for the Central Universities.	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Oncol.	DEC 18	2018	8								629	10.3389/fonc.2018.00629			17	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HE7WO	WOS:000453651800003	30619763	gold, Green Published			2022-04-25	
J	Yan, ZL; Ohuchida, K; Fei, S; Zheng, B; Guan, WY; Feng, HM; Kibe, S; Ando, Y; Koikawa, K; Abe, T; Iwamoto, C; Shindo, K; Moriyama, T; Nakata, K; Miyasaka, Y; Ohtsuka, T; Mizumoto, K; Hashizume, M; Nakamura, M				Yan, Zilong; Ohuchida, Kenoki; Fei, Shuang; Zheng, Biao; Guan, Weiyu; Feng, Haimin; Kibe, Shin; Ando, Yohei; Koikawa, Kazuhiro; Abe, Toshiya; Iwamoto, Chika; Shindo, Koji; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Ohtsuka, Takao; Mizumoto, Kazuhiro; Hashizume, Makoto; Nakamura, Masafumi			Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH			English	Article						ERK1/2; Pancreatic cancer; Cancer-stromal interaction; Pancreatic stellate cell; Cellular senescence	SENESCENCE; PATHWAY; GROWTH; TUMORS; DESMOPLASIA; PROGRESSION; AUTOPHAGY; MODELS	BackgroundExtracellular signal-regulated kinases (ERKs) have been related to multiple cancers, including breast cancer, hepatocellular cancer, lung cancer and colorectal cancer. ERK1/2 inhibitor can suppress growth of KRAS-mutant pancreatic tumors by targeting cancer cell. However, no studies have shown the expression of ERK1/2 on pancreatic stromal and its effect on pancreatic cancer-stromal interaction.MethodsImmunohistochemistry and western blotting were performed to detect the expression of p-ERK1/2 in pancreatic tissues and cells. Cell viability assay was used to study IC50 of ERK inhibitor on pancreatic cancer cells (PCCs) and primary cancer-associated pancreatic stellate cells (PSCs). Transwell migration, invasion, cell viability assay, senescence -galactosidase staining were performed to determine the effect of ERK inhibitor on PCCs and PSCs in vitro and in vivo. The expression of key factors involved in autophagy and epithelial-to-mesenchymal transition (EMT) process were evaluated by western blotting. The expression of key factors related to cell invasiveness and malignancy were confirmed by qRT-PCR. Co-transplantation of PCC Organoid and PSC using a splenic xenograft mouse model was used to evaluated combined treatment of ERK inhibitor and autophagy inhibitor.ResultsImmunohistochemical staining in pancreatic tumor samples and transgenetic mice detected p-ERK1/2 expression in both cancer cells and stromal cells. In pancreatic tissues, p-ERK1/2 was strongly expressed in cancer-associated PSCs compared with cancer cells and normal PSCs. PSCs were also significantly more sensitive to ERK1/2 inhibitor treatment. Inhibition of ERK1/2 suppressed EMT transition in HMPCCs, upregulated cellular senescence markers, activated autophagy in cancer-associated PSCs; and suppressed cancer-stromal interaction, which enhanced invasiveness and viability of cancer cells. We also found that chloroquine, an autophagy inhibitor, suppressed ERK inhibition-induced autophagy and promoted PSC cellular senescence, leading to significantly decreased cell proliferation. The combination of an ERK inhibitor and autophagy inhibitor suppressed liver metastasis in a splenic pancreatic cancer organoid xenograft mouse model.ConclusionsThese data indicate that inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis.	[Yan, Zilong; Ohuchida, Kenoki; Fei, Shuang; Zheng, Biao; Guan, Weiyu; Feng, Haimin; Kibe, Shin; Ando, Yohei; Koikawa, Kazuhiro; Abe, Toshiya; Shindo, Koji; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Ohtsuka, Takao; Nakamura, Masafumi] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan; [Ohuchida, Kenoki; Iwamoto, Chika; Hashizume, Makoto] Kyushu Univ, Grad Sch Med Sci, Dept Adv Med Initiat, Fukuoka, Fukuoka, Japan; [Zheng, Biao] Shenzhen Univ, Gen Hosp, Dept Gen Surg, Shenzhen, Peoples R China; [Mizumoto, Kazuhiro] Kyushu Univ Hosp, Canc Ctr, Fukuoka, Fukuoka, Japan		Ohuchida, K; Nakamura, M (corresponding author), Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan.	kenoki@surg1.med.kyushu-u.ac.jp; mnaka@surg1.med.kyushu-u.ac.jp	Abe, Toshiya/AAT-2579-2021	Koikawa, Kazuhiro/0000-0002-3208-9447	JSPS KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [26108010, 26293305, 15 K10185, 25713050, 16 K15621, 16 K10601, 16 K10600, 16H05417, 15 K15498, 15H04933, 16H05418, 17H04284, 17 K19602, 17 K19605]	This work was supported by JSPS KAKENHI (Grant numbers: 26108010, 26293305, 15 K10185, 25713050, 16 K15621, 16 K10601, 16 K10600, 16H05417, 15 K15498, 15H04933, 16H05418, 17H04284, 17 K19602 and 17 K19605).	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Exp. Clin. Cancer Res.	MAY 27	2019	38								221	10.1186/s13046-019-1226-8			16	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IA2MM	WOS:000469395500001	31133044	Green Published, gold			2022-04-25	
J	Lenis-Rojas, OA; Cabral, R; Carvalho, B; Friaes, S; Roma-Rodrigues, C; Fernandez, JAA; Vila, SF; Sanchez, L; Gomes, CSB; Fernandes, AR; Royo, B				Lenis-Rojas, Oscar A.; Cabral, Rui; Carvalho, Beatriz; Friaes, Sofia; Roma-Rodrigues, Catarina; Fernandez, Jhonathan A. A.; Vila, Sabela F.; Sanchez, Laura; Gomes, Clara S. B.; Fernandes, Alexandra R.; Royo, Beatriz			Triazole-Based Half-Sandwich Ruthenium(II) Compounds: From In Vitro Antiproliferative Potential to In Vivo Toxicity Evaluation	INORGANIC CHEMISTRY			English	Article							CYTOTOXIC RUTHENIUM(II); ANTICANCER DRUGS; CROSS-RESISTANCE; CANCER CELLS; COMPLEXES; APOPTOSIS; INVASION; BINDING; DETERMINANTS; MODULATION	A new series of half-sandwich ruthenium(II) compounds [(eta(6)-arene)Ru(L)Cl][CF3SO3] bearing 1,2,3-triazole ligands (arene = p-cymene, L = L1 (1); arene = p-cymene, L = L2 (2); arene = benzene, L = L1 (3); arene = benzene, L2 (4); L1 = 2-[1-(p-tolyl)-1H-1,2,3-triazol-4-yl]pyridine and L2 = 1,1'-di-p-tolyl-1H,1'H-4,4'-bi(1,2,3-triazole) have been synthesized and fully characterized by H-1 and C-13 NMR and IR spectroscopy, mass spectrometry, and elemental analysis. The molecular structures of 1, 2, and 4 have been determined by single-crystal X-ray diffraction. The cytotoxic activity of 1-4 was evaluated using the MTS assay against human tumor cells, namely ovarian carcinoma (A2780), colorectal carcinoma (HCT116), and colorectal carcinoma resistant to doxorubicin (HCT116dox), and against normal primary fibroblasts. Whereas compounds 2 and 4 showed no cytotoxic activity toward tumor cell lines, compounds 1 and 3 were active in A2780, while showing no antiproliferative effect in human normal dermal fibroblasts at the IC50 concentrations of the A2780 cell line. Exposure of ovarian carcinoma cells to IC50 concentrations of compound 1 or 3 led to an accumulation of reactive oxygen species and an increase of apoptotic and autophagic cells. While compound 3 displayed low levels of angiogenesis induction, compound 1 showed an ability to induce cell cycle delay and to interfere with cell migration. When the in vivo toxicity studies using zebrafish and chicken embryos are considered, compounds 1 and 3, which were not lethal, are promising candidates as anticancer agents against ovarian cancer due to their good cytotoxic activity in tumor cells and their low toxicity both in vitro and in vivo.	[Cabral, Rui; Carvalho, Beatriz; Roma-Rodrigues, Catarina; Fernandes, Alexandra R.] Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO, P-2829516 Caparica, Portugal; [Lenis-Rojas, Oscar A.; Friaes, Sofia; Royo, Beatriz] Univ Nova Lisboa, ITQB NOVA, Inst Tecnol Quim & Biol Antonio Xavier, P-2780157 Oeiras, Portugal; [Fernandez, Jhonathan A. A.] Univ Estadual Campinas, UNICAMP, Sch Med Sci, Lab Zebrafish,Dept Med Genet & Genom Med, BR-13083887 Campinas, SP, Brazil; [Fernandez, Jhonathan A. A.; Vila, Sabela F.; Sanchez, Laura] Univ Santiago de Compostela, Fac Vet, Dept Zool Genet & Antropol Fis, Lugo 27002, Spain; [Sanchez, Laura] Hlth Res Inst Santiago de Compostela IDIS, Preclin Anim Models Grp, La Coruna, Spain; [Gomes, Clara S. B.] Univ NOVA Lisboa, Fac Ciencias & Tecnol, Dept Quim, LAQV REQUIMTE UCIBIO, P-2829516 Caparica, Portugal		Fernandes, AR (corresponding author), Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO, P-2829516 Caparica, Portugal.; Lenis-Rojas, OA; Royo, B (corresponding author), Univ Nova Lisboa, ITQB NOVA, Inst Tecnol Quim & Biol Antonio Xavier, P-2780157 Oeiras, Portugal.	oscar.rojas@itqb.unl.pt; ma.fernandes@fct.unl.pt; broyo@itqb.unl.pt	Gomes, Clara S. B./H-7759-2012; Rojas, Oscar/ABE-2206-2021; Roma-Rodrigues, Catarina/S-6144-2016; Roma-Rodrigues, Catarina/AAT-5658-2021; Sanchez Pinon, Laura/L-2411-2014; Fernandes, Alexandra/C-7465-2011	Gomes, Clara S. B./0000-0003-3672-0045; Rojas, Oscar/0000-0002-5914-5787; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Sanchez Pinon, Laura/0000-0001-7927-5303; Fernandes, Alexandra/0000-0003-2054-4438	Fundacao da Ciencia e a Tecnologia, FCT [UIDB/04612/2020, UIDP/04612/2020]; Applied Molecular Biosciences Unit-UCIBIO - FCT [UIDP/04378/2020, UIDB/04378/2020]; Coordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorBrasil (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); program CAPES/PRINT [88887.470075/2019-00]; Applied Molecular Biosciences Unit-UCIBIO [UIDP/04378/2020, UIDB/04378/2020, UIDB/50006/2020, UIDP/50006/2020]; FCT-MCTESPortuguese Foundation for Science and TechnologyEuropean Commission [RECI/BBB-BEP/0124/2012];  [022162]	We are grateful to the Fundacao da Ciencia e a Tecnologia, FCT, fo rthe project MOSTMICRO-ITQB NOVA with references UIDB/04612/2020 and UIDP/04612/2020. The NMR spectrometers at CERMAX are integrated in the national NMR Network and partially supported through project 022162. We also thank the Analytic Services of ITQB and C. Almeida for elemental analysis and HRMS spectrometry. O.A.L.-R. acknowledges FCT, POPH-Programa Operacional Potencial Humano, and FSE (European Social Fund) for the CEEC 2017 Initiative. Also, this work was supported by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT (UIDP/04378/2020 and UIDB/04378/2020). J.A.A.F. acknowledges Coordenacao de Aperfeicoamento de Pessoal de Niv ' el SuperiorBrasil (CAPES) and the program CAPES/PRINT Proc. 88887.470075/2019-00. C.S.B.G. acknowledges the Associate Laboratory for Green Chemistry-LAQV, the Applied Molecular Biosciences Unit-UCIBIO (UIDB/50006/2020, UIDP/50006/2020, UIDB/04378/2020, UIDP/04378/2020), and Xray infrastructure financed by FCT-MCTES through project RECI/BBB-BEP/0124/2012.	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Chem.	JUN 7	2021	60	11					8011	8026		10.1021/acs.inorgchem.1c00527		MAY 2021	16	Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	SR8OY	WOS:000661306200043	33973771				2022-04-25	
J	Zhang, H; Yi, JK; Huang, H; Park, S; Park, S; Kwon, W; Kim, E; Jang, S; Kim, SY; Choi, SK; Kim, SH; Liu, KD; Dong, ZG; Ryoo, ZY; Kim, MO				Zhang, Haibo; Yi, Jun-Koo; Huang, Hai; Park, Song; Park, Sijun; Kwon, Wookbong; Kim, Eungyung; Jang, Soyoung; Kim, Si-Yong; Choi, Seong-Kyoon; Kim, Sung-Hyun; Liu, Kangdong; Dong, Zigang; Ryoo, Zae Young; Kim, Myoung Ok			Rhein Suppresses Colorectal Cancer Cell Growth by Inhibiting the mTOR Pathway In Vitro and In Vivo	CANCERS			English	Article						Rhein; colorectal cancer; mTOR; xenograft	SHOCK FACTOR-1 HSF1; S-PHASE ARREST; HEAT-SHOCK; DOWN-REGULATION; POOR-PROGNOSIS; EXPRESSION; INITIATION; DEGRADATION; RECURRENCE; AUTOPHAGY	Simple Summary Colorectal cancer (CRC) is the fourth most common cancer and the second most common cause of cancer-related deaths globally. Rhein is a natural anthraquinone extract from rhubarb, which exhibits potent anticancer activity in various cancers. In this study, we show that rhein significantly inhibited the growth, migration, and invasion of CRC cells by directly binding to mTOR and inhibiting the mTOR signaling pathway. Rhein promotes mTOR degradation through the ubiquitin-proteasome pathway. In addition, rhein significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity. Our results indicate that rhein is a promising anticancer agent that may be useful for the prevention and treatment of CRC. Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. Rhein has demonstrated therapeutic effects in various cancer models. However, its effects and underlying mechanisms of action in CRC remain poorly understood. We investigated the potential anticancer activity and underlying mechanisms of rhein in CRC in vitro and in vivo. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of rhein on CRC cells. Wound-healing and Transwell assays were conducted to assess cell migration and invasion capacity. Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. A tissue microarray was used to detect mTOR expression in CRC patient tissues. Gene overexpression and knockdown were done to analyze the function of mTOR in CRC. The anticancer effect of rhein in vivo was assessed in a CRC xenograft mouse model. The results show that rhein significantly inhibited CRC cell growth by inducing S-phase cell cycle arrest and apoptosis. Rhein inhibited CRC cell migration and invasion through the epithelial-mesenchymal transition (EMT) process. mTOR was highly expressed in CRC cancer tissues and cells. Overexpression of mTOR promoted cell growth, migration, and invasion, whereas mTOR knockdown diminished these phenomena in CRC cells in vitro. In addition, rhein directly targeted mTOR and inhibited the mTOR signaling pathway in CRC cells. Rhein promoted mTOR degradation through the ubiquitin-proteasome pathway. Intraperitoneal administration of rhein inhibited HCT116 xenograft tumor growth through the mTOR pathway. In conclusion, rhein exerts anticancer activity in vitro and in vivo by targeting mTOR and inhibiting the mTOR signaling pathway in CRC. Our results indicate that rhein is a potent anticancer agent that may be useful for the prevention and treatment of CRC.	[Zhang, Haibo; Huang, Hai; Kim, Eungyung; Kim, Myoung Ok] Kyungpook Natl Univ, Dept Anim Sci & Biotechnol, ITRD, Sangju 37224, South Korea; [Yi, Jun-Koo] Gyeongbuk Livestock Res Inst, Yeongju 36052, South Korea; [Park, Song; Choi, Seong-Kyoon] DGIST, Core Prot Resources Ctr, Daegu 41566, South Korea; [Park, Song] DGIST, Dept Brain & Cognit Sci, Daegu 41566, South Korea; [Park, Sijun; Jang, Soyoung; Kim, Si-Yong; Ryoo, Zae Young] Kyungpook Natl Univ, BK21 FOUR KNU Creat Bioresearch, Sch Life Sci, Daegu 41566, South Korea; [Kwon, Wookbong; Choi, Seong-Kyoon] DGIST, Div Biotechnol, Daegu 41566, South Korea; [Kim, Sung-Hyun] Korea Polytech Coll, Dept Biomed Anal, Chungnam 34134, South Korea; [Liu, Kangdong; Dong, Zigang] China US Henan Hormel Canc Inst, Zhengzhou 450008, Peoples R China		Kim, MO (corresponding author), Kyungpook Natl Univ, Dept Anim Sci & Biotechnol, ITRD, Sangju 37224, South Korea.; Ryoo, ZY (corresponding author), Kyungpook Natl Univ, BK21 FOUR KNU Creat Bioresearch, Sch Life Sci, Daegu 41566, South Korea.	2018326925@knu.ac.kr; 79lee38@korea.kr; huanghai@knu.ac.kr; stemsj@knu.ac.kr; cristaling@dgist.ac.kr; bongdaling@dgist.ac.kr; kge99777@knu.ac.kr; jangsy@knu.ac.kr; kim_si-yong@knu.ac.kr; cskbest@dgist.ac.kr; shkim92@kopo.ac.kr; kdliu@zzu.edu.cn; zgdong@hi.umm.edu; jaewoong64@knu.ac.kr; ok4325@knu.ac.kr		Park, Song/0000-0001-6217-2017; Park, Sijun/0000-0002-8791-8249; Yi, JunKoo/0000-0003-2593-6529; Liu, Kangdong/0000-0002-4425-5625; Kwon, Wookbong/0000-0002-0655-6531	Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of EducationNational Research Foundation of Korea [2020R1I1A2075315, 2020R1A4A1018280]	This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1I1A2075315 and 2020R1A4A1018280).	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J	Dan, XL; Liu, WL; Wong, JH; Ng, TB				Dan, Xiuli; Liu, Wenlong; Wong, Jack H.; Ng, Tzi B.			A Ribonuclease Isolated from Wild Ganoderma Lucidum Suppressed Autophagy and Triggered Apoptosis in Colorectal Cancer Cells	FRONTIERS IN PHARMACOLOGY			English	Article						Ganoderma lucidum; ribonucleases; colorectal cancer cells; apoptosis; autophagy	FRESH FRUITING BODIES; CHINA BLACK BEANS; ANTIPROLIFERATIVE ACTIVITY; INHIBITORY-ACTIVITY; CONCANAVALIN-A; MUSHROOM; THERAPY; PURIFICATION; EXPRESSION; INDUCTION	The mushroom Ganoderma lucidum (G. lucidum) has been consumed in China as a medicine for promoting health and longevity for thousands of years. Due to its paramount and multiple pharmaceutical effects, G. lucidum has received considerable attention from researchers and its chemical constituents as well as their respective functions were gradually unveiled by using modern research methods. Herein, we reported the isolation of a protein (Ganoderma lucidum ribonuclease, GLR) with anti colorectal cancer activities from G. lucidum. This protein is a 17.4-kDa RNA degrading enzyme (ribonuclease) and was purified by using liquid chromatography procedures. GLR manifested potent anti proliferative and anti colony formation activities on HT29 and HCT116 colorectal cancer cells by inducing cell cycle arrest in G1 phase through the regulation of cyclin D1 and P53 expression. GLR was demonstrated to induce cell apoptosis in HCT116 cells by activating unfolded protein response and caspase-9 regulated pathways. Besides, the ability to undergo autophagy which is a stress adaption mechanism to cope with metabolic crisis was significantly suppressed by GLR treatment in HCT116 cells. The activation of apoptosis in GLR-treated HT29 cells was, however, independent of caspase-9 and the suppression of autophagy was also relatively minor. Thus the apoptosis of HT29 cells triggered by GLR was much milder than that in HCT116 cells. Our findings show that the RNase from G. lucidum may be one of the bioactive components that contribute to the anti-colorectal cancer activity of G. lucidum.	[Dan, Xiuli; Wong, Jack H.; Ng, Tzi B.] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China; [Liu, Wenlong] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Marine Biomed Mat, Shenzhen, Peoples R China		Wong, JH; Ng, TB (corresponding author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.	b111590@mailserv.cuhk.edu.hk; b021770@mailserv.cuhk.edu.hk		Liu, Wenlong/0000-0003-2988-7963; WONG, Jack/0000-0002-9732-986X	award of Health and Medical Research Fund from Food and Health Bureau, Hong Kong [12131221]	We gratefully acknowledge the award of Health and Medical Research Fund (research grant number: 12131221) from Food and Health Bureau, Hong Kong. Special Administration Region Government.	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Pharmacol.	JUL 25	2016	7								217	10.3389/fphar.2010.00217			13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	DR7QI	WOS:000380094400001	27504094				2022-04-25	
J	Yan, C; Luo, L; Guo, CY; Goto, S; Urata, Y; Shao, JH; Li, TS				Yan, Chen; Luo, Lan; Guo, Chang-Ying; Goto, Shinji; Urata, Yoshishige; Shao, Jiang-Hua; Li, Tao-Sheng			Doxorubicin-induced mitophagy contributes to drug resistance in cancer stem cells from HCT8 human colorectal cancer cells	CANCER LETTERS			English	Article						Cancer stem cells; Drug resistance; Mitophagy; BNIP3L; Autophagy	STEM/PROGENITOR CELLS; INITIATING CELLS; AUTOPHAGY; APOPTOSIS; THERAPY; MITOCHONDRIA; CHEMOTHERAPY; INHIBITION; DISCOVERY; PATHWAY	Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133(+)/CD44(+) CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs. Interestingly, the level of mitochondria(superoxide was detected to be significantly lower in CSCs than in parental cells after DXR treatment. Furthermore, the mitophagy level and expression of BNIP3L, a mitophagy regulator, were significantly higher in CSCs than in parental cells after DXR treatment. Silencing BNIP3L significantly halted mitophagy and enhanced the sensitivity to DXR in CSCs. Our data suggested that mitophagy, but not non-selective autophagy, likely contributes to drug resistance in CSCs isolated from HCT8 cells. Further studies in other cancer cell lines will be needed to confirm our findings. (C) 2016 Elsevier Ireland Ltd. All rights reserved.	[Yan, Chen; Luo, Lan; Guo, Chang-Ying; Goto, Shinji; Urata, Yoshishige; Li, Tao-Sheng] Nagasaki Univ, Grad Sch Biomed Sci, Dept Stem Cell Biol, 1-12-4 Sakamoto, Nagasaki 8528523, Japan; [Guo, Chang-Ying] Jiangxi Canc Hosp, Dept Thorac Surg, Nanchang 330029, Jiangxi, Peoples R China; [Shao, Jiang-Hua] Nanchang Univ, Dept Gen Surg, Affiliated Hosp 2, Nanchang 330006, Jiangxi, Peoples R China		Li, TS (corresponding author), Nagasaki Univ, Grad Sch Biomed Sci, Dept Stem Cell Biol, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.	litaoshe@nagasaki-u.ac.jp	chang-ying, guo/F-2770-2018	Li, Tao-Sheng/0000-0002-7653-8873; Luo, Lan/0000-0001-7549-9852	Ministry of Education, Science, Sports, Culture and Technology, JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [26293279]; Collaborative Research Program of the Atomic-bomb Disease Institute of Nagasaki University	This study was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Sports, Culture and Technology, Japan (NO. 26293279), and the Collaborative Research Program of the Atomic-bomb Disease Institute of Nagasaki University. The funder played no role in the study design, the data collection and analysis, decision to publish, or preparation of the manuscript.	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MAR 1	2017	388						34	42		10.1016/j.canlet.2016.11.018			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EN4EC	WOS:000395959800004	27913197				2022-04-25	
J	Xia, XJ; Wang, X; Cheng, Z; Qin, WH; Lei, LC; Jiang, JQ; Hu, JH				Xia, Xiaojing; Wang, Xin; Cheng, Zhe; Qin, Wanhai; Lei, Liancheng; Jiang, Jinqing; Hu, Jianhe			The role of pyroptosis in cancer: pro-cancer or pro-"host"?	CELL DEATH & DISEASE			English	Review							CELL-DEATH PATHWAYS; GASDERMIN-D; INFLAMMASOME ACTIVATION; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; MOLECULAR-MECHANISMS; INDUCE PYROPTOSIS; COLORECTAL-CANCER; AIM2 EXPRESSION; CASPASE 1	Programmed cell death (PCD) refers to the way in which cells die depending on specific genes encoding signals or activities. Apoptosis, autophagy, and pyroptosis are all mechanisms of PCD. Among these mechanisms, pyroptosis is mediated by the gasdermin family, accompanied by inflammatory and immune responses. The relationship between pyroptosis and cancer is complex, and the effects of pyroptosis on cancer vary in different tissues and genetic backgrounds. On one hand, pyroptosis can inhibit the occurrence and development of tumors; on the other hand, as a type of proinflammatory death, pyroptosis can form a suitable microenvironment for tumor cell growth and thus promote tumor growth. In addition, the induction of tumor pyroptosis is also considered a potential cancer treatment strategy. Studies have shown that DFNA5 (nonsyndromic hearing impairment protein 5)/GSDME (Gasdermin-E) mRNA methylation results in lower expression levels of DFNA5/GSDME in most tumor cells than in normal cells, making it difficult to activate the pyroptosis in most tumor cells. During the treatment of malignant tumors, appropriate chemotherapeutic drugs can be selected according to the expression levels of DFNA5/GSDME, which can be upregulated in tumor cells, thereby increasing the sensitivity to chemotherapeutic drugs and reducing drug resistance. Therefore, induced pyroptosis may play a predominant role in the treatment of cancer. Here, we review the latest research on the anti- and protumor effects of pyroptosis and its potential applications in cancer treatment.	[Xia, Xiaojing; Cheng, Zhe; Jiang, Jinqing; Hu, Jianhe] Henan Inst Sci & Technol, Coll Anim Sci & Vet Med, Xinxiang, Henan, Peoples R China; [Wang, Xin] Linyi Univ, Coll Agr & Forestry Sci, Linyi, Shandong, Peoples R China; [Qin, Wanhai] Univ Amsterdam, Amsterdam UMC, Ctr Expt & Mol Med, Amsterdam Infect & Immun, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands; [Lei, Liancheng] Jilin Univ, Coll Vet Med, Changchun, Jilin, Peoples R China		Xia, XJ (corresponding author), Henan Inst Sci & Technol, Coll Anim Sci & Vet Med, Xinxiang, Henan, Peoples R China.	quik500@163.com	qin, wanhai/M-1773-2019; Xia, Xiaojing/O-7934-2018; Qin, Wanhai/R-8266-2016	qin, wanhai/0000-0002-7776-5007; Xia, Xiaojing/0000-0001-7717-8411; Qin, Wanhai/0000-0002-7776-5007	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31702263]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2017M622346]	This review was funded by the National Natural Science Foundation of China (no. 31702263) and the China Postdoctoral Science Foundation (no. 2017M622346).	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SEP 9	2019	10								650	10.1038/s41419-019-1883-8			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	JK6RN	WOS:000494969700009	31501419	Green Published, gold			2022-04-25	
J	Xu, LJ; Qiao, YQ; Zheng, Q				Xu, Lijun; Qiao, Yuqi; Zheng, Qing			Identification of an autophagy-related gene expression signature for colorectal cancer	ALL LIFE			English	Article						Autophagy; colorectal cancer; prognostic signature; survival analysis; TCGA		Autophagy, a major lysosomal degradation process, has been implicated in the pathogenesis of colorectal cancer (CRC). However, it still remains unclear what role all the autophagy-related genes (ARGs) play in CRC prognosis. A univariate Cox analysis was conducted to select ARGs related with overall survival (OS) for CRC cohort of the TCGA database. A multivariate Cox analysis was used to develop an ARGs expression signature, whose risk score stratified CRC patients into two groups. The OS time between the above two groups was estimated using the Kaplan-Meier curve and log-rank test. In order to evaluate the predictive performance of this expression signature and other clinicopathological parameters for CRC prognosis, the area under the curve (AUC) was calculated. Nine out of 20 OS-related ARGs were finally incorporated into this ARGs expression signature, whose risk score stratified CRC patients into either high-risk or low-risk group. The OS time of patients in low-risk group was higher than that in high-risk group and the difference was statistically significant (P < 0.001). The AUC for this risk score was higher than other clinicopathological parameters, including TNM stage. This study presents an ARGs expression signature, which outperforms other clinicopathological parameters in predicting CRC prognosis.	[Xu, Lijun; Qiao, Yuqi; Zheng, Qing] Shanghai Jiao Tong Univ, Div Gastroenterol & Hepatol, Minist Hlth,Inflammatory Bowel Dis Res Ctr, Shanghai Inst Digest Dis,Renji Hosp,Sch Med,Key L, 160 Pu Jian Ave, Shanghai 200127, Peoples R China		Qiao, YQ; Zheng, Q (corresponding author), Shanghai Jiao Tong Univ, Div Gastroenterol & Hepatol, Minist Hlth,Inflammatory Bowel Dis Res Ctr, Shanghai Inst Digest Dis,Renji Hosp,Sch Med,Key L, 160 Pu Jian Ave, Shanghai 200127, Peoples R China.	qiaoyuqi@renji.com; qingzheng124@126.com					Abu N, 2020, FRONT CELL DEV BIOL, V8, DOI 10.3389/fcell.2020.564648; Ait-Aissa K, 2020, CARDIOVASC DIABETOL, V19, DOI 10.1186/s12933-020-01107-3; Al Bandar MH, 2017, ONCOL REP, V37, P2553, DOI 10.3892/or.2017.5531; Amin MB, 2017, CA-CANCER J CLIN, V67, P93, DOI 10.3322/caac.21388; An YY, 2018, J CANCER, V9, P4058, DOI 10.7150/jca.25587; Bagherniya M, 2018, AGEING RES REV, V47, P183, DOI 10.1016/j.arr.2018.08.004; Chowdhury S, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0069132; Conroy MJ, 2020, ADV EXP MED BIOL, V1231, P1, DOI 10.1007/978-3-030-36667-4_1; Cooks T, 2013, CANCER CELL, V23, P634, DOI 10.1016/j.ccr.2013.03.022; Dekker E, 2019, LANCET, V394, P1467, DOI 10.1016/S0140-6736(19)32319-0; Fang YY, 2020, FRONT CELL DEV BIOL, V8, DOI 10.3389/fcell.2020.602574; Hoe KK, 2014, NAT REV DRUG DISCOV, V13, P217, DOI 10.1038/nrd4236; Huang Z, 2019, DOSE-RESPONSE, V17, DOI 10.1177/1559325819894179; Levy JMM, 2017, NAT REV CANCER, V17, P528, DOI 10.1038/nrc.2017.53; Li J, 2016, MEDICINE, V95, DOI 10.1097/MD.0000000000002711; Li J, 2014, WORLD J GASTROENTERO, V20, P5104, DOI 10.3748/wjg.v20.i17.5104; Li MJ, 2017, CELL COMMUN SIGNAL, V15, DOI 10.1186/s12964-017-0208-8; Li T, 2020, AGING DIS, V11, P967, DOI 10.14336/AD.2019.0901; Li XL, 2015, WORLD J GASTROENTERO, V21, P84, DOI 10.3748/wjg.v21.i1.84; Maloverjan A, 2010, EXP CELL RES, V316, P627, DOI 10.1016/j.yexcr.2009.10.018; Mauri G, 2019, MOL ONCOL, V13, P109, DOI 10.1002/1878-0261.12417; Mo SB, 2019, CARCINOGENESIS, V40, P861, DOI 10.1093/carcin/bgz031; Mokarram P, 2017, AUTOPHAGY, V13, P781, DOI 10.1080/15548627.2017.1290751; Packer M, 2020, CARDIOVASC DIABETOL, V19, DOI 10.1186/s12933-020-01041-4; Patel M, 2018, TRANSL RES, V197, P43, DOI 10.1016/j.trsl.2018.02.002; Shi FY, 2018, SEMIN CANCER BIOL, V50, P124, DOI 10.1016/j.semcancer.2017.09.009; Steinmann S, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-2122-z; Su QH, 2015, BMC GASTROENTEROL, V15, DOI 10.1186/s12876-015-0336-9; Wang SS, 2019, ONCOTARGETS THER, V12, P3695, DOI 10.2147/OTT.S197676; Wei R, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1043-0; Xie JM, 2019, BIOSCIENCE REP, V39, DOI 10.1042/BSR20180480; Xu JL, 2020, FRONT CELL DEV BIOL, V8, DOI 10.3389/fcell.2020.621428; Yu TC, 2017, CELL, V170, P548, DOI 10.1016/j.cell.2017.07.008; Zhao YG, 2019, CURR OPIN CELL BIOL, V61, P117, DOI 10.1016/j.ceb.2019.08.003; Zhou XH, 2020, BMC ENDOCR DISORD, V20, DOI 10.1186/s12902-020-00647-9	35	1	1	2	4	TAYLOR & FRANCIS LTD	ABINGDON	2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND	2689-5293	2689-5307		ALL LIFE	All Life	JAN 1	2021	14	1					91	101		10.1080/26895293.2021.1872716			11	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	PZ7ZI	WOS:000612960700001		gold			2022-04-25	
J	Fontana, R; Ranieri, M; La Mantia, G; Vivo, M				Fontana, Rosa; Ranieri, Michela; La Mantia, Girolama; Vivo, Maria			Dual Role of the Alternative Reading Frame ARF Protein in Cancer	BIOMOLECULES			English	Review						tumor suppression; autophagy; anoikis; CDKN2a; ARF locus; chemoresistance; FAK sumoylation; actin cytoskeleton	TUMOR-SUPPRESSOR PROTEIN; N-TERMINAL POLYUBIQUITINATION; P53-INDEPENDENT FUNCTIONS; NUCLEOLAR LOCALIZATION; PHYSICAL INTERACTION; MITOCHONDRIAL FORM; GERMLINE MUTATION; OXIDATIVE STRESS; INK4A/ARF LOCUS; STABILIZES P53	The CDKN2a/ARF locus expresses two partially overlapping transcripts that encode two distinct proteins, namely p14ARF (p19Arf in mouse) and p16INK4a, which present no sequence identity. Initial data obtained in mice showed that both proteins are potent tumor suppressors. In line with a tumor-suppressive role, ARF-deficient mice develop lymphomas, sarcomas, and adenocarcinomas, with a median survival rate of one year of age. In humans, the importance of ARF inactivation in cancer is less clear whereas a more obvious role has been documented for p16INK4a. Indeed, many alterations in human tumors result in the elimination of the entire locus, while the majority of point mutations affect p16INK4a. Nevertheless, specific mutations of p14ARF have been described in different types of human cancers such as colorectal and gastric carcinomas, melanoma and glioblastoma. The activity of the tumor suppressor ARF has been shown to rely on both p53-dependent and independent functions. However, novel data collected in the last years has challenged the traditional and established role of this protein as a tumor suppressor. In particular, tumors retaining ARF expression evolve to metastatic and invasive phenotypes and in humans are associated with a poor prognosis. In this review, the recent evidence and the molecular mechanisms of a novel role played by ARF will be presented and discussed, both in pathological and physiological contexts.	[Fontana, Rosa] Univ Calif San Diego, Moores Canc Ctr, Dept Pharmacol, La Jolla, CA 92093 USA; [Ranieri, Michela] NYU, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, Div Hematol & Med Oncol, New York, NY 10016 USA; [La Mantia, Girolama; Vivo, Maria] Univ Naples Federico II, Dept Biol, I-80126 Naples, Italy		Vivo, M (corresponding author), Univ Naples Federico II, Dept Biol, I-80126 Naples, Italy.	rofontana@ucsd.edu; Michela.Ranieri@nyulangone.org; lamantia@unina.it; maria.vivo@unina.it	Fontana, Rosa/AAD-7852-2019; Vivo, Maria/S-3390-2017	Fontana, Rosa/0000-0003-0445-6016; Vivo, Maria/0000-0003-2458-4226; Ranieri, Michela/0000-0002-3833-3594	University of Naples Federico II [GLAMANTIA 2018]	This research received funding from Grant GLAMANTIA 2018 assigned to GLM from University of Naples Federico II.	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J	Zhou, J; Zhang, L; Wang, M; Zhou, L; Feng, XP; Yu, LL; Lan, J; Gao, W; Zhang, CD; Bu, YQ; Huang, CH; Zhang, HY; Lei, YL				Zhou, Jing; Zhang, Lu; Wang, Meng; Zhou, Li; Feng, Xuping; Yu, Linli; Lan, Jiang; Gao, Wei; Zhang, Chundong; Bu, Youquan; Huang, Canhua; Zhang, Haiyuan; Lei, Yunlong			CPX Targeting DJ-1 Triggers ROS-induced Cell Death and Protective Autophagy in Colorectal Cancer	THERANOSTICS			English	Article						Ciclopirox olamine; DJ-1; mitochondria; ROS; Autophagy	OXIDATIVE STRESS; DRUG-RESISTANCE; STAGE-II; CICLOPIROX; EXPRESSION; REGULATOR; CHEMOTHERAPY; ANTIOXIDANTS; ACTIVATION; GENES	Rationale: Colorectal cancer (CRC) is one of the most common cancers worldwide. Ciclopirox olamine (CPX) has recently been identified to be a promising anticancer candidate; however, novel activities and detailed mechanisms remain to be uncovered. Methods: The cytotoxic potential of CPX towards CRC cells was examined in vitro and in vivo. The global gene expression pattern, ROS levels, mitochondrial function, autophagy, apoptosis, etc. were determined between control and CPX-treated CRC cells. Results: We found that CPX inhibited CRC growth by inhibiting proliferation and inducing apoptosis both in vitro and in vivo. The anti-cancer effects of CPX involved the downregulation of DJ-1, and overexpression of DJ-1 could reverse the cytotoxic effect of CPX on CRC cells. The loss of DJ-1 resulted in mitochondrial dysfunction and ROS accumulation, thus leading to CRC growth inhibition. The cytoprotective autophagy was provoked simultaneously, and blocking autophagy pharmacologically or genetically could further enhance the anti-cancer efficacy of CPX. Conclusion: Our study demonstrates that DJ-1 loss-induced ROS accumulation plays a pivotal role in CPX-mediated CRC inhibition, providing a further understanding for CRC treatment via modulating compensatory protective autophagy.	[Zhou, Jing; Yu, Linli; Zhang, Chundong; Bu, Youquan; Lei, Yunlong] Chongqing Med Univ, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [Zhou, Jing; Zhang, Lu; Wang, Meng; Zhou, Li; Feng, Xuping; Lan, Jiang; Gao, Wei; Huang, Canhua] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Zhou, Jing; Zhang, Lu; Wang, Meng; Zhou, Li; Feng, Xuping; Lan, Jiang; Gao, Wei; Huang, Canhua] Sichuan Univ, Canc Ctr, West China Hosp, Chengdu 610041, Sichuan, Peoples R China; [Zhou, Jing; Zhang, Lu; Wang, Meng; Zhou, Li; Feng, Xuping; Lan, Jiang; Gao, Wei; Huang, Canhua] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Sichuan, Peoples R China; [Zhou, Jing; Zhang, Lu; Wang, Meng; Zhou, Li; Feng, Xuping; Lan, Jiang; Gao, Wei; Huang, Canhua] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China; [Zhang, Haiyuan] Hainan Med Univ, Key Lab Trop Dis & Translat Med, Minist Educ, Haikou, Hainan, Peoples R China; [Zhang, Haiyuan] Hainan Med Univ, Dept Neurol, Affiliated Hosp 1, Haikou, Hainan, Peoples R China		Zhang, HY (corresponding author), Hainan Med Univ, Key Lab Trop Dis & Translat Med, Minist Educ, Haikou, Hainan, Peoples R China.; Zhang, HY (corresponding author), Hainan Med Univ, Dept Neurol, Affiliated Hosp 1, Haikou, Hainan, Peoples R China.; Lei, YL (corresponding author), Chongqing Med Univ, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China.; Lei, YL (corresponding author), Chongqing Med Univ, Mol Med & Canc Res Ctr, Chongqing 400016, Peoples R China.	hyzhang_88@163.com; leiyunlong@cqmu.edu.cn		Lei, Yunlong/0000-0002-7918-0221	Chinese NSFCNational Natural Science Foundation of China (NSFC) [81660499, 81872014, 81401951]; Chongqing Natural Science FoundationNatural Science Foundation of Chongqing [cstc2016jcyjA0227]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN201800429]	This work was supported by grants from Chinese NSFC (81660499, 81872014, and 81401951), Chongqing Natural Science Foundation (cstc2016jcyjA0227), and Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJQN201800429).	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J	Son, HJ; Jo, YS; Kim, MS; Yoo, NJ; Lee, SH				Son, Hyun Ji; Jo, Yun Sol; Kim, Min Sung; Yoo, Nam Jin; Lee, Sug Hyung			DAB2IP with tumor-inhibiting activities exhibits frameshift mutations in gastrointestinal cancers	PATHOLOGY RESEARCH AND PRACTICE			English	Article						DAB2; DAB2IP; Tumor suppressor gene; Frameshift mutation; GI cancer; Microsatellite instability	ABERRANT PROMOTER METHYLATION; PROTEIN HDAB2IP GENE; PROSTATE-CANCER; DOWN-REGULATION; MICROSATELLITE INSTABILITY; UROTHELIAL CARCINOMA; EXPRESSION; HETEROGENEITY; DOC-2/DAB2; AUTOPHAGY	A scaffold protein DAB2 and its interaction partner DAB2IP have putative tumor suppressor gene (TSG) functions. Previous studies identified that both DAB2 and DAB2IP genes were inactivated by promoter hypermethylation in human cancers, but their mutational alterations in cancers remain largely unknown. The aim of our study was to find whether DAB2 and DAB2IP were mutated in gastric (GCs) and colorectal cancers (CRCs) by DNA sequencing. Both DAB2 and DAB2IP have mononucleotide repeats in their coding sequence that could be mutation targets in high microsatellite instability (MSI-H) cancers. We analyzed GC and CRC tissues and found that 8 of 34 GCs (23.5%) and 15 of 79 CRCs (20.0%) with MSI-H harbored DAB2IP frameshift mutations. DAB2 frameshift mutations were found in 2 of 79 CRCs (2.5%) with MSI-H. These mutations were not detected in microsatellite stable (MSS) cancers. We also found intratumoral heterogeneity (ITH) of DAB2IP frameshift mutations in 7 of 16 CRCs (43.8%). Loss of DAB2IP protein expression was found in approximately 20% of GCs and CRCs irrespective of MSI and DAB2IP frameshift mutation status. Our study shows that the TSG DAB2IP harbored frameshift mutations and ITH as well as expression loss. Together these tumor alterations might play a role in tumorigenesis of GC and CRC with MSI-H by down-regulating the tumor-inhibiting activities of DAB2IP.	[Son, Hyun Ji; Jo, Yun Sol; Kim, Min Sung; Yoo, Nam Jin; Lee, Sug Hyung] Catholic Univ Korea, Dept Pathol, Coll Med, 505 Banpo Dong, Seoul 137701, South Korea		Lee, SH (corresponding author), Catholic Univ Korea, Dept Pathol, Coll Med, 505 Banpo Dong, Seoul 137701, South Korea.	suhulee@catholic.ac.kr			National Research Foundation of KoreaNational Research Foundation of Korea [2012R1A5A2047939]	This study was supported by grants from National Research Foundation of Korea (2012R1A5A2047939).	Akiyama Y, 2003, MOL CELL BIOL, V23, P8429, DOI 10.1128/MCB.23.23.8429-8439.2003; Bellazzo A, 2017, CELL DEATH DIFFER, V24, P15, DOI 10.1038/cdd.2016.134; Chen H, 2005, J BIOL CHEM, V280, P22437, DOI 10.1074/jbc.M501379200; Dote H, 2005, BRIT J CANCER, V92, P1117, DOI 10.1038/sj.bjc.6602458; Finkielstein CV, 2016, BIOESSAYS, V38, pS45, DOI 10.1002/bies.201670907; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Imai K, 2008, CARCINOGENESIS, V29, P673, DOI 10.1093/carcin/bgm228; Jiang Y, 2009, ONCOGENE, V28, P2999, DOI 10.1038/onc.2009.157; Jou YC, 2016, VIRCHOWS ARCH, V468, P733, DOI 10.1007/s00428-016-1924-y; Kang MR, 2009, J PATHOL, V217, P702, DOI 10.1002/path.2509; Karam JA, 2007, CLIN CANCER RES, V13, P4400, DOI 10.1158/1078-0432.CCR-07-0287; Kim HS, 2003, GASTROENTEROLOGY, V125, P708, DOI 10.1016/S0016-5085(03)01059-X; Kim MS, 2008, HUM PATHOL, V39, P1059, DOI 10.1016/j.humpath.2007.11.013; Kim MS, 2015, PATHOLOGY, V47, P598, DOI 10.1097/PAT.0000000000000305; Kim TM, 2014, J PATHOL, V233, P425, DOI 10.1002/path.4380; Kleeff J, 2002, DIS COLON RECTUM, V45, P1242, DOI 10.1007/s10350-004-6399-2; Kong ZL, 2010, CANCER RES, V70, P2829, DOI 10.1158/0008-5472.CAN-09-2919; Li C, 2015, AM J MED SCI, V349, P425, DOI 10.1097/MAJ.0000000000000436; Liu L, 2016, ONCOTARGET, V7, P3766, DOI 10.18632/oncotarget.6501; Marusyk A, 2012, NAT REV CANCER, V12, P323, DOI 10.1038/nrc3261; McGranahan N, 2015, CANCER CELL, V27, P15, DOI 10.1016/j.ccell.2014.12.001; Mok SC, 1998, ONCOGENE, V16, P2381, DOI 10.1038/sj.onc.1201769; Murphy KM, 2006, J MOL DIAGN, V8, P305, DOI 10.2353/jmoldx.2006.050092; Oh HR, 2015, PATHOLOGY, V47, P101, DOI 10.1097/PAT.0000000000000212; Tong JH, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-253; Wang Z, 2002, J BIOL CHEM, V277, P12622, DOI 10.1074/jbc.M110568200; Yano M, 2005, INT J CANCER, V113, P59, DOI 10.1002/ijc.20531; Yu L, 2012, NEOPLASIA, V14, P1203, DOI 10.1593/neo.121310; Zhang XJ, 2012, J GASTROEN HEPATOL, V27, P1117, DOI 10.1111/j.1440-1746.2011.07049.x; Zhou J, 2001, J BIOL CHEM, V276, P27793, DOI 10.1074/jbc.M102803200	30	2	2	0	1	ELSEVIER GMBH, URBAN & FISCHER VERLAG	JENA	OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY	0344-0338			PATHOL RES PRACT	Pathol. Res. Pract.	DEC	2018	214	12					2075	2080		10.1016/j.prp.2018.10.005			6	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	HG0YQ	WOS:000454675600023	30477644				2022-04-25	
J	Wang, XK; Lan, ZX; He, J; Lai, QH; Yao, X; Li, QY; Liu, YF; Lai, HS; Gu, CC; Yan, Q; Fang, YX; Zhang, Y; Li, AM; Liu, SD				Wang, Xinke; Lan, Zhixian; He, Juan; Lai, Qiuhua; Yao, Xiang; Li, Qingyuan; Liu, Yongfeng; Lai, Huasheng; Gu, Chuncai; Yan, Qun; Fang, Yuxin; Zhang, Yue; Li, Aimin; Liu, Side			LncRNA SNHG6 promotes chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in colorectal cancer cells	CANCER CELL INTERNATIONAL			English	Article						Colorectal cancer; SNHG6; ULK1-induced autophagy; Chemoresistance; ceRNA	COMPETING ENDOGENOUS RNA; LONG NONCODING RNA; SIGNALING PATHWAY; EXPRESSION; PROLIFERATION; PROGRESSION; MECHANISMS; UPF1; EMT	Background Chemotherapy resistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to poor prognosis. Long noncoding RNAs (lncRNAs) have been reported to regulate chemoresistance. We aimed to determine the role of the lncRNA small nucleolar RNA host gene 6 (SNHG6) in CRC cell chemoresistance. Methods Cell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. Animal models were used to determine chemoresistance in vivo, and micro RNA (miRNA) binding sites were detected by dual-luciferase reporter assays. Bioinformatics analysis was performed to predict miRNAs binding to SNHG6 and target genes of miR-26a-5p. SNHG6/miR-26a-5p/ULK1 axis and autophagy-related proteins were detected by qRT-PCR and western blotting. Furthermore, immunofluorescence was employed to confirm the presence of autophagosomes. Results SNHG6 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted autophagy, inhibited 5-FU-induced apoptosis, and increased 5-FU resistance in vivo. Bioinformatics analysis showed that miR-26a-5p might bind to SNHG6 and target ULK1, and dual-luciferase reporter assays confirmed this activity. qRT-PCR and western blotting showed that SNHG6 was able to negatively regulate miR-26a-5p but correlated positively with ULK1. Conclusion SNHG6 may promote chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in CRC cells.	[Wang, Xinke; Lan, Zhixian; He, Juan; Lai, Qiuhua; Yao, Xiang; Li, Qingyuan; Liu, Yongfeng; Lai, Huasheng; Gu, Chuncai; Yan, Qun; Fang, Yuxin; Zhang, Yue; Li, Aimin; Liu, Side] Southern Med Univ, Guangdong Prov Key Lab Gastroenterol, Dept Gastroenterol, Nanfang Hosp, 1838 Guangzhou Ave North, Guangzhou, Guangdong, Peoples R China		Li, AM; Liu, SD (corresponding author), Southern Med Univ, Guangdong Prov Key Lab Gastroenterol, Dept Gastroenterol, Nanfang Hosp, 1838 Guangzhou Ave North, Guangzhou, Guangdong, Peoples R China.	Lam0725@163.com; Liuside2011@163.com			China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2018M643130]; Medical Scientific Research Foundation of Guangdong Province, China [A2019538]; Guangdong gastrointestinal disease research center [2017B020209003]; Special Scientific Research Fund of Public Welfare Profession of National Health and Family Planning Commission [201502026]	This research was funded by China Postdoctoral Science Foundation, Grant Number 2018M643130; Medical Scientific Research Foundation of Guangdong Province, China, Grant Number A2019538; Guangdong gastrointestinal disease research center, Grant Number 2017B020209003; the Special Scientific Research Fund of Public Welfare Profession of National Health and Family Planning Commission, Grant Number 201502026.	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SEP 9	2019	19	1							234	10.1186/s12935-019-0951-6			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IW4MU	WOS:000484955100003	31516391	Green Published, gold			2022-04-25	
J	Lin, SC; Yang, LH; Yao, YL; Xu, LY; Xiang, YQ; Zhao, HY; Wang, LX; Zuo, ZG; Huang, XY; Zhao, CG				Lin, Shichong; Yang, Lehe; Yao, Yulei; Xu, Lingyuan; Xiang, Youqun; Zhao, Haiyang; Wang, Liangxing; Zuo, Zhigui; Huang, Xiaoying; Zhao, Chengguang			Flubendazole demonstrates valid antitumor effects by inhibiting STAT3 and activating autophagy	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH			English	Article						Flubendazole; Colorectal cancer; STAT3; Autophagy; Apoptosis	CANCER; RESISTANCE; OVERCOMES	BackgroundSignal transducer and activator of transcription 3 (STAT3) is an oncogene, which upregulates in approximately 70% of human cancers. Autophagy is an evolutionarily conserved process which maintains cellular homeostasis and eliminates damaged cellular components. Moreover, the STAT3 signaling pathway, which may be triggered by cancer cells, has been implicated in the autophagic process.MethodsIn this study, we found that the anthelmintic flubendazole exerts potent antitumor activity in three human colorectal cancer (CRC) cell lines and in the nude mouse model. The inhibition of cell proliferation in vitro by flubendazole was evaluated using a clonogenic assay and the MTT assay. Western blot analysis, flow cytometry analysis, siRNA growth experiment and cytoplasmic and nuclear protein extraction were used to investigate the mechanisms of inhibiting STAT3 signaling and activation of autophagy induced by flubendazole. Additionally, the expression of STAT3 and mTOR was analyzed in paired colorectal cancer and normal tissues collected from clinical patients.ResultsFlubendazole blocked the IL6-induced nuclear translocation of STAT3, which led to inhibition of the transcription of STAT3 target genes, such as MCL1, VEGF and BIRC5. In addition, flubendazole also reduced the expression of P-mTOR, P62, BCL2, and upregulated Beclin1 and LC3-I/II, which are major autophagy-related genes. These processes induced potent cell apoptosis in CRC cells. In addition, flubendazole displayed a synergistic effect with the chemotherapeutic agent 5-fluorouracil in the treatment of CRC.ConclusionsTaken together, these results indicate that flubendazole exerts antitumor activities by blocking STAT3 signaling and inevitably affects the autophagy pathway. Flubendazole maybe a novel anticancer drug and offers a distinctive therapeutic strategy in neoadjuvant chemotherapy of CRC.	[Lin, Shichong; Yang, Lehe; Yao, Yulei; Xu, Lingyuan; Zhao, Chengguang] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China; [Lin, Shichong; Yang, Lehe; Yao, Yulei; Xu, Lingyuan; Xiang, Youqun; Wang, Liangxing; Zuo, Zhigui; Huang, Xiaoying] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China; [Zhao, Haiyang] Wenzhou Univ, Inst Life Sci, Wenzhou 325035, Zhejiang, Peoples R China		Zhao, CG (corresponding author), Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China.; Zuo, ZG; Huang, XY (corresponding author), Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China.	zuozg007@126.com; zjwzhxy@126.com; zhaochengguang@wmu.edu.cn	Zhao, Chengguang/AAK-2981-2021		Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LY17H160055]; Medical Scientific Research Fund of Zhejiang Province [2019322308]; Wenzhou science and technology project [Y20170280]	This work was financially supported by the Zhejiang Provincial Natural Science Foundation of China (LY17H160055), Medical Scientific Research Fund of Zhejiang Province (2019322308) and Wenzhou science and technology project (Y20170280).	Beebe JD, 2018, PHARMACOL THERAPEUT, V191, P74, DOI 10.1016/j.pharmthera.2018.06.006; Canova Kristyna, 2017, Acta Medica (Hradec Kralove), V60, P5, DOI 10.14712/18059694.2017.44; Chauhan S, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms9620; Fu SL, 2019, CANCER LETT, V448, P11, DOI 10.1016/j.canlet.2019.01.026; Huang Z, 2018, THERANOSTICS, V8, P4995, DOI 10.7150/thno.26627; Huynh J, 2019, NAT REV CANCER, V19, P82, DOI 10.1038/s41568-018-0090-8; Johnson DE, 2018, NAT REV CLIN ONCOL, V15, P234, DOI 10.1038/nrclinonc.2018.8; Keklikoglou I, 2019, NAT CELL BIOL, V21, P190, DOI 10.1038/s41556-018-0256-3; Kim YJ, 2018, CANCER LETT, V412, P118, DOI 10.1016/j.canlet.2017.10.020; Kuo WY, 2017, THERANOSTICS, V7, P647, DOI 10.7150/thno.16827; Liu PF, 2018, THERANOSTICS, V8, P830, DOI 10.7150/thno.22012; Lu L, 2018, ONCOGENE, V37, P5292, DOI 10.1038/s41388-018-0340-y; Oh E, 2018, INT J CANCER, V143, P1978, DOI 10.1002/ijc.31585; Siegel RL, 2019, CA-CANCER J CLIN, V69, P7, DOI 10.3322/caac.21551; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; Spagnuolo PA, 2010, BLOOD, V115, P4824, DOI 10.1182/blood-2009-09-243055; Wei J, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1072-8; Wei N, 2019, ONCOGENE, V38, P1676, DOI 10.1038/s41388-018-0547-y; Wolf AMD, 2018, CA-CANCER J CLIN, V68, P250, DOI 10.3322/caac.21457; Yang LH, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-018-1015-9; You LK, 2015, AUTOPHAGY, V11, P729, DOI 10.1080/15548627.2015.1017192; Yu H, 2014, NAT REV CANCER, V14, P736, DOI 10.1038/nrc3818; Zhang T, 2017, ONCOGENE, V36, P6627, DOI 10.1038/onc.2017.270; Zhao CG, 2016, TRENDS PHARMACOL SCI, V37, P47, DOI 10.1016/j.tips.2015.10.001; Zheng HL, 2019, MOL CARCINOGEN, V58, P565, DOI 10.1002/mc.22951; Zheng K, 2019, THERANOSTICS, V9, P104, DOI 10.7150/thno.30308; Zhu H, 2018, THERANOSTICS, V8, P676, DOI 10.7150/thno.21463	27	23	24	1	3	BMC	LONDON	CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	1756-9966			J EXP CLIN CANC RES	J. Exp. Clin. Cancer Res.	JUL 8	2019	38								293	10.1186/s13046-019-1303-z			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IJ1SX	WOS:000475679700002	31287013	Green Published, gold			2022-04-25	
J	Liu, MH; Zhao, G; Zhang, D; An, WX; Lai, HL; Li, XF; Cao, SS; Lin, XK				Liu, Minghua; Zhao, Ge; Zhang, Dan; An, Weixiao; Lai, Honglin; Li, Xiaofang; Cao, Shousong; Lin, Xiukun			Active fraction of clove induces apoptosis via PI3K/Akt/mTOR-mediated autophagy in human colorectal cancer HCT-116 cells	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						clove; apoptosis; autophagy; coloretal cancer; phosphoinositide 3-kinase; Akt; mechanistic target of rapamycin pathway	SYZYGIUM-AROMATICUM L.; OLEANOLIC ACID; EUGENIA-CARYOPHYLLATA; ESSENTIAL OIL; IN-VITRO; INHIBITION; INDUCTION; PATHWAYS; CYCLE; SUPPRESSION	Previous studies by our group have demonstrated that extract of clove exhibits potent anticancer effects in vitro and in vivo. In the present study, the effect of an extracted and isolated active fraction of clove (AFC) on induction of cellular apoptosis in human colorectal cancer HCT-116 cells was investigated by morphological observation, flow cytometry, and western blotting analysis. The results revealed that AFC induced apoptosis of HCT-116 cells. AFC also induced autophagy, demonstrated by increased punctuate microtubule-associated protein 1A/1B-light chain 3 (LC3) staining, and LC3-II and Beclin-1 protein expression levels. Furthermore, the autophagy inhibitors 3-MA and baflomycin A1 potentiated the pro-apoptotic activity of AFC in HCT-116 cells. AFC also inhibited the phosphorylation of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin signaling pathway. The present study may improve the existing understanding of the anticancer mechanisms of clove and provide a scientific rationale for AFC to be further developed as a promising novel anticancer agent for the treatment of colorectal cancer.	[Liu, Minghua; Zhao, Ge; Zhang, Dan; An, Weixiao; Lai, Honglin; Li, Xiaofang; Cao, Shousong; Lin, Xiukun] Southwest Med Univ, Sch Pharm, Dept Pharmacol, 319 Zhongshan Rd, Luzhou 646000, Sichuan, Peoples R China		Cao, SS; Lin, XK (corresponding author), Southwest Med Univ, Sch Pharm, Dept Pharmacol, 319 Zhongshan Rd, Luzhou 646000, Sichuan, Peoples R China.	shousongc@gmail.com; linxiukun@yahoo.com		Lin, Xiukun/0000-0002-0306-4953	National innovative drug development projects of China [014ZX-09102043-001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81302906, 81273550, 41306157]; Distinguished Professor Research Startup Funding from Southwest Medical University; Sichuan Sci. and Tech Dept., China [2017SZ0201, 17GJHZ0074]	The present study was supported by grants from the National innovative drug development projects of China (grant no. 014ZX-09102043-001), National Natural Science Foundation of China (grant nos. 81302906, 81273550 and 41306157), and the Distinguished Professor Research Startup Funding (SC and XKL) from Southwest Medical University. This study was also supported in part by the grants from Sichuan Sci. and Tech Dept., China (grant nos. 2017SZ0201 and 17GJHZ0074).	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J	Itahana, Y; Itahana, K				Itahana, Yoko; Itahana, Koji			Emerging Roles of Mitochondrial p53 and ARF	CURRENT DRUG TARGETS			English	Review						ARF; apoptosis; autophagy; mitochondria; mitochondrial localization; mitochondrial metabolism; p53; tumor suppressor	DNA-BINDING DOMAIN; COLORECTAL-CANCER CELLS; BASE EXCISION-REPAIR; TUMOR-SUPPRESSOR P53; NUCLEOLAR LOCALIZATION; P53-DEPENDENT APOPTOSIS; FUNCTIONAL INTERACTIONS; INDUCE APOPTOSIS; ACTIVATES P53; PROTEIN	After mitochondria colonized eukaryotic cells more than a billion years ago, they acquired numerous functions over the course of evolution, such as those involved in controlling apoptosis, autophagy, and cellular metabolism together with host cells. The major tumor suppressors, p53 and ARF in the nucleus also participate in such crosstalk between host cells and mitochondria by activating p53 target genes involved in varied mitochondrial functions. However, recent evidence suggests that p53 and ARF can also directly localize to mitochondria and contribute to this cross talk to maintain tissue homeostasis for the prevention of various diseases. Here, we discuss the functions of mitochondrial p53 and ARF via interactions with mitochondrial proteins as well as the mechanism of the localization of p53 and ARF to mitochondria. Because mitochondrial dysregulation is involved in the development of several disease types, such as cancer, neurodegenerative diseases, and age-related diseases, understanding the roles of p53 and ARF in mitochondria may facilitate the development of novel mitochondrial-specific drug targets against such diseases.	[Itahana, Yoko; Itahana, Koji] Duke NUS Grad Med Sch Singapore, Canc & Stem Cell Biol Program, Singapore 169857, Singapore		Itahana, K (corresponding author), Duke NUS Grad Med Sch Singapore, Canc & Stem Cell Biol Program, Rm 07-18,Level 7,8 Coll Rd, Singapore 169857, Singapore.	koji.itahana@duke-nus.edu.sg	Itahana, Koji/J-5505-2013	Itahana, Koji/0000-0002-7241-2894	NMRC IRG grant [NMRC/1303/2011]; St. Baldrick's Foundation International Beneficiary grant; Duke-National University of Singapore core grant	We acknowledge the funding from NMRC IRG grant (NMRC/1303/2011), St. Baldrick's Foundation International Beneficiary grant, and Duke-National University of Singapore core grant.	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J	Galadari, S; Rahman, A; Pallichankandy, S; Thayyullathil, F				Galadari, Sehamuddin; Rahman, Anees; Pallichankandy, Siraj; Thayyullathil, Faisal			Tumor suppressive functions of ceramide: evidence and mechanisms	APOPTOSIS			English	Article						Ceramide; Apoptosis; Autophagy; Senescence; Tumor suppression; Molecular targets	ACTIVATED PROTEIN-KINASE; DAUNORUBICIN-INDUCED APOPTOSIS; CHRONIC MYELOID-LEUKEMIA; COLORECTAL-CANCER CELLS; CYTOCHROME-C RELEASE; LONGEVITY ASSURANCE GENE-1; ENDOTHELIAL GROWTH-FACTOR; ANALOG LCL29. EVIDENCE; RETICULUM ER STRESS; ACID SPHINGOMYELINASE	Studies over the past two decades have identified ceramide as a multifunctional central molecule in the sphingolipid biosynthetic pathway. Given its diverse tumor suppressive activities, molecular understanding of ceramide action will produce fundamental insights into processes that limit tumorigenesis and may identify key molecular targets for therapeutic intervention. Ceramide can be activated by a diverse array of stresses such as heat shock, genotoxic damage, oxidative stress and anticancer drugs. Ceramide triggers a variety of tumor suppressive and anti-proliferative cellular programs such as apoptosis, autophagy, senescence, and necroptosis by activating or repressing key effector molecules. Defects in ceramide generation and metabolism in cancer contribute to tumor cell survival and resistance to chemotherapy. The potent and versatile anticancer activity profile of ceramide has motivated drug development efforts to (re-)activate ceramide in established tumors. This review focuses on our current understanding of the tumor suppressive functions of ceramide and highlights the potential downstream targets of ceramide which are involved in its tumor suppressive action.	[Galadari, Sehamuddin; Rahman, Anees; Pallichankandy, Siraj; Thayyullathil, Faisal] UAE Univ, Coll Med & Hlth Sci, Dept Biochem, Cell Signaling Lab, Abu Dhabi, U Arab Emirates; [Galadari, Sehamuddin] Al Jalila Fdn Res Ctr, Dubai, U Arab Emirates		Galadari, S (corresponding author), UAE Univ, Coll Med & Hlth Sci, Dept Biochem, Cell Signaling Lab, POB 17666, Abu Dhabi, U Arab Emirates.	sehamuddin@uaeu.ac.ae	Galadari, Sehamuddin/AAK-6039-2020		UAE University-National Research Foundation [31M097]; Terry Fox Foundation for Cancer Research [21M093]; Sheikh Hamdan Award for Medical Sciences [MRG-60/2011-2012]; Al Jalila Foundation for Medical Education and Research	This work was financially supported by grants from the UAE University-National Research Foundation (31M097), Terry Fox Foundation for Cancer Research (21M093), The Sheikh Hamdan Award for Medical Sciences (MRG-60/2011-2012). SG is supported by the Al Jalila Foundation for Medical Education and Research.	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Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	CE5VY	WOS:000351905000010	25702155				2022-04-25	
J	Jamali, L; Sadeghi, H; Ghasemi, MR; Mohseni, R; Nazemalhosseini-Mojarad, E; Yassaee, VR; Larki, P; Zali, MR; Mirfakhraie, R				Jamali, Leila; Sadeghi, Hossein; Ghasemi, Mohammad-Reza; Mohseni, Roohollah; Nazemalhosseini-Mojarad, Ehsan; Yassaee, Vahid Reza; Larki, Pegah; Zali, Mohammad Reza; Mirfakhraie, Reza			Autophagy ATG16L1 rs2241880 impacts the colorectal cancer risk: A case-control study	JOURNAL OF CLINICAL LABORATORY ANALYSIS			English	Article						ATG5; autophagy; colorectal cancer (CRC); single-nucleotide polymorphism (SNP)	POLYMORPHISM	Background Despite many efforts to discover the important role of the autophagy process in the pathogenesis of colorectal cancer (CRC), the exact involved molecular mechanism still remains to be elucidated. Recently, a limited number of studies have been employed to discover the impact of autophagy genes' variants on the development and progression of CRC. Here, we evaluated the association between two single-nucleotide polymorphisms (SNPs) in the main components of the autophagy genes, ATG16L1 rs2241880, and ATG5 rs1475270, and the CRC risk in an Iranian population. Methods During this investigation, a total of 369 subjects, including 179 CRC patients and 190 non-cancer controls have been genotyped using Tetra-primer amplification refractory mutation system-polymerase chain reaction (TP-ARMS-PCR) method. Result The results demonstrated that the T allele of the ATG16L1 rs2241880 was significantly associated with the increased risk of CRC in the studied population (OR 1.64, 95% CI: 1.21-2.22, p = 0.0015). Moreover, ATG16L1 rs2241880 TT genotype increased the susceptibility to CRC (OR 3.31, 95% CI: 1.64-6.69, p = 0.0008). Furthermore, a significant association was observed under the recessive and dominant inheritance models (p = 0.0015 and p = 0.017, respectively). No statistically significant differences were found in the ATG5 rs1475270 alleles and genotypes between the cases and controls. Conclusion The results of the present study may be helpful concerning the risk stratification in CRC patients based on the genotyping approach of autophagy pathways and emphasize the need for further investigations among different populations and ethnicities to refine our conclusions.	[Jamali, Leila; Ghasemi, Mohammad-Reza; Mirfakhraie, Reza] Shahid Beheshti Univ Med Sci, Sch Med, Dept Med Genet, Koodakyar St,Velenjak Ave,Chamran Highway, Tehran 193954719, Iran; [Sadeghi, Hossein; Yassaee, Vahid Reza; Larki, Pegah] Shahid Beheshti Univ Med Sci, Genom Res Ctr, Yeman St,Chamran Highway, Tehran, Iran; [Mohseni, Roohollah] Shahrekord Univ Med Sci, Clin Biochem Res Ctr, Basic Hlth Sci Inst, Shahrekord, Iran; [Nazemalhosseini-Mojarad, Ehsan; Zali, Mohammad Reza] Shahid Beheshti Univ Med Sci, Gastroenterol & Liver Dis Res Ctr, Res Inst Gastroenterol & Liver Dis, Dept Gastrointestinal Canc, Tehran, Iran; [Mirfakhraie, Reza] Shahid Beheshti Univ Med Sci, Hematopoiet Stem Cell Res Ctr, Tehran, Iran		Mirfakhraie, R (corresponding author), Shahid Beheshti Univ Med Sci, Sch Med, Dept Med Genet, Koodakyar St,Velenjak Ave,Chamran Highway, Tehran 193954719, Iran.; Sadeghi, H (corresponding author), Shahid Beheshti Univ Med Sci, Genom Res Ctr, Yeman St,Chamran Highway, Tehran, Iran.	Hsadeqi86@gmail.com; reza_mirfakhraie@yahoo.com		Mirfakhraie, Reza/0000-0003-1709-8975; Ghasemi, Mohammad-Reza/0000-0002-3183-5495	Genomic Research Center, Shahid Beheshti University of Medical Sciences	Y The authors would like to thank the "Genomic Research Center, Shahid Beheshti University of Medical Sciences" for financial support	Al-Ali R, 2017, GENE REP, V7, P74, DOI 10.1016/j.genrep.2017.02.001; Amaravadi R, 2016, GENE DEV, V30, P1913, DOI 10.1101/gad.287524.116; Budak Diler Songul, 2018, Asian Pac J Cancer Prev, V19, P2625, DOI 10.22034/APJCP.2018.19.9.2625; Burada F, 2015, WORLD J GASTRO ONCOL, V7, P271, DOI 10.4251/wjgo.v7.i11.271; Burada F, 2016, PATHOL ONCOL RES, V22, P317, DOI 10.1007/s12253-015-0006-9; Cao H, 2016, INT J CLIN EXP PATHO, V9, P8586; Collins A., 2012, OPEN BIOINFORM J, V6, P55, DOI [10.2174/1875036201206010055, DOI 10.2174/1875036201206010055]; Dolatkhah R, 2015, BMC PUBLIC HEALTH, V15, DOI 10.1186/s12889-015-2342-9; Fernandez-Mateos J, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-07270-0; Gaaib JN, 2011, TIKRIT J PURE SCI, V16, P9; Gandomani HS, 2017, BIOMED RES THER, V4, P1656, DOI 10.15419/bmrat.v4i10.372; Grimm WA, 2016, GUT, V65, P456, DOI 10.1136/gutjnl-2014-308735; Guerrero-Martinez JA, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-20217-3; Guo LY, 2014, NUCLEIC ACIDS RES, V42, pD1033, DOI 10.1093/nar/gkt1167; Haggar Fatima A, 2009, Clin Colon Rectal Surg, V22, P191, DOI 10.1055/s-0029-1242458; Huxley RR, 2009, INT J CANCER, V125, P171, DOI 10.1002/ijc.24343; Janji B, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.00887; Johnson CM, 2013, CANCER CAUSE CONTROL, V24, P1207, DOI 10.1007/s10552-013-0201-5; Klionsky DJ, 2014, NAT STRUCT MOL BIOL, V21, P336, DOI 10.1038/nsmb.2787; Lesurf R, 2016, NUCLEIC ACIDS RES, V44, pD126, DOI 10.1093/nar/gkv1203; Li MY, 2018, CHIN J CANCER, V37, DOI 10.1186/s40880-018-0268-1; Marinkovic M, 2018, OXID MED CELL LONGEV, V2018, DOI 10.1155/2018/8023821; Messeguer X, 2002, BIOINFORMATICS, V18, P333, DOI 10.1093/bioinformatics/18.2.333; Migliore L, 2011, J BIOMED BIOTECHNOL, DOI 10.1155/2011/792362; Mokarram P, 2017, AUTOPHAGY, V13, P781, DOI 10.1080/15548627.2017.1290751; Nicoli ER, 2014, ROM J MORPHOL EMBRYO, V55, P57; Nissar S., 2021, GENETIC POLYMORPHISM, P1; Pourhoseingholi MA, 2012, WORLD J GASTRO ONCOL, V4, P68, DOI 10.4251/wjgo.v4.i4.68; Sameer AS, 2013, FRONT ONCOL, V3, DOI 10.3389/fonc.2013.00114; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; Sole X, 2006, BIOINFORMATICS, V22, P1928, DOI 10.1093/bioinformatics/btl268; Vargas AJ, 2012, NUTR CLIN PRACT, V27, P613, DOI 10.1177/0884533612454885; Ward LD, 2016, NUCLEIC ACIDS RES, V44, pD877, DOI 10.1093/nar/gkv1340; Westbrook TF, 2005, CELL, V121, P837, DOI 10.1016/j.cell.2005.03.033; White KAM, 2016, CANCER MED-US, V5, P3336, DOI 10.1002/cam4.929; Wu WKK, 2012, ONCOGENE, V31, P939, DOI 10.1038/onc.2011.295; Yu JH, 2019, MOL CELL BIOCHEM, V457, P191, DOI 10.1007/s11010-019-03523-w; Zhang HF, 2009, HUM GENET, V125, P627, DOI 10.1007/s00439-009-0660-7	38	0	0	3	3	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN, NJ 07030 USA	0887-8013	1098-2825		J CLIN LAB ANAL	J. Clin. Lab. Anal.	JAN	2022	36	1							e24169	10.1002/jcla.24169		DEC 2021	5	Medical Laboratory Technology	Science Citation Index Expanded (SCI-EXPANDED)	Medical Laboratory Technology	YH0NC	WOS:000729173200001	34894411	Green Published, gold			2022-04-25	
J	Kageyama, S; Ii, H; Taniguchi, K; Kubota, S; Yoshida, T; Isono, T; Chano, T; Yoshiya, T; Ito, K; Yoshiki, T; Kawauchi, A; Nakata, S				Kageyama, Susumu; Ii, Hiromi; Taniguchi, Keiko; Kubota, Shigehisa; Yoshida, Tetsuya; Isono, Takahiro; Chano, Tokuhiro; Yoshiya, Taku; Ito, Kosei; Yoshiki, Tatsuhiro; Kawauchi, Akihiro; Nakata, Susumu			Mechanisms of Tumor Growth Inhibition by Depletion of gamma-Glutamylcyclotransferase (GGCT): A Novel Molecular Target for Anticancer Therapy	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						GGCT; C7orf24; cancer; cellular senescence; autophagy	CANCER-CELL-PROLIFERATION; HUMAN C7ORF24 GENE; GLUTAMYL CYCLOTRANSFERASE; IDENTIFICATION; EXPRESSION; KNOCKDOWN; APOPTOSIS; BIOMARKER; SYSTEM; ENZYME	gamma-Glutamylcyclotransferase (GGCT), which is one of the major enzymes involved in glutathione metabolism, is upregulated in a wide range of cancers-glioma, breast, lung, esophageal, gastric, colorectal, urinary bladder, prostate, cervical, ovarian cancers and osteosarcoma-and promotes cancer progression; its depletion leads to the suppression of proliferation, invasion, and migration of cancer cells. It has been demonstrated that the suppression or inhibition of GGCT has an antitumor effect in cancer-bearing xenograft mice. Based on these observations, GGCT is now recognized as a promising therapeutic target in various cancers. This review summarizes recent advances on the mechanisms of the antitumor activity of GGCT inhibition.	[Kageyama, Susumu; Kubota, Shigehisa; Yoshida, Tetsuya; Yoshiki, Tatsuhiro; Kawauchi, Akihiro] Shiga Univ Med Sci, Dept Urol, Otsu, Shiga 5202192, Japan; [Ii, Hiromi; Taniguchi, Keiko; Yoshiki, Tatsuhiro; Nakata, Susumu] Kyoto Pharmaceut Univ, Dept Clin Oncol, Kyoto 6078414, Japan; [Isono, Takahiro] Shiga Univ Med Sci, Cent Res Lab, Otsu, Shiga 5202192, Japan; [Chano, Tokuhiro] Shiga Univ Med Sci, Dept Clin Lab Med, Otsu, Shiga 5202192, Japan; [Yoshiya, Taku] Peptide Inst Inc, Osaka 5670085, Japan; [Ito, Kosei] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Bone Biol, Nagasaki 8528588, Japan		Nakata, S (corresponding author), Kyoto Pharmaceut Univ, Dept Clin Oncol, Kyoto 6078414, Japan.	kageyama@belle.shiga-med.ac.jp; iihiromi@mb.kyoto-phu.ac.jp; kd16006@poppy.kyoto-phu.ac.jp; kubota@belle.shiga-med.ac.jp; yoshida9@belle.shiga-med.ac.jp; isono@belle.shiga-med.ac.jp; chano@belle.shiga-med.ac.jp; t.yoshiya@peptide.co.jp; itok@nagasaki-u.ac.jp; yoshiki@mb.kyoto-phu.ac.jp; kawauchi@belle.shiga-med.ac.jp; snakata@mb.kyoto-phu.ac.jp	Chano, Tokuhiro/F-5816-2018	Chano, Tokuhiro/0000-0002-9959-1183; Kageyama, Susumu/0000-0001-7150-647X	JSPS KAKENHI by the Ministry of Education, Culture, Sports, Science and Technology [17K11131, 18K09192, 16K08722, 26461436]	This research was funded by JSPS KAKENHI Grant Numbers 17K11131, 18K09192, 16K08722, and 26461436 by the Ministry of Education, Culture, Sports, Science and Technology-Supported Program for the Strategic Research Foundation at Private Universities 2015-2019.	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J. Mol. Sci.	JUL	2018	19	7							2054	10.3390/ijms19072054			11	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	GR6UX	WOS:000442807400233	30011933	Green Submitted, Green Published, gold			2022-04-25	
J	Zhao, HG; Zhou, SL; Lin, YY; Wang, H; Dai, HF; Huang, FY				Zhao, Huan-Ge; Zhou, Song-Lin; Lin, Ying-Ying; Wang, Hua; Dai, Hao-Fu; Huang, Feng-Ying			Autophagy plays a protective role against apoptosis induced by toxicarioside N via the Akt/mTOR pathway in human gastric cancer SGC-7901 cells	ARCHIVES OF PHARMACAL RESEARCH			English	Article						Toxicarioside N; Autophagy; Apoptosis; SGC-7901 cells; Akt; mTOR	CARDIAC-GLYCOSIDES; COLORECTAL-CANCER; MODULATION; DISCOVERY; INDUCTION; GROWTH; AGENTS; KINASE; TARGET	Toxicarioside N (Tox N), a natural product extract from Antiaris toxicaria, has been reported to induce apoptosis in human gastric cancer cells. However, the mechanism and actual role of autophagy in Tox N-induced apoptosis of human gastric cancer cells remains poorly understood. In the current study, we demonstrated that Tox N could induce autophagy by inhibiting the Akt/mTOR signaling pathway in SGC-7901 cells. Moreover, we found that the inhibition of autophagy by 3-methyladenine, an autophagy inhibitor, enhanced Tox N-induced apoptotic cell death. However, the stimulation of autophagy by rapamycin, an autophagy activator, remarkably suppressed Tox N-induced apoptosis, suggesting that autophagy plays a protective role in Tox N-induced apoptosis. Thus, the results from this study suggested that Tox N combination with an autophagy inhibitor might be a promising strategy to enhance the anticancer activity of Tox N for the treatment of human gastric cancer.	[Zhao, Huan-Ge; Zhou, Song-Lin; Lin, Ying-Ying; Wang, Hua; Huang, Feng-Ying] Minist Educ, Hainan Med Coll, Key Lab Trop Dis & Translat Med, Haikou 571199, Hainan, Peoples R China; [Zhao, Huan-Ge; Zhou, Song-Lin; Lin, Ying-Ying; Wang, Hua; Huang, Feng-Ying] Hainan Med Coll, Hainan Prov Key Lab Trop Med, Haikou 571199, Hainan, Peoples R China; [Dai, Hao-Fu] Chinese Acad Trop Agr Sci, Inst Trop Biosci, Haikou 571199, Hainan, Peoples R China; [Dai, Hao-Fu] Chinese Acad Trop Agr Sci, Inst Biotechnol, Haikou 571199, Hainan, Peoples R China		Huang, FY (corresponding author), Minist Educ, Hainan Med Coll, Key Lab Trop Dis & Translat Med, Haikou 571199, Hainan, Peoples R China.; Huang, FY (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, Haikou 571199, Hainan, Peoples R China.; Dai, HF (corresponding author), Chinese Acad Trop Agr Sci, Inst Biotechnol, Haikou 571199, Hainan, Peoples R China.	daihaofu@itbb.org.cn; fyhuang16@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81560484, 81460557]; Hainan province natural science foundation of China [817147]	The authors acknowledge the financial support provided by The National Natural Science Foundation of China, Project Nos 81560484 and 81460557, Hainan province natural science foundation of China, Project No. 817147.	Brothers KM, 2018, EXP EYE RES, V168, P12, DOI 10.1016/j.exer.2017.12.010; Chang YT, 2011, EUR J CLIN INVEST, V41, P84, DOI 10.1111/j.1365-2362.2010.02383.x; Charalampakis N, 2018, CANCER MED-US, V7, P123, DOI 10.1002/cam4.1274; Cho KH, 2014, ONCOL REP, V31, P248, DOI 10.3892/or.2013.2809; Cragg GM, 2016, MED PRIN PRACT, V25, P41, DOI 10.1159/000443404; Dou QH, 2016, CANCER RES, V76, P4457, DOI 10.1158/0008-5472.CAN-15-2887; Foukakis T, 2007, ACTA ONCOL, V46, P277, DOI 10.1080/02841860701218634; Fulda S, 2015, ONCOGENE, V34, P5105, DOI 10.1038/onc.2014.458; Huang FY, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0050351; Huang YH, 2017, ONCOTARGET, V8, P52783, DOI 10.18632/oncotarget.17189; Lee HW, 2014, BMB REP, V47, P697, DOI 10.5483/BMBRep.2014.47.12.069; Levin-Salomon V, 2014, APOPTOSIS, V19, P346, DOI 10.1007/s10495-013-0918-3; Li X, 2013, ACTA PHARMACOL SIN, V34, P612, DOI 10.1038/aps.2013.23; Liu C, 2017, WORLD J GASTROENTERO, V23, P1964, DOI 10.3748/wjg.v23.i11.1964; Newman RA, 2008, MOL INTERV, V8, P36, DOI 10.1124/mi.8.1.8; Prassas I, 2008, NAT REV DRUG DISCOV, V7, P926, DOI 10.1038/nrd2682; Prassas I, 2011, MOL CANCER THER, V10, P2083, DOI 10.1158/1535-7163.MCT-11-0421; Rubinsztein DC, 2012, NAT REV DRUG DISCOV, V11, P709, DOI 10.1038/nrd3802; Shi LS, 2010, J NAT PROD, V73, P1214, DOI 10.1021/np9005212; Singh SS, 2018, ONCOGENE, V37, P1142, DOI 10.1038/s41388-017-0046-6; Tanida I, 2010, METHODS MOL BIOL, V648, P193, DOI 10.1007/978-1-60761-756-3_13; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; Van Cutsem E, 2016, LANCET, V388, P2654, DOI 10.1016/S0140-6736(16)30354-3; Vitale I, 2015, INT J DEV BIOL, V59, P95, DOI 10.1387/ijdb.150082iv; Zhang Y, 2015, DRUG DES DEV THER, V9, P2001, DOI 10.2147/DDDT.S77071; Zhao HG, 2018, ARCH PHARM RES, V41, P71, DOI 10.1007/s12272-017-0956-4; Zheng Hai-yang, 2012, Cancer Biology Medicine, V9, P105, DOI 10.3969/j.issn.2095-3941.2012.02.004; Zou N, 2017, BMC COMPLEM ALTERN M, V17, DOI 10.1186/s12906-017-2017-4; Zuo WJ, 2013, PHYTOCHEM LETT, V6, P1, DOI 10.1016/j.phytol.2012.10.001	29	7	9	3	9	PHARMACEUTICAL SOC KOREA	SEOUL	1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA	0253-6269	1976-3786		ARCH PHARM RES	Arch. Pharm. Res.	OCT	2018	41	10					986	994		10.1007/s12272-018-1049-8			9	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	GU3NF	WOS:000445185100005	29992400				2022-04-25	
J	Thongchot, S; Ferraresi, A; Vidoni, C; Loilome, W; Yongvanit, P; Namwat, N; Isidoro, C				Thongchot, Suyanee; Ferraresi, Alessandra; Vidoni, Chiara; Loilome, Watcharin; Yongvanit, Puangrat; Namwat, Nisana; Isidoro, Ciro			Resveratrol interrupts the pro-invasive communication between cancer associated fibroblasts and cholangiocarcinoma cells	CANCER LETTERS			English	Article						Autophagy; Desmoplastic stroma; Nutraceuticals; Cancer therapy; Cytokines; Cholangiocarcinoma; Cancer associated fibroblasts; Resveratrol; Tumor invasion; Cadherins	EPITHELIAL-MESENCHYMAL TRANSITION; FLUKE OPISTHORCHIS-VIVERRINI; COLORECTAL-CANCER; MIGRATION; AUTOPHAGY; PROGRESSION; ACTIVATION; EXPRESSION; PROMOTE; GROWTH	Cholangiocarcinoma (CCA), the cancer arising from the epithelial cells of bile ducts, is a prototype of inflammatory-driven cancer. Cytokines released by cancer associated fibroblasts (CAFs) play a pivotal role in CCA progression, driving the epigenetic Epithelial-to-Mesenchymal transition and the growth and metastasization of CCA cells. Consistently, the conditioned medium from CCA-derived CAFs further stimulated the secretion of IL-6, and to a lesser extent of IL-8, by CCA cells. CCA has a poor prognosis, because of late diagnosis and of high resistance to radio- and chemo-therapy of CCA cells. Targeting the CAFs and their secretion could be an alternative option. We found that while IL-6 indeed promoted the cell migration of invasive CCA cells, the nutraceutical Resveratrol strongly counteracted this effect both in CCA cells and in immortalized cholangiocytes. More importantly, here we show that Resveratrol has the potential to abrogate the secretion of IL-6 by CAFs. While the conditioned medium from CAFs strongly induced IL-6 mediated motility of CCA cells, the conditioned medium from CAFs pre-treated with Resveratrol completely halted cancer cell motility and reverted the N-to E-cadherin switch in migrating cells. This effect was associated with stimulation of autophagy in the cancer cells. This is the first demonstration that CAFs secretory products directly affect the regulation of autophagy and consequently the behavior of CCA cells, and that a nutraceutical may revert the malignant phenotype of cancer cells by acting on CAFs metabolism and secretion.	[Thongchot, Suyanee; Ferraresi, Alessandra; Vidoni, Chiara; Isidoro, Ciro] Univ Piemonte Orientale, Dept Hlth Sci, Lab Mol Pathol, I-28100 Novara, Italy; [Thongchot, Suyanee; Loilome, Watcharin; Namwat, Nisana] Khon Kaen Univ, Cholangiocarcinoma Res Inst, Fac Med, Dept Biochem, Khon Kaen 40002, Thailand; [Yongvanit, Puangrat] Khon Kaen Univ, Cholangiocarcinoma Res Inst, Khon Kaen 40002, Thailand		Isidoro, C (corresponding author), Univ Piemonte Orientale, Dept Hlth Sci, Novara, Italy.	ciro.isidoro@med.uniupo.it	Ferraresi, Alessandra/H-1518-2017; Isidoro, Ciro/J-6063-2016; Loilome, Watcharin/AAW-6203-2021	Ferraresi, Alessandra/0000-0002-7192-9672; Isidoro, Ciro/0000-0002-5494-3034; 	Khon Kaen University (Thailand); University del Piemonte Orientale "A. Avogadro" (Italy); Thailand Research Fund through the Royal Golden Jubilee PhD ProgramThailand Research Fund (TRF) [PHD/0048/2557]; Mid-Career Grant of Thailand Research Fund (Thailand) [RSA5980012]	This work was supported by Khon Kaen University (Thailand), University del Piemonte Orientale "A. Avogadro" (Italy), the Thailand Research Fund through the Royal Golden Jubilee PhD Program (Grant No. PHD/0048/2557) to ST and NN, and a grant from a Mid-Career Grant (RSA5980012) of Thailand Research Fund (Thailand) to NN. The fluorescence imaging facility in the CI's laboratory was donated by Comoli, Ferrari & SpA (Novara, Italy). Thanks are due to Rocco Bettua (Thermo Fisher Scientific, Monza, Italy) for kind assistance in videoclip filming with EVOS FL Auto 2 Imaging System.	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J	Li, R; Hao, YY; Wang, QH; Meng, Y; Wu, KH; Liu, CQ; Xu, LJ; Liu, ZG; Zhao, L				Li, Rui; Hao, Yanyu; Wang, Qiuhan; Meng, Yuan; Wu, Kunhe; Liu, Chaoqun; Xu, Lijun; Liu, Ziguang; Zhao, Liang			ECHS1, an interacting protein of LASP1, induces sphingolipid-metabolism imbalance to promote colorectal cancer progression by regulating ceramide glycosylation	CELL DEATH & DISEASE			English	Article							INHIBITS CELL-PROLIFERATION; SH3 PROTEIN-1; 1 EXPRESSION; METASTASIS; MIGRATION; LIM; ATTENUATION; PROTEASOME; RESISTANCE; AUTOPHAGY	Sphingolipid metabolic dysregulation has increasingly been considered to be a drug-resistance mechanism for a variety of tumors. In this study, through an LC-MS assay, LIM and SH3 protein 1 (LASP1) was identified as a sphingolipid-metabolism-involved protein, and short-chain enoyl-CoA hydratase (ECHS1) was identified as a new LASP1-interacting protein through a protein assay in colorectal cancer (CRC). Gain- and loss-of-function analyses demonstrated the stimulatory role played by ECHS1 in CRC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies of the underlying tumor-supportive oncometabolism indicate that ECHS1 enables altering ceramide (Cer) metabolism that increases glycosphingolipid synthesis (HexCer) by promoting UDP-glucose ceramide glycosyltransferase (UGCG). Further analysis showed that ECHS1 promotes CRC progression and drug resistance by releasing reactive oxygen species (ROS) and interfering mitochondrial membrane potential via the PI3K/Akt/mTOR-dependent signaling pathway. Meanwhile, the phenomenon of promoting the survival and drug resistance of CRC cells caused by ECHS1 could be reversed by Eliglustat, a specific inhibitor of UCCG, in vitro and in vivo. IHC assay showed that ECHS1 was overexpressed in CRC tissues, which was related to the differentiation and poor prognosis of CRC patients. This study provides new insight into the mechanism by which phospholipids promote drug resistance in CRC and identifies potential targets for future therapies.	[Li, Rui; Liu, Ziguang; Zhao, Liang] Southern Med Univ, Shunde Hosp, Dept Pathol, Peoples Hosp Shunde 1, Foshan, Peoples R China; [Li, Rui; Hao, Yanyu; Wang, Qiuhan; Liu, Chaoqun; Xu, Lijun; Zhao, Liang] Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou, Peoples R China; [Li, Rui; Hao, Yanyu; Wang, Qiuhan; Liu, Chaoqun; Xu, Lijun; Zhao, Liang] Southern Med Univ, Sch Basic Med Sci, Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou, Peoples R China; [Meng, Yuan] Second Peoples Hosp Longgang Dist, Dept Pathol, Shenzhen, Peoples R China; [Wu, Kunhe] Guangdong Women & Children Hosp, Dept Pathol, Guangzhou 511442, Guangdong, Peoples R China		Zhao, L (corresponding author), Southern Med Univ, Shunde Hosp, Dept Pathol, Peoples Hosp Shunde 1, Foshan, Peoples R China.; Zhao, L (corresponding author), Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou, Peoples R China.; Zhao, L (corresponding author), Southern Med Univ, Sch Basic Med Sci, Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou, Peoples R China.	liangsmu@foxmail.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972813, 81902946]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [F119280111]; Guangdong Basic and Applied Basic Research Foundation [2019A1515010974]	This work was supported by the National Natural Science Foundation of China (Nos. 81972813, 81902946), China Postdoctoral Science Foundation (F119280111), and Guangdong Basic and Applied Basic Research Foundation (2019A1515010974).	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OCT 6	2021	12	10							911	10.1038/s41419-021-04213-6			12	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	WD2RV	WOS:000704795500002	34615856	Green Published, gold			2022-04-25	
J	Yen, JH; Huang, ST; Huang, HS; Fong, YC; Wu, YY; Chiang, JH; Su, YC				Yen, Jia-Hau; Huang, Sheng-Teng; Huang, Hung-Sen; Fong, Yi-Chin; Wu, Yi-Ying; Chiang, Jen-Huai; Su, Yuan-Chih			HGK-sestrin 2 signaling-mediated autophagy contributes to antitumor efficacy of Tanshinone IIA in human osteosarcoma cells	CELL DEATH & DISEASE			English	Article							PROGNOSTIC-SIGNIFICANCE; PI3K/AKT/MTOR PATHWAY; COLORECTAL-CANCER; CERVICAL-CANCER; TUMOR-GROWTH; IN-VITRO; EXPRESSION; APOPTOSIS; INHIBITION; KINASE	Tanshinone IIA (TIIA) is a diterpenoid naphthoquinone isolated from the herb Salvia miltiorrhiza with antitumor effects manifested at multiple levels that are mechanistically obscure. In our previous studies, we illustrated that TIIA treatment triggered apoptosis in human osteosarcoma 143B cells both in vitro and in vivo, accompanied with mitochondrial dysfunction. Importantly, the overall survival rate of patients with osteosarcoma who were randomly recruited to S. miltiorrhiza treatment was significantly higher than those without. Pursuing this observation, we evaluated the potential effect of TIIA on autophagy induction in osteosarcoma both in vivo and in vitro. We discovered that TIIA inhibited osteosarcoma cell survival through class I PI3K and Akt signaling pathways. In contrast, expression of class III PI3K required in the early stages of autophagosome generation was predominantly enhanced by TIIA treatment. Our study indicated that treatment of TIIA effectively induced autophagy in human osteosarcoma cells, which contributed to the blockade of anchorage-independent growth of osteosarcoma cells and ameliorated tumor progression in NOD/SCID mice. We demonstrated that TIIA-mediated autophagy occurred in a sestrin 2 (SESN2)-dependent but not Beclin 1-dependent manner. In addition, we defined the activation of HGK (MAP4K4 or mitogenactivated protein kinase kinase kinase kinase)/SAPK/JNK1/Jun kinase pathways in upregulating transcription of SESN2, in which TIIA triggered HGK/JNK1-dependent Jun activation and led to increased Jun recruitment to AP-1-binding site in the SESN2 promoter region. Our results offer novel mechanistic insight into how TIIA inhibits osteosarcoma growth and suggest TIIA as a promising therapeutic agent for the treatment of cancer.	[Yen, Jia-Hau; Huang, Sheng-Teng; Huang, Hung-Sen] China Med Univ Hosp, Res Canc Ctr Tradit Chinese Med, Dept Med Res, Taichung, Taiwan; [Huang, Sheng-Teng] China Med Univ Hosp, Dept Chinese Med, Taichung, Taiwan; [Huang, Sheng-Teng] China Med Univ, Sch Chinese Med, Taichung, Taiwan; [Fong, Yi-Chin] China Med Univ Hosp, Dept Orthopaed & Traumatol, Taichung, Taiwan; [Fong, Yi-Chin] China Med Univ, Coll Hlth Care, Dept Sports Med, Taichung, Taiwan; [Fong, Yi-Chin] China Med Univ, Beigang Hosp, Dept Surg, Yunlin, Taiwan; [Wu, Yi-Ying] China Med Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan; [Chiang, Jen-Huai; Su, Yuan-Chih] China Med Univ Hosp, Management Off Hlth Data, Taichung, Taiwan; [Chiang, Jen-Huai; Su, Yuan-Chih] China Med Univ, Sch Chinese Med, Grad Inst Integrated Med, Taichung, Taiwan		Huang, ST (corresponding author), China Med Univ Hosp, Res Canc Ctr Tradit Chinese Med, Dept Med Res, Taichung, Taiwan.; Huang, ST (corresponding author), China Med Univ Hosp, Dept Chinese Med, Taichung, Taiwan.; Huang, ST (corresponding author), China Med Univ, Sch Chinese Med, Taichung, Taiwan.	sheng.teng@yahoo.com			Ministry of Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [MOST 106-2320-B-039-022]; National Research Institute of Chinese Medicine, Ministry of Health and Welfare [MOHW106-NRICM-C-104-000002]; Health and welfare surcharge of tobacco products, China Medical University Hospital Cancer Research Center of Excellence [MOHW107-TDU-B-212-114024]; China Medical University Hospital [DMR-107-003, DMR-107-006]; China Medical University under the Aim for Top University Plan of the Ministry of Education, Taiwan [CHM106-7, CHM106-8]; Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence [MOHW107-TDU-B-212-123004]; China Medical University Hospital, Academia Sinica Stroke Biosignature Project [BM10701010021]; MOST Clinical Trial Consortium for Stroke [MOST 106-2321-B-039-005]; Tseng-Lien Lin Foundation, Taichung, Taiwan; Katsuzo and Kiyo Aoshima Memorial Funds, Japan	This work was supported and funded by Ministry of Science and Technology with MOST 106-2320-B-039-022, National Research Institute of Chinese Medicine, Ministry of Health and Welfare (MOHW106-NRICM-C-104-000002), Health and welfare surcharge of tobacco products, China Medical University Hospital Cancer Research Center of Excellence (MOHW107-TDU-B-212-114024) China Medical University Hospital (DMR-107-003 and DMR-107-006), and China Medical University under the Aim for Top University Plan of the Ministry of Education, Taiwan (CHM106-7 and CHM106-8). This study was also supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW107-TDU-B-212-123004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005)", Tseng-Lien Lin Foundation, Taichung, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. We are thankful to Dr. Gregory J Tsay for his kind help with collection of human tissue specimen and James Waddell for the critical reading and revision of our manuscript.	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SEP 26	2018	9								1003	10.1038/s41419-018-1016-9			14	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	GV6YY	WOS:000446268400001	30258193	Green Published, gold			2022-04-25	
J	Kitazawa, S; Nishizawa, S; Nakagawa, H; Funata, M; Nishimura, K; Soga, T; Hara, T				Kitazawa, Satoshi; Nishizawa, Satoru; Nakagawa, Hideyuki; Funata, Masaaki; Nishimura, Kazuho; Soga, Tomoyoshi; Hara, Takahito			Cancer with low cathepsin D levels is susceptible to vacuolar (H+)-ATPase inhibition	CANCER SCIENCE			English	Article						Cathepsin D; colorectal cancer; patient selection marker; V-ATPase; vulnerability	H+-ATPASE; TRANSFER-RNA; AMINO-ACIDS; CELL-LINE; ASPARTIC PROTEASE; BREAST-CANCER; PROTON PUMP; APOPTOSIS; ACTIVATION; MTORC1	Vacuolar (H+)-ATPases (V-ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V-ATPases are attractive therapeutic targets for cancer. However, the clinical use of V-ATPase inhibitors as anticancer drugs has not been realized, possibly owing to their high toxicity in humans. Inhibition of V-ATPase may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V-ATPase inhibitor sensitivity. V-ATPase inhibitors led to pH impairment in acidic intracellular compartments, suppression of macropinocytosis, and decreased intracellular amino acid levels. The sensitivity of cells to V-ATPase inhibitors was correlated with low cathepsin D expression, and cancer cells showed increased sensitivity to V-ATPase inhibitors after pretreatment with a cathepsin D inhibitor and siRNA targeting the cathepsin D gene (CTSD). In addition, V-ATPase inhibitor treatment led to the induction of the amino acid starvation response, upregulation of endoplasmic reticulum stress markers, and suppression of mammalian target of rapamycin (mTOR) signaling in cells expressing low levels of cathepsin D. Some colorectal cancer patients showed the downregulation of cathepsin D in tumor tissues compared with matched normal tissues. These findings indicate that V-ATPase inhibitors are promising therapeutic options for cancers with downregulated cathepsin D.	[Kitazawa, Satoshi; Nishizawa, Satoru; Nishimura, Kazuho; Hara, Takahito] Takeda Pharmaceut Co Ltd, Oncol Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa 2518555, Japan; [Nakagawa, Hideyuki; Funata, Masaaki] Takeda Pharmaceut Co Ltd, Biomol Res Labs, Fujisawa, Kanagawa, Japan; [Soga, Tomoyoshi] Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata, Japan		Hara, T (corresponding author), Takeda Pharmaceut Co Ltd, Oncol Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa 2518555, Japan.	takahito.hara@takeda.com	Soga, Tomoyoshi/B-8105-2014	Soga, Tomoyoshi/0000-0001-9502-2509	Takeda Pharmaceutical Company Limited, JapanTakeda Pharmaceutical Company Ltd; Japan Agency for Medical Research and DevelopmentJapan Agency for Medical Research and Development (AMED); Yamagata prefectural government; City of Tsuruoka	Takeda Pharmaceutical Company Limited, Japan; Japan Agency for Medical Research and Development; Yamagata prefectural government; City of Tsuruoka.	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JUN	2017	108	6					1185	1193		10.1111/cas.13240			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EY5LZ	WOS:000404020000011	28317223	hybrid, Green Published			2022-04-25	
J	Wang, ZH; Wang, JH; Wang, KQ; Zhou, Y; Wang, J				Wang, Z-H; Wang, J-H; Wang, K-Q; Zhou, Y.; Wang, J.			LncRNA FEZF1-AS1 promoted chemoresistance, autophagy and epithelial- mesenchymal transition (EMT) through regulation of miR-25-3p/ITGB8 axis in prostate cancer	EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES			English	Article						FEZF1-AS1; Chemoresistance; Autophagy; EMT; Prostate cancer	CELL-PROLIFERATION; COLORECTAL-CANCER; METASTASIS; RNA; EXPRESSION; PACLITAXEL; RESISTANCE; MIGRATION; INVASION; MIRNA	OBJECTIVE: Accumulating evidence determined that lncRNA plays important roles in the development and occurrence of cancers. Prostate cancer is the second most common type of cancer and one of the top five cancers for the cause of male death in the world. Therefore, this study was to explore the regulatory mechanism of lncRNA in chemoresistance of PC. MATERIALS AND METHODS: qRT-PCR was used to detect the mRNA expression of FEZF1AS1, miR-25- 3p and ITGB8. Western blot was applied to measure the protein expression of ITGB8 E- cadherin, N-cadherin, Vimentin, LC3I, LC3II, ATG5 and Beclin-1. In addition, CCK-8 assay was used to assess cell proliferation of transfected cells. Luciferase reporter assay and RIP assay were used to determine the relationship among FEZF1-AS1, miR-25-3p and ITGB8. RESULTS: In this study, the expression of FEZF1-AS1 and ITGB8 was upregulated, whereas the expression of miR-25-3p was downregulated in PC tumor tissues and PC/PTX cells. Luciferase reporter assay and RIP assay determined that miR-25-3p was a target of FEZF1-AS1 and ITGB8 was a target mRNA of miR-25-3p. Interestingly, knockdown of FEZF1-AS1 could inhibit cell viability and EMT and promoted cell autophagy in PC/PTX cells, but inhibition of miR25-3p or promotion of ITGB8 could reverse the effects of si-FEZF1-AS1 on PC/PTX cells. CONCLUSIONS: In this study, we found that lncRNA FEZF1-AS1 promoted chemoresistance, autophagy and epithelial-mesenchymal transition (EMT) through regulation of miR-25- 3p/ ITGB8 axis in PC, providing a new regulatory mechanism of PC and a novel therapeutic target.	[Wang, Z-H; Wang, J-H; Wang, J.] Sichuan Univ, West China Hosp, Dept Urol, Chengdu, Peoples R China; [Wang, K-Q] Daguan Hosp Jinjiang Dist, Dept Urol, Chengdu, Peoples R China; [Zhou, Y.] Peoples Hosp Kaizhou Dist, Dept Urol, Chongqing, Peoples R China		Wang, J (corresponding author), Sichuan Univ, West China Hosp, Dept Urol, Chengdu, Peoples R China.	hjxwoq@163.com					Al-Batran SE, 2007, J CLIN ONCOL, V25, P729, DOI 10.1200/JCO.2006.09.4896; Aoyama Y, 2017, BIOCHEM BIOPH RES CO, V486, P551, DOI 10.1016/j.bbrc.2017.03.084; Armstrong DK, 2006, NEW ENGL J MED, V354, P34, DOI 10.1056/NEJMoa052985; Cabili MN, 2011, GENE DEV, V25, P1915, DOI 10.1101/gad.17446611; Chakravarty D, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms6383; Chen HY, 2015, INT J CLIN EXP PATHO, V8, P12718; Chen N, 2016, ONCOTARGET, V7, P11271, DOI 10.18632/oncotarget.7168; Cochetti G, 2016, ONCOTARGETS THER, V9, P7545, DOI 10.2147/OTT.S119027; Cui YJ, 2018, ONCOL REP, V39, P1649, DOI 10.3892/or.2018.6259; Esfandiar A, 2017, SCIENCE, V358, P511, DOI 10.1126/science.aan5275; Garcia-Becerra R, 2013, INT J MOL SCI, V14, P108, DOI 10.3390/ijms14010108; Goldsmith J, 2014, METHOD ENZYMOL, V542, P25, DOI 10.1016/B978-0-12-416618-9.00002-9; Guo JB, 2019, J CELL BIOCHEM, V120, P17975, DOI 10.1002/jcb.29064; Han P, 2017, MOL CANCER, V16, DOI 10.1186/s12943-017-0583-1; Hong L, 2013, CURR DRUG TARGETS, V14, P1118, DOI 10.2174/13894501113149990183; Hu YR, 2017, MOL CANCER, V16, DOI 10.1186/s12943-017-0743-3; Huang L, 2017, AM J CANCER RES, V7, P1996; Ivanovic RF, 2018, CANCER CELL INT, V18, DOI 10.1186/s12935-018-0516-0; Jia JG, 2019, J CELL MOL MED, V23, P656, DOI 10.1111/jcmm.13970; Keating B, 2014, AM J TRANSPLANT, V14, P223; Kumar V, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-01764-7; Lanzi C, 2001, PROSTATE, V48, P254, DOI 10.1002/pros.1105; LaPointe VLS, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0082035; Li J, 2016, ONCOL RES, V23, P205, DOI 10.3727/096504016X14549667334007; Li L, 2015, ONCOTARGET, V6, P14179, DOI 10.18632/oncotarget.3651; Liu JH, 2014, ASIAN PAC J CANCER P, V15, P2971, DOI 10.7314/APJCP.2014.15.7.2971; Liu YN, 2017, PROCEEDINGS OF THE 2017 INTERNATIONAL CONFERENCE ON WIRELESS COMMUNICATIONS, NETWORKING AND APPLICATIONS (WCNA2017), P16, DOI 10.1145/3180496.3180601; Malik R, 2016, CANCER RES, V76, DOI 10.1158/1538-7445.AM2016-983; Mertens-Walker I, 2015, BMC CANCER, V15, DOI 10.1186/s12885-015-1164-6; Muluhngwi P, 2015, ENDOCR-RELAT CANCER, V22, pR279, DOI 10.1530/ERC-15-0355; NW, 2006, CANCER EPIDEM BIOMAR, V15, pED01; Prensner JR, 2014, NEOPLASIA, V16, P900, DOI 10.1016/j.neo.2014.09.001; Reddy KB, 2015, CANCER CELL INT, V15, DOI 10.1186/s12935-015-0185-1; Ru P, 2012, MOL CANCER THER, V11, P1166, DOI 10.1158/1535-7163.MCT-12-0100; Safavy A, 1999, J MED CHEM, V42, P4919, DOI 10.1021/jm990355x; Schaefer A, 2010, EXP MOL MED, V42, P749, DOI 10.3858/emm.2010.42.11.076; Shen CJ, 2017, J DRUG TARGET, V25, P637, DOI 10.1080/1061186X.2017.1307379; Shi XL, 2020, INT J CANCER, V146, P475, DOI 10.1002/ijc.32422; Si XX, 2016, ONCOTARGET, V7, P81452, DOI 10.18632/oncotarget.13263; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Wang H, 2017, ONCOTARGET, V9, P7501; Wang WW, 2015, INT J CLIN EXP MED, V8, P3063; Wang ZW, 2010, DRUG RESIST UPDATE, V13, P109, DOI 10.1016/j.drup.2010.07.001; Weaver BA, 2014, MOL BIOL CELL, V25, P2677, DOI 10.1091/mbc.E14-04-0916; Wu Jin-Bo, 2017, Zhongguo Ying Yong Sheng Li Xue Za Zhi, V33, P146, DOI 10.12047/j.cjap.5449.2017.037; Wu XL, 2017, MOL MED REP, V16, P4293, DOI 10.3892/mmr.2017.7103; Xu ZG, 2012, ANAT REC, V295, P1446, DOI 10.1002/ar.22521; Xue D, 2018, J CELL MOL MED, V22, P3223, DOI 10.1111/jcmm.13604; Ye S, 2014, CELL BIOCHEM BIOPHYS, V70, P1849, DOI 10.1007/s12013-014-0142-y; Zhang PF, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-09482-6; Zhang W, 2018, BIOCHIMIE, V144, P21, DOI 10.1016/j.biochi.2017.10.002; Zhou CW, 2018, ONCOL RES, V26, P1335, DOI 10.3727/096504018X15188367859402; Zhu LF, 2019, EUR REV MED PHARMACO, V23, P5122, DOI 10.26355/eurrev_201906_18176; Zhu MJ, 2014, FEBS J, V281, P3766, DOI 10.1111/febs.12902	54	11	12	1	4	VERDUCI PUBLISHER	ROME	VIA GREGORIO VII, ROME, 186-00165, ITALY	1128-3602			EUR REV MED PHARMACO	Eur. Rev. Med. Pharmacol. Sci.		2020	24	5					2281	2293		10.26355/eurrev_202003_20493			13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	KY2JG	WOS:000522397800014	32196579				2022-04-25	
J	Liu, Y; Peng, XL; Li, H; Jiao, WH; Peng, X; Shao, JR; Xu, YL; Wang, R; Wang, W; Kong, DX				Liu, Yao; Peng, Xiaolin; Li, Hui; Jiao, Wenhui; Peng, Xin; Shao, Jingrong; Xu, Yanglu; Wang, Ran; Wang, Wei; Kong, Dexin			STAT3 Inhibitor Napabucasin Inhibits Tumor Growth and Cooperates with Proteasome Inhibition in Human Ovarian Cancer Cells	RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY			English	Article						Ovarian cancer; STAT3; Napabucasin; proteasome inhibitor; G2; M phase arrest; autophagy	COLORECTAL-CANCER; PROSTATE-CANCER; EXPRESSION; INVASION; STRATEGIES; THERAPIES; APOPTOSIS; PROMOTES; PROTEIN; OBESITY	Background: Ovarian cancer is a disease with the highest mortality in gynecologic malignancies. Activation of STAT3 pathway is well known to be associated with tumor progression and metastasis in a number of cancers, including ovarian cancer. Therefore, STAT3 may be an ideal target for ovarian cancer treatment. Objective: The present study aims to determine the antitumor activity of STAT3 inhibitor Napabucasin as a single agent or in combination with proteasome inhibitor MG-132 in ovarian cancer cells. Methods: MTT was performed to determine the anti-proliferative effect of Napabucasin on ovarian cancer SKOV-3 cells. The involved anti-tumor mechanism was explored by flow cytometry, qRTPCR and western blot. MDC staining and tandem mRFP-GFP-LC3 fluorescence microscopy were used to analyze the autophagy-inducing capability of Napabucasin with or without MG-132. The combinational anticancer effect of Napabucasin and MG-132 was evaluated according to Chou and Talalay's method (1984). Results: Napabucasin showed obvious tumor-inhibitory effects against SKOV-3 cells. Treatment by Napabucasin arrested cell cycle progression in G2/M phase. Mechanistically, elevated expression of p21 may contribute to the blockade of the cell cycle. Moreover, we demonstrated that Napabucasin induced autophagy in SKOV-3 cells by using various assays, including MDC staining, autophagic flux examination, and detection of the autophagy markers. In addition, a combination of Napabucaisin with MG-132 exhibited a significant synergistic anti-proliferative effect, probably by inducing apoptosis through a mitochondria-dependent pathway. The two compounds induced pro-survival autophagies, and co-treatment with autophagy inhibiter might further enhance their antitumor effects. Conclusion: Napabucasin alone or in combination with MG-132 might be promising treatment strategy for ovarian cancer patients.	[Liu, Yao; Peng, Xiaolin; Li, Hui; Jiao, Wenhui; Peng, Xin; Shao, Jingrong; Xu, Yanglu; Wang, Ran; Kong, Dexin] Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China; [Liu, Yao; Peng, Xiaolin; Wang, Wei] Tianjin First Cent Hosp, Inst Otolaryngol Tianjin, Dept Otorhinolaryngol Head & Neck Surg, Key Lab Auditory Speech & Balance Med, Tianjin 300192, Peoples R China; [Kong, Dexin] Tianyuan Univ, Tianjin Tianshi Coll, Sch Med, Tianjin 301700, Peoples R China		Wang, R; Wang, W; Kong, DX (corresponding author), Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China.	wangran@tmu.edu.cn; wwei1106@hotmail.com; kongdexin@tmu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81673464, 81373441, 81971698]; Tianjin for New Drug Development, China [17ZXXYSY00050]	The work was supported by a grant from the National Natural Science Foundation of China (Grant Nos. 81673464, 81373441 and 81971698) and the grant for Major Project of Tianjin for New Drug Development, China (Grant No. 17ZXXYSY00050) .	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Drug Discov.		2021	16	3					350	362		10.2174/1574892816666210224155403			13	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	US8MP	WOS:000697680100004	33655847				2022-04-25	
J	Signorile, ML; Grossi, V; Di Franco, S; Forte, G; Disciglio, V; Fasano, C; Sanese, P; De Marco, K; Susca, FC; Mangiapane, LR; Nicotra, A; Di Carlo, G; Dituri, F; Giannelli, G; Ingravallo, G; Canettieri, G; Stassi, G; Simone, C				Signorile, Martina Lepore; Grossi, Valentina; Di Franco, Simone; Forte, Giovanna; Disciglio, Vittoria; Fasano, Candida; Sanese, Paola; De Marco, Katia; Susca, Francesco Claudio; Mangiapane, Laura Rosa; Nicotra, Annalisa; Di Carlo, Gabriella; Dituri, Francesco; Giannelli, Gianluigi; Ingravallo, Giuseppe; Canettieri, Gianluca; Stassi, Giorgio; Simone, Cristiano			Pharmacological targeting of the novel beta-catenin chromatin-associated kinase p38 alpha in colorectal cancer stem cell tumorspheres and organoids	CELL DEATH & DISEASE			English	Article							P38 MAPK; IN-VITRO; INHIBITORS; PATHWAY; GROWTH; DEATH; PHOSPHORYLATION; MUTATIONS; MECHANISM; AUTOPHAGY	The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/beta -catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38 alpha and are "addicted" to its kinase activity. Of note, we found that stage III CRC patients with high p38 alpha levels display reduced disease-free and progression-free survival. Extensive molecular analysis in patient-derived CRC-SC tumorspheres and APC(Min/+) mice intestinal organoids revealed that p38 alpha acts as a beta -catenin chromatin-associated kinase required for the regulation of a signaling platform involved in tumor proliferation, metastatic dissemination, and chemoresistance in these CRC model systems. In particular, the p38 alpha kinase inhibitor ralimetinib, which has already entered clinical trials, promoted sensitization of patient-derived CRC-SCs to chemotherapeutic agents commonly used for CRC treatment and showed a synthetic lethality effect when used in combination with the MEK1 inhibitor trametinib. Taken together, these results suggest that p38 alpha may be targeted in CSCs to devise new personalized CRC treatment strategies.	[Signorile, Martina Lepore; Grossi, Valentina; Forte, Giovanna; Disciglio, Vittoria; Fasano, Candida; Sanese, Paola; De Marco, Katia; Simone, Cristiano] IRCCS S Bellis Res Hosp, Natl Inst Gastroenterol, Med Genet, I-70013 Castellana Grotte, BA, Italy; [Di Franco, Simone; Mangiapane, Laura Rosa; Nicotra, Annalisa; Stassi, Giorgio] Univ Palermo, Dept Surg & Oncol Sci, Cellular & Mol Pathophysiol Lab, I-90127 Palermo, Italy; [Susca, Francesco Claudio; Simone, Cristiano] Univ Bari Aldo Moro, Med Genet, Dept Biomed Sci & Human Oncol DIMO, I-70124 Bari, Italy; [Di Carlo, Gabriella; Ingravallo, Giuseppe] Univ Bari Aldo Moro, Operating Unit Pathol Anat, Dept Emergency & Organ Transplantat, I-70124 Bari, Italy; [Dituri, Francesco; Giannelli, Gianluigi] IRCCS S de Bellis Res Hosp, Natl Inst Gastroenterol, Personalized Med, I-70013 Castellana Grotte, BA, Italy; [Canettieri, Gianluca] Sapienza Univ Rome, Dept Mol Med, I-00161 Rome, Italy		Grossi, V; Simone, C (corresponding author), IRCCS S Bellis Res Hosp, Natl Inst Gastroenterol, Med Genet, I-70013 Castellana Grotte, BA, Italy.	grossi.labsimone@gmail.com; cristianosimone73@gmail.com	Fasano, Candida/K-3372-2018; Stassi, Giorgio/AAC-1175-2022; Grossi, Valentina/K-9821-2016; SIMONE, Cristiano/K-3452-2018	Grossi, Valentina/0000-0003-3843-1618; SIMONE, Cristiano/0000-0002-2628-7658; CANETTIERI, Gianluca/0000-0001-6694-2613; Mangiapane, Laura Rosa/0000-0003-4186-0157	Italian Ministry of HealthMinistry of Health, Italy [SG-2019-12371540]; PRIN-Research Projects of National Relevance (PRIN 2017) from the Italian MIUR [2017WNKSLrLS4]; AIRCFondazione AIRC per la ricerca sul cancro [IG-23794]	This work was supported by the Italian Ministry of Health 'Ricerca Corrente 2018-2020; 2019-2021' to C.S. and 'Starting Grant' SG-2019-12371540 to P.S., PRIN-Research Projects of National Relevance (PRIN 2017, no. 2017WNKSLrLS4) from the Italian MIUR to C.S. and G.S., AIRC IG-23794 2020-2024 to C.S.	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MAR 25	2021	12	4							316	10.1038/s41419-021-03572-4			18	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	RG0EE	WOS:000635208800001	33767160	Green Published, gold			2022-04-25	
S	Wechman, SL; Pradhan, AK; DeSalle, R; Das, SK; Emdad, L; Sarkar, D; Fisher, PB		Tew, KD; Fisher, PB		Wechman, Stephen L.; Pradhan, Anjan K.; DeSalle, Rob; Das, Swadesh K.; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.			New Insights Into Beclin-1: Evolution and Pan-Malignancy Inhibitor Activity	ADVANCES IN CANCER RESEARCH, VOL 137	Advances in Cancer Research		English	Review; Book Chapter							DIFFERENTIATION-ASSOCIATED GENE; AUTOPHAGY-RELATED PROTEIN; BREAST-CANCER CELLS; MELANOMA-DIFFERENTIATION; TUMOR-SUPPRESSOR; REGULATES AUTOPHAGY; COLORECTAL-CANCER; PROGNOSTIC-SIGNIFICANCE; SELECTIVE APOPTOSIS; CYTOTOXIC AUTOPHAGY	Autophagy is a functionally conserved self-degradation process that facilitates the survival of eukaryotic life via the management of cellular bioenergetics and maintenance of the fidelity of genomic DNA. The first known autophagy inducer was Beclin-1. Beclin-1 is expressed in multicellular eukaryotes ranging throughout plants to animals, comprising a nonmonophyllic group, as shown in this report via aggressive BLAST searches. In humans, Beclin-1 is a haploinsuffient tumor suppressor as biallelic deletions have not been observed in patient tumors clinically. Therefore, Beclin-1 fails the Knudson hypothesis, implicating expression of at least one Beclin-1 allele is essential for cancer cell survival. However, Beclin-1 is frequently monoallelically deleted in advanced human cancers and the expression of two Beclin-1 allelles is associated with greater anticancer effects. Overall, experimental evidence suggests that Beclin-1 inhibits tumor formation, angiogenesis, and metastasis alone and in cooperation with the tumor suppressive molecules UVRAG, Bif-1, Ambra1, and MDA-7/IL-24 via diverse mechanisms of action. Conversely, Beclin-1 is upregulated in cancer stem cells (CSCs), portending a role in cancer recurrence, and highlighting this molecule as an intriguing molecular target for the treatment of CSCs. Many aspects of Beclin-1's biological effects remain to be studied. The consequences of these BLAST searches on the molecular evolution of Beclin-1, and the eukaryotic branches of the tree of life, are discussed here in greater detail with future inquiry focused upon protist taxa. Also in this review, the effects of Beclin-1 on tumor suppression and cancer malignancy are discussed. Beclin-1 holds significant promise for the development of novel targeted cancer therapeutics and is anticipated to lead to a many advances in our understanding of eukaryotic evolution, multicellularity, and even the treatment of CSCs in the coming decades.	[Wechman, Stephen L.; Pradhan, Anjan K.; Das, Swadesh K.; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23284 USA; [Das, Swadesh K.; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.] Virginia Commonwealth Univ, VCU Inst Mol Med, Sch Med, Richmond, VA 23284 USA; [Das, Swadesh K.; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.] Virginia Commonwealth Univ, VCU Massey Canc Ctr, Sch Med, Richmond, VA 23284 USA; [DeSalle, Rob] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA		Fisher, PB (corresponding author), Virginia Commonwealth Univ, VCU Inst Mol Med, Sch Med, Richmond, VA 23284 USA.; Fisher, PB (corresponding author), Virginia Commonwealth Univ, VCU Massey Canc Ctr, Sch Med, Richmond, VA 23284 USA.	paul.fisher@vcuhealth.org	Pradhan, Anjan K/O-2555-2014		NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01 CA168517, R01 CA097318, P30 CA016059] Funding Source: Medline; 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J	Ko, H; Kim, YJ; Amor, EC; Lee, JW; Kim, HC; Kim, HJ; Yang, HO				Ko, Hyeonseok; Kim, Young-Joo; Amor, Evangeline C.; Lee, Jong Wha; Kim, Han-Cheon; Kim, Hee Ju; Yang, Hyun Ok			Induction of Autophagy by Dimethyl Cardamonin Is Associated With Proliferative Arrest in Human Colorectal Carcinoma HCT116 and LOVO Cells	JOURNAL OF CELLULAR BIOCHEMISTRY			English	Article						DIMETHYL CARDAMONIN; AUTOPHAGY; G(2)/M CELL CYCLE ARREST; HCT116; LOVO	MALIGNANT GLIOMA-CELLS; SYZYGIUM-SAMARANGENSE; UP-REGULATION; APOPTOSIS; DEATH; CYTOTOXICITY; INHIBITION; FLAVONOIDS; ROLES	Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; DMC) is a naturally occurring chalcone, and it is the major compound isolated from the leaves of Syzygium samarangense (Blume) Merr. & L. M. Perry (Myrtaceae). Experiments were conducted to determine the effects of DMC on cell proliferation, cell-cycle distribution, and programmed cell death in cultures of human colorectal carcinoma HCT116 and LOVO cells. Results showed that DMC inhibited HCT116 and LOVO cell proliferation and induced G(2)/M cell cycle arrest, which was associated with the conversion of microtubule associated protein light chain 3 (LC3)-I-LC3-II, an autophagosome marker, and the incorporation of monodansylcadaverine (MDC), a marker for the acidic compartment of autolysosomes or acidic vesicular organelles. The treatment of HCT116 and LOVO cells using a combination of DMC with an autophagy inhibitor, such as 3-methyladenine (3-MA), beclin 1 siRNA, or atg5 siRNA, suppressed the effect of DMC-mediated anti-proliferation. These results imply that DMC can suppress colorectal carcinoma HCT116 and LOVO cell proliferation through a G(2)/M phase cell-cycle delay, and can induce autophagy, the hallmark of Type II programmed cell death (PCD). Taken together, our results suggest that DMC may be an effective chemotherapeutic agent for HCT116 and LOVO colorectal carcinoma cells. J. Cell. Biochem. 112:2471-2479, 2011. (C) 2011 Wiley-Liss, Inc.	[Ko, Hyeonseok; Kim, Young-Joo; Kim, Han-Cheon; Kim, Hee Ju; Yang, Hyun Ok] Korea Inst Sci & Technol, Nat Prod Res Ctr, Kangnung 210340, Gangwon Do, South Korea; [Amor, Evangeline C.; Lee, Jong Wha] Univ Philippines, Inst Chem, Coll Sci, Quezon City 1101, Philippines		Yang, HO (corresponding author), Korea Inst Sci & Technol, Nat Prod Res Ctr, 290 Daejeon Dong, Kangnung 210340, Gangwon Do, South Korea.	hoyang@kist.re.kr			Korea Institute of Science and Technology, KoreaKorea Institute of Science & Technology (KIST) [2Z03401]	Grant sponsor: Korea Institute of Science and Technology, Korea; Grant number: 2Z03401.	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Cell. Biochem.	SEP	2011	112	9					2471	2479		10.1002/jcb.23171			9	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	818QN	WOS:000294769500030	21538483				2022-04-25	
J	Zheng, YS; Tan, KL; Huang, HP				Zheng, Yansheng; Tan, Kanglian; Huang, Haipeng			RETRACTED: Long noncoding RNA HAGLROS regulates apoptosis and autophagy in colorectal cancer cells via sponging miR-100 to target ATG5 expression (Retracted article. See vol. 122, 2021)	JOURNAL OF CELLULAR BIOCHEMISTRY			English	Article; Retracted Publication						apoptosis; autophagy; colorectal cancer; HOXD antisense growth-associated long noncoding RNA; long noncoding RNA; microRNA-100	CETUXIMAB RESISTANCE; POOR-PROGNOSIS; METASTASIS; ONCOGENE; PATHWAY; GENES	The aim of this study was to explore the relationship between the expression of HOXD antisense growth-associated long noncoding RNA (HAGLROS) and prognosis of patients with colorectal cancer (CRC), as well as the roles and regulatory mechanism of HAGLROS in CRC development. The HAGLROS expression in CRC tissues and cells was detected. The correlation between HAGLROS expression and survival time of CRC patients was investigated. Moreover, HAGLROS was overexpressed and suppressed in HCT-116 cells, followed by detection of cell viability, apoptosis, and the expression of apoptosis-related proteins and autophagy markers. Furthermore, the association between HAGLROS and miR-100 and the potential targets of miR-100 were investigated. Besides, the regulatory relationship between HAGLROS and PI3K/AKT/mTOR pathway was elucidated. The results showed that HAGLROS was highly expressed in CRC tissues and cells. Highly expression of HAGLROS correlated with a shorter survival time of CRC patients. Moreover, knockdown of HAGLROS in HCT-116 cells induced apoptosis by increasing the expression of Bax/Bcl-2 ratio, cleaved-caspase-3, and cleaved-caspase-9, and inhibited autophagy by decreasing the expression of LC3II/LC3I and Beclin-1 and increasing P62 expression. Furthermore, HAGLROS negatively regulated the expression of miR-100, and HAGLROS controlled HCT-116 cell apoptosis and autophagy through negatively regulation of miR-100. Autophagy related 5 (ATG5) was verified as a functional target of miR-100 and miR-100 regulated HCT-116 cell apoptosis and autophagy through targeting ATG5. Besides, HAGLROS overexpression activated phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. In conclusion, a highly expression of HAGLROS correlated with shorter survival time of CRC patients. Downregulation of HAGLROS may induce apoptosis and inhibit autophagy in CRC cells by regulation of miR-100/ATG5 axis and PI3K/AKT/mTOR pathway.	[Zheng, Yansheng; Tan, Kanglian; Huang, Haipeng] Tradit Chinese Med Hosp Guangdong Prov, Dept Gastrointestinal Surg, 111 Dade Rd, Guangzhou 510000, Guangdong, Peoples R China		Zheng, YS (corresponding author), Tradit Chinese Med Hosp Guangdong Prov, Dept Gastrointestinal Surg, 111 Dade Rd, Guangzhou 510000, Guangdong, Peoples R China.	yanshengzhang26@163.com		Zheng, Yansheng/0000-0002-2785-7923			Aherne ST, 2015, BMC CANCER, V15, DOI 10.1186/s12885-015-1327-5; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Bahrami A, 2018, J CELL BIOCHEM, V119, P2460, DOI 10.1002/jcb.25950; Chen JF, 2018, MOL CANCER, V17, DOI 10.1186/s12943-017-0756-y; Chen P, 2014, MED ONCOL, V31, DOI 10.1007/s12032-013-0775-5; Cho DH, 2012, ANTICANCER RES, V32, P4091; Christensen LL, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0096767; de Groen FLM, 2014, GENE CHROMOSOME CANC, V53, P339, DOI 10.1002/gcc.22144; Dey BK, 2014, TRANSCR-AUSTIN, V5, DOI 10.4161/21541272.2014.944014; Dikaiakos P, 2015, CANCER BIOMARK, V15, P157, DOI 10.3233/CBM-140449; Fan XJ, 2016, ONCOL REP, V36, P3559, DOI 10.3892/or.2016.5138; Fatica A, 2014, NAT REV GENET, V15, P7, DOI 10.1038/nrg3606; Fujino Y, 2017, CANCER SCI, V108, P390, DOI 10.1111/cas.13152; Huarte M, 2015, NAT MED, V21, P1253, DOI 10.1038/nm.3981; Iguchi T, 2015, ANTICANCER RES, V35, P1385; Jemal A, 2011, CA-CANCER J CLIN, V61, P69, DOI [10.3322/caac.20107, 10.3322/caac.20115]; Jiao CJ, 2016, ONCOL REP, V36, P2960, DOI 10.3892/or.2016.5121; Johnson SM, 2010, J AM COLL SURGEONS, V210, P767, DOI 10.1016/j.jamcollsurg.2009.12.008; Kang MR, 2009, J PATHOL, V217, P702, DOI 10.1002/path.2509; Kim TW, 2018, CANCER LETT, V417, P89, DOI 10.1016/j.canlet.2017.12.033; Lee KW, 2015, CLIN CANCER RES, V21, P357, DOI 10.1158/1078-0432.CCR-14-1374; Li W, 2016, EUR REV MED PHARMACO, V20, P4874; Lu M, 2017, J CANCER RES CLIN, V143, P71, DOI 10.1007/s00432-016-2252-y; Okazaki Y, 2002, NATURE, V420, P563, DOI 10.1038/nature01266; Peng H, 2014, ONCOL REP, V31, P2055, DOI 10.3892/or.2014.3075; Porta C, 2014, FRONT ONCOL, V4, DOI 10.3389/fonc.2014.00064; Pritchard CC, 2011, GUT, V60, P116, DOI 10.1136/gut.2009.206250; Qi P, 2016, MOL CANCER, V15, DOI 10.1186/s12943-016-0524-4; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; Sirnes S, 2012, INT J CANCER, V131, P570, DOI 10.1002/ijc.26392; Slattery ML, 2017, GENE CHROMOSOME CANC, V56, P769, DOI 10.1002/gcc.22481; Slattery ML, 2017, MODERN PATHOL, V30, P1152, DOI 10.1038/modpathol.2017.38; Smolle M, 2014, INT J MOL SCI, V15, P13993, DOI 10.3390/ijms150813993; Thomas H, 2017, NAT REV GASTRO HEPAT, V14, P691, DOI 10.1038/nrgastro.2017.156; Wang HY, 2014, INT J MED SCI, V11, P841, DOI 10.7150/ijms.8128; Won SJ, 2015, J CELL PHYSIOL, V230, P930, DOI 10.1002/jcp.24825; Xue Y, 2015, MUTAGENESIS, V30, P303, DOI 10.1093/mutage/geu076; Yang L, 2016, ONCOL LETT, V12, P3771, DOI 10.3892/ol.2016.5213; Yang XD, 2015, AM J CANCER RES, V5, P545; Zhang XF, 2018, ONCOTARGET, V9, P3519, DOI 10.18632/oncotarget.23336	40	43	44	2	12	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0730-2312	1097-4644		J CELL BIOCHEM	J. Cell. Biochem.	MAR	2019	120	3					3922	3933		10.1002/jcb.27676			12	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	HL1LP	WOS:000458459600125	30430634	hybrid			2022-04-25	
J	Yu, Y; Yu, XF; Ma, JX; Tong, YL; Yao, JF				Yu, Yang; Yu, Xiaofeng; Ma, Jianxia; Tong, Yili; Yao, Jianfeng			Effects of NVP-BEZ235 on the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						NVP-BEZ235; cis-diamminedichloroplatinum; HT-29; colorectal adenocarcinoma; PI3K/mTOR	PI3K/MTOR INHIBITOR NVP-BEZ235; SIGNALING PATHWAY; CANCER CELLS; STEM-CELLS; IN-VITRO; 3-KINASE/MAMMALIAN TARGET; RAPAMYCIN INHIBITOR; MTOR INHIBITION; COMBINATION; CISPLATIN	The phosphoinositide 3 kinase (PI3K)/Akt/ mammalian target of the rapamycin (mTOR) pathway plays a significant role in colorectal adenocarcinoma. NVP-BEZ235 (dactolisib) is a novel dual inhibitor of PI3K/mTOR. The effects of NVP-BEZ235 in human colorectal adenocarcinoma are still unclear. In the present study, we aimed to explore the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells. HT-29 human colorectal adenocarcinoma cells were treated with NVP-BEZ235 (0, 0.001, 0.01, 0.1,1 and 3 mu M) for 24 and 48 h, respectively. Cells were also treated with NVP-BEZ235 (0.1 mu M), DDP (100, 300 and 1,000 mu M), and NVP-BEZ235 (0.1 mu M) combined with DDP (100, 300 and 1,000 mu M) respectively, and cultured for 24 h after treatment. MTT assay was utilized to evaluate the effects of NVP-BEZ235 alone or NVP-BEZ235 combined with cis-diammin.edichloroplatinum (DDP) on proliferation of HT-29 cells. Cell wound-scratch assay was used detect cell migration. In addition, expression of microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B and LC3B) in HT-29 cells was detected by immunofluorescence at 48 h after NVP-BEZ235 (1 mu M) treatment. Expression of proteins involved in cell cycle and proliferation (p-Akt, p-mTOR and cyclin Dl), apoptosis (cleaved caspase-3), and autophagy (cleaved LC3B and Beclin-1) were detected by western blot analysis. NVP-BEZ235 inhibited the proliferation and migration of HT-29 human colorectal adenocarcinoma cells. NVP-BEZ235 decreased protein expression of p-Akt, p-mTOR and cyclin Dl, and increased protein expression of cleaved caspase-3, cleaved LC3B and Beclin-1 as the concentrations and the incubation time of NVP-BEZ235 increased. In addition, NVP-BEZ235 and DDP had synergic effects in inhibiting cell proliferation and migration. The expression of protein involved in apoptosis (cleaved caspase-3) was higher in drug combination group compared to the NVP-BEZ235 single treatment group. NVP-BEZ235 inhibited the proliferation and migration, and induced apoptosis and autophagy of HT -29 human colorectal adenocarcinoma cells.	[Yu, Yang; Yu, Xiaofeng; Ma, Jianxia; Tong, Yili; Yao, Jianfeng] Fudan Univ, Hua Dong Hosp, Dept Gastroenterol, 221 West Yanan Rd, Shanghai 200040, Peoples R China		Yao, JF (corresponding author), Fudan Univ, Hua Dong Hosp, Dept Gastroenterol, 221 West Yanan Rd, Shanghai 200040, Peoples R China.	yaojianfeng037@hotmail.com					Apps MG, 2015, ENDOCR-RELAT CANCER, V22, pR219, DOI 10.1530/ERC-15-0237; Cakir E, 2011, APMIS, V119, P574, DOI 10.1111/j.1600-0463.2011.02778.x; Chen JZ, 2015, CLIN EXP PHARMACOL P, V42, P1317, DOI 10.1111/1440-1681.12493; Chen ZH, 2010, P NATL ACAD SCI USA, V107, P18880, DOI 10.1073/pnas.1005574107; Cherra SJ, 2010, J CELL BIOL, V190, P533, DOI 10.1083/jcb.201002108; Cohen SM, 2000, BIOCHEMISTRY-US, V39, P11771, DOI 10.1021/bi001352l; Dubrovska A, 2010, CLIN CANCER RES, V16, P5692, DOI 10.1158/1078-0432.CCR-10-1601; Dubrovska A, 2009, P NATL ACAD SCI USA, V106, P268, DOI 10.1073/pnas.0810956106; Hernlund E, 2012, EUR J CANCER, V48, P396, DOI 10.1016/j.ejca.2011.11.013; Horie R, 2016, INT J ONCOL, V48, P37, DOI 10.3892/ijo.2015.3227; Ji YH, 2015, CLIN LAB, V61, P1043, DOI 10.7754/Clin.Lab.2015.150144; Jin ZJ, 2004, ACTA PHARMACOL SIN, V25, P146; Kanai R, 2011, CLIN CANCER RES, V17, P3686, DOI 10.1158/1078-0432.CCR-10-3142; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Li Chun-hong, 2008, Zhonghua Zhong Liu Za Zhi, V30, P418; Li CT, 2015, CANCER CELL INT, V15, DOI 10.1186/s12935-015-0213-1; Lin SJ, 2015, ONCOTARGET, V6, P39329, DOI 10.18632/oncotarget.5744; Liu TJ, 2009, MOL CANCER THER, V8, P2204, DOI 10.1158/1535-7163.MCT-09-0160; Meyer G, 2013, CURR PHARM DESIGN, V19, P6912, DOI 10.2174/138161281939131127122510; O'Reilly KE, 2006, CANCER RES, V66, P1500, DOI 10.1158/0008-5472.CAN-05-2925; Ojeda L, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0023414; Peltier J, 2007, DEV NEUROBIOL, V67, P1348, DOI 10.1002/dneu.20506; Populo H, 2012, INT J MOL SCI, V13, P1886, DOI 10.3390/ijms13021886; Pruefer FG, 2008, J CHEMOTHERAPY, V20, P348, DOI 10.1179/joc.2008.20.3.348; Rafalski VA, 2011, PROG NEUROBIOL, V93, P182, DOI 10.1016/j.pneurobio.2010.10.007; Sacco A, 2010, ONCOTARGET, V1, P578; Sarbassov DD, 2005, SCIENCE, V307, P1098, DOI 10.1126/science.1106148; Shen Y, 2011, EXP THER MED, V2, P1171, DOI 10.3892/etm.2011.330; Shimura T, 2016, ONCOTARGET, V7, P3559, DOI 10.18632/oncotarget.6518; Sui HY, 2015, DRUG DES DEV THER, V9, P3183, DOI 10.2147/DDDT.S82035; Sui L, 2008, LEARN MEMORY, V15, P762, DOI 10.1101/lm.1067808; Tabernero J, 2008, J CLIN ONCOL, V26, P1603, DOI 10.1200/JCO.2007.14.5482; Wang GH, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0055298; Wang WJ, 2013, ACTA PHARMACOL SIN, V34, P681, DOI 10.1038/aps.2013.22; Wani ZA, 2016, FOOD CHEM TOXICOL, V87, P1, DOI 10.1016/j.fct.2015.11.016; Weng YJ, 2011, J HUAZHONG U SCI-MED, V31, P550, DOI 10.1007/s11596-011-0488-y; Wyatt LA, 2014, J COMP NEUROL, V522, P2741, DOI 10.1002/cne.23580; Zou MJ, 2015, MOL CARCINOGEN, V54, P1363, DOI 10.1002/mc.22212	38	17	21	0	7	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1019-6439	1791-2423		INT J ONCOL	Int. J. Oncol.	JUL	2016	49	1					285	293		10.3892/ijo.2016.3507			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	DO2WD	WOS:000377640800026	27176231	Bronze			2022-04-25	
J	Lin, Y; Stevens, C; Hrstka, R; Harrison, B; Fourtouna, A; Pathuri, S; Vojtesek, B; Hupp, T				Lin, Yao; Stevens, Craig; Hrstka, Roman; Harrison, Ben; Fourtouna, Argyro; Pathuri, Suresh; Vojtesek, Borek; Hupp, Ted			An alternative transcript from the death-associated protein kinase 1 locus encoding a small protein selectively mediates membrane blebbing	FEBS JOURNAL			English	Article							TUMOR-SUPPRESSOR DAPK; KINASE; STRESS; FIBERS; DOMAIN	Death-associated protein kinase 1 (DAPK-1) is a multidomain protein kinase with diverse roles in autophagic, apoptotic and survival pathways. Bioinformatic screens were used to identify a small internal mRNA from the DAPK-1 locus (named s-DAPK-1). This encodes a 295 amino acid polypeptide encompassing part of the ankyrin-repeat domain, the P-loop motifs, part of the cytoskeletal binding domain of DAPK-1, and a unique C-terminal 'tail' extension not present in DAPK-1. Expression of s-DAPK-1 mRNA was detected in a panel of normal human tissues as well as primary colorectal cancers, indicating that its expression occurs in vivo. s-DAPK-1 gene transfection into cells produces two protein products: one with a denatured mass of 44 kDa, and a smaller product of 40 kDa. Double alanine mutation of the C-terminal tail extension of s-DAPK-1 (Gly296/Arg297) prevented production of the 40 kDa fragment, suggesting that the smaller product is generated by in vivo proteolytic processing. The s-DAPK-1 gene cannot substitute for full-length DAPK-1 in an mitogen-activated protein kinase kinase/extracellular signal-regulated kinase-dependent apoptotic transfection assay. However, the transfection of s-DAPK-1 was able to mimic full-length DAPK-1 in the induction of membrane blebbing. The 44 kDa protease-resistant mutant s-DAPK-1G296A/R297A had very low activity in membrane blebbing, whereas the 40 kDa s-DAPK-1 Delta tail protein exhibited the highest levels of membrane blebbing. Deletion of the tail extension of s-DAPK-1 increased its half-life, shifted the equilibrium of the protein from cytoskeletal to soluble cytosolic pools, and altered green fluorescent protein-tagged s-DAPK-1 protein localization as observed by confocal microscopy. These data highlight the existence of an alternative product of the DAPK-1 locus, and suggest that proteolytic removal of the C-terminal tail of s-DAPK-1 is required to stimulate maximally its membrane-blebbing function.	[Lin, Yao; Stevens, Craig; Harrison, Ben; Fourtouna, Argyro; Pathuri, Suresh; Hupp, Ted] Univ Edinburgh, Inst Genet & Mol Med, Cell Signaling Unit, CRUK p53 Signal Transduct Grp, Edinburgh EH4 2XR, Midlothian, Scotland; [Hrstka, Roman; Vojtesek, Borek] Masaryk Mem Canc Inst, Brno, Czech Republic		Hupp, T (corresponding author), Univ Edinburgh, Inst Genet & Mol Med, Cell Signaling Unit, CRUK p53 Signal Transduct Grp, Edinburgh EH4 2XR, Midlothian, Scotland.	ted.hupp@ed.ac.uk	Hrstka, Roman/AAM-4430-2020	Hrstka, Roman/0000-0002-6139-2664; Harrison, Benjamin/0000-0002-6078-5060; , yao/0000-0002-0493-0155	Cancer Research UKCancer Research UK Funding Source: Medline		Bialik S, 2004, CELL DEATH DIFFER, V11, P631, DOI 10.1038/sj.cdd.4401386; Bialik S, 2006, ANNU REV BIOCHEM, V75, P189, DOI 10.1146/annurev.biochem.75.103004.142615; Charras GT, 2006, J CELL BIOL, V175, P477, DOI 10.1083/jcb.200602085; Chen CH, 2005, EMBO J, V24, P294, DOI 10.1038/sj.emboj.7600510; Gozuacik D, 2006, AUTOPHAGY, V2, P74, DOI 10.4161/auto.2.2.2459; HARRISON B, 2008, IN PRESS J BIOL CHEM; Houle F, 2007, J CELL SCI, V120, P3666, DOI 10.1242/jcs.003251; Inbal B, 2002, J CELL BIOL, V157, P455, DOI 10.1083/jcb.200109094; Jin YJ, 2002, J BIOL CHEM, V277, P46980, DOI 10.1074/jbc.M208585200; Kuo JC, 2006, J CELL BIOL, V172, P619, DOI 10.1083/jcb.200505138; Kuo JC, 2003, J CELL SCI, V116, P4777, DOI 10.1242/jcs.00794; Li JN, 2006, BIOCHEMISTRY-US, V45, P15168, DOI 10.1021/bi062188q; Lin Y, 2007, J BIOL CHEM, V282, P16792, DOI 10.1074/jbc.M611559200; Llambi F, 2005, EMBO J, V24, P1192, DOI 10.1038/sj.emboj.7600584; Raval A, 2007, CELL, V129, P879, DOI 10.1016/j.cell.2007.03.043; Raveh T, 2001, NAT CELL BIOL, V3, P1, DOI 10.1038/35050500; Stevens C, 2007, J BIOL CHEM, V282, P13791, DOI 10.1074/jbc.M605649200; Torgerson RR, 1998, J CELL SCI, V111, P2911; Wang WJ, 2007, MOL CELL, V27, P701, DOI 10.1016/j.molcel.2007.06.037	19	4	6	1	2	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1742-464X	1742-4658		FEBS J	FEBS J.	MAY	2008	275	10					2574	2584		10.1111/j.1742-4658.2008.06404.x			11	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	292SF	WOS:000255285700020	18422656	Bronze			2022-04-25	
J	Kim, ER; Kim, KM; Lee, JY; Joo, M; Kim, S; Noh, JH; Ward, SM; Koh, SD; Rhee, PL				Kim, Eun Ran; Kim, Kyoung Mee; Lee, Ji Yeon; Joo, Mee; Kim, Sung; Noh, Jae Hyung; Ward, Sean M.; Koh, Sang Don; Rhee, Poong-Lyul			The clue of Interstitial Cell of Cajalopathy (ICCpathy) in human diabetic gastropathy The ultrastructural and electrical clues of ICCpathy in human diabetic gastropathy	EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY			English	Article						Diabetic gastropathy; Ultrastructure; Electrophysiology; Slow waves; Interstitial Cells of Cajal (ICC)	NITRIC-OXIDE SYNTHASE; MYENTERIC PLEXUS; CAJAL; EXPRESSION; PATHOPHYSIOLOGY; DEFICIENCY; PACEMAKERS; MUSCLE; COLON; GUT	Recent studies of diabetic animal models suggest an important role of ICC in the pathogenesis of gastropathy. The aim of this study was to characterize the ultrastructural features of ICC and record the electrical properties in the stomach of patients with type 2 DM. Gastric specimens were obtained from 13 diabetic patients and 6 control subjects with gastric cancer that underwent gastrectomy. All specimens were taken from disease-free areas. The samples were processed for both electron microscopic and electrophysiologic examination. The characteristic ultrastructural changes of the ICC were observed in both the nucleus and cytoplasm in patients with type 2 DM. Wrinkling of the nuclear envelope and changes in the cytoplasm such as dilatation of the endoplasmic reticulum, an increase of autophagic vacuoles, were more frequently observed in the diabetic patients. Apoptosis characterized by nuclear karyorrhexis or pyknosis was observed only in the diabetic patients. Slow waves were recorded in the circular muscle of stomach. In diabetic patients, the mean resting membrane. potential was higher and amplitude was lower than controls. These changes of electrical activities of slow waves were accompanied with ultrastructural changes of ICC, particularly the characteristic nuclear changes. In human diabetic patients, the characteristic ultrastructural changes of ICC such as preapoptosis, accompanied with electrical dysrhythmia of slow waves, were observed. These results show several evidence converging to support that degeneration of the ICC may be associated with the pathogenesis of diabetic gastropathy. (C) 2010 Elsevier GmbH. All rights reserved.	[Rhee, Poong-Lyul] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Gastroenterol,Dept Med, Seoul 135710, South Korea; [Kim, Kyoung Mee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul 135710, South Korea; [Lee, Ji Yeon] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Biomed Res Inst, Seoul 135710, South Korea; [Joo, Mee] Inje Univ, Sch Med, Ilsan Paik Hosp, Dept Pathol, Gyeonggi Do, South Korea; [Kim, Sung; Noh, Jae Hyung] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, Seoul 135710, South Korea; [Ward, Sean M.; Koh, Sang Don] Univ Nevada, Sch Med, Dept Physiol & Cell Biol, Reno, NV 89557 USA		Rhee, PL (corresponding author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Gastroenterol,Dept Med, 50 Irwon Dong, Seoul 135710, South Korea.	plrhee@skku.edu	Kim, Eun Ran/AAD-8003-2022; Kim, Sung/G-4114-2014	Kim, Eun Ran/0000-0002-0495-2565; Rhee, Poong-Lyul/0000-0003-0495-5296	Samsung Biomedical Research InstituteSamsung [SBRI C-A8-226-1]; 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) [R01DK057236, P01DK041315, R01DK045713] Funding Source: NIH RePORTER	This work was supported by Samsung Biomedical Research Institute grant (SBRI C-A8-226-1).	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Toxicol. Pathol.	JUL	2012	64	5					521	526		10.1016/j.etp.2010.11.008			6	Pathology; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology; Toxicology	948OU	WOS:000304513300019	21185163				2022-04-25	
J	Park, E; Park, MH; Na, HS; Chung, J				Park, Eunjoo; Park, Mi Hee; Na, Hee Sam; Chung, Jin			Xylitol induces cell death in lung cancer A549 cells by autophagy	BIOTECHNOLOGY LETTERS			English	Article						Anti-cancer agent; Autophagy; Cancer; Lung cancer; Xylitol	PORPHYROMONAS-GINGIVALIS; ULCERATIVE-COLITIS; COLORECTAL-CANCER; THERAPY; INFLAMMATION	Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.	[Park, Eunjoo; Park, Mi Hee; Na, Hee Sam; Chung, Jin] Pusan Natl Univ, Sch Dent, Dept Oral Microbiol, Yangsan Si 626870, Gyeongsangnam D, South Korea		Chung, J (corresponding author), Pusan Natl Univ, Sch Dent, Dept Oral Microbiol, Yangsan Si 626870, Gyeongsangnam D, South Korea.	jchung@pusan.ac.kr			National Research Foundation of Korea (NRF) - Korea government (MEST)Ministry of Education, Science and Technology, Republic of KoreaNational Research Foundation of KoreaKorean Government [2012R1A2A2A01015470]	A National Research Foundation of Korea (NRF) Grant funded by the Korea government (MEST; No. 2012R1A2A2A01015470) supported this research.	Brown ER, 2008, ANN ONCOL, V19, P1340, DOI 10.1093/annonc/mdn054; Coussens LM, 2002, NATURE, V420, P860, DOI 10.1038/nature01322; Eaden J, 2000, ALIMENT PHARM THERAP, V14, P145; Fu L, 2009, CANCER RES, V69, P8967, DOI 10.1158/0008-5472.CAN-09-2190; Han SJ, 2005, CLIN DIAGN LAB IMMUN, V12, P1285, DOI 10.1128/CDLI.12.11.1285-1291.2005; Hippert MM, 2006, CANCER RES, V66, P9349, DOI 10.1158/0008-5472.CAN-06-1597; Hudson JD, 1999, J EXP MED, V190, P1375, DOI 10.1084/jem.190.10.1375; Janku F, 2011, NAT REV CLIN ONCOL, V8, P528, DOI 10.1038/nrclinonc.2011.71; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Klionsky DJ, 2000, SCIENCE, V290, P1717, DOI 10.1126/science.290.5497.1717; Kung CP, 2011, CRIT REV EUKAR GENE, V21, P71, DOI 10.1615/CritRevEukarGeneExpr.v21.i1.50; Lynch Heather, 2003, J Calif Dent Assoc, V31, P205; Moody GA, 1996, EUR J GASTROEN HEPAT, V8, P1179, DOI 10.1097/00042737-199612000-00009; Park E, 2014, J PERIODONTOL, V85, pE212, DOI 10.1902/jop.2014.130455; Philip M, 2004, SEMIN CANCER BIOL, V14, P433, DOI 10.1016/j.semcancer.2004.06.006	15	11	12	3	17	SPRINGER	DORDRECHT	VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS	0141-5492	1573-6776		BIOTECHNOL LETT	Biotechnol. Lett.	MAY	2015	37	5					983	990		10.1007/s10529-014-1757-1			8	Biotechnology & Applied Microbiology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology	CF6BP	WOS:000352641700004	25650339				2022-04-25	
J	Akter, M; Ullah, AKMA; Banik, S; Sikder, MT; Hosokawa, T; Saito, T; Kurasaki, M				Akter, Mahmuda; Atique Ullah, A. K. M.; Banik, Subrata; Sikder, Md. Tajuddin; Hosokawa, Toshiyuki; Saito, Takeshi; Kurasaki, Masaaki			Green Synthesized Silver Nanoparticles-Mediated Cytotoxic Effect in Colorectal Cancer Cells: NF-kappa B Signal Induced Apoptosis Through Autophagy	BIOLOGICAL TRACE ELEMENT RESEARCH			English	Article						Apoptosis; Autophagy; Brassica silver nanoparticles; NF&#954; B; Caco-2 cells	OXIDATIVE STRESS; ACTIVATION; TOXICITY; DEATH; MTOR	Green synthesized silver nanoparticles (Ag-NPs) have demonstrated promising effects, including cytotoxicity and anticancer potential, in different cell lines. Therefore, in our previous study, Ag-NPs were synthesized from the reduction of AgNO3 using Brassica rapa var. japonica (Bj) leaf extract as a reducing and stabilizing agent. The synthesized Ag-NPs were spherical in shape, with a size range of 15-30 nm. They had phase-centered cubic structure with strong growth inhibition potential against some bacteria. In continuation with our previous study, in the present study, we aimed to investigate the autophagy-regulated cytotoxic effect of Ag-NPs against human epithelial colorectal adenocarcinoma cells (Caco-2 cells). We found that the Bj leaf aqueous extract facilitated Brassica silver nanoparticles (Brassica Ag-NPs)-induced NF-kappa B mediated autophagy in Caco-2 cells. Results showed that Ag-NPs reduced cell viability of Caco-2 cells by inducing oxidative stress and DNA damage. Therefore, to understand the mechanism underlying the death-promoting activity of Ag-NPs in Caco-2 cells, western blotting was performed. Western blot analysis showed decreased expression of NF kappa B and increased expression of I kappa B, which is a sign of autophagy initiation. In addition, autophagosome formation was accelerated by the activity of p53 and light chain 3 (LC3) II. In addition, inhibition of Akt and mTOR also played a pivotal role in autophagy formation. Finally, excessive expansion of autophagy promoted apoptosis, which subsequently resulted in necrosis. These findings support a novel cell death-promoting function of autophagy by Ag-NPs in Caco-2 cells.	[Akter, Mahmuda; Kurasaki, Masaaki] Hokkaido Univ, Grp Environm Adaptat Sci, Fac Environm Earth Sci, Kita Ku, Kita 10,Nishi 5, Sapporo, Hokkaido 0600810, Japan; [Atique Ullah, A. K. M.] Bangladesh Atom Energy Commiss, Nanosci & Technol Res Lab, Chem Div, Atom Energy Ctr, Dhaka 1000, Bangladesh; [Banik, Subrata; Kurasaki, Masaaki] Hokkaido Univ, Grad Sch Environm 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; [Saito, Takeshi] Hokkaido Univ, Fac Hlth Sci, Sapporo, Hokkaido 0600812, Japan		Kurasaki, M (corresponding author), Hokkaido Univ, Grp Environm Adaptat Sci, Fac Environm Earth Sci, Kita Ku, Kita 10,Nishi 5, Sapporo, Hokkaido 0600810, Japan.; Kurasaki, M (corresponding author), Hokkaido Univ, Grad Sch Environm Sci, Sapporo, Hokkaido 0600810, Japan.	kura@ees.hokuda.ac.jp	KURASAKI, Masaaki/B-8207-2012	KURASAKI, Masaaki/0000-0003-2125-095X; Sikder, Dr. Md. 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Trace Elem. Res.	SEP	2021	199	9					3272	3286		10.1007/s12011-020-02463-7		NOV 2020	15	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	TE2TW	WOS:000592136600001	33236292				2022-04-25	
J	Bai, S; Tian, B; Li, A; Yao, Q; Zhang, G; Li, F				Bai, S.; Tian, B.; Li, A.; Yao, Q.; Zhang, G.; Li, F.			MicroRNA-125b promotes tumor growth and suppresses apoptosis by targeting DRAM2 in retinoblastoma	EYE			English	Article							RETINAL DYSTROPHY; CANCER; IDENTIFICATION; PROLIFERATION; EXPRESSION; AUTOPHAGY; MUTATIONS; CELLS	Purpose It is known that microRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms involving miRNAs in retinoblastoma (RB) remain largely unknown. The miRNA miR-125b is dysregulated in various human cancers such as breast cancer, human hepatocellular carcinoma, ovarian cancer, and colorectal cancer. However, the significance of miR-125b in RB has not been sufficiently investigated. Our objective was to explore the role of the miR-125b in RB. Methods In this study, we measured miR-125b levels using real-time polymerase chain reaction in human RB cell lines, including HXO-Rb44, Y79, SO-RB50, and the normal human retinal pigment epithelial cell line ARPE-19; a total of 38 pairs of primary RB tissues and adjacent noncancerous tissues were also measured. In addition, overexpression of miR-125b in RB cell lines was performed to determine the role of miR-125b in RB. Results We found that miR-125b is significantly upregulated in RB, and closely associated with tumor cell proliferation and apoptosis. In addition, overexpression of miR-125b apparently promotes RB cell proliferation and migration in vitro. Gain-of-function in vitro experiments further showed that the miR-125b mimic significantly suppressed RB cell apoptosis. A subsequent dual-luciferase reporter assay identified the suppressor gene DRAM2 as direct target of miR-125b. Conclusions Our data collectively demonstrate that miR-125b is a suppressor gene miRNA that can promote RB cell proliferation and migration by downregulating the suppressor gene DRAM2, indicating that miR-125b may represent a new potential diagnostic and therapeutic target for RB treatment.	[Bai, S.; Tian, B.; Yao, Q.; Zhang, G.; Li, F.] Xi An Jiao Tong Univ, Guangren Hosp, Xian Hosp 4, Dept Ophthalmol, Xian, Peoples R China; [Li, A.] Jilin Univ, Hosp 1, Dept Ophthalmol, Xinmin St 71, Changchun 130021, Jilin Province, Peoples R China		Li, A (corresponding author), Jilin Univ, Hosp 1, Dept Ophthalmol, Xinmin St 71, Changchun 130021, Jilin Province, Peoples R China.	aipengli4@163.com			National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81302198]	We are grateful to all the patients and individuals in the study who made this work possible. We thank the clinicians and hospital staff who contributed to data collection for this study. This study was funded by the National Natural Science Foundation (No. 81302198). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki declaration and its later amendments, or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.	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JUN 24	2020	20	1							273	10.1186/s12935-020-01370-0			11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	MS0ER	WOS:000553960800008	32587480	gold, Green Published			2022-04-25	
J	Bostad, M; Olsen, CE; Peng, Q; Berg, K; Hogset, A; Selbo, PK				Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Hogset, Anders; Selbo, Pal Kristian			Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy	JOURNAL OF CONTROLLED RELEASE			English	Article						Controlled drug delivery; Photochemical internalization; Endosomal escape; Targeting; CD133; Immunotoxin; Cancer stem cells; Photodynamic therapy; Cancer therapy; Autophagy	PHOTODYNAMIC THERAPY; COLORECTAL-CANCER; CD133 EXPRESSION; DRUG-DELIVERY; OVARIAN-CANCER; BREAST-CANCER; TUMOR-GROWTH; AUTOPHAGY; MARKER; APOPTOSIS	The cancer stem cell (CSC) marker CD133 is an attractive target to improve antitumor therapy. We have used photochemical internalization (PCI) for the endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133-saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which generates reactive oxygen species upon light-activation causing a rupture of the vesicle membranes and endosomal escape of entrapped drugs. Here we show that AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation and induced 100% inhibition of cell viability and colony forming ability at the highest light doses, whereas no cytotoxicity was obtained in the absence of light. Efficient PCI-based CD133-targeting was in addition demonstrated in the stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin induced mainly necrosis and a minimal apoptotic response based on assessing cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in S phase arrest and reduced LC3-II conversion compared to control treatments. Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II conversion, indicating a termination of the autophagic flux in WiDr cells. For the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor response was observed after PCIAC133-saporin. The present PCI-based endosomal escape technology represents a minimally invasive strategy for spatio-temporal, light-controlled targeting of CD133+ cells in localized primary tumors or metastasis. (C) 2015 Elsevier B.V. All rights reserved.	[Bostad, Monica; Olsen, Cathrine Elisabeth; Berg, Kristian; Selbo, Pal Kristian] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Radiat Biol, N-0424 Oslo, Norway; [Bostad, Monica; Olsen, Cathrine Elisabeth; Hogset, Anders; Selbo, Pal Kristian] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Canc Stem Cell Innovat Ctr SFI CAST, N-0424 Oslo, Norway; [Peng, Qian] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Pathol, N-0424 Oslo, Norway; [Hogset, Anders] PCI Biotech AS, Lysaker, Norway		Selbo, PK (corresponding author), Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Radiat Biol, Postboks 4953 Nydalen, N-0424 Oslo, Norway.	selbo@rr-research.no	Selbo, Pål Kristian/B-4638-2009	Selbo, Pål Kristian/0000-0002-5310-057X; Berg, Kristian/0000-0002-7816-7543	Norwegian Research Council (SFI-CAST)Research Council of Norway; Norwegian Radium Hospital Research Foundation [FU0803]; Norwegian Cancer SocietyNorwegian Cancer Society [3327285]	This work was supported by grants from the Norwegian Research Council (SFI-CAST), the Norwegian Radium Hospital Research Foundation (FU0803) and the Norwegian Cancer Society (3327285). We thank Mette Forsund at the Department of Pathology for skilful technical assistance with the IHC preparation and staining and Idun Dale Rein at the Flow Cytometry Core Facility for excellent technical assistance with the live/dead and TUNEL assay.	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Control. Release	MAY 28	2015	206						37	48		10.1016/j.jconrel.2015.03.008			12	Chemistry, Multidisciplinary; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	CG5UM	WOS:000353361400004	25758331				2022-04-25	
J	Cheng, TC; Tu, SH; Chen, LC; Chen, MY; Chen, WY; Lin, YK; Ho, CT; Lin, SY; Wu, CH; Ho, YS				Cheng, Tzu-Chun; Tu, Shih-Hsin; Chen, Li-Ching; Chen, Ming-Yao; Chen, Wen-Ye; Lin, Yen-Kuang; Ho, Chi-Tang; Lin, Shyr-Yi; Wu, Chih-Hsiung; Ho, Yuan-Soon			Down-regulation of alpha-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface	ONCOTARGET			English	Article						alpha-L-fucosidase; triple-negative breast cancer; overall survival rate; glycosylation; metastasis	FOCAL ADHESION KINASE; L-FUCOSE MOIETIES; SIALYL-LEWIS-X; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; CYCLE ARREST; SIGNALING PATHWAY; IN-VITRO; LINES; AUTOPHAGY	alpha-L-fucosidase 1 (FUCA1) is a lysosomal enzyme that catalyzes the hydrolytic cleavage of the terminal fucose residue in breast cancer cells. FUCA1 mRNA levels were detected by real-time PCR, and there was a greater than 139-fold increase in FUCA1 mRNA expression in breast tumor samples compared with normal breast tissue samples (*P = 0.005, n = 236). Higher FUCA1 mRNA expression was preferentially detected in early-stage tumors (stage 0 to 2) compared with advanced-stage tumors (stage 3 to 4) (stage 0-1 versus stage 3, *P = 0.015; stage 0-1 versus stage 4, *P = 0.024). FUCA1 protein levels were higher in advanced-stage tumors concomitant with decreased fucosylated Lewis-x antigen expression, as evidenced using the immunohistochemical staining H-score method (*P < 0.001). Statistical analysis revealed that lower FUCA1 levels significantly predicted an inferior overall survival rate among triple-negative breast cancer (TNBC) patients compared with non-TNBC patients (*P = 0.009). Two stable FUCA1 siRNA knock-down MDA-MB-231 cell lines were established, and the results suggest that transient FUCA inhibition creates a selective pressure that triggers the metastasis of primary tumor cells, as detected by wound healing and invasion assays (*P < 0.01). The results suggest that FUCA1 may be a potential prognostic molecular target for clinical use, especially in TNBC patients.	[Cheng, Tzu-Chun; Ho, Yuan-Soon] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei, Taiwan; [Tu, Shih-Hsin; Wu, Chih-Hsiung] Taipei Med Univ, Coll Med, Sch Med, Dept Surg, Taipei, Taiwan; [Chen, Li-Ching; Chen, Ming-Yao] Taipei Med Univ, Shuang Ho Hosp, Dept Internal Med, Div Gastroenterol, Taipei, Taiwan; [Chen, Li-Ching] Taipei Med Univ, Coll Med, Grad Inst Clin Med, Taipei, Taiwan; [Chen, Wen-Ye; Ho, Yuan-Soon] Taipei Med Univ, Coll Med Sci & Technol, Sch Med Lab Sci & Biotechnol, Taipei, Taiwan; [Lin, Yen-Kuang] Taipei Med Univ, Biol Stat & Res Consultat Ctr, Taipei, Taiwan; [Ho, Chi-Tang] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08903 USA; [Lin, Shyr-Yi] Taipei Med Univ, Coll Med, Sch Med, Dept Gen Med, Taipei, Taiwan; [Wu, Chih-Hsiung] Taipei Med Univ, Shuang Ho Hosp, Dept Surg, Div Gen Surg, Taipei, Taiwan; [Ho, Yuan-Soon] Taipei Med Univ Hosp, Dept Lab Med, Taipei, Taiwan; [Ho, Yuan-Soon] Taipei Med Univ, Ctr Comprehens Canc, Taipei, Taiwan		Ho, YS (corresponding author), Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei, Taiwan.	chwu@tmu.edu.tw; hoyuansn@tmu.edu.tw		Tu, Shih-Hsin/0000-0002-4106-8146	Health and Welfare Surcharge on tobacco products [MOHW104-TDU-B-212-124-001]; Ministry of Science and TechnologyMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [MOST 103-2320-B-038-045-MY3]	This study was supported by the Health and Welfare Surcharge on tobacco products (MOHW104-TDU-B-212-124-001) and by the Ministry of Science and Technology (MOST 103-2320-B-038-045-MY3).	Abdelkarim M, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0023334; Ayude D, 2003, DIS MARKERS, V19, P267; Ayukawa T, 2012, P NATL ACAD SCI USA, V109, P15318, DOI 10.1073/pnas.1202369109; BACUS SS, 1993, CANCER RES, V53, P5251; Bjorkoy G, 2005, J CELL BIOL, V171, P603, DOI 10.1083/jcb.200507002; CAILLEAU R, 1978, IN VITRO CELL DEV B, V14, P911; CAILLEAU R, 1974, J NATL CANCER I, V53, P661, DOI 10.1093/jnci/53.3.661; Chen LC, 2012, BREAST CANCER RES TR, V134, P989, DOI 10.1007/s10549-012-1986-8; Chen RJ, 2000, TOXICOL APPL PHARM, V169, P132, DOI 10.1006/taap.2000.9062; Chittaranjan S, 2014, CLIN CANCER RES, V20, P3159, DOI 10.1158/1078-0432.CCR-13-2060; Chou YH, 2007, FOOD CHEM TOXICOL, V45, P1356, DOI 10.1016/j.fct.2007.01.012; Clarke K, 2000, CLIN CANCER RES, V6, P3621; delaCadena M, 1996, INT J ONCOL, V9, P747; Fujita T, 2011, JPN J CLIN ONCOL, V41, P394, DOI 10.1093/jjco/hyq190; GIARDINA MG, 1992, CANCER, V70, P1044, DOI 10.1002/1097-0142(19920901)70:5<1044::AID-CNCR2820700506>3.0.CO;2-U; Greene F.L., 2002, AJCC CANC STAGING HD; Ho YS, 2001, INT J CANCER, V91, P393, DOI 10.1002/1097-0215(200002)9999:9999&lt;::AID-IJC1070&gt;3.0.CO;2-#; Huang C, 2007, CANCER GENET CYTOGEN, V175, P19, DOI 10.1016/j.cancergencyto.2007.01.003; Julien S, 2011, CANCER RES, V71, P7683, DOI 10.1158/0008-5472.CAN-11-1139; Kaklamani Virginia G, 2003, Clin Breast Cancer, V4 Suppl 1, pS26, DOI 10.3816/CBC.2003.s.012; Kanzawa T, 2003, CANCER RES, V63, P2103; Koh YW, 2013, AM J CLIN PATHOL, V139, P746, DOI 10.1309/AJCP2E6QNDIDPTTC; LASFARGUES EY, 1978, J NATL CANCER I, V61, P967; Lee CH, 2011, BREAST CANCER RES TR, V129, P331, DOI 10.1007/s10549-010-1209-0; Lee CH, 2010, JNCI-J NATL CANCER I, V102, P1322, DOI 10.1093/jnci/djq300; Lee WS, 2003, INT J CANCER, V106, P125, DOI 10.1002/ijc.11194; Lien YC, 2011, ANN SURG ONCOL, V18, P2671, DOI 10.1245/s10434-011-1598-2; Listinsky JJ, 2011, AM J TRANSL RES, V3, P292; Liu JJ, 2009, J EXP CLIN CANC RES, V28, DOI 10.1186/1756-9966-28-154; Liu TW, 2009, P NATL ACAD SCI USA, V106, P14581, DOI 10.1073/pnas.0903286106; Liu YC, 2011, P NATL ACAD SCI USA, V108, P11332, DOI 10.1073/pnas.1107385108; Madjd Z, 2005, BREAST CANCER RES, V7, pR780, DOI 10.1186/bcr1305; Martinez J, 2011, P NATL ACAD SCI USA, V108, P17396, DOI 10.1073/pnas.1113421108; Milde-Langosch K, 2014, BREAST CANCER RES TR, V145, P295, DOI 10.1007/s10549-014-2949-z; Moscat J, 2009, CELL, V137, P1001, DOI 10.1016/j.cell.2009.05.023; Paglin S, 2001, CANCER RES, V61, P439; Pille JY, 2005, MOL THER, V11, P267, DOI 10.1016/j.ymthe.2004.08.029; Robles E, 2006, NAT NEUROSCI, V9, P1274, DOI 10.1038/nn1762; RUSSO J, 1976, J NATL CANCER I, V56, P279, DOI 10.1093/jnci/56.2.279; Sturla L, 2003, J BIOL CHEM, V278, P26727, DOI 10.1074/jbc.M304068200; Sun Y, 2009, POSTGRAD MED J, V85, P134, DOI 10.1136/pgmj.2008.072629; TAKAHASHI H, 1994, HEPATOLOGY, V19, P1414, DOI 10.1002/hep.1840190615; Tappel A, 2005, MED HYPOTHESES, V64, P288, DOI 10.1016/j.mehy.2004.07.025; TRAGANOS F, 1994, METHOD CELL BIOL, V41, P185; Wu YH, 2011, BREAST CANCER RES TR, V127, P397, DOI 10.1007/s10549-010-1013-x; Yuan K, 2008, PATHOL ONCOL RES, V14, P145, DOI 10.1007/s12253-008-9036-x; Yuan K, 2008, INT J ONCOL, V32, P797; Zhou SM, 2015, BREAST CANCER RES, V17, DOI 10.1186/s13058-015-0544-9	48	23	24	3	16	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA		1949-2553		ONCOTARGET	Oncotarget	AUG 28	2015	6	25					21283	21300		10.18632/oncotarget.4238			18	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	CQ9XO	WOS:000360969200046	26204487	Green Published, Green Submitted, gold			2022-04-25	
J	Lu, C; Zhou, DT; Wang, Q; Liu, WL; Yu, FL; Wu, F; Chen, C				Lu, Can; Zhou, Danting; Wang, Qiang; Liu, Wenliang; Yu, Fenglei; Wu, Fang; Chen, Chen			Crosstalk of MicroRNAs and Oxidative Stress in the Pathogenesis of Cancer	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY			English	Review							EPITHELIAL-MESENCHYMAL TRANSITION; NF-KAPPA-B; AUTOPHAGIC CELL-DEATH; PANCREATIC-CANCER; COLORECTAL-CANCER; GASTRIC-CANCER; INHIBITS PROLIFERATION; DOWN-REGULATION; MITOCHONDRIAL METABOLISM; NRF2 ACTIVATION	Oxidative stress refers to an imbalance between reactive oxygen species (ROS) generation and body's capability to detoxify the reactive mediators or to fix the relating damage. MicroRNAs are considered to be important mediators that play essential roles in the regulation of diverse aspects of carcinogenesis. Growing studies have demonstrated that the ROS can regulate microRNA biogenesis and expression mainly through modulating biogenesis course, transcription factors, and epigenetic changes. On the other hand, microRNAs may in turn modulate the redox signaling pathways, altering their integrity, stability, and functionality, thus contributing to the pathogenesis of multiple diseases. Both ROS and microRNAs have been identified to be important regulators and potential therapeutic targets in cancers. However, the information about the interplay between oxidative stress and microRNA regulation is still limited. The present review is aimed at summarizing the current understanding of molecular crosstalk between microRNAs and the generation of ROS in the pathogenesis of cancer.	[Lu, Can] Cent South Univ, Xiangya Hosp, Ctr Stomatol, Changsha 410008, Peoples R China; [Zhou, Danting; Wang, Qiang; Liu, Wenliang; Yu, Fenglei; Chen, Chen] Cent South Univ, Xiangya Hosp 2, Dept Thorac Surg, Changsha 410011, Hunan, Peoples R China; [Wu, Fang] Cent South Univ, Xiangya Hosp 2, Dept Oncol, Changsha 410011, Hunan, Peoples R China		Chen, C (corresponding author), Cent South Univ, Xiangya Hosp 2, Dept Thorac Surg, Changsha 410011, Hunan, Peoples R China.; Wu, F (corresponding author), Cent South Univ, Xiangya Hosp 2, Dept Oncol, Changsha 410011, Hunan, Peoples R China.	494801611@qq.com; 16748191@qq.com; rummer925@163.com; liuwenliang@csu.edu.cn; dajiubei925@163.com; wufang4461@csu.edu.cn; chenchen1981412@hotmail.com	chen, chen/M-6561-2017	chen, chen/0000-0003-4569-6032	China National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81000905, 81902351, 81972638]; Hunan Provincial Key Area RD Program [2019SK2253]; Hunan Provincial Natural Science FoundationNatural Science Foundation of Hunan Province [14JJ4014, 2019JJ50953]; CSCO Cancer Research Foundation [CSCO-Y-young2019-034, CSCO-2019Roche-073]	This study was funded by the China National Natural Science Foundation (No. 81000905, No. 81902351, and No. 81972638), the Hunan Provincial Key Area R&D Program (No. 2019SK2253), the Hunan Provincial Natural Science Foundation (No. 14JJ4014 and No. 2019JJ50953), and the CSCO Cancer Research Foundation (CSCO-Y-young2019-034 and CSCO-2019Roche-073).	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Cell. Longev.	APR 28	2020	2020								2415324	10.1155/2020/2415324			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	LN9WY	WOS:000533282500002	32411322	Green Published, gold			2022-04-25	
J	Mi, YJ; Geng, GJ; Zou, ZZ; Gao, J; Luo, XY; Liu, Y; Li, N; Li, CL; Chen, YQ; Yu, XY; Jiang, J				Mi, Yan-jun; Geng, Guo-jun; Zou, Zheng-zhi; Gao, Jing; Luo, Xian-yang; Liu, Yu; Li, Ning; Li, Chun-lei; Chen, Yu-qiang; Yu, Xiu-yi; Jiang, Jie			Dihydroartemisinin Inhibits Glucose Uptake and Cooperates with Glycolysis Inhibitor to Induce Apoptosis in Non-Small Cell Lung Carcinoma Cells	PLOS ONE			English	Article							COLORECTAL-CANCER CELLS; MAMMALIAN TARGET; METABOLISM; EXPRESSION; MTOR; RESISTANCE; AUTOPHAGY; GROWTH	Despite recent advances in the therapy of non-small cell lung cancer (NSCLC), the chemotherapy efficacy against NSCLC is still unsatisfactory. Previous studies show the herbal antimalarial drug dihydroartemisinin (DHA) displays cytotoxic to multiple human tumors. Here, we showed that DHA decreased cell viability and colony formation, induced apoptosis in A549 and PC-9 cells. Additionally, we first revealed DHA inhibited glucose uptake in NSCLC cells. Moreover, glycolytic metabolism was attenuated by DHA, including inhibition of ATP and lactate production. Consequently, we demonstrated that the phosphorylated forms of both S6 ribosomal protein and mechanistic target of rapamycin (mTOR), and GLUT1 levels were abrogated by DHA treatment in NSCLC cells. Furthermore, the upregulation of mTOR activation by high expressed Rheb increased the level of glycolytic metabolism and cell viability inhibited by DHA. These results suggested that DHA-suppressed glycolytic metabolism might be associated with mTOR activation and GLUT1 expression. Besides, we showed GLUT1 overexpression significantly attenuated DHA-triggered NSCLC cells apoptosis. Notably, DHA synergized with 2-Deoxy-D-glucose (2DG, a glycolysis inhibitor) to reduce cell viability and increase cell apoptosis in A549 and PC-9 cells. However, the combination of the two compounds displayed minimal toxicity to WI-38 cells, a normal lung fibroblast cell line. More importantly, 2DG synergistically potentiated DHA-induced activation of caspase-9, -8 and -3, as well as the levels of both cytochrome c and AIF of cytoplasm. However, 2DG failed to increase the reactive oxygen species (ROS) levels elicited by DHA. Overall, the data shown above indicated DHA plus 2DG induced apoptosis was involved in both extrinsic and intrinsic apoptosis pathways in NSCLC cells.	[Mi, Yan-jun; Geng, Guo-jun; Liu, Yu; Li, Ning; Li, Chun-lei; Yu, Xiu-yi; Jiang, Jie] Xiamen Univ, Affiliated Hosp 1, Dept Thorac Surg, Xiamen, Peoples R China; [Mi, Yan-jun; Chen, Yu-qiang] Xiamen Univ, Chenggong Hosp, Dept Med Oncol, Xiamen, Peoples R China; [Zou, Zheng-zhi] S China Normal Univ, Coll Biophoton, MOE Key Lab Laser Life Sci, Guangzhou, Guangdong, Peoples R China; [Zou, Zheng-zhi] S China Normal Univ, Coll Biophoton, Inst Laser Life Sci, Guangzhou, Guangdong, Peoples R China; [Gao, Jing; Luo, Xian-yang] Xiamen Univ, Affiliated Hosp 1, Dept Head & Neck Surg, Xiamen, Peoples R China		Yu, XY (corresponding author), Xiamen Univ, Affiliated Hosp 1, Dept Thorac Surg, Xiamen, Peoples R China.	Xiuyiyu@126.com; Jiejiangfy@163.com			Postdoctoral Science Foundation of ChinaChina Postdoctoral Science Foundation [2014M561853]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402187]; South China Normal University Science Fund for Young Scholars [670325]; Fujian Provincial Department of Science Technology [2014D020]; Fujian Provincial Department of Health [wzhw201304, wst201214]	This study was supported by grants from the Postdoctoral Science Foundation of China (No. 2014M561853 to YJM), the National Natural Science Foundation of China (No. 81402187 to ZZZ), the South China Normal University Science Fund for Young Scholars (No. 670325 to ZZZ), the Fujian Provincial Department of Science & Technology (No. 2014D020 to JJ) and Fujian Provincial Department of Health (wzhw201304, wst201214). 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	Giuliano, S; Pages, G				Giuliano, Sandy; Pages, Gilles			Mechanisms of resistance to anti-angiogenesis therapies	BIOCHIMIE			English	Review						Anti-angiogenesis; Resistance; Targeted therapies; Predictive markers; Autophagy	ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; BEVACIZUMAB PLUS IRINOTECAN; MARROW-DERIVED CELLS; CANCER STEM-CELLS; PHASE-II TRIAL; BREAST-CANCER; TUMOR ANGIOGENESIS	Angiogenesis, the formation of new blood vessels from preexisting ones, provides oxygen and nutrients to actively proliferating tumor cells. Hence, it represents a critical aspect of tumor progression and metastasis. Because inhibition of angiogenesis represents a major approach to cancer treatment, the development of inhibitors of angiogenesis is a major challenge. The first FDA approved anti-angiogenic drug bevacizumab, a humanized monoclonal antibody directed against the Vascular Endothelial Growth Factor (VEGF), has been approved for the treatment of metastatic colorectal, lung, breast, and kidney cancers. The encouraging results have lead to the development, in the past few years, of other agents targeting angiogenic pathways as potent anti-cancer drugs and a number of them have been approved for metastatic breast, lung, kidney, and central nervous system cancers. Despite a statistically significant increase in progression free survival, which has accelerated FDA approval, no major benefit to overall survival was described and patients inevitably relapsed due to acquired resistance. However, while progression free survival was increased by only a few months for the majority of the patients, some clearly benefited from the treatment with a real increase in life span. The objective of this review is to present an overview of the different treatments targeting angiogenesis, their efficacy and the mechanisms of resistance that have been identified in different cancer types. It is essential to understand how resistance (primary or acquired over time) develops and how it may be overcome. (C) 2013 Elsevier Masson SAS. All rights reserved.	[Giuliano, Sandy; Pages, Gilles] Univ Nice Sophia Antipolis, IRCAN, CNRS, U7284,INSERM,U1081, F-06189 Nice, France		Pages, G (corresponding author), Univ Nice Sophia Antipolis, IRCAN, CNRS, U7284,INSERM,U1081, 33 Ave Valombrose, F-06189 Nice, France.	gpages@unice.fr	Pages, Gilles/N-7135-2017; Giuliano, Sandy/U-2498-2019		Institut National pour la Sante et la Recherche Medicale (INSERM)Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS)Centre National de la Recherche Scientifique (CNRS); National Institute of Cancer (INCA)Institut National du Cancer (INCA) France; Association for Cancer Research (ARC); Fondation de FranceFondation de France; Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale; Association pour la Recherche sur les Tumeurs du Rein (ARTuR); ROCHE FranceRoche Holding	This work was supported by the Institut National pour la Sante et la Recherche Medicale (INSERM) and the Centre National de la Recherche Scientifique (CNRS). This work was supported by the National Institute of Cancer (INCA), the Association for Cancer Research (ARC), the Fondation de France, the Fondation pour la Recherche Medicale (FRM), the "Association pour la Recherche sur les Tumeurs du Rein (ARTuR)" and ROCHE France. We thank Dr M Christiane Brahimi-Horn for editorial assistance.	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J	Sachdeva, UM; Thompson, CB				Sachdeva, Uma M.; Thompson, Craig B.			Diurnal rhythms of autophagy - Implications for cell biology and human disease	AUTOPHAGY			English	Review						autophagy; diurnal; circadian; fasting; metabolic cycle; insulin; glucagon	GLUCAGON-INDUCED AUTOPHAGY; CIRCADIAN GENE-EXPRESSION; LIFE-SPAN EXTENSION; RAT-LIVER; VISUAL CELLS; AEROBIC GLYCOLYSIS; PERIPHERAL-TISSUES; COLORECTAL-CANCER; TERM STARVATION; METABOLIC CYCLE	Autophagy is a key mechanism for cell survival under conditions of nutrient limitation. On the organismal level, autophagy is essential for survival of lower eukaryotes during extended periods of starvation, and it is induced in mammals during short-term starvation. As a consequence of the induction of autophagy during short periods of fasting, animals experience diurnal rhythms of autophagy in concert with their circadian cycle. Autophagy has also been identified as a component of the metabolic cycle of yeast, an ultradian rhythm that bears many similarities to the circadian rhythm of plants, flies and mammals. The circadian clock, which is present in almost all mammalian cell types studied to date, temporally regulates expression of multiple genes, gating cell processes such as nutrient uptake, glycolysis and proliferation, to particular times of day. Whether the circadian clock directly regulates autophagy in mammalian cells, or whether autophagy may play a role in the cycling of mammalian cell clocks is not yet clear. Nevertheless, the relationship between circadian cycles and autophagy is an intriguing area for future study and has implications for multiple human diseases, including aging, neurodegeneration and cancer.	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J	Kutikhin, AG				Kutikhin, Anton G.			Role of NOD1/CARD4 and NOD2/CARD15 gene polymorphisms in cancer etiology	HUMAN IMMUNOLOGY			English	Article						NOD1/CARD4; NOD2/CARD15; Single nucleotide polymorphisms; Cancer; Inflammation	INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTORS; INTESTINAL EPITHELIAL-CELLS; NON-HODGKIN-LYMPHOMA; FACTOR-KAPPA-B; NOD2 3020INSC MUTATION; INNATE IMMUNE-RESPONSE; CROHNS-DISEASE; COLORECTAL-CANCER; NUCLEOTIDE-BINDING	NOD1/CARD4 and NOD2/CARD15 are members of Nod-like receptor family. They are located in cytosol, bind bacterial and viral ligands and play a key role in realization of innate and adaptive immune response, apoptosis, autophagy, and reactive oxygen species generation. Polymorphisms in NOD1/CARD4 and NOD2/CARD15 genes may shift balance between pro- and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation and cancer. NOD1/CARD4 and NOD2/CARD15 gene polymorphisms may be associated with altered risk of gastric, colorectal, breast, ovarian, prostate, testicular, lung, laryngeal, liver, gallbladder, biliary tract, pancreatic, small bowel, kidney, urinary bladder cancer, skin cancer, nonthyroid endocrine tumors, lymphoma and leukemia. The short list of such polymorphisms perspective for oncogenomic investigations may include rs2006847, rs2066845, rs2066844, rs2066842, ND(1)+32656, rs2075820 whereas rs104895493, rs104895476, rs104895475, rs104895474, rs104895473, rs104895472, rs104895462, rs104895461, rs104895460, rs104895438, rs5743291, rs5743260, rs2076756, rs2066843, Pro371Thr, Ala794Pro, Gln908His, rs72551113, rs72551107, rs6958571, rs2907749, rs2907748, rs2075822, rs2075819, rs2075818 may be added to the extended list. Reasons of discrepancies between different studies include confounding host genetic, bacterial, or environmental factors modulating penetrance of variant allele and affecting risk of condition increasing cancer risk, different bacterial impact in aetiology of such conditions, differences in sample size, clinicopathological characteristics, diagnostics, stratification, genotyping methods, and chance. (C) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.	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Immunol.	OCT	2011	72	10					955	968		10.1016/j.humimm.2011.06.003			14	Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Immunology	833QX	WOS:000295901100030	21745515				2022-04-25	
J	Chang, TC; Wei, PL; Makondi, PT; Chen, WT; Huang, CY; Chang, YJ				Chang, Tung-Cheng; Wei, Po-Li; Makondi, Precious Takondwa; Chen, Wei-Ting; Huang, Chien-Yu; Chang, Yu-Jia			Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy	PLOS ONE			English	Article							INDUCED CYTOKINE PRODUCTION; INDUCED APOPTOSIS; OXIDATIVE STRESS; STATISTICS; PATHWAY; LC3; EXPRESSION; AIF	Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies.	[Chang, Tung-Cheng; Wei, Po-Li; Makondi, Precious Takondwa; Chen, Wei-Ting; Chang, Yu-Jia] Taipei Med Univ, Coll Med, Grad Inst Clin Med, Taipei, Taiwan; [Chang, Tung-Cheng; Wei, Po-Li; Huang, Chien-Yu] Taipei Med Univ, Coll Med, Dept Surg, Taipei, Taiwan; [Chang, Tung-Cheng; Huang, Chien-Yu] Taipei Med Univ, Shuang Ho Hosp, Div Gen Surg, Dept Surg, New Taipei, Taiwan; [Wei, Po-Li] Taipei Med Univ, Taipei Med Univ Hosp, Dept Surg, Div Colorectal Surg, Taipei, Taiwan; [Wei, Po-Li; Chang, Yu-Jia] Taipei Med Univ, Taipei Med Univ Hosp, Canc Res Ctr, Taipei, Taiwan; [Wei, Po-Li; Chang, Yu-Jia] Taipei Med Univ, Taipei Med Univ Hosp, Dept Med Res, Translat Lab, Taipei, Taiwan; [Wei, Po-Li] Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan; [Makondi, Precious Takondwa; Chang, Yu-Jia] Taipei Med Univ, Int PhD Program Med, Taipei, Taiwan		Chang, YJ (corresponding author), Taipei Med Univ, Coll Med, Grad Inst Clin Med, Taipei, Taiwan.; Huang, CY (corresponding author), Taipei Med Univ, Coll Med, Dept Surg, Taipei, Taiwan.; Huang, CY (corresponding author), Taipei Med Univ, Shuang Ho Hosp, Div Gen Surg, Dept Surg, New Taipei, Taiwan.; Chang, YJ (corresponding author), Taipei Med Univ, Taipei Med Univ Hosp, Canc Res Ctr, Taipei, Taiwan.; Chang, YJ (corresponding author), Taipei Med Univ, Taipei Med Univ Hosp, Dept Med Res, Translat Lab, Taipei, Taiwan.; Chang, YJ (corresponding author), Taipei Med Univ, Int PhD Program Med, Taipei, Taiwan.	cyh@tmu.edu.tw; r5424012@tmu.edu.tw			Taipei Medical University; Shuang Ho Hospital [105TMU-SHH-19]; Shuang Ho Hospital, Taipei Medical University [105TMU-SHH-19]	This work was supported by a grant form Taipei Medical University and Shuang Ho Hospital (105TMU-SHH-19). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; This study was supported by a grant from Taipei Medical University and Shuang Ho Hospital, Taipei Medical University (105TMU-SHH-19).	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J	Zhou, JB; Kang, Y; Chen, L; Wang, H; Liu, JQ; Zeng, S; Yu, LS				Zhou, Jiabei; Kang, Yu; Chen, Lu; Wang, Hua; Liu, Junqing; Zeng, Su; Yu, Lushan			The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents	FRONTIERS IN PHARMACOLOGY			English	Review						platinum-based anticancer drugs; transporter; apoptosis; autophagy; DNA repair; resistance	OVARIAN-CANCER CELLS; COPPER TRANSPORTER CTR1; ORGANIC CATION TRANSPORTERS; OVERCOMES CISPLATIN RESISTANCE; LUNG ADENOCARCINOMA CELLS; COLORECTAL-CANCER; GASTRIC-CANCER; CHEMOTHERAPY RESISTANCE; CELLULAR ACCUMULATION; BLADDER-CANCER	Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.	[Zhou, Jiabei; Kang, Yu; Chen, Lu; Zeng, Su; Yu, Lushan] Zhejiang Univ, Coll Pharmaceut Sci, Inst Drug Metab & Pharmaceut Anal, Hangzhou, Peoples R China; [Wang, Hua] Canc Hosp Zhejiang Prov, Dept Urol, Hangzhou, Peoples R China; [Liu, Junqing] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Hangzhou, Peoples R China		Yu, LS (corresponding author), Zhejiang Univ, Coll Pharmaceut Sci, Inst Drug Metab & Pharmaceut Anal, Hangzhou, Peoples R China.	yuls@zju.edu.cn	Kang, Yu/L-2912-2013	Kang, Yu/0000-0002-0999-8802	Leading Talent of "Ten Thousand Plan" - National High-Level Talents Special Support Plan; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773805, 81703616]	This work was supported by the Leading Talent of "Ten Thousand Plan" - National High-Level Talents Special Support Plan and the grants from National Natural Science Foundation of China (81773805 and 81703616)	Aguilar Andrea, 2016, Nat Rev Nephrol, V12, P581, DOI 10.1038/nrneph.2016.122; Ahmed AA, 2010, J PATHOL, V221, P49, DOI 10.1002/path.2696; Ahmed EM, 2018, CELL ONCOL, V41, P319, DOI 10.1007/s13402-018-0374-8; Ai ZH, 2016, CANCER LETT, V373, P36, DOI 10.1016/j.canlet.2016.01.009; Akerfeldt MC, 2017, J BIOL INORG CHEM, V22, P765, DOI 10.1007/s00775-017-1467-y; Akkari L, 2016, CELL RES, V26, P867, DOI 10.1038/cr.2016.82; Al-Eisawi Z, 2013, J OVARIAN RES, V6, DOI 10.1186/1757-2215-6-78; Al-Minawi AZ, 2009, NUCLEIC ACIDS RES, V37, P6400, DOI 10.1093/nar/gkp705; Aoyama K, 2013, INT J MOL SCI, V14, P21021, DOI 10.3390/ijms141021021; Arora S, 2010, DNA REPAIR, V9, P745, DOI 10.1016/j.dnarep.2010.03.010; Bai LC, 2014, ANNU REV MED, V65, P139, DOI 10.1146/annurev-med-010713-141310; Bao LJ, 2017, MOL CARCINOGEN, V56, P1543, DOI 10.1002/mc.22615; Basu S, 2016, CELL CYCLE, V15, P2557, DOI 10.1080/15384101.2016.1215390; Belli C, 2018, CANCER TREAT REV, V65, P22, DOI 10.1016/j.ctrv.2018.02.004; Benard A, 2014, APOPTOSIS, V19, P1769, DOI 10.1007/s10495-014-1042-8; Beretta GL, 2010, BIOCHEM PHARMACOL, V79, P1108, DOI 10.1016/j.bcp.2009.12.002; Bertout JA, 2008, NAT REV CANCER, V8, P967, DOI 10.1038/nrc2540; Blair BG, 2011, MOL PHARMACOL, V79, P157, DOI 10.1124/mol.110.068411; Blair BG, 2009, CLIN CANCER RES, V15, P4312, DOI 10.1158/1078-0432.CCR-09-0311; Boal AK, 2009, J AM CHEM SOC, V131, P14196, DOI 10.1021/ja906363t; Bompiani KM, 2016, METALLOMICS, V8, P951, DOI 10.1039/c6mt00076b; Borst P, 2000, JNCI-J NATL CANCER I, V92, P1295, DOI 10.1093/jnci/92.16.1295; Brozovic A, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0076397; Brozovic A, 2010, CRIT REV TOXICOL, V40, P347, DOI 10.3109/10408441003601836; Bruno PM, 2017, NAT MED, V23, P461, DOI 10.1038/nm.4291; Burger H, 2010, BRIT J PHARMACOL, V159, P898, DOI 10.1111/j.1476-5381.2009.00569.x; Buss I, 2018, METALLOMICS, V10, P414, DOI 10.1039/c7mt00334j; Byun SS, 2005, BJU INT, V95, P1086, DOI 10.1111/j.1464-410X.2005.05472.x; Cadoni E, 2017, J INORG BIOCHEM, V173, P126, DOI 10.1016/j.jinorgbio.2017.05.004; Chaney SG, 2005, CRIT REV ONCOL HEMAT, V53, P3, DOI 10.1016/j.critrevonc.2004.08.008; Chang CH, 2017, INT J ONCOL, V50, P873, DOI 10.3892/ijo.2017.3866; Chapman TM, 2015, BIOORG MED CHEM LETT, V25, P4097, DOI 10.1016/j.bmcl.2015.08.031; Chen Helen H. 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Pharmacol.	MAR 20	2020	11								343	10.3389/fphar.2020.00343			17	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	KZ7TK	WOS:000523461800001	32265714	gold, Green Published	Y	N	2022-04-25	
J	An, X; Sarmiento, C; Tan, T; Zhu, H				An, Xin; Sarmiento, Cesar; Tan, Tao; Zhu, Hua			Regulation of multidrug resistance by microRNAs in anti-cancer therapy	ACTA PHARMACEUTICA SINICA B			English	Review						Multidrug resistance; miRNA; Cancer; Therapy; Autophagy; Redox Homeostasis	GLUTATHIONE-S-TRANSFERASE; BREAST-CANCER CELLS; HUMAN HEPATOCELLULAR-CARCINOMA; P53 PROTEIN EXPRESSION; DRUG-RESISTANCE; GASTRIC-CANCER; DOWN-REGULATION; COLORECTAL-CANCER; MDR1/P-GLYCOPROTEIN EXPRESSION; CISPLATIN RESISTANCE	Multidrug resistance (MDR) remains a major clinical obstacle to successful cancer treatment. Although diverse mechanisms of MDR have been well elucidated, such as dysregulation of drugs transporters, defects of apoptosis and autophagy machinery, alterations of drug metabolism and drug targets, disrupti on of redox homeostasis, the exact mechanisms of MDR in a specific cancer patient and the cross-talk among these different mechanisms and how they are regulated are poorly understood. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that could control the global activity of the cell by post-transcriptionally regulating a large variety of target genes and proteins expression. Accumulating evidence shows that miRNAs play a key regulatory role in MDR through modulating various drug resistant mechanisms mentioned above, thereby holding much promise for developing novel and more effective individualized therapies for cancer treatment. This review summarizes the various MDR mechanisms and mainly focuses on the role of miRNAs in regulating MDR in cancer treatment. (C) 2017 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.	[An, Xin] Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China; [An, Xin; Sarmiento, Cesar; Tan, Tao; Zhu, Hua] Ohio State Univ, Dept Surg, Davis Heart & Lung Res Inst, Wexner Med Ctr, Columbus, OH 43210 USA		Tan, T; Zhu, H (corresponding author), Ohio State Univ, Dept Surg, Davis Heart & Lung Res Inst, Wexner Med Ctr, Columbus, OH 43210 USA.	Tao.Tan@osumc.edu; Hua.Zhu@osumc.edu		Zhu, Hua/0000-0001-7136-7326	U.S. National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HL124122, AR067766]; American Heart AssociationAmerican Heart Association [12SDG12070174]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81401155]; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL124122] 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) [R01AR067766] Funding Source: NIH RePORTER	The Zhu's laboratory is supported by U.S. National Institute of Health Grants R01 HL124122, AR067766 and American Heart Association Grant 12SDG12070174. The Tan's laboratory is supported by the National Natural Science Foundation of China (Grant No. 81401155).	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Sin. B	JAN	2017	7	1					38	51		10.1016/j.apsb.2016.09.002			14	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	EO1FB	WOS:000396442700006	28119807	Green Published, gold	Y	N	2022-04-25	
J	Ha, TK; Her, NG; Lee, MG; Ryu, BK; Lee, JH; Han, J; Jeong, SI; Kang, MJ; Kim, NH; Kim, HJ; Chi, SG				Ha, Tae-Kyu; Her, Nam-Gu; Lee, Min-Goo; Ryu, Byung-Kyu; Lee, Jin-Hee; Han, Jikhyon; Jeong, Seong-In; Kang, Min-Ju; Kim, Nam-Hoon; Kim, Hyo-Jong; Chi, Sung-Gil			Caveolin-1 Increases Aerobic Glycolysis in Colorectal Cancers by Stimulating HMGA1-Mediated GLUT3 Transcription	CANCER RESEARCH			English	Article							BREAST-CANCER; GENE; METASTASIS; EXPRESSION; PROSTATE	Caveolin-1 (CAV1) acts as a growth suppressor in various human malignancies, but its expression is elevated in many advanced cancers, suggesting the oncogenic switch of its role during tumor progression. To understand the molecular basis for the growth-promoting function of CAV1, we characterized its expression status, differential roles for tumor growth, and effect on glucose metabolism in colorectal cancers. Abnormal elevation of CAV1 was detected in a substantial fraction of primary tumors and cell lines and tightly correlated with promoter CpG sites hypomethylation. Depletion of elevated CAV1 led to AMPK activation followed by a p53-dependent G(1) cell-cycle arrest and autophagy, suggesting that elevated CAV1 may contribute to ATP generation. Furthermore, CAV1 depletion downregulated glucose uptake, lactate accumulation, and intracellular ATP level, supporting that aerobic glycolysis is enhanced by CAV1. Consistently, CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization. Ectopic expression of HMGA1 increased glucose uptake, whereas its knockdown caused AMPK activation. In addition, GLUT3 expression was strongly induced by cotransfection of CAV1 and HMGA1, and its overexpression was observed predominantly in tumors harboring high levels of CAV1 and HMGA1. Together, these data show that elevated CAV1 upregulates glucose uptake and ATP production through HMGA1-mediated GLUT3 transcription, suggesting that CAV1 may render tumor cells growth advantages by enhancing aerobic glycolysis. Cancer Res; 72(16); 4097-109. (C) 2012 AACR.	[Ha, Tae-Kyu; Her, Nam-Gu; Lee, Min-Goo; Ryu, Byung-Kyu; Lee, Jin-Hee; Han, Jikhyon; Jeong, Seong-In; Kang, Min-Ju; Chi, Sung-Gil] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea; [Kim, Hyo-Jong] Kyung Hee Univ, Dept Internal Med, Sch Med, Seoul, South Korea; [Kim, Nam-Hoon] Inje Univ, Dept Internal Med, Ilsan Paik Hosp, Coll Med, Goyang, South Korea		Chi, SG (corresponding author), Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea.	chi6302@korea.ac.kr	Her, Nam-Gu/AGY-5470-2022; Kang, Min-Ju/AAY-8706-2021; Han, Jikhyon/L-7891-2014	Han, Jikhyon/0000-0002-7767-3305; KANG, MIN-JU/0000-0001-5040-1388	National Research Foundation of KoreaNational Research Foundation of Korea [2009-0078864, 2009-0087099]; National Cancer Center, Republic of Korea [0820070]	This work was supported in part by grants from National Research Foundation of Korea (2009-0078864 and 2009-0087099) and the National Cancer Center (0820070), Republic of Korea.	Budanov AV, 2008, CELL, V134, P451, DOI 10.1016/j.cell.2008.06.028; Byun DS, 2003, CANCER RES, V63, P7068; Capozza F, 2003, AM J PATHOL, V162, P2029, DOI 10.1016/S0002-9440(10)64335-0; Chae KS, 2011, ONCOGENE, V30, P1213, DOI 10.1038/onc.2010.498; Detterbeck FC, 2004, CHEST, V126, P1656, DOI 10.1378/chest.126.5.1656; Eng CH, 2011, ONCOGENE, V30, P4687, DOI 10.1038/onc.2011.220; Fernandez MA, 2006, SCIENCE, V313, P1628, DOI 10.1126/science.1130773; Fusco A, 2007, NAT REV CANCER, V7, P899, DOI 10.1038/nrc2271; Gustavsson J, 1999, FASEB J, V13, P1961, DOI 10.1096/fasebj.13.14.1961; Hardie DG, 2011, AM J CLIN NUTR, V93, p891S, DOI 10.3945/ajcn.110.001925; Hayashi K, 2001, CANCER RES, V61, P2361; Heiden MGV, 2009, SCIENCE, V324, P1029, DOI 10.1126/science.1160809; Hulit J, 2000, J BIOL CHEM, V275, P21203, DOI 10.1074/jbc.M000321200; Jones RG, 2005, MOL CELL, V18, P283, DOI 10.1016/j.molcel.2005.03.027; KOLESKE AJ, 1995, P NATL ACAD SCI USA, V92, P1381, DOI 10.1073/pnas.92.5.1381; Lopez-Lazaro M, 2007, INT J CANCER, V120, P1378, DOI 10.1002/ijc.22493; Medina RA, 2002, BIOL RES, V35, P9, DOI 10.4067/S0716-97602002000100004; Mori Y, 2006, GASTROENTEROLOGY, V131, P797, DOI 10.1053/j.gastro.2006.06.006; Parton RG, 2007, NAT REV MOL CELL BIO, V8, P185, DOI 10.1038/nrm2122; Pavlides S, 2009, CELL CYCLE, V8, P3984, DOI 10.4161/cc.8.23.10238; Resar LMS, 2010, CANCER RES, V70, P436, DOI 10.1158/0008-5472.CAN-09-1212; Shatz M, 2008, INT J RADIAT BIOL, V84, P177, DOI 10.1080/09553000701745293; Simpson IA, 2008, AM J PHYSIOL-ENDOC M, V295, pE242, DOI 10.1152/ajpendo.90388.2008; Sotgia F, 2012, ANNU REV PATHOL-MECH, V7, P423, DOI 10.1146/annurev-pathol-011811-120856; Tahir SA, 2001, CANCER RES, V61, P3882; Timme TL, 2000, ONCOGENE, V19, P3256, DOI 10.1038/sj.onc.1203654; Van den Eynden GG, 2006, BREAST CANCER RES TR, V95, P219, DOI 10.1007/s10549-005-9002-1; Williams TM, 2005, AM J PHYSIOL-CELL PH, V288, pC494, DOI 10.1152/ajpcell.00458.2004; Yang G, 1998, CLIN CANCER RES, V4, P1873	29	81	82	2	16	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	2012	72	16					4097	4109		10.1158/0008-5472.CAN-12-0448			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	993SY	WOS:000307881100022	22706202				2022-04-25	
J	Guo, ZX; Zhou, C; Zhong, X; Shi, JX; Wu, ZH; Tang, KW; Wang, ZN; Song, YX				Guo, Zhexu; Zhou, Cen; Zhong, Xi; Shi, Jinxin; Wu, Zhonghua; Tang, Kaiwen; Wang, Zhenning; Song, Yongxi			The long noncoding RNA CTA-941F9.9 is frequently downregulated and may serve as a biomarker for carcinogenesis in colorectal cancer	JOURNAL OF CLINICAL LABORATORY ANALYSIS			English	Article						biomarker; carcinogenesis; colorectal cancer; 9; long noncoding RNAs	POOR-PROGNOSIS; CELL-PROLIFERATION; EXPRESSION; AUTOPHAGY; PROMOTES; CCAT1; LC3; INHIBITION; INVASION	Background Long noncoding RNAs (lncRNAs) participate in the carcinogenesis of many different cancers. This study aimed to detect expression of lncRNA CTA-941F9.9 in colorectal cancer tissues compared with matched nontumorous adjacent tissues (NATs). Moreover, we investigated whether this molecule is able to influence carcinogenesis in colorectal cancer (CRC). Methods Colorectal cancer tissues and NATs from two cohorts of patients were examined. Quantitative PCR was performed to quantify levels of CTA-941F9.9 expression in these samples. The association between CTA-941F9.9 expression and clinicopathological features, including receiver operating characteristic (ROC) curves, was also analyzed to evaluate the diagnostic value of CTA-941F9.9 in CRC. Potential effects of lncRNA CTA-941F9.9 on CRC cells were assessed via autophagy, transwell assay, CCK8 assays, and flow cytometry. Results Our experimental results showed lncRNA CTA-941F9.9 to be significantly downregulated in CRC tissues in both cohorts, with areas under the ROC curve (AUC) of 0.802 and 0.876. However, no significant correlations between CTA-941F9.9 expression levels and clinicopathological characteristics or patient outcomes were observed. We also found that CTA-941F9.9 promotes autophagy in CRC cell lines but no significant function of CTA-941F9.9 in regulating cancer cell proliferation or migration. Conclusions LncRNA CTA-941F9.9 is frequently downregulated in CRC compared with NATs and might play an important role in CRC carcinogenesis.	[Guo, Zhexu; Zhou, Cen; Zhong, Xi; Shi, Jinxin; Wu, Zhonghua; Tang, Kaiwen; Wang, Zhenning; Song, Yongxi] China Med Univ, Dept Surg Oncol & Gen Surg, Hosp 1, 155 North Nanjing St, Shenyang 110001, Liaoning, Peoples R China		Wang, ZN; Song, YX (corresponding author), China Med Univ, Dept Surg Oncol & Gen Surg, Hosp 1, 155 North Nanjing St, Shenyang 110001, Liaoning, Peoples R China.	josieon826@sina.cn; songyongxi840309@126.com	wang, zhen ning/E-1878-2011	wang, zhen ning/0000-0003-0557-3097; Song, Yongxi/0000-0002-5736-9453	Natural Science Foundation of Liaoning ProvinceNatural Science Foundation of Liaoning Province [20180550582]; National Nature Science Foundation-Outstanding Youth Foundation Training Project of China Medical University [YQ20160001]; Project of Science and Technology of Shenyang [18-014-4-07]	This work was supported by Natural Science Foundation of Liaoning Province (No. 20180550582), National Nature Science Foundation-Outstanding Youth Foundation Training Project of China Medical University (YQ20160001), and Project of Science and Technology of Shenyang (18-014-4-07).	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Clin. Lab. Anal.	NOV	2019	33	9							e22986	10.1002/jcla.22986		JUL 2019	11	Medical Laboratory Technology	Science Citation Index Expanded (SCI-EXPANDED)	Medical Laboratory Technology	JR2OL	WOS:000479450200001	31343781	Green Published, gold			2022-04-25	
J	Nahimana, A; Attinger, A; Aubry, D; Greaney, P; Ireson, C; Thougaard, AV; Tjornelund, J; Dawson, KM; Dupuis, M; Duchosal, MA				Nahimana, Aimable; Attinger, Antoine; Aubry, Dominique; Greaney, Peter; Ireson, Christopher; Thougaard, Annemette V.; Tjornelund, Jette; Dawson, Keith M.; Dupuis, Marc; Duchosal, Michel A.			The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies	BLOOD			English	Article							NICOTINAMIDE ADENINE-DINUCLEOTIDE; MAMMALIAN-CELLS; COLORECTAL-CANCER; DNA-DAMAGE; DEPLETION; APOPTOSIS; FK866; AUTOPHAGY; DEATH; CASCADE	APO866 inhibits nicotinamide phosphoribosyltransferase (NMPRTase), a key enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis from the natural precursor nicotinamide. Intracellular NAD is essential for cell survival, and NAD depletion resulting from APO866 treatment elicits tumor cell death. Here, we determine the in vitro and in vivo sensitivities of hematologic cancer cells to APO866 using a panel of cell lines (n = 45) and primary cells (n = 32). Most cancer cells (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], mantle cell lymphoma [MCL], chronic lymphocytic leukemia [CLL], and T-cell lymphoma), but not normal hematopoietic progenitor cells, were sensitive to low concentrations of APO866 as measured in cytotoxicity and clonogenic assays. Treatment with APO866 decreased intracellular NAD and adenosine triphosphate (ATP) at 24 hours and 48 to 72 hours, respectively. The NAD depletion led to cell death. At 96 hours, APO866-mediated cell death occurred in a caspase-independent mode, and was associated with mitochondrial dysfunction and autophagy. Further, in vivo administration of APO866 as a single agent prevented and abrogated tumor growth in animal models of human AML, lymphoblastic lymphoma, and leukemia without significant toxicity to the animals. The results support the potential of APO866 for treating hematologic malignancies. (Blood. 2009; 113:3276-3286)	[Nahimana, Aimable; Aubry, Dominique; Duchosal, Michel A.] Univ Lausanne Hosp, Serv Hematol, Lausanne, Switzerland; [Attinger, Antoine; Greaney, Peter; Ireson, Christopher; Dawson, Keith M.; Dupuis, Marc] TopoTarget Switzerland, Lausanne, Switzerland; [Thougaard, Annemette V.; Tjornelund, Jette] TopoTarget Denmark, Copenhagen, Denmark		Duchosal, MA (corresponding author), Univ Hosp Lausanne CHUV, Serv Hematol, 46 Rue Bugnon, CH-1011 Lausanne, Switzerland.	michel.duchosal@chuv.ch		Thougaard, Annemette Vinding/0000-0001-5407-2315	Swiss Federal Office for Professional Education and Technology [8368.2 LSPP-LS]	This work was supported by a contract (no. 8368.2 LSPP-LS) from the innovation promotion agency at the Swiss Federal Office for Professional Education and Technology.	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J	Cazzanelli, G; Pereira, F; Alves, S; Francisco, R; Azevedo, L; Carvalho, PD; Almeida, A; Corte-Real, M; Oliveira, MJ; Lucas, C; Sousa, MJ; Preto, A				Cazzanelli, Giulia; Pereira, Flavia; Alves, Sara; Francisco, Rita; Azevedo, Luisa; Carvalho, Patricia Dias; Almeida, Ana; Corte-Real, Manuela; Oliveira, Maria Jose; Lucas, Candida; Sousa, Maria Joao; Preto, Ana			The Yeast Saccharomyces cerevisiae as a Model for Understanding RAS Proteins and Their Role in Human Tumorigenesis	CELLS			English	Review						RAS proteins; S. cerevisiae; model; homologues; colorectal cancer; autophagy; KRAS	GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; ANCHORAGE-INDEPENDENT GROWTH; ADENYLATE-CYCLASE PATHWAY; PROGRAMMED CELL-DEATH; GENOME-WIDE SCREEN; CDC25 GENE-PRODUCT; K-RAS; H-RAS; CYCLIC-AMP	The exploitation of the yeast Saccharomyces cerevisiae as a biological model for the investigation of complex molecular processes conserved in multicellular organisms, such as humans, has allowed fundamental biological discoveries. When comparing yeast and human proteins, it is clear that both amino acid sequences and protein functions are often very well conserved. One example of the high degree of conservation between human and yeast proteins is highlighted by the members of the RAS family. Indeed, the study of the signaling pathways regulated by RAS in yeast cells led to the discovery of properties that were often found interchangeable with RAS proto-oncogenes in human pathways, and vice versa. In this work, we performed an updated critical literature review on human and yeast RAS pathways, specifically highlighting the similarities and differences between them. Moreover, we emphasized the contribution of studying yeast RAS pathways for the understanding of human RAS and how this model organism can contribute to unveil the roles of RAS oncoproteins in the regulation of mechanisms important in the tumorigenic process, like autophagy.	[Cazzanelli, Giulia; Pereira, Flavia; Alves, Sara; Francisco, Rita; Azevedo, Luisa; Carvalho, Patricia Dias; Almeida, Ana; Corte-Real, Manuela; Lucas, Candida; Sousa, Maria Joao; Preto, Ana] Univ Minho, Dept Biol, CBMA Ctr Mol & Environm Biol, Campus Gualtar, P-4710057 Braga, Portugal; [Pereira, Flavia; Alves, Sara; Azevedo, Luisa; Carvalho, Patricia Dias; Oliveira, Maria Jose] Univ Porto, Inst Invest & Inovacao Saude, Rua Alfredo Allen 208, P-4200135 Porto, Portugal; [Pereira, Flavia; Oliveira, Maria Jose] INEB Inst Biomed Engn, New Therapies Grp, P-4200135 Porto, Portugal; [Alves, Sara; Azevedo, Luisa; Carvalho, Patricia Dias] Univ Porto, IPATIMUP Inst Mol Pathol & Immunol, Rua Julio Amaral de Carvalho 45, P-4200135 Porto, Portugal; [Azevedo, Luisa] Univ Porto, Dept Biol, Fac Sci, Rua Campo Alegre S-N, P-4169007 Porto, Portugal		Sousa, MJ; Preto, A (corresponding author), Univ Minho, Dept Biol, CBMA Ctr Mol & Environm Biol, Campus Gualtar, P-4710057 Braga, Portugal.	giulia.cazzanelli88@gmail.com; flaviabrandao.fcbp@gmail.com; sara.csa@gmail.com; rita.francisco.28@gmail.com; lazevedo@ipatimup.pt; pat.dcarvalho@gmail.com; anafmalmeida@gmail.com; mcortereal@bio.uminho.pt; mariajo@ineb.up.pt; clucas@bio.uminho.pt; mjsousa@bio.uminho.pt; apreto@bio.uminho.pt	Preto, Ana/H-8112-2012; Almeida, Ana/AAB-8709-2020; Corte-Real, Manuela/B-6328-2013; Alves, Sara/U-5006-2019; Sousa, Maria João/H-8775-2013; Oliveira, Maria Jose/K-3275-2013; Azevedo, Luisa/J-4051-2013; Lucas, Candida/A-3663-2010	Preto, Ana/0000-0002-7302-0630; Almeida, Ana/0000-0001-6663-6851; Corte-Real, Manuela/0000-0002-1423-1331; Sousa, Maria João/0000-0001-9424-4150; Oliveira, Maria Jose/0000-0002-0724-0272; Francisco, Rita/0000-0002-4398-3401; Azevedo, Luisa/0000-0002-3157-7342; Alves, Sara/0000-0003-0404-5954; Lucas, Candida/0000-0001-8605-4525; Dias Carvalho, Patricia/0000-0002-8110-8157	national funds through the FCT I. P [UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569)]; ERDF through the COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI); Portuguese Foundation for Science and Technology (FCT)Portuguese Foundation for Science and Technology [UID/BIO/04469/2013]; COMPETE [POCI-01-0145-FEDER-006684]; FCT fellowships: Sara Alves [FCT SFRH/BD/64695/2009]; Marie Curie Initial Training NetworkEuropean Commission [PITN-GA-2012-317297]	This work was supported by the strategic program UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I. P. and by the ERDF through the COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI). It was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of the UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and FCT fellowships: Sara Alves (FCT SFRH/BD/64695/2009). This work was also the Marie Curie Initial Training Network: PITN-GA-2012-317297 (GC PhD Grant).	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J	Zhen, YF; Li, ST; Zhu, YR; Wang, XD; Zhou, XZ; Zhu, LQ				Zhen, Yun-fang; Li, Song-tao; Zhu, Yun-rong; Wang, Xiao-dong; Zhou, Xiao-zhong; Zhu, Lun-qing			Identification of DNA-PKcs as a primary resistance factor of salinomycin in osteosarcoma cells	ONCOTARGET			English	Article						osteosarcoma (OS); salinomycin; DNA-PKcs; microRNA-101; autophagy	DEPENDENT PROTEIN-KINASE; COLORECTAL-CANCER CELLS; INDUCED APOPTOSIS; INHIBITOR; ACTIVATION; PATHWAY; PROLIFERATION; TARGET; REPAIR; TRANSCRIPTION	Malignant osteosarcoma (OS) is still a deadly disease for many affected patients. The search for the novel anti-OS agent is extremely urgent and important. Our previous study has proposed that salinomycin is a novel anti-OS agent. Here we characterized DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a primary salinomycin resistance factor in OS cells. DNA-PKcs inhibitors (NU7026, NU7441 and LY294002) or DNA-PKcs shRNA knockdown dramatically potentiated salinomycin-induced death and apoptosis of OS cells (U2OS and MG-63 lines). Further, forced-expression of microRNA-101 ("miR-101") downregulated DNA-PKcs and augmented salinomycin's cytotoxicity against OS cells. Reversely, over-expression of DNA-PKcs in OS cells inhibited salinomycin's lethality. For the mechanism study, we show that DNA-PKcs is required for salinomycin-induced pro-survival autophagy activation. DNA-PKcs inhibition (by NU7441), shRNA knockdown or miR-101 expression inhibited salinomycin-induced Beclin-1 expression and autophagy induction. Meanwhile, knockdown of Beclin-1 by shRNA significantly sensitized salinomycin-induced OS cell lethality. In vivo, salinomycin administration suppressed U2OS xenograft tumor growth in severe combined immuno-deficient (SCID) mice, and its anti-tumor activity was dramatically potentiated with co-administration of the DNA-PKcs inhibitor NU7026. Together, these results suggest that DNA-PKcs could be a primary resistance factor of salinomycin in OS cells. DNA-PKcs inhibition or silence may thus significantly increase salinomycin's sensitivity in OS cells.	[Zhen, Yun-fang; Wang, Xiao-dong; Zhu, Lun-qing] Soochow Univ, Childrens Hosp, Ctr Diag & Treatment Childrens Bone Dis, Suzhou, Peoples R China; [Li, Song-tao; Zhou, Xiao-zhong] Soochow Univ, Affiliated Hosp 2, Dept Orthoped, Suzhou, Peoples R China; [Zhu, Yun-rong] Southeast Univ, Affiliated Jiangyin Hosp, Coll Med, Dept Orthoped, Jiangyin, Peoples R China		Wang, XD; Zhu, LQ (corresponding author), Soochow Univ, Childrens Hosp, Ctr Diag & Treatment Childrens Bone Dis, Suzhou, Peoples R China.; Zhou, XZ (corresponding author), Soochow Univ, Affiliated Hosp 2, Dept Orthoped, Suzhou, Peoples R China.	xiaodongwangsz@163.com; zhouxiaozhongorth@163.com; zhulunqingszgk@163.com			nature science foundation of ChinaNational Natural Science Foundation of China (NSFC) [81171712, 81402475]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20151213]; Innovation Project of JiangSu Province [201423]	The study was supported by the nature science foundation of China (81171712 and 81402475). Grants from Natural Science Foundation of Jiangsu Province (BK20151213) and Innovation Project of JiangSu Province (201423).	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J	Anestakis, D; Petanidis, S; Kalyvas, S; Nday, CM; Tsave, O; Kioseoglou, E; Salifoglou, A				Anestakis, Doxakis; Petanidis, Savvas; Kalyvas, Spyridon; Nday, Christiane M.; Tsave, Olga; Kioseoglou, Efrosini; Salifoglou, Athanasios			Mechanisms and Applications of Interleukins in Cancer Immunotherapy	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						interleukins; cancer immunotherapy; immunoediting; immunosurveilance; microRNA; cancer stem cells; tumor microenvironment (TME); inflammation; DNA methylation; epithelial-mesenchymal transition (EMT); autophagy	EPITHELIAL-MESENCHYMAL TRANSITION; REGULATORY T-CELLS; COLORECTAL-CANCER; TUMOR MICROENVIRONMENT; IMMUNE MICROENVIRONMENT; COMBINATION THERAPY; GENE-THERAPY; CYTOKINES; PROMOTES; GROWTH	Over the past years, advances in cancer immunotherapy have resulted in innovative and novel approaches in molecular cancer diagnostics and cancer therapeutic procedures. However, due to tumor heterogeneity and inter-tumoral discrepancy in tumor immunity, the clinical benefits are quite restricted. The goal of this review is to evaluate the major cytokines-interleukins involved in cancer immunotherapy and project their basic biochemical and clinical applications. Emphasis will be given to new cytokines in pre-clinical development, and potential directions for future investigation using cytokines. Furthermore, current interleukin-based approaches and clinical trial data from combination cancer immunotherapies will also be discussed. It appears that continuously increasing comprehension of cytokine-induced effects, cancer stemness, immunoediting, immune-surveillance as well as understanding of molecular interactions emerging in the tumor microenvironment and involving microRNAs, autophagy, epithelial-mesenchymal transition (EMT), inflammation, and DNA methylation processes may hold much promise in improving anti-tumor immunity. To this end, the emerging in-depth knowledge supports further studies on optimal synergistic combinations and additional adjuvant therapies to realize the full potential of cytokines as immunotherapeutic agents.	[Anestakis, Doxakis] Aristotle Univ Thessaloniki, Sch Med, Lab Gen Biol, Thessaloniki 54124, Greece; [Anestakis, Doxakis] Aristotle Univ Thessaloniki, Sch Med, Lab Forens Med & Toxicol, Thessaloniki 54124, Greece; [Petanidis, Savvas; Nday, Christiane M.; Tsave, Olga; Kioseoglou, Efrosini] Aristotle Univ Thessaloniki, Dept Chem Engn, Thessaloniki 54124, Greece; [Kalyvas, Spyridon] Gen Hosp Halkidiki, Dept Internal Med, Poligiros 63100, Greece		Salifoglou, A (corresponding author), Aristotle Univ Thessaloniki, Dept Chem Engn, Thessaloniki 54124, Greece.	anestaki@auth.gr; spetanid@auth.gr; roskal@otenet.gr; christiane.nday@yahoo.com; tsaveolga@gmail.com; efi.kioseoglou@gmail.com; salif@auth.gr	petanidis, savvas/P-5637-2018; Petanidis, Savvas/AAC-3082-2022	Anestakis, Doxakis/0000-0001-8004-7666	Research Committee of Aristotle University of Thessaloniki, Greece	This work was supported by funding from the Research Committee of Aristotle University of Thessaloniki, Greece.	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J. Mol. Sci.	JAN	2015	16	1					1691	1710		10.3390/ijms16011691			20	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	AZ7MN	WOS:000348403100096	25590298	gold, Green Submitted, Green Published			2022-04-25	
J	Wei, YJ; Li, CH; Zhang, Y; He, HL; Zilang, GZ; Hao, XH; Liu, HL; Wang, HL; Tian, W				Wei, Yanjie; Li, Chenhao; Zhang, Yuan; He, Hailan; Zhang, Guozhi; Hao, Xiaohui; Liu, Heliang; Wang, Hongli; Tian, Wei			Hydroxycamptothecin mediates antiproliferative effects through apoptosis and autophagy in A549 cells	ONCOLOGY LETTERS			English	Article						lung cancer; non-small cell lung cancer; autophagy; apoptosis; autophagy inhibitor; hydroxycamptothecin	COLORECTAL-CANCER; KINASE; BAX; ACTIVATION; 10-HYDROXYCAMPTOTHECIN; RESISTANCE; INHIBITORS; PROTEIN; TARGET; ROLES	Hydroxycamptothecin (HCPT) represents a new generation of anticancer drugs, with almost no side effects when used for the treatment of a number of types of cancer. Autophagy is becoming recognized as an important biological mechanism in human cancer, including lung cancer. However, the involvement of autophagy in the antiproliferative effects of HCPT on lung cancer remains unclear. In the present study, A549 cells, an accepted model of non-small cell lung cancer (NSCLC) cells, were employed. It was demonstrated that HCPT was able to suppress proliferation and induce apoptosis and autophagy in A549 cells. The molecular mechanism underlying HCPT-induced cell death was attributed to apoptosis and autophagy. Furthermore, it was demonstrated that an autophagy inhibitor, 3-methyladenine, accelerated HCPT-induced cell death in A549 cells. The results of the present study may lead to a deeper understanding of the molecular mechanism by which HCPT regulates NSCLC A549 cells. These results highlight the potential use of autophagy inhibitors in combination with traditional chemotherapy drugs for the treatment of lung cancer.	[Wei, Yanjie; Zhang, Yuan; He, Hailan; Hao, Xiaohui; Liu, Heliang; Wang, Hongli; Tian, Wei] North China Univ Sci & Technol, Med Res Ctr, 57 Jianshenan Rd, Tangshan 063000, Hebei, Peoples R China; [Li, Chenhao] Cangzhou Cent Hosp, Dept Oncol, Cangzhou 061000, Hebei, Peoples R China; [Zhang, Guozhi] North China Univ Sci & Technol, Affiliated Hosp, Dept Gen Surg, Tarigshan 063000, Hebei, Peoples R China; [Wang, Hongli] North China Univ Sci & Technol, Publ Hlth Sch, 57 Jianshenan Rd, Tarigshan 063000, Hebei, Peoples R China		Tian, W (corresponding author), North China Univ Sci & Technol, Med Res Ctr, 57 Jianshenan Rd, Tangshan 063000, Hebei, Peoples R China.; Wang, HL (corresponding author), North China Univ Sci & Technol, Publ Hlth Sch, 57 Jianshenan Rd, Tarigshan 063000, Hebei, Peoples R China.	tsruoshui@163.com; twhzm@aliyun.com			North China University of Science and Technology Research [201610081026, X2016026]; Key Projects of Science and Technology Research in Hebei Province [ZD2017063]; Tangshan International Technological Cooperation Projects [14160201B]	The present study was supported by the North China University of Science and Technology Research (grant no. 201610081026), the Key Projects of Science and Technology Research in Hebei Province (grant no. ZD2017063), the North China University of Science and Technology Research (grant no. X2016026) and the Tangshan International Technological Cooperation Projects (grant no. 14160201B).	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Lett.	MAY	2018	15	5					6322	6328		10.3892/ol.2018.8107			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GF3DN	WOS:000431825900031	29616109	Green Submitted, Green Published, gold			2022-04-25	
J	Ha, HA; Chiang, JH; Tsai, FJ; Bau, DT; Juan, YN; Lo, YH; Hour, MJ; Yang, JS				Ha, Hai-Anh; Chiang, Jo-Hua; Tsai, Fuu-Jen; Bau, Da-Tian; Juan, Yu-Ning; Lo, Yu-Hsiang; Hour, Mann-Jen; Yang, Jai-Sing			Novel quinazolinone MJ-33 induces AKT/mTOR-mediated autophagy-associated apoptosis in 5FU-resistant colorectal cancer cells	ONCOLOGY REPORTS			English	Article						MJ-33; colorectal cancer; fluorouracil-resistant HT-29 cells; autophagy; apoptosis	ENDOPLASMIC-RETICULUM STRESS; NF-KAPPA-B; THYMIDYLATE SYNTHASE; 1ST-LINE TREATMENT; DRUG-RESISTANCE; IN-VITRO; INHIBITION; PATHWAY; ANGIOGENESIS; FLUOROURACIL	Novel quinazolinone compounds have been studied in the field of drug discovery for a long time. Among their broad range of pharmacological effects, certain compounds effectively inhibit cancer cell proliferation. MJ-33 is a quinazolinone derivative with proposed anticancer activities that was synthesized in our laboratory. The present study aimed to evaluate the anticancer activity of MJ-33 in fluorouracil (5FU)-resistant colorectal cancer cells (HT-29/5FUR) and to investigate the underlying molecular mechanisms. The cell viability assay results indicated that HT-29/5FUR cell viability was inhibited by MJ-33 treatment in a concentration-dependent manner compared with the control group. The cellular morphological alterations observed following MJ-33 treatment indicated the occurrence of apoptosis and autophagy, as well as inhibition of cell proliferation in a time-dependent manner compared with the control group. The acridine orange, LysoTracker Red and LC3-green fluorescent protein staining results indicated that MJ-33 treatment significantly induced autophagy compared with the control group. The DAPI/TUNEL dual staining results demonstrated increased nuclear fragmentation and condensation following MJ-33 treatment compared with the control group. The Annexin V apoptosis assay and image cytometry analysis results demonstrated a significant increase in apoptotic cells following MJ-33 treatment compared with the control group. The western blotting results demonstrated markedly decreased Bcl-2, phosphorylated (p)-BAD, pro-caspase-9 and pro-caspase-3 expression levels, and notably increased cytochrome c and apoptotic peptidase activating factor 1 expression levels following MJ-33 treatment compared with the control group. Moreover, the expression levels of autophagy-related proteins, including autophagy related (ATG)-5, ATG-7, ATG-12, ATG-16, p62 and LC3-II, were increased following MJ-33 treatment compared with the control group. Furthermore, MJ-33-treated HT-29/5FUR cells displayed decreased expression levels of p-AKT and p-mTOR compared with control cells. The results suggested that MJ-33-induced apoptosis was mediated by AKT signaling, and subsequently modulated via the mitochondria-dependent signaling pathway. Therefore, the results suggested that suppression of AKT/mTOR activity triggered autophagy in the HT-29/5FUR cell line. In summary, the results indicated that MJ-33 inhibited HT-29/5FUR cell viability, and induced apoptosis and autophagy via the AKT/mTOR signaling pathway. The present study may provide novel insight into the anticancer effects and mechanisms underlying MJ-33 in 5FU-resistant colorectal cancer cells.	[Ha, Hai-Anh; Hour, Mann-Jen] China Med Univ, Sch Pharm, 91 Hsueh Shih Rd, Taichung 40402, Taiwan; [Ha, Hai-Anh] Duy Tan Univ, Fac Pharm, Da Nang 550000, Vietnam; [Chiang, Jo-Hua] Chung Jen Jr Coll Nursing Hlth Sci & Management, Dept Nursing, Chiayi 62241, Taiwan; [Tsai, Fuu-Jen] China Med Univ, China Med Univ Hosp, Dept Med Res, Human Genet Ctr, Taichung 40447, Taiwan; [Tsai, Fuu-Jen] China Med Univ, China Med Univ Hosp, Dept Med Genet, Taichung 40447, Taiwan; [Tsai, Fuu-Jen] China Med Univ, Sch Chinese Med, Taichung 40402, Taiwan; [Bau, Da-Tian] China Med Univ, Grad Inst Biomed Sci, Taichung 40402, Taiwan; [Bau, Da-Tian] China Med Univ, China Med Univ Hosp, Terry Fox Canc Res Lab, Taichung 40447, Taiwan; [Bau, Da-Tian] Asia Univ, Dept Bioinformat & Med Engn, Taichung 41354, Taiwan; [Juan, Yu-Ning; Lo, Yu-Hsiang; Yang, Jai-Sing] China Med Univ, China Med Univ Hosp, Dept Med Res, 2 Yude Rd, Taichung 40447, Taiwan		Hour, MJ (corresponding author), China Med Univ, Sch Pharm, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.; Yang, JS (corresponding author), China Med Univ, China Med Univ Hosp, Dept Med Res, 2 Yude Rd, Taichung 40447, Taiwan.	mjhou@mail.cmu.edu.tw; jaisingyang@gmail.com	HA, HAI-ANH/AAR-1652-2021; Ha, Hai-Anh/AAD-3454-2022	Ha, Hai-Anh/0000-0002-4252-2128	Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [MOST 109-2320-B-039-041]; China Medical University Hospital [DMR-108-106]	The present study was supported by the Ministry of Science and Technology, Taiwan (grant no. MOST 109-2320-B-039-041) and China Medical University Hospital (grant no. DMR-108-106).	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Rep.	FEB	2021	45	2					680	692		10.3892/or.2020.7882			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	PR2HV	WOS:000607063300024	33416156	Green Published, hybrid			2022-04-25	
J	Zhou, WJ; Fang, C; Zhang, LW; Wang, Q; Li, D; Zhu, DX				Zhou, Wenjie; Fang, Cheng; Zhang, Liwen; Wang, Qi; Li, Dong; Zhu, Danxia			Thioredoxin domain-containing protein 9 (TXNDC9) contributes to oxaliplatin resistance through regulation of autophagy-apoptosis in colorectal adenocarcinoma	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						TXNDC9; Oxaliplatin resistance; Autophagy; Apoptosis; Nrf2 pathway	TRANSCRIPTION FACTOR NRF2; PATHWAY; CANCER; STRESS; ACTIVATION; MECHANISMS; PACLITAXEL; PATTERNS; CELLS	Colorectal cancer (CRC) is the third most commonly malignancy worldwide. The incidence of CRC is on the rise and leads to indisputable society burden due to the high cost of cancer treatments. Resistance to oxaliplatin-chemotherapy is the major cause for treatment failure and CRC-related death. In this study, we anticipated that TXNDC9 might demonstrate a protective role in oxaliplatin-resistant CRC cells. TXNDC9 was found significantly upregulated when treated with oxaliplatin. Manipulation of TXNDC9 expression largely affected the oxaliplatin-induced cell death. Moreover, TXNDC9 regulates autophagy and apoptosis in response to oxaliplatin treatment in HT29 cells via the Nrf2 pathway. Taken together, our findings explore the biological role of TXNDC9 in oxaliplatin resistance in CRC cells and may identify a novel therapeutic target to counteract drug resistance to oxaliplatin in CRC. (C) 2020 Elsevier Inc. All rights reserved.	[Zhou, Wenjie; Fang, Cheng; Zhang, Liwen; Wang, Qi; Li, Dong; Zhu, Danxia] Soochow Univ, Dept Oncol, Affiliated Hosp 3, Changzhou 213003, Jiangsu, Peoples R China		Zhou, WJ; Zhu, DX (corresponding author), Soochow Univ, Dept Oncol, Affiliated Hosp 3, Changzhou 213003, Jiangsu, Peoples R China.	Wenjie_czyy@163.com; Danxia_czyy@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770212]	This research was supported by grants from the National Natural Science Foundation of China (No.81770212).	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Biophys. Res. Commun.	APR 9	2020	524	3					582	588		10.1016/j.bbrc.2020.01.092			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	LE5WX	WOS:000526792800009	32029274				2022-04-25	
J	Feng, JB; Zhang, Y; Ren, X; Li, D; Fu, HJ; Liu, CH; Zhou, W; Liu, Q; Liu, Q; Wu, MH				Feng, Jianbo; Zhang, Yan; Ren, Xing; Li, Di; Fu, Haijuan; Liu, Changhong; Zhou, Wen; Liu, Qing; Liu, Qiang; Wu, Minghua			Leucine-rich repeat containing 4 act as an autophagy inhibitor that restores sensitivity of glioblastoma to temozolomide	ONCOGENE			English	Article							COLORECTAL-CANCER; GLIOMA-CELLS; BETA-TRCP; RESISTANCE; MTOR; CHEMORESISTANCE; PROLIFERATION; EXPRESSION; APOPTOSIS; CYTOKINE	Temozolomide (TMZ) insensitivity and resistance are major causes of treatment failure and poor prognosis for GBM patients. Here, we identify LRRC4 as a novel autophagy inhibitor that restores the sensitivity of GBMs to TMZ. LRRC4 was associated with the DEPTOR/mTOR complex, and this interaction resulted in autophagy inhibition. Further investigation demonstrated that the PDZ binding domain of LRRC4 binds to the PDZ domain of DEPTOR. This binding decreases the half-life of DEPTOR via ubiquitination, thus inhibiting GBM cell autophagy and increasing the TMZ treatment response of GBM. Combined LRRC4 expression and TMZ treatment prolonged the survival of mice with tumour xenografts. Furthermore, the levels of LRRC4, DEPTOR and autophagy are clinically relevant for GBM, indicating that LRRC4 is likely to have significant potential as a therapeutic marker and target for TMZ treatment in glioma patients.	[Feng, Jianbo; Zhang, Yan; Ren, Xing; Li, Di; Fu, Haijuan; Liu, Changhong; Wu, Minghua] Cent South Univ, Hunan Prov Tumor Hosp, Changsha 410006, Hunan, Peoples R China; [Feng, Jianbo; Zhang, Yan; Ren, Xing; Li, Di; Fu, Haijuan; Liu, Changhong; Wu, Minghua] Cent South Univ, Xiangya Med Sch, Affiliated Tumor Hosp, Changsha 410006, Hunan, Peoples R China; [Feng, Jianbo; Zhang, Yan; Ren, Xing; Li, Di; Fu, Haijuan; Liu, Changhong; Zhou, Wen; Wu, Minghua] Cent South Univ, Canc Res Inst, Sch Basic Med Sci, Changsha 410078, Hunan, Peoples R China; [Feng, Jianbo; Zhang, Yan; Ren, Xing; Li, Di; Fu, Haijuan; Liu, Changhong; Zhou, Wen; Wu, Minghua] Minist Educ, Key Lab Carcinogenesis & Canc Invas, Changsha 410078, Hunan, Peoples R China; [Feng, Jianbo; Zhang, Yan; Ren, Xing; Li, Di; Fu, Haijuan; Liu, Changhong; Zhou, Wen; Wu, Minghua] Minist Hlth, Key Lab Carcinogenesis, Changsha 410078, Hunan, Peoples R China; [Liu, Changhong] Shandong Univ, Hosp 2, Inst Med Sci, Jinan 250033, Shandong, Peoples R China; [Liu, Qing] Cent South Univ, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China; [Liu, Qiang] Cent South Univ, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China		Wu, MH (corresponding author), Cent South Univ, Hunan Prov Tumor Hosp, Changsha 410006, Hunan, Peoples R China.; Wu, MH (corresponding author), Cent South Univ, Xiangya Med Sch, Affiliated Tumor Hosp, Changsha 410006, Hunan, Peoples R China.; Wu, MH (corresponding author), Cent South Univ, Canc Res Inst, Sch Basic Med Sci, Changsha 410078, Hunan, Peoples R China.; Wu, MH (corresponding author), Minist Educ, Key Lab Carcinogenesis & Canc Invas, Changsha 410078, Hunan, Peoples R China.; Wu, MH (corresponding author), Minist Hlth, Key Lab Carcinogenesis, Changsha 410078, Hunan, Peoples R China.	wuminghua554@aliyun.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81874150]; Graduate Student Research Innovation Project in Hunan Province [2019zzts084]	This works was supported by the National Natural Science Foundation of China (Grant No. 81874150) and Graduate Student Research Innovation Project in Hunan Province (2019zzts084).	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J	Shu, CW; Weng, JR; Chang, HW; Liu, PF; Chen, JJ; Peng, CC; Huang, JW; Lin, WY; Yen, CY				Shu, Chih-Wen; Weng, Jing-Ru; Chang, Hsueh-Wei; Liu, Pei-Feng; Chen, Jih-Jung; Peng, Chien-Chi; Huang, Jia-Wen; Lin, Wei-Yu; Yen, Ching-Yu			Tribulus terrestris fruit extract inhibits autophagic flux to diminish cell proliferation and metastatic characteristics of oral cancer cells	ENVIRONMENTAL TOXICOLOGY			English	Article						ATG4B; autophagy; oral cancer; plant extract		Elevated autophagy is highly associated with cancer development and progression. Fruit extracts of several plants inhibit activity of autophagy-related protease ATG4B and autophagy activity in colorectal cancer cells. However, the effects of these plant extracts in oral cancer cells remain unclear. In this study, we found that the extracted Tribulus terrestris fruit (TT-(fr)) and Xanthium strumarium fruit had inhibitory effects on autophagy inhibition in both SAS and TW2.6 oral cancer cells. Moreover, the fruit extracts had differential effects on cell proliferation of oral cancer cells. In addition, the fruit extracts hampered cell migration and invasion of oral cancer cells, particularly in TT-(fr) extracts. Our results indicated that TT-(fr) extracts consistently inhibited autophagic flux, cell growth and metastatic characteristics of oral cancer cells, suggesting TT-(fr) might contain function ingredient to suppress oral cancer cells.	[Shu, Chih-Wen; Peng, Chien-Chi] Natl Sun Yat Sen Univ, Inst Biopharmaceut Sci, Kaohsiung, Taiwan; [Shu, Chih-Wen; Liu, Pei-Feng] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung, Taiwan; [Shu, Chih-Wen; Chang, Hsueh-Wei; Liu, Pei-Feng] Kaohsiung Med Univ, Dept Biomed Sci & Environm Biol, Kaohsiung, Taiwan; [Weng, Jing-Ru] Natl Sun Yat Sen Univ, Dept Marine Biotechnol & Resources, Kaohsiung, Taiwan; [Chang, Hsueh-Wei] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Canc Ctr, Kaohsiung, Taiwan; [Liu, Pei-Feng] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung, Taiwan; [Chen, Jih-Jung] Natl Yang Ming Chiao Tung Univ, Fac Pharm, Sch Pharmaceut Sci, Taipei, Taiwan; [Huang, Jia-Wen; Yen, Ching-Yu] Chi Mei Med Ctr, Oral & Maxillofacial Surg Sect, Tainan, Taiwan; [Lin, Wei-Yu] Kinmen Hosp, Dept Pharm, Kinmen, Taiwan; [Yen, Ching-Yu] Taipei Med Univ, Dept Dent, Taipei, Taiwan		Yen, CY (corresponding author), Chi Mei Med Ctr, Oral & Maxillofacial Surg Sect, Tainan, Taiwan.	ycysmc@gmail.com		Liu, Pei-Feng/0000-0002-7849-8940; Shu, Chih-Wen/0000-0002-7774-0002	Ministry of Science and Technology [MOST107-2314-B384-005, MOST 108-2320-B-075B-003, MOST 108-2320-B-110-008-MY3]	This work was supported by the Ministry of Science and Technology (MOST107-2314-B384-005, MOST 108-2320-B-075B-003, and MOST 108-2320-B-110-008-MY3).	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Toxicol.	JUN	2021	36	6					1173	1180		10.1002/tox.23116		MAR 2021	8	Environmental Sciences; Toxicology; Water Resources	Science Citation Index Expanded (SCI-EXPANDED)	Environmental Sciences & Ecology; Toxicology; Water Resources	RO8CH	WOS:000626936100001	33751830				2022-04-25	
J	Lin, CM; Chen, HH; Lin, CA; Wu, HC; Sheu, JJC; Chen, HJ				Lin, Chung-Ming; Chen, Hsin-Han; Lin, Chun-An; Wu, Hui-Chung; Sheu, Jim Jinn-Chyuan; Chen, Hui-Jye			Apigenin-induced lysosomal degradation of beta-catenin in Wnt/beta catenin signaling	SCIENTIFIC REPORTS			English	Article							COLORECTAL-CANCER; PRODEATH AUTOPHAGY; CELL-LINE; STEM; INHIBITION; LC3; CHEMOTHERAPY; EXPRESSION; DISCOVERY; PORCUPINE	The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/beta-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human diseases including cancers. However, the underlying mechanism of apigenin in this pathway and its link to anti-cancer activities remain largely unknown. Here we showed that apigenin reduced the amount of total, cytoplasmic, and nuclear beta-catenin, leading to the suppression in the beta-catenin/TCF-mediated transcriptional activity, the expression of Wnt target genes, and cell proliferation of Wnt-stimulated P19 cells and Wnt-driven colorectal cancer cells. Western blotting and immunofluorescent staining analyses further revealed that apigenin could induce autophagy-mediated down-regulation of beta-catenin in treated cells. Treatment with autophagy inhibitors wortmannin and chloroquine compromised this effect, substantiating the involvement of autophagy-lysosomal system on the degradation of beta-catenin during Wnt signaling through inhibition of the AKT/mTOR signaling pathway. Our data not only pointed out a route for the inhibition of canonical Wnt signaling through the induction of autophagy-lysosomal degradation of key player beta-catenin, but also suggested that apigenin or other treatments which can initiate this degradation event are potentially used for the therapy of Wnt-related diseases including cancers.	[Lin, Chung-Ming; Wu, Hui-Chung] Ming Chuan Univ, Dept Biotechnol, Taoyuan 33348, Taiwan; [Chen, Hsin-Han] China Med Univ Hosp, Div Plast & Reconstruct Surg, Dept Surg, Taichung 40402, Taiwan; [Lin, Chun-An; Chen, Hui-Jye] China Med Univ, Grad Inst Basic Med Sci, Taichung 40402, Taiwan; [Sheu, Jim Jinn-Chyuan] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan; [Chen, Hui-Jye] Asia Univ, Dept Nursing, Taichung 40354, Taiwan; [Chen, Hui-Jye] China Med Univ, Grad Inst Biomed Sci, Taichung 40402, Taiwan		Chen, HJ (corresponding author), China Med Univ, Grad Inst Basic Med Sci, Taichung 40402, Taiwan.; Chen, HJ (corresponding author), Asia Univ, Dept Nursing, Taichung 40354, Taiwan.; Chen, HJ (corresponding author), China Med Univ, Grad Inst Biomed Sci, Taichung 40402, Taiwan.	huijyechen@mail.cmu.edu.tw			Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [104-2314-B039-027]; China Medical UniversityChina Medical University [CMU103-S-08]; Research Center for Tumor Medical Science, China Medical University, Taiwan [CMU104-S-05]	This paper was sponsored by grants from the Ministry of Science and Technology, Taiwan (MOST 104-2314-B039-027), China Medical University (CMU103-S-08), and partially from the Research Center for Tumor Medical Science, China Medical University, Taiwan (CMU104-S-05) to H.J.C. We thank the Medical Research Core Facilities Center, Office of Research & Development at China Medical University, Taichung, Taiwan, R.O.C. for all the help with the flow cytometry.	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J	Shen, MY; Lin, L				Shen, Mingyang; Lin, Lin			Functional variants of autophagy-related genes are associated with the development of hepatocellular carcinoma	LIFE SCIENCES			English	Article						Hepatocellular carcinoma; Genetic; Autophagy; Expression quantitative trait loci	COLORECTAL-CANCER; THR300ALA VARIANT; BREAST-CANCER; TARGET GENES; POLYMORPHISMS; EXPRESSION; ATG10; PROLIFERATION; SURVIVAL; RISK	Aims: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and accounts for substantial morbidity and mortality. Autophagy plays an essential role in the development and progression of HCC. This study aims to evaluate whether genetic variants in autophagy-related genes (ATGs) affect the development of HCC. Materials and methods: We conducted a case-control study with 986 HCC cases and 1000 healthy controls to analyze 14 functional variants of five ATGs (ATG3, ATG5, ATG10, ATG12 and ATG16L1) among a Chinese population. Key findings: We found ATG5 rs17067724 (G vs A: OR=0.80; 95% CI=0.65-0.98; P=0.031), ATG10 rs1864183 (G vs A: OR=1.29; 95% CI=1.07-1.57; P=0.009), ATG10 rs10514231 (C vs T: OR=1.41; 95% CI=1.15-1.73; P=0.001), ATG12 rs26537 (C vs T: OR=1.16; 95% CI=1.02-1.33; P=0.030), and ATG16L1 rs4663402 (T vs A: OR=1.28; 95% CI=1.01-1.63; P=0.044) were significantly associated with HCC risk. Specifically, ATG10 rs10514231 kept significant association even adjusted for Bonferroni correction (P=0.001x14=0.014). Bioinformatics analyses showed that allele C of ATG10 rs10514231 was significantly correlated with higher expression of ATG10 gene in both HCC tissues and normal liver tissues. Dual-luciferase reporter assay presented that cell lines transfected with vectors containing the risk allele C of rs10514231 showed higher relative luciferase activity compared to that containing the allele T. Significance: These results suggested that ATG10 rs10514231 might contribute to an allele-specific effect on the expression of host gene ATG10 and explain a fraction of HCC genetic susceptibility. Our study would benefit the construction of early warning model, early prevention, screening, even therapeutic target of HCC.	[Shen, Mingyang; Lin, Lin] China Med Univ, Affiliated Hosp 4, Dept Gen Surg, Shenyang 110032, Liaoning, Peoples R China		Lin, L (corresponding author), 4 Chongshandong Rd, Shenyang 110032, Liaoning, Peoples R China.	linlin_sy@aliyun.com					Berger MD, 2017, EUR J CANCER, V77, P13, DOI 10.1016/j.ejca.2017.02.020; Cao QH, 2016, AM J TRANSL RES, V8, P3831; Chandrashekar DS, 2017, NEOPLASIA, V19, P649, DOI 10.1016/j.neo.2017.05.002; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Fan Q, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0673-y; Fernandez-Mateos J, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-07270-0; Fujioka Y, 2010, J BIOL CHEM, V285, P1508, DOI 10.1074/jbc.M109.053520; Gong J, 2018, NUCLEIC ACIDS RES, V46, pD971, DOI 10.1093/nar/gkx861; Grimm WA, 2016, GUT, V65, P456, DOI 10.1136/gutjnl-2014-308735; Guo XY, 2018, AM J HUM GENET, V102, P890, DOI 10.1016/j.ajhg.2018.03.016; Hanada T, 2005, AUTOPHAGY, V1, P110, DOI 10.4161/auto.1.2.1858; Hong SB, 2012, ACTA CRYSTALLOGR D, V68, P1409, DOI 10.1107/S0907444912034166; Jo YK, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0052705; Kim H., 2017, INT J MOL SCI, V18; Kunanopparat A, 2016, WORLD J GASTROENTERO, V22, P8361, DOI 10.3748/wjg.v22.i37.8361; Li J, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0329-z; Li MS, 2005, BMC CANCER, V5, DOI 10.1186/1471-2407-5-96; Li N, 2019, IMMUNOL INVEST, V48, P378, DOI 10.1080/08820139.2019.1567532; Li QX, 2017, AUTOPHAGY, V13, P1053, DOI 10.1080/15548627.2017.1308997; Liu BL, 2018, CANCER COMMUN, V38, DOI 10.1186/s40880-018-0343-7; Lonsdale J, 2013, NAT GENET, V45, P580, DOI 10.1038/ng.2653; Mak Lung-Yi, 2018, Am Soc Clin Oncol Educ Book, V38, P262, DOI 10.1200/EDBK_200939; McGlynn KA, 2015, CLIN LIVER DIS, V19, P223, DOI 10.1016/j.cld.2015.01.001; Nikseresht M., 2018, J CELL BIOCHEM; Nooraei Marzieh Shams, 2018, Iranian Biomedical Journal, V22, P15, DOI 10.22034/ibj.22.1.15; Plantinga TS, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0094086; Qin ZZ, 2013, GENE, V527, P491, DOI 10.1016/j.gene.2013.06.067; Roth GA, 2018, LANCET, V392, P1736, DOI [10.1016/S0140-6736(18)32203-7, 10.1016/s0140-6736(18)32203-7]; Siegel RL, 2019, CA-CANCER J CLIN, V69, P7, DOI 10.3322/caac.21551; Song XY, 2018, MOL CARCINOGEN, V57, P1030, DOI 10.1002/mc.22823; Tan J, 2018, INT J CANCER, V143, P80, DOI 10.1002/ijc.31288; Wang Shiming, 2017, Yichuan, V39, P250, DOI 10.16288/j.yczz.16-294; Ward LD, 2016, NUCLEIC ACIDS RES, V44, pD877, DOI 10.1093/nar/gkv1340; Wei HM, 2019, INT IMMUNOPHARMACOL, V73, P72, DOI 10.1016/j.intimp.2019.04.049; Wu SY, 2018, HEPATOLOGY, V68, P141, DOI 10.1002/hep.29781; Xie KP, 2016, INT J CANCER, V139, P1564, DOI 10.1002/ijc.30205; Yamaguchi M, 2012, STRUCTURE, V20, P1244, DOI 10.1016/j.str.2012.04.018; Yuan JP, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-18165-5; Zhang K, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0344-0; Zhao ZZ, 2018, CANCER LETT, V421, P73, DOI 10.1016/j.canlet.2018.02.024	40	11	11	1	6	PERGAMON-ELSEVIER SCIENCE LTD	OXFORD	THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND	0024-3205	1879-0631		LIFE SCI	Life Sci.	OCT 15	2019	235								116675	10.1016/j.lfs.2019.116675			6	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	JG8RS	WOS:000492345900002	31340167				2022-04-25	
J	Ginet, V; Puyal, J; Rummel, C; Aubry, D; Breton, C; Cloux, AJ; Majjigapu, SR; Sordat, B; Vogel, P; Bruzzone, S; Nencioni, A; Duchosal, MA; Nahimana, A				Ginet, Vanessa; Puyal, Julien; Rummel, Coralie; Aubry, Dominique; Breton, Caroline; Cloux, Anne-Julie; Majjigapu, Somi R.; Sordat, Bernard; Vogel, Pierre; Bruzzone, Santina; Nencioni, Alessio; Duchosal, Michel A.; Nahimana, Aimable			A critical role of autophagy in antileukemia/lymphoma effects of APO866, an inhibitor of NAD biosynthesis	AUTOPHAGY			English	Article						NAD; ATG; CATALASE; ROS; autophagy; APO866; lymphoma; leukemia; therapy	ADENINE-DINUCLEOTIDE BIOSYNTHESIS; MULTIPLE-MYELOMA CELLS; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; CASPASE-ACTIVATION; COLORECTAL-CANCER; LEUKEMIA-CELLS; DEATH; FK866; APOPTOSIS; DEGRADATION	APO866, an inhibitor of NAD biosynthesis, exhibits potent antitumor properties in various malignancies. Recently, it has been shown that APO866 induces apoptosis and autophagy in human hematological cancer cells, but the role of autophagy in APO866-induced cell death remains unclear. Here, we report studies on the molecular mechanisms underlying APO866-induced cell death with emphasis on autophagy. Treatment of leukemia and lymphoma cells with APO866 induced both autophagy, as evidenced by an increase in autophagosome formation and in SQSTM1/p62 degradation, but also increased caspase activation as revealed by CASP3/caspase 3 cleavage. As an underlying mechanism, APO866-mediated autophagy was found to deplete CAT/catalase, a reactive oxygen species (ROS) scavenger, thus promoting ROS production and cell death. Inhibition of autophagy by ATG5 or ATG7 silencing prevented CAT degradation, ROS production, caspase activation, and APO866-induced cell death. Finally, supplementation with exogenous CAT also abolished APO866 cytotoxic activity. Altogether, our results indicated that autophagy is essential for APO866 cytotoxic activity on cells from hematological malignancies and also indicate an autophagy-dependent CAT degradation, a novel mechanism for APO866-mediated cell killing. Autophagy-modulating approaches could be a new way to enhance the antitumor activity of APO866 and related agents.	[Ginet, Vanessa; Puyal, Julien; Rummel, Coralie] Univ Lausanne, Dept Fundamental Neurosci, Fac Biol & Med, Lausanne, Switzerland; [Aubry, Dominique; Breton, Caroline; Cloux, Anne-Julie; Duchosal, Michel A.; Nahimana, Aimable] Univ Lausanne Hosp, Serv & Cent Lab Hematol, Lausanne, Switzerland; [Majjigapu, Somi R.; Sordat, Bernard; Vogel, Pierre] Swiss Fed Inst Technol EPFL, Lab Glycochem & Asymmetr Synth, Lausanne, Switzerland; [Bruzzone, Santina] Univ Genoa, Sect Biochem, Dept Expt Med, Genoa, Italy; [Nencioni, Alessio] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy		Nahimana, A (corresponding author), Univ Lausanne Hosp, Serv & Cent Lab Hematol, Lausanne, Switzerland.	aimable.nahimana@chuv.ch	Puyal, Julien P/G-4210-2018; Bruzzone, Santina/A-4264-2015; Nencioni, Alessio/K-3692-2018	Puyal, Julien P/0000-0002-8140-7026; Bruzzone, Santina/0000-0003-2034-3716; NENCIONI, ALESSIO/0000-0001-5068-8884	Faculty of Biology and Medicine of the University of Lausanne; Fondation Dr Henri Dubois-Ferriere Dinu Lipatti; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission; AIRCFondazione AIRC per la ricerca sul cancro; FP7 project PANACREAS	We thank TopoTarget for kindly providing us with clinical grade APO866. We also thank Peter GH Clarke for critical reading of the manuscript. This work was supported by a grant from the Faculty of Biology and Medicine of the University of Lausanne (A Nahimana, J Puyal), the Fondation Dr Henri Dubois-Ferriere Dinu Lipatti (A Nahimana), the Swiss National Science Foundation (J Puyal), the AIRC (A Nencioni), and the FP7 project PANACREAS (A Nahimana, A Nencioni, MA Duchosal).	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J	Wang, QX; Lv, L; Ye, DR; Sun, YH; Pan, XX; Bhandari, A; Zhang, XH; Wang, OC; Liu, HG				Wang, Qing-Xuan; Lv, Lin; Ye, Dan-Rong; Sun, Yi-Han; Pan, Xin-Xin; Bhandari, Adheesh; Zhang, Xiao-Hua; Wang, Ou-Chen; Liu, Hai-Guang			Downregulation of CD44v6 Enhances Chemosensitivity by Promoting Apoptosis and Inhibiting Autophagy in Colorectal Cancer HT29 Cells	ANNALS OF CLINICAL AND LABORATORY SCIENCE			English	Article						colorectal cancer; CD44v6; chemosensitivity; knockdown	PROGNOSTIC IMPACT; POOR-PROGNOSIS; EXPRESSION; STATISTICS; METASTASIS	Background. Chemotherapy resistance reduces the effectiveness of chemotherapeutic drugs greatly, resulting in treatment failure. Therefore, exploring chemoresistance-related genes and the corresponding mechanism is extremely important. The central role of CD44v6 in colorectal cancer has been previously reported. However, the effects of CD44v6 gene knockdown on the chemosensitivity of colorectal cancer cells are not conclusive. Material and Methods. A stable CD44v6 knockdown cell model in HT29 cells (HT29-KD) was established via lentiviral transduction. A quantitative real-time polymerase chain reaction (PCR) was carried out to confirm the knockdown efficiency. The chemosensitivity of cells to 5-fluorouracil (5-FU) was determined by a cell counting kit (CCK)-8 assay. Cell apoptosis and the cell cycle were assessed by flow cytometry. Results. The CD44v6 knockdown cell model was successfully constructed by using lentiviral transduction. Upon treatment with 5-FU, the inhibitory rate for cell activity of HT29-KD cells was significantly higher than that of the control group (HT29-NC). CD44v6 gene knockdown did not significantly affect HT-29 cell proliferation, according to the CCK-8 assay and cell cycle analysis. The cell apoptosis assay revealed that CD44v6 gene knockdown promoted HT-29 cell apoptosis. Without 5-FU treatment, there was no significant difference in terms of the relative expression level of the autophagy-related gene BECN1 between the two groups. However, with 5-FU treatment, the relative expression level of BECN1 in HT29-KD cells was much lower than that in HT29-NC cells. Conclusion. Our study confirms that CD44v6 gene knockdown can enhance chemosensitivity in HT29 cells by promoting apoptosis and inhibiting autophagy, thus affirming the effects of CD44v6 on the chemosensitivity of colorectal cancer.	[Wang, Qing-Xuan; Ye, Dan-Rong; Sun, Yi-Han; Pan, Xin-Xin; Bhandari, Adheesh; Zhang, Xiao-Hua; Wang, Ou-Chen; Liu, Hai-Guang] Wenzhou Med Univ, Affiliated Hosp 1, Dept Thyroid & Breast Surg, Wenzhou 325000, Zhejiang, Peoples R China; [Lv, Lin] Zhejiang Univ, Jinhua Hosp, Jinhua Municipal Cent Hosp, Dept Oncol, Jinhua, Zhejiang, Peoples R China		Liu, HG (corresponding author), Wenzhou Med Univ, Affiliated Hosp 1, Dept Thyroid & Breast Surg, Wenzhou 325000, Zhejiang, Peoples R China.	liuhgwzmc@yahoo.com	Bhandari, Adheesh/L-4023-2018	Bhandari, Adheesh/0000-0002-0406-2685	Science Foundation of the Health Bureau of Wenzhou City of Zhejiang, China [Y20140173]; Scientific Research Incubator Project of The First Affiliated Hospital of Wenzhou Medical University [FHY2014013]; 2016 annual CSCO Cancer Research Fund from Merck Serono [Y-MX2016-070]; Wenzhou Science and Technology Planning Project [2017Y0336]	This work was supported by the Science Foundation of the Health Bureau of Wenzhou City of Zhejiang, China (Y20140173), Scientific Research Incubator Project of The First Affiliated Hospital of Wenzhou Medical University (No. FHY2014013), the 2016 annual CSCO Cancer Research Fund from Merck Serono (Y-MX2016-070), and the Wenzhou Science and Technology Planning Project (2017Y0336).	Bellerby R, 2016, FRONT ONCOL, V6, DOI 10.3389/fonc.2016.00145; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Ji FH, 2014, ONCOL LETT, V7, P1284, DOI 10.3892/ol.2014.1824; Kodama H, 2017, BRIT J CANCER, V116, P186, DOI 10.1038/bjc.2016.401; Lai K, 2014, J CLIN PATHOL, V67, P854, DOI 10.1136/jclinpath-2014-202529; Loh TJ, 2015, ONCOL REP, V34, P1231, DOI 10.3892/or.2015.4110; Lv L, 2016, TUMOR BIOL, V37, P8811, DOI 10.1007/s13277-015-4755-6; Maida M, 2017, EXPERT REV ANTICANC, V17, P1131, DOI 10.1080/14737140.2017.1392243; Saito S, 2013, ONCOL REP, V29, P1570, DOI 10.3892/or.2013.2273; Senbanjo LT, 2017, FRONT CELL DEV BIOL, V5, DOI 10.3389/fcell.2017.00018; 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; Snyder EL, 2009, LAB INVEST, V89, P857, DOI 10.1038/labinvest.2009.54; Tjhay F, 2015, CANCER SCI, V106, P1421, DOI 10.1111/cas.12765; Todaro M, 2014, CELL STEM CELL, V14, P342, DOI 10.1016/j.stem.2014.01.009; van der Stok EP, 2017, NAT REV CLIN ONCOL, V14, P297, DOI 10.1038/nrclinonc.2016.199; Verma M, 2015, CA-CANCER J CLIN, V65, P496, DOI 10.3322/caac.21295; Vogel A, 2017, CANCER TREAT REV, V59, P54, DOI 10.1016/j.ctrv.2017.04.007; Wang JL, 2017, ONCOTARGET, V8, P12866, DOI 10.18632/oncotarget.14163; Wang LL, 2015, INT J CLIN EXP PATHO, V8, P14283; Wang Z, 2016, ONCOTARGET, V7, P55409, DOI 10.18632/oncotarget.10580; Xu YY, 2017, ONCOTARGET, V8, P45848, DOI 10.18632/oncotarget.17435; Zhi XC, 2015, INT J NANOMED, V10, P2775, DOI 10.2147/IJN.S72263; Zlobec I, 2009, HISTOPATHOLOGY, V55, P564, DOI 10.1111/j.1365-2559.2009.03421.x	24	2	3	0	1	ASSOC CLINICAL SCIENTISTS	MIDDLEBURY	PO BOX 1287, MIDDLEBURY, VT 05753 USA	0091-7370	1550-8080		ANN CLIN LAB SCI	Ann. Clin. Lab. Sci.	JUL-AUG	2019	49	4					481	487					7	Medical Laboratory Technology	Science Citation Index Expanded (SCI-EXPANDED)	Medical Laboratory Technology	JW6KP	WOS:000503158800008	31471337				2022-04-25	
J	Sajithlal, GB; Hamed, HA; Cruickshanks, N; Booth, L; Tavallai, S; Syed, J; Grant, S; Poklepovic, A; Dent, P				Sajithlal, Gangadharan B.; Hamed, Hossein A.; Cruickshanks, Nichola; Booth, Laurence; Tavallai, Seyedmehrad; Syed, Jahangir; Grant, Steven; Poklepovic, Andrew; Dent, Paul			Sorafenib/Regorafenib and Phosphatidyl Inositol 3 Kinase/Thymoma Viral Proto-Oncogene Inhibition Interact to Kill Tumor Cells	MOLECULAR PHARMACOLOGY			English	Article							ENDOPLASMIC-RETICULUM STRESS; PI3K INHIBITORS; CANCER-CELLS; SOLID TUMORS; SORAFENIB; KINASE; CARCINOMA; APOPTOSIS; COMBINATION; AUTOPHAGY	The present studies were undertaken to determine whether the multikinase inhibitors sorafenib/regorafenib cooperated with clinically relevant, phosphatidyl inositol 3 kinase (PI3K)-thymoma viral proto-oncogene (AKT) inhibitors to kill tumor cells. In liver, colorectal, lung, breast, kidney, and brain cancer cells, at clinically achievable doses, sorafenib/regorafenib and the PI3K inhibitor acetic acid (1S, 4E, 10R, 11R, 13S, 14R)-[4-diallylaminomethylene-6-hydroxy-1-methoxymethyl-10,13-dimethyl-3,7,17-trioxo-1,3,4, 7,10,11,12,13,14,15,16,17-dodecahydro-2-oxa-cyclopenta[a]phenanthren-11-yl ester (PX-866) cooperated in a greater than additive fashion to kill tumor cells. Cells lacking phosphatase and tensin homolog were as sensitive to the drug combination as cells expressing the protein. Similar data were obtained using the AKT inhibitors perifosine and 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-1,2,4-triazolo[3,4-f][1,6]naphthyridin-3(2H)-one hydrochloride (MK2206). PX-866 treatment abolished AKT/glycogen synthase kinase 3 (GSK3) phosphorylation, and cell killing correlated with reduced activity of AKT and mammalian target of rapamycin (mTOR). Expression of activated AKT and to a lesser extent activated mTOR reduced drug combination lethality. Expression of B-cell lymphoma-extra large or dominant negative caspase 9, but not cellular FLICE (FADD-like IL-1b-converting enzyme)-inhibitory protein short, protected cells from the drug combination. Treatment of cells with PX-866 increased protein levels of p62, lysosome-associated membrane protein 2 (LAMP2), and microtubule-associated protein light chain (LC) 3 and LC3II that correlated with a large increase in LC3-green fluorescent protein (GFP) vesicle numbers. Exposure of PX-866 treated cells to sorafenib reduced p62 and LAMP2 levels, decreased the ratio of LC3 to LC3II, and reduced LC3-GFP vesicle levels. Knockdown of Beclin1 or autophagy-related 5 suppressed drug toxicity by similar to 40%. In vivo, sorafenib and PX-866 or regorafenib and MK2206 cooperated to suppress the growth of established HuH7 and HCT116 tumors, respectively. Collectively our data demonstrate that the combination of sorafenib family kinase inhibitors with inhibitors of the PI3K/AKT pathway kills tumor cells in vitro and in vivo.	[Sajithlal, Gangadharan B.; Hamed, Hossein A.; Cruickshanks, Nichola; Booth, Laurence; Tavallai, Seyedmehrad; Syed, Jahangir; Dent, Paul] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA 23298 USA; [Grant, Steven; Poklepovic, Andrew] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA		Dent, P (corresponding author), Virginia Commonwealth Univ, Dept Neurosurg, Massey Canc Ctr, 401 Coll St,Box 980035, Richmond, VA 23298 USA.	pdent@vcu.edu			National Institutes of Health National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01-CA141704, R01-CA150214]; National Institutes of Health 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) [R01-DK52825]; Department of DefenseUnited States Department of Defense [W81XWH-10-1-0009]; Universal Inc. Professorship in Signal Transduction Research; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA141703, R01CA150214] 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) [R01DK052825] Funding Source: NIH RePORTER	This work was funded from PHS grants from the National Institutes of Health National Cancer Institute [Grants R01-CA141704 and R01-CA150214]; the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK52825]; and the Department of Defense [W81XWH-10-1-0009]. P. D. is the holder of the Universal Inc. Professorship in Signal Transduction Research. The authors have no conflicts of interest to report.	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Pharmacol.	OCT	2013	84	4					562	571		10.1124/mol.113.088005			10	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	216YN	WOS:000324322900008	23877009	Green Published			2022-04-25	
J	Wang, M; Han, D; Yuan, ZM; Hu, HQ; Zhao, ZX; Yang, RK; Jin, YH; Zou, CX; Chen, YG; Wang, GY; Gao, X; Wang, XS				Wang, Meng; Han, Dong; Yuan, Ziming; Hu, Hanqing; Zhao, Zhixun; Yang, Runkun; Jin, Yinghu; Zou, Chaoxia; Chen, Yinggang; Wang, Guiyu; Gao, Xu; Wang, Xishan			Long non-coding RNA H19 confers 5-Fu resistance in colorectal cancer by promoting SIRT1-mediated autophagy	CELL DEATH & DISEASE			English	Article							IN-VITRO; SIRT1; METASTASIS; CELLS; INHIBITION; EXPRESSION; CETUXIMAB	Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer (CRC) patients. The role of the differentially expressed IncRNAs in 5-Fluorouracil chemoresistance has not fully explained. Here, we observed IncRNA H19 was associated with the 5-Fu resistance in CRC. Quantitative analysis indicated that H19 was significantly increased in recurrent CRC patient samples. Kaplan-Meier survival analysis indicated that high H19 expression in CRC tissues was significantly associated with poor recurrent free survival. Our functional studies demonstrated that H19 promoted colorectal cells 5-Fu resistance. Mechanistically, H19 triggered autophagy via SIRT1 to induce cancer chemoresistance. Furthermore, bioinformatics analysis showed that miR-194-5p could directly bind to H19, suggesting H19 might work as a ceRNA to sponge miR-194-5p, which was confirmed by Dual-luciferase reporter assay and Immunoprecipitation assay. Extensively, our study also showed that SIRT1 is the novel direct target of miR-194-5p in CRC cells. Taken together, our study suggests that H19 mediates 5-Fu resistance in CRC via SIRT1 mediated autophagy. Our finding provides a novel mechanistic role of H19 in CRC chemoresistance, suggesting that H19 may function as a marker for prediction of chemotherapeutic response to 5-Fu.	[Wang, Meng; Yuan, Ziming; Hu, Hanqing; Zhao, Zhixun; Yang, Runkun; Jin, Yinghu; Chen, Yinggang; Wang, Guiyu; Wang, Xishan] Harbin Med Univ, Dept Colorectal Surg, Affiliated Hosp 2, Harbin 150081, Heilongjiang, Peoples R China; [Han, Dong; Zou, Chaoxia; Gao, Xu] Harbin Med Univ, Dept Biochem & Mol Biol, Harbin 150081, Heilongjiang, Peoples R China; [Wang, Xishan] Chinese Acad Med Sci, Peking Union Med Coll, Canc Inst & Hosp, Dept Colorectal Surg, Beijing 100000, Peoples R China		Wang, XS (corresponding author), Harbin Med Univ, Dept Colorectal Surg, Affiliated Hosp 2, Harbin 150081, Heilongjiang, Peoples R China.; Gao, X (corresponding author), Harbin Med Univ, Dept Biochem & Mol Biol, Harbin 150081, Heilongjiang, Peoples R China.	gaoxu_671227@163.com; wxshan1208@126.com	jin, yinghu/AAI-5725-2020; gao, xu/U-4765-2019		National Key Research and Development Program of the Ministry of Science and Technology of China [2016YFC0905303]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001]; Beijing Science and Technology Program [D17110002617004]; Heilongjiang Health and Family Planning Commission Research project [2017064]; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81501998]; Postdoctoral Foundation of Heilongjiang Province [LBH-Q15079]; Innovation Talent Training Plan for Ordinary Colleges and Universities of Heilongjiang Province [UNPYSCT-2017072]	This study was partly supported by National Key Research and Development Program of the Ministry of Science and Technology of China (2016YFC0905303), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001), Beijing Science and Technology Program (D17110002617004), Heilongjiang Health and Family Planning Commission Research project (2017064), Natural Science Foundation of China (81501998), the Postdoctoral Foundation of Heilongjiang Province (LBH-Q15079), the Innovation Talent Training Plan for Ordinary Colleges and Universities of Heilongjiang Province (UNPYSCT-2017072).	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NOV 19	2018	9								1149	10.1038/s41419-018-1187-4			14	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	HA8TC	WOS:000450565200006	30451820	gold, Green Published			2022-04-25	
J	Dai, HT; Liu, CM; Liu, YH; Zhang, Z; Peng, CW; Wang, ZY; Zheng, J; Li, CL; Yu, WM; Cheng, F				Dai, Haitao; Liu, Changmao; Liu, Yuanhua; Zhang, Zhong; Peng, Changwei; Wang, Zhongyu; Zheng, Jiang; Li, Chenglong; Yu, Weimin; Cheng, Fan			Research on mechanism of miR-130a in regulating autophagy of bladder cancer cells through CYLD	JOURNAL OF BUON			English	Article						miR-130a; CYLD; bladder cancer cells; autophagy	COLORECTAL-CANCER; PROLIFERATION; MIGRATION; INVASION; MICRORNA-130A	Purpose: The study aimed to explore the regulatory mechanism of micro ribonucleic acid (miR)-130a in the autophagy of bladder cancer cells through cylindromatosis (CYLD). Methods: Human bladder cancer T24 cell line was used as the objects of the study. After miR-130a was knocked down using small-interfering RNA (siRNA) in T24 cell line, the changes in expressions of miR-130a and CYLD in each group were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The cell proliferation in each group was detected using cell counting kit-8 (CCK8) assay and flow cytometry. The changes in mRNA and protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 were determined using qRT-PCR and Western blotting. The autolysosomes were detected through acridine orange (AO)/ethidium staining bromide (ER) staining. Moreover, CYLD was knocked down using siRNA, and then the changes in mRNA expressions of miR-130a, LC3 and Beclin1 in each group were detected through qRT-PCR. Results: After interference in miR-130a with siRNA, miR-130a-siRNA group had a significantly lower mRNA expression of miR-130a compared with NC-siRNA group and a significantly higher mRNA expression of CYLD (p<0.05), obviously inhibited cell proliferation (p<0.05), and decreased significantly mRNA and protein expressions of LC3 showing Beclin1 (p<0.05), and an evidently smaller number of autolysosomes. After knockdown of CYLD using siRNA, the mRNA expression of miR-130a had no significant changes (p>0.05), while the mRNA expressions of LC3 and Beclin1 declined significantly in CYLD-siRNA group compared with those in NC-siRNA group (p<0.05). Conclusion: MiR-130 can promote the autophagy of bladder cancer cells through regulating CYLD, thus facilitating the proliferation of tumor cells.	[Dai, Haitao; Liu, Changmao; Liu, Yuanhua; Zhang, Zhong; Peng, Changwei; Wang, Zhongyu; Zheng, Jiang] Yangtze Univ, Affiliated Hosp 1, Peoples Hosp Jingzhou 1, Dept Urol, Jingzhou 434000, Hubei, Peoples R China; [Dai, Haitao; Li, Chenglong; Yu, Weimin; Cheng, Fan] Wuhan Univ, Hubei Gen Hosp, Renmin Hosp, Dept Urol, 238 Jiefang Rd,99 Zhangzhidong Rd, Wuhan 430060, Hubei, Peoples R China		Cheng, F (corresponding author), Wuhan Univ, Hubei Gen Hosp, Renmin Hosp, Dept Urol, 238 Jiefang Rd,99 Zhangzhidong Rd, Wuhan 430060, Hubei, Peoples R China.	jiha77@126.com					Acunzo M, 2012, ONCOGENE, V31, P634, DOI 10.1038/onc.2011.260; Bartel DP, 2009, CELL, V136, P215, DOI 10.1016/j.cell.2009.01.002; Bauckman KA, 2016, AUTOPHAGY, V12, P850, DOI 10.1080/15548627.2016.1160176; Chen L, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0085771; Chen WZ, 2017, MOL MED REP, V16, P5241, DOI 10.3892/mmr.2017.7257; Hunstig F, 2016, J CANCER RES CLIN, V142, P845, DOI 10.1007/s00432-015-2079-y; Jiang H, 2015, ONCOL REP, V34, P1153, DOI 10.3892/or.2015.4099; Kong PZ, 2016, ONCOTARGET, V7, P55601, DOI 10.18632/oncotarget.10876; Li BK, 2014, MED ONCOL, V31, DOI 10.1007/s12032-014-0230-2; Liu L, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0055532; Liu S, 2015, ONCOL REP, V33, P1372, DOI 10.3892/or.2014.3693; Navarro M, 2017, WORLD J GASTROENTERO, V23, P3632, DOI 10.3748/wjg.v23.i20.3632; Ozpolat B, 2015, CANCER MANAG RES, V7, P291, DOI 10.2147/CMAR.S34859; Pan YQ, 2015, INT J CLIN EXP PATHO, V8, P384; Sun L, 2015, PLOS ONE, V10, DOI [10.1371/journal.pone.0117695, 10.1371/journal.pone.0143820]; Yang G, 2010, INT J BIOL SCI, V6, P1; Yang JM, 2003, MOL CANCER RES, V1, P420; Yang Ling-Yun, 2012, Sichuan Da Xue Xue Bao Yi Xue Ban, V43, P60; Zhang Y, 2014, INT J MOL SCI, V15, P19330, DOI 10.3390/ijms151119330; Zhao YG, 2015, J BIOL CHEM, V290, P22076, DOI 10.1074/jbc.M115.658096; Zheng YZ, 2015, MOL CLIN ONCOL, V3, P713, DOI 10.3892/mco.2015.511; Zhu X, 2015, CANCER GENE THER, V22, P573, DOI 10.1038/cgt.2015.50	22	1	1	2	3	IMPRIMATUR PUBLICATIONS	ATHENS	30 DEM POLIORKETES ST, ATHENS, 136 76, GREECE	1107-0625	2241-6293		J BUON	J. BUON	MAY-JUN	2020	25	3					1636	1642					7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	MM0PH	WOS:000549861700021	32862616				2022-04-25	
J	Jiso, A; Demuth, P; Bachowsky, M; Haas, M; Seiwert, N; Heylmann, D; Rasenberger, B; Christmann, M; Dietrich, L; Brunner, T; Riyanti; Schaberle, TF; Plubrukarn, A; Fahrer, J				Jiso, Apisada; Demuth, Philipp; Bachowsky, Madeleine; Haas, Manuel; Seiwert, Nina; Heylmann, Daniel; Rasenberger, Birgit; Christmann, Markus; Dietrich, Lea; Brunner, Thomas; Riyanti; Schaeberle, Till F.; Plubrukarn, Anuchit; Fahrer, Joerg			Natural Merosesquiterpenes Activate the DNA Damage Response via DNA Strand Break Formation and Trigger Apoptotic Cell Death in p53-Wild-Type and Mutant Colorectal Cancer	CANCERS			English	Article						colorectal cancer; chemotherapy; tumor suppressor p53; apoptosis; natural compounds; DNA damage	MARINE SPONGE METABOLITES; LIPOIC ACID; P53 MUTATIONS; ILIMAQUINONE; ETHYLSMENOQUINONE; SMENOSPONGINE; AMINOQUINONE; DERIVATIVES; EXPRESSION; AUTOPHAGY	Simple Summary Bowel cancer is a serious disease, which affects many people worldwide. Unfortunately, the disease is often diagnosed in an advanced stage, which impairs the chance of survival. Furthermore, resistance to therapy occurs frequently. Thus, novel therapeutic approaches are required to improve cancer therapy. Here, we studied whether merosesquiterpenes might be useful for cancer treatment. These compounds occur in marine sponges and were isolated by our group. We were able to identify three compounds with potent cytotoxic activity in different cell lines established from human large bowel cancer. Our experiments provided evidence that the compounds cause DNA damage and trigger cell death, so-called mitochondrial apoptosis, which was attested in cancer cells with expression of wild-type and mutated p53 tumor suppressor. Finally, we show that merosesquiterpenes also kill intestinal tumor organoids, an ex vivo model of large bowel cancer. Colorectal cancer (CRC) is a frequently occurring malignant disease with still low survival rates, highlighting the need for novel therapeutics. Merosesquiterpenes are secondary metabolites from marine sponges, which might be useful as antitumor agents. To address this issue, we made use of a compound library comprising 11 isolated merosesquiterpenes. The most cytotoxic compounds were smenospongine > ilimaquinone approximate to dactylospontriol, as shown in different human CRC cell lines. Alkaline Comet assays and gamma H2AX immunofluorescence microscopy demonstrated DNA strand break formation in CRC cells. Western blot analysis revealed an activation of the DNA damage response with CHK1 phosphorylation, stabilization of p53 and p21, which occurred both in CRC cells with p53 knockout and in p53-mutated CRC cells. This resulted in cell cycle arrest followed by a strong increase in the subG1 population, indicative of apoptosis, and typical morphological alterations. In consistency, cell death measurements showed apoptosis following exposure to merosesquiterpenes. Gene expression studies and analysis of caspase cleavage revealed mitochondrial apoptosis via BAX, BIM, and caspase-9 as the main cell death pathway. Interestingly, the compounds were equally effective in p53-wild-type and p53-mutant CRC cells. Finally, the cytotoxic activity of the merosesquiterpenes was corroborated in intestinal tumor organoids, emphasizing their potential for CRC chemotherapy.	[Jiso, Apisada; Demuth, Philipp; Bachowsky, Madeleine; Haas, Manuel; Seiwert, Nina; Fahrer, Joerg] Tech Univ Kaiserslautern, Div Food Chem & Toxicol, Dept Chem, D-67663 Kaiserslautern, Germany; [Jiso, Apisada; Plubrukarn, Anuchit] Prince Songkla Univ, Fac Pharmaceut Sci, Dept Pharmacognosy & Pharmaceut Bot, Hat Yai 90112, Songkhla, Thailand; [Heylmann, Daniel; Fahrer, Joerg] Justus Liebig Univ Giessen, Rudolf Buchheim Inst Pharmacol, D-35392 Giessen, Germany; [Rasenberger, Birgit; Christmann, Markus] Univ Med Ctr Mainz, Inst Toxicol, D-55131 Mainz, Germany; [Dietrich, Lea; Brunner, Thomas] Univ Konstanz, Dept Biol, Biochem Pharmacol, D-78464 Constance, Germany; [Riyanti; Schaeberle, Till F.] Justus Liebig Univ Giessen, Inst Insect Biotechnol, D-35392 Giessen, Germany; [Riyanti] Jenderal Soedirman Univ, Fac Fisheries & Marine Sci, Purwokerto 53122, Indonesia; [Schaeberle, Till F.] Fraunhofer Inst Mol Biol & Appl Ecol IME, Branch Bioresources, D-35392 Giessen, Germany		Fahrer, J (corresponding author), Tech Univ Kaiserslautern, Div Food Chem & Toxicol, Dept Chem, D-67663 Kaiserslautern, Germany.; Fahrer, J (corresponding author), Justus Liebig Univ Giessen, Rudolf Buchheim Inst Pharmacol, D-35392 Giessen, Germany.	jiso.apisada@gmail.com; pdemuth@rhrk.uni-kl.de; madele.bach@online.de; manhaas@rhrk.uni-kl.de; seiwert@rhrk.uni-kl.de; Daniel.Heylmann@pharma.med.uni-giessen.de; rasebi00@uni-mainz.de; mchristm@uni-mainz.de; lea.dietrich@uni-konstanz.de; thomas.brunner@uni-konstanz.de; Riyanti@bio.uni-giessen.de; Till.F.Schaeberle@agrar.uni-giessen.de; anuchit.pl@psu.ac.th; fahrer@chemie.uni-kl.de		Christmann, Markus/0000-0002-9672-231X; Jiso, Apisada/0000-0002-4297-7819; Heylmann, Daniel/0000-0002-8335-2313; Schaberle, Till/0000-0001-9947-8079; Seiwert, Nina/0000-0003-2169-3670; Dietrich, Lea/0000-0002-5931-7964	Wilhelm Sander Foundation [2016.039.2]; Royal Golden Jubilee PhD ProgramThailand Research Fund (TRF) [PHD/0094/2556]; German Federal Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF) [01DP17037]; Indonesia Endowment Fund for Education (LPDP) [20160222305487]	This research was partially supported by Wilhelm Sander Foundation, Grant Number 2016.039.2 (to J.F.). A.J. was supported by a grant from the Royal Golden Jubilee PhD Program (PHD/0094/2556). T.F.S. and A.P. were supported by the German Federal Ministry of Education and Research (BMBF) Grant Number 01DP17037. R. received a PhD fellowship from the Indonesia Endowment Fund for Education (LPDP), Grant Number 20160222305487.	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J	Huang, YH; Zhou, J; Luo, SL; Wang, Y; He, JT; Luo, P; Chen, ZL; Liu, T; Tan, X; Ou, JJ; Miao, HM; Liang, HJ; Shi, CM				Huang, Yinghui; Zhou, Jie; Luo, Shenglin; Wang, Yang; He, Jintao; Luo, Peng; Chen, Zelin; Liu, Tao; Tan, Xu; Ou, Juanjuan; Miao, Hongming; Liang, Houjie; Shi, Chunmeng			Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44	GUT			English	Article							HEPTAMETHINE DYE; DRUG-DELIVERY; IR-780 DYE; NANOPARTICLES; ACCUMULATION; METFORMIN; PROGRESSION; RISK; GENE	Objective As the modulation of autophagic processes can be therapeutically beneficial to cancer treatment, the identification of novel autophagic enhancers is highly anticipated. However, current autophagy-inducing anticancer agents exert undesired side effects owing to their non-specific biodistribution in off-target tissues. This study aims to develop a multifunctional agent to integrate cancer targeting, imaging and therapy and to investigate its mechanism. Design A series of mitochondria-targeting near-infrared (NIR) fluorophores were synthesised, screened and identified for their autophagy-enhancing activity. The optical properties and biological effects were tested both in vitro and in vivo. The underlying mechanism was investigated using inhibitors, small interfering RNA (siRNA), RNA sequencing, mass spectrometry and human samples. Results We have screened and identified a new NIR autophagy-enhancer, IR-58, which exhibits significant tumour-selective killing effects. IR-58 preferentially accumulates in the mitochondria of colorectal cancer (CRC) cells and xenografts, a process that is glycolysis-dependent and organic anion transporter polypeptide-dependent. IR-58 kills tumour cells and induces apoptosis via inducing excessive autophagy, which is mediated through the reactive oxygen species (ROS)-Akt-mammalian target of rapamycin (mTOR) pathway. RNA sequencing, mass spectrometry and siRNA interference studies demonstrate that translocase of inner mitochondrial membrane 44 (TIM44)-superoxide dismutase 2 (SOD2) pathway inhibition is responsible for the excessive ROS, autophagy and apoptosis induced by IR-58. TIM44 expression correlates positively with CRC development and poor prognosis in patients. Conclusions A novel NIR small-molecule autophagy-enhancer, IR-58, with mitochondria-targeted imaging and therapy capabilities was developed for CRC treatment. Additionally, TIM44 was identified for the first time as a potential oncogene, which plays an important role in autophagy through the TIM44-SOD2-ROS-mTOR pathway.	[Huang, Yinghui; Luo, Shenglin; Wang, Yang; He, Jintao; Luo, Peng; Chen, Zelin; Liu, Tao; Tan, Xu; Shi, Chunmeng] Third Mil Med Univ, Coll Prevent Med, Chongqing Engn Res Ctr Nanomed,Inst Combined Inju, State Key Lab Trauma Burns & Combined Injury, Chongqing 400038, Peoples R China; [Zhou, Jie; Ou, Juanjuan; Miao, Hongming; Liang, Houjie] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Dept Oncol, Chongqing, Peoples R China		Shi, CM (corresponding author), Third Mil Med Univ, Coll Prevent Med, Chongqing Engn Res Ctr Nanomed,Inst Combined Inju, State Key Lab Trauma Burns & Combined Injury, Chongqing 400038, Peoples R China.	shicm@sina.com	Sung, Joseph J. Y./R-3203-2018; miao, hongming/AAV-8561-2020; Chen, Zhiwei/B-7793-2019	Sung, Joseph J. Y./0000-0003-3125-5199; Chen, Zhiwei/0000-0002-4511-2888; Shi, Chunmeng/0000-0002-8264-738X; Huang, Yinghui/0000-0002-9263-1111; Luo, Peng/0000-0002-9668-4771	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81130026, 81372727]; State Key Basic Research Development Program [2012CB518103]; Ministry of Education [NCET-11-0869]	This work was supported by the National Natural Science Foundation of China (Grant No. 81130026 and 81372727), State Key Basic Research Development Program (2012CB518103), Program of New Century Excellent Talents in University (NCET-11-0869) from the Ministry of Education.	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J	Li, ZJ; Li, YS; Zhou, X; Dai, PY; Li, CM				Li, Zhaojian; Li, Yansen; Zhou, Xin; Dai, Pengyuan; Li, Chunmei			Autophagy involved in the activation of the Nrf2-antioxidant system in testes of heat-exposed mice	JOURNAL OF THERMAL BIOLOGY			English	Article						Heat exposure; Nrf2; p62; Autophagy; Testis; Mice	TRANSCRIPTION FACTOR NRF2; CUL3-BASED E3 LIGASE; OXIDATIVE STRESS; ANTIOXIDANT RESPONSE; APOPTOSIS; KEAP1; CANCER; GROWTH; P62; PATHWAY	Hyperthermia causes oxidative stress in testes, which triggers antioxidant signals including autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2). However, their relationship in testes under oxidative stress is unclear. In this study, we conducted testes injection for autophagy alteration and heat exposure to reveal the interaction between autophagy and the Nrf2-antioxidant system. Male mice were injected once with normal saline as control (Cont group), autophagy inhibitor 3-methyladenine (3-MA group) or autophagy inducer rapaihycin (Rapa group). Then, each group was divided into two parts: one received a 2-h 42 degrees C heat treatment for eight days (HT groups), and the other was kept thermal neutral (NT groups). Heat-exposed mice showed significantly increased rectal, scrotal surface and body surface temperatures. Histology of the testes revealed many vacuoles inserted in the seminiferous tubules in the HT Cont group and two 3-MA groups. Ultrastructural changes in germ cells revealed autophagosomes in two 3-MA groups. Immunohistochemical detection of Nrf2 and p62/SQSTM1 proteins showed prominent expression in Leydig cells. Heat exposure increased Nrf2 protein and mRNA levels. 3-MA and Rapa testes injection also resulted in Nrf2 cytoplasm accumulation. Massive conversion of LC3 (microtubule-associated protein light chain 3)1 to LC3II was detected in two 3-MA groups, accompanied by decreased ATG5 (autophagy related gene 5) mRNA levels in the HT 3-MA group. These results indicated autophagy alteration triggered the Nrf2 signaling pathway with consequences such that the autophagy inducer protected the testes and the autophagy inhibitor enhanced the detrimental effects caused by heat exposure.	[Li, Zhaojian; Li, Yansen; Zhou, Xin; Dai, Pengyuan; Li, Chunmei] Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China		Li, CM (corresponding author), Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China.	chunmeili@njau.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31402116, 31272485]; National Key Research and Development Program of China [2016YFD0500505]	This work was supported by the National Natural Science Foundation of China (Nos. 31402116 and 31272485) and the National Key Research and Development Program of China (2016YFD0500505).	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J	Otterpohl, KL; Gould, KA				Otterpohl, Karla L.; Gould, Karen A.			Evaluation of Rint1 as a modifier of intestinal tumorigenesis and cancer risk	PLOS ONE			English	Article							GOLGI-ER RETROGRADE; RAD50-INTERACTING PROTEIN; COMPLEX; ZW10; LOCALIZATION; TRAFFICKING; BREAST; LOCUS; MOM5	The Rad50 Interacting Protein 1 (Rint1) influences cellular homeostasis through maintenance of endoplasmic reticulum, Golgi and centrosome integrity and regulation of vesicle transport, autophagy and the G(2)/M checkpoint. Rint1 has been postulated to function as a tumor suppressor as well as an oncogene, with its role depending perhaps upon the precise cellular and/or experimental context. In humans, heterozygosity for germline missense variants in RINT1 have, in some studies, been associated with increased risk of both breast and Lynch syndrome type cancers. However, it is not known if these germline variants represent loss of function alleles or gain of function alleles. Based upon these findings, as well as our initial consideration of Rint1 as a potential candidate for Mom5, a genetic modifier of intestinal tumorigenesis in Apc(Min/+) mice, we sought to explicitly examine the impact of Rint1 on tumorigenesis in Apc(Min/+) mice. However, heterozygosity for a knockout of Rint1 had no impact on tumorigenesis in Rint1(+/-); Apc(Min/+) mice. Likewise, we found no evidence to suggest that the remaining Rint1 allele was lost somatically in intestinal tumors in Apc(Min/+) mice. Interestingly, in contrast to what has been observed in Rint1(+/-) mice on a mixed genetic background, Rint1(+/-) mice on a pure C57BL/6J background did not show spontaneous tumor development. We also evaluated colorectal cancer data available in the COSMIC and ONCOMINE databases and found that RINT1 overexpression, as well as the presence of somatic missense mutations in RINT1 were associated with colorectal cancer development. In vitro evaluation of two missense variants in RINT1 suggested that such variants do have the potential to impact RINT1 function.	[Otterpohl, Karla L.; Gould, Karen A.] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA; [Otterpohl, Karla L.] Sanford Res, Childrens Hlth Res Ctr, Sioux Falls, SD USA		Gould, KA (corresponding author), Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA.	kagould@unmc.edu			NCRRUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [5P20RR016469, RR018788]; National Institute for General Medical Science (NIGMS) [8P20GM103427, P20GM103471]	The University of Nebraska DNA Sequencing Core receives partial support from the NCRR (5P20RR016469, RR018788) and the National Institute for General Medical Science (NIGMS) (8P20GM103427, P20GM103471). The author(s) received no other specific funding for this work.	Arasaki K, 2007, BIOCHEM BIOPH RES CO, V359, P811, DOI 10.1016/j.bbrc.2007.05.188; Arasaki K, 2006, MOL BIOL CELL, V17, P2780, DOI 10.1091/mbc.E05-10-0973; Arasaki K, 2013, MOL BIOL CELL, V24, P2907, DOI 10.1091/mbc.E13-01-0014; DIETRICH WF, 1993, CELL, V75, P631, DOI 10.1016/0092-8674(93)90484-8; Grigaravicius P, 2016, CELL DEATH DIFFER, V23, P454, DOI 10.1038/cdd.2015.113; Haines DC, 2001, TOXICOL PATHOL, V29, P653, DOI 10.1080/019262301753385988; He SS, 2014, AUTOPHAGY, V10, P180, DOI 10.4161/auto.26917; He SS, 2013, NAT CELL BIOL, V15, P1206, DOI 10.1038/ncb2848; Hirose H, 2004, EMBO J, V23, P1267, DOI 10.1038/sj.emboj.7600135; Kong LJ, 2006, MOL CELL, V22, P63, DOI 10.1016/j.molcel.2006.02.016; Li N, 2016, BREAST CANCER RES TR, V159, P385, DOI 10.1007/s10549-016-3944-3; Lin XQ, 2007, MOL CELL BIOL, V27, P4905, DOI 10.1128/MCB.02396-06; Oikarinen SI, 2009, CARCINOGENESIS, V30, P1591, DOI 10.1093/carcin/bgp159; Otterpohl KL, 2015, MAMM GENOME, V26, P235, DOI 10.1007/s00335-015-9567-x; Park DJ, 2014, CANCER DISCOV, V4, P804, DOI 10.1158/2159-8290.CD-14-0212; Quayle SN, 2012, NEURO-ONCOLOGY, V14, P1325, DOI 10.1093/neuonc/nos246; Xiao J, 2001, J BIOL CHEM, V276, P6105, DOI 10.1074/jbc.M008893200	17	4	4	1	2	PUBLIC LIBRARY SCIENCE	SAN FRANCISCO	1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA	1932-6203			PLOS ONE	PLoS One	MAR 6	2017	12	3							e0172247	10.1371/journal.pone.0172247			13	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	EN5OE	WOS:000396054300009	28264000	gold, Green Published, Green Submitted			2022-04-25	
J	Kitahara, T; Haraguchi, N; Takahashi, H; Nishimura, J; Hata, T; Takemasa, I; Mizushima, T; Yamamoto, H; Doki, Y; Mori, M				Kitahara, Tomohiro; Haraguchi, Naotsugu; Takahashi, Hidekazu; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Yamamoto, Hirofumi; Doki, Yuichiro; Mori, Masaki			Identification and Characterization of CD107a as a Marker of Low Reactive Oxygen Species in Chemoresistant Cells in Colorectal Cancer	ANNALS OF SURGICAL ONCOLOGY			English	Article							STEM-CELLS; OXIDATIVE STRESS; OXALIPLATIN; APOPTOSIS; THERAPY; DIFFERENTIATION; CYTOTOXICITY; EXPRESSION; CARCINOMA; AUTOPHAGY	Background. Reactive oxygen species (ROS) generated by chemoradiotherapy lead to cancer cell death. Although ROS regulation mechanisms play important roles in chemoradioresistance, few markers exist that indicated intracellular ROS status. This study aimed to identify novel cell surface markers that represented intracellular ROS status to characterize cells with low ROS (ROSlow) in colorectal cancer (CRC). Methods. We used ROS indicators and an antibody array with 242 cell surface antibodies to identify markers of ROSlow cells. After validation, we performed immunohistochemical analyses and chemosensitivity assays. We used small interfering RNA to assess the effect of silencing the identified markers. We tested cell differentiation assays with spheroid cell assays. Results. CD107a was identified as a common marker of ROSlow cells in several CRC cell lines and clinical specimens. CD107a(+)/ROSlow cells were enriched in HT29 and DLD1 cultures after treatments with oxaliplatin, 5-fluorouracil, and the irinotecan metabolite SN38. CD107a silencing improved chemosensitivity by increasing ROS production. Immunohistochemistry showed enhanced CD107a surface expression on cells that formed immature cell clusters and on cells located in the invasive fronts of cancer foci. CD107a expression was also enhanced on specimens from patients with poorly differentiated adenocarcinoma who had received neoadjuvant chemotherapy. Cell surface CD107a expression was enhanced on cells that formed colonospheres, but expression diminished during cell differentiation. Conclusions. CD107a was identified as a novel marker of ROSlow cells in CRC. CD107a expression was closely related to chemoresistance and the immature cell phenotype. Anti-CD107a treatments represent a novel approach for targeting chemoresistant cells in CRC.	[Kitahara, Tomohiro; Haraguchi, Naotsugu; Takahashi, Hidekazu; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Yamamoto, Hirofumi; Doki, Yuichiro; Mori, Masaki] Osaka Univ, Grad Sch Med, Dept Surg Gastroenterol, Osaka, Japan		Haraguchi, N (corresponding author), Osaka Univ, Grad Sch Med, Dept Surg Gastroenterol, Osaka, Japan.	nharaguchi@gesurg.med.osaka-u.ac.jp			Pharma-Link between Academia and Shionogi (FLASH)	Supported in part by the Foundation of the Pharma-Link between Academia and Shionogi (FLASH), an initiative between Osaka University and Shionogi & Co .Ltd.	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Surg. Oncol.	APR	2017	24	4					1110	1119		10.1245/s10434-016-5671-8			10	Oncology; Surgery	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Surgery	EQ4LC	WOS:000398047600040	27834032				2022-04-25	
J	Coni, S; Serrao, SM; Yurtsever, ZN; Di Magno, L; Bordone, R; Bertani, C; Licursi, V; Ianniello, Z; Infante, P; Moretti, M; Petroni, M; Guerrieri, F; Fatica, A; Macone, A; De Smaele, E; Di Marcotullio, L; Giannini, G; Maroder, M; Agostinelli, E; Canettieri, G				Coni, Sonia; Serrao, Silvia Maria; Yurtsever, Zuleyha Nihan; Di Magno, Laura; Bordone, Rosa; Bertani, Camilla; Licursi, Valerio; Ianniello, Zaira; Infante, Paola; Moretti, Marta; Petroni, Marialaura; Guerrieri, Francesca; Fatica, Alessandro; Macone, Alberto; De Smaele, Enrico; Di Marcotullio, Lucia; Giannini, Giuseppe; Maroder, Marella; Agostinelli, Enzo; Canettieri, Gianluca			Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation	CELL DEATH & DISEASE			English	Article							TARGETING ORNITHINE-DECARBOXYLASE; TRANSLATION FACTOR EIF5A; C-MYC; GENOMIC TARGETS; CELL-GROWTH; EXPRESSION; INITIATION; PROMOTES; IDENTIFICATION; REQUIREMENT	Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and deoxyhypusine hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, polyamine homeostasis, energy metabolism, and plays a role in cancer. However, the effects of EIF5A inhibition in preclinical cancer models, the mechanism of action, and specific translational targets are still poorly understood. We show here that hypusinated EIF5A promotes growth of colorectal cancer (CRC) cells by directly regulating MYC biosynthesis at specific pausing motifs. Inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through lentiviral-mediated knockdown of DHPS or EIF5A reduces the growth of various CRC cells. Multiplex gene expression analysis reveals that inhibition of hypusination impairs the expression of transcripts regulated by MYC, suggesting the involvement of this oncogene in the observed effect. Indeed, we demonstrate that EIF5A regulates MYC elongation without affecting its mRNA content or protein stability, by alleviating ribosome stalling at five distinct pausing motifs in MYC CDS. Of note, we show that blockade of the hypusination axis elicits a remarkable growth inhibitory effect in preclinical models of CRC and significantly reduces the size of polyps in APC(Min/+) mice, a model of human familial adenomatous polyposis (FAP). Together, these data illustrate an unprecedented mechanism, whereby the tumor-promoting properties of hypusinated EIF5A are linked to its ability to regulate MYC elongation and provide a rationale for the use of DHPS/EIF5A inhibitors in CRC therapy.	[Coni, Sonia; Serrao, Silvia Maria; Di Magno, Laura; Bordone, Rosa; Bertani, Camilla; Petroni, Marialaura; Di Marcotullio, Lucia; Giannini, Giuseppe; Maroder, Marella; Canettieri, Gianluca] Sapienza Univ Rome, Dept Mol Med, Viale Regina Elena 291, I-00161 Rome, Italy; [Yurtsever, Zuleyha Nihan; Macone, Alberto] Sapienza Univ Rome, Dept Biochem Sci A Rossi Fanelli, Piazzale Aldo Moro 5, I-00185 Rome, Italy; [Licursi, Valerio; Ianniello, Zaira; Fatica, Alessandro] Sapienza Univ Rome, Dept Biol & Biotechnol Charles Darwin, Piazzale Aldo Moro 5, I-00185 Rome, Italy; [Infante, Paola] Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, Viale Regina Elena 291, I-00161 Rome, Italy; [Moretti, Marta; De Smaele, Enrico] Sapienza Univ Rome, Dept Expt Med, Viale Regina Elena 324, I-00161 Rome, Italy; [Guerrieri, Francesca] Canc Res Ctr Lyon CRCL, UMR Inserm U1052, CNRS 5286, Lyon, France; [Di Marcotullio, Lucia; Canettieri, Gianluca] Sapienza Univ Rome, Ist Pasteur, Fdn Cenci Bolognetti, Viale Regina Elena 291, I-00161 Rome, Italy; [Agostinelli, Enzo; Canettieri, Gianluca] Int Polyamines Fdn ONLUS, Via Forte Tiburtino 98, I-00159 Rome, Italy; [Agostinelli, Enzo] Sapienza Univ Rome, Policlin Umberto I, Dept Sense Organs, Viale Policlin 155, I-00161 Rome, Italy		Canettieri, G (corresponding author), Sapienza Univ Rome, Dept Mol Med, Viale Regina Elena 291, I-00161 Rome, Italy.; Canettieri, G (corresponding author), Sapienza Univ Rome, Ist Pasteur, Fdn Cenci Bolognetti, Viale Regina Elena 291, I-00161 Rome, Italy.; Canettieri, G (corresponding author), Int Polyamines Fdn ONLUS, Via Forte Tiburtino 98, I-00159 Rome, Italy.	gianluca.canettieri@uniroma1.it	petroni, marialaura/AAB-8637-2019; guerrieri, francesca/G-3908-2013; De Smaele, Enrico/C-1124-2013; Giannini, Giuseppe/B-5672-2013	petroni, marialaura/0000-0002-6021-1657; De Smaele, Enrico/0000-0003-4524-4423; DI MARCOTULLIO, LUCIA/0000-0003-0274-7178; Guerrieri, Francesca/0000-0002-2021-4394; Fatica, Alessandro/0000-0002-0743-7905; CANETTIERI, Gianluca/0000-0001-6694-2613; Giannini, Giuseppe/0000-0003-0299-4056; Infante, Paola/0000-0003-0682-3916	AIRCFondazione AIRC per la ricerca sul cancro [IG 17575, IG 20801]; Istituto Pasteur - Fondazione Cenci-BolognettiIstituto Pasteur Italia Fondazione Cenci Bolognetti; Italian MIUR (Ministero dell'Istruzione, dell'Universita e della Ricerca), Dipartimenti di Eccellenza [L.232/2016]; SAPIENZA University; International Polyamines Foundation-ONLUS-ETS; AFM-Telethon grant [21025]; Fondazione "Enrico ed Enrica Sovena"; Istituto Pasteur (Fondazione Cenci-Bolognetti)Istituto Pasteur Italia Fondazione Cenci Bolognetti	We are grateful to Dr Raghu Mimira (Indianapolis, USA) for sharing the Hypusine antibody, Drs Sergio Nasi and Barbara Illi (lBPM-CNR, Rome, Italy) for MYC Mouse plasmid, and Dr. Debora Salerno and Ms. Martina Schito for technical assistance. The studies reported herein were financially supported by the following grants: AIRC IG 17575, IG 20801; Istituto Pasteur - Fondazione Cenci-Bolognetti; Italian MIUR (Ministero dell'Istruzione, dell'Universita e della Ricerca), Dipartimenti di Eccellenza -L.232/2016; SAPIENZA University; "International Polyamines Foundation-ONLUS-ETS"; AFM-Telethon grant #21025; Fondazione "Enrico ed Enrica Sovena" (scholarship to Z.N.Y. for supporting her PhD); S.C., L. Di Magno, and S.M.S. were supported by fellowships from Istituto Pasteur (Fondazione Cenci-Bolognetti).	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DEC 10	2020	11	12							1045	10.1038/s41419-020-03174-6			14	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	PD3ZQ	WOS:000597627300001	33303756	Green Published, gold			2022-04-25	
J	Zhang, YX; Lv, CS; Dong, Y; Yang, QK				Zhang, Yixiang; Lv, Changsheng; Dong, Yan; Yang, Qingkai			Aspirin-targeted PD-L1 in lung cancer growth inhibition	THORACIC CANCER			English	Article						Aspirin; growth; lung cancer; PD-L1; TAZ	COLORECTAL-CANCER; ANTIPLATELET THERAPY; DIAGNOSIS; SURVIVAL; EXPRESSION; AUTOPHAGY; RISK	Background Aspirin is a classic anti-inflammatory drug and its anticancer effect has been previously explored in many types of cancer including colorectal cancer therapy. Programmed cell death-ligand 1 (PD-L1) is widely expressed in tumor cells and displays an inhibitory role in antitumor immunity. This study aimed to clarify the role of PD-L1 in aspirin-suppressed lung cancer. Methods The inhibitory effect of aspirin on lung cancer cell proliferation was assessed using an MTT cell viability assay. The role of aspirin in the modulation of PD-L1 expression was analyzed by western blot or RT-PCR assays. In lung cancer cells, the influence of aspirin on PD-L1 promoter activity was detected using a luciferase reporter assay. The interaction of TAZ with PD-L1 promoter in the cells, with or without aspirin administration, was tested via chromatin immunoprecipitation (ChIP) analysis. The function of PD-L1 in aspirin-mediated growth inhibition of lung cancer was examined using a cell viability assay. Results Following treatment with aspirin, lung cancer cell growth was markedly suppressed. Aspirin was able to markedly decrease the expression of PD-L1 at the mRNA and protein levels in lung cancer cells. For the mechanism study, we found that the promoter of PD-L1 was inactivated by aspirin via TAZ transcriptional coactivator in the cells. With regard to the functional investigation, aspirin was capable of resisting cell proliferation and PD-L1 overexpression abolished aspirin-depressed cell proliferation in lung cancer. Conclusions Aspirin suppressed the growth of lung cancer cells via targeting the TAZ/PD-L1 axis.	[Zhang, Yixiang; Lv, Changsheng] Dalian Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Dalian, Peoples R China; [Dong, Yan] Dalian Med Univ, Dept Oncol, Affiliated Hosp 1, Dalian 116000, Peoples R China; [Yang, Qingkai] Dalian Med Univ, Dept Canc Stem Cell, Dalian 116044, Peoples R China		Dong, Y (corresponding author), Dalian Med Univ, Dept Oncol, Affiliated Hosp 1, Dalian 116000, Peoples R China.; Yang, QK (corresponding author), Dalian Med Univ, Dept Canc Stem Cell, Dalian 116044, Peoples R China.	dongyan100@aliyun.com; dalianmed@163.com	Yang, Qingkai/D-1566-2011	Yang, Qingkai/0000-0001-6628-5393	Funding of natural science foundation of Liaoning province, china [20180550106] Funding Source: Medline		Benamouzig R, 2010, GUT, V59, P622, DOI 10.1136/gut.2008.175406; Cai GF, 2004, CELL IMMUNOL, V230, P89, DOI 10.1016/j.cellimm.2004.09.004; Cao DL, 2019, CANCER RES, V79, P2604, DOI 10.1158/0008-5472.CAN-18-3842; Chan AT, 2009, JAMA-J AM MED ASSOC, V302, P649, DOI 10.1001/jama.2009.1112; Choi BH, 2013, EXP MOL MED, V45, DOI 10.1038/emm.2013.91; Clark CA, 2016, CANCER RES, V76, P6964, DOI 10.1158/0008-5472.CAN-16-0258; Din FVN, 2012, GASTROENTEROLOGY, V142, P1504, DOI 10.1053/j.gastro.2012.02.050; Downer MK, 2017, EUR UROL, V72, P821, DOI 10.1016/j.eururo.2017.01.044; Feng J, 2017, ONCOGENE, V36, P5829, DOI 10.1038/onc.2017.188; Fujita Y, 2015, MOL THER, V23, P717, DOI 10.1038/mt.2015.10; Galipeau PC, 2007, PLOS MED, V4, P342, DOI 10.1371/jourmal.pmed.0040067; Hersey P, 2013, CLIN CANCER RES, V19, P514, DOI 10.1158/1078-0432.CCR-12-3312; Huo XF, 2018, GUT, V67, P606, DOI 10.1136/gutjnl-2016-313584; Li PW, 2015, GUT, V64, P1419, DOI 10.1136/gutjnl-2014-308260; Lim SO, 2016, CANCER CELL, V30, P925, DOI 10.1016/j.ccell.2016.10.010; Marshall SF, 2005, JNCI-J NATL CANCER I, V97, P805, DOI 10.1093/jnci/dji140; McCowan C, 2013, EUR J CANCER, V49, P1049, DOI 10.1016/j.ejca.2012.10.024; Pardoll DM, 2012, NAT REV CANCER, V12, P252, DOI 10.1038/nrc3239; Ritprajak P, 2015, ORAL ONCOL, V51, P221, DOI 10.1016/j.oraloncology.2014.11.014; Rothwell PM, 2012, LANCET, V379, P1591, DOI 10.1016/S0140-6736(12)60209-8; Sitia G, 2013, J HEPATOL, V59, P1135, DOI 10.1016/j.jhep.2013.05.040; Sitia G, 2012, P NATL ACAD SCI USA, V109, pE2165, DOI 10.1073/pnas.1209182109; Trabert B, 2014, JNCI-J NATL CANCER I, V106, DOI 10.1093/jnci/djt431; Wang SJ, 2018, ONCOGENE, V37, P4164, DOI 10.1038/s41388-018-0252-x	24	4	4	6	16	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1759-7706	1759-7714		THORAC CANCER	Thorac. Cancer	JUN	2020	11	6					1587	1593		10.1111/1759-7714.13433			7	Oncology; Respiratory System	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Respiratory System	LS9CP	WOS:000536676900025	32297484	Green Published, gold			2022-04-25	
J	Zhang, J; Shen, LM; Li, X; Song, WT; Liu, Y; Huang, L				Zhang, Jing; Shen, Limei; Li, Xiang; Song, Wantong; Liu, Yun; Huang, Leaf			Nanoformulated Codelivery of Quercetin and Alantolactone Promotes an Antitumor Response through Synergistic Immunogenic Cell Death for Microsatellite-Stable Colorectal Cancer	ACS NANO			English	Article						quercetin; alantolactone; immunogenic cell death; micelle; tumor microenvironment	GEMCITABINE MONOPHOSPHATE; POLYMERIC MICELLES; IMMUNOTHERAPY; NANOPARTICLES; CHEMOTHERAPY; APOPTOSIS; AUTOPHAGY; MECHANISMS; CISPLATIN; SYNTHASE	Microsatellite-stable colorectal cancer (CRC) is known to be resistant to immunotherapy. The combination of quercetin (Q) and alantolactone (A) was found to induce synergistic immunogenic cell death (ICD) at a molar ratio of 1:4 (Q:A). To achieve ratiometric loading and delivery, the micellar delivery of Q and A (QA-M) was developed with high entrapment efficiency and drug loading at an optimal ratio. QA-M achieved prolonged blood circulation and increased tumor accumulation for both drugs. More importantly, QA-M retained the desired drug ratio (molar ratio of Q to A = 1:4) in tumors at 2 and 4 h after intravenous injection for synergistic immunotherapy. Tumor growth was significantly inhibited in murine orthotopic CRC by the treatment of QA-M compared to PBS and the combination of free drugs (p < 0.005). The combination of nanotherapy stimulated the host immune response to induce long-term tumor destruction and induced memory tumor surveillance with a 1.3-fold increase in survival median time compared to PBS (p < 0.0001) and a combination of free drugs (p < 0.0005). The synergistic therapeutic effect induced by codelivery of Q and A is capable of reactivating antitumor immunity by inducing ICD, causing cell toxicity and modulating the immune-suppressive tumor microenvironment. Such a combination of Q and A with synergistic effects entrapped in a simple and safe nanodelivery system may provide the potential for scale-up manufacturing and clinical applications as immunotherapeutic agents for CRC.	[Zhang, Jing; Shen, Limei; Song, Wantong; Liu, Yun; Huang, Leaf] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27599 USA; [Zhang, Jing; Li, Xiang] Jiangxi Univ Tradit Chinese Med, Key Lab Modern Preparat TCM, Minist Educ, Nanchang 330004, Jiangxi, Peoples R China; [Song, Wantong] Chinese Acad Sci, Changchun Inst Appl Chem, Key Lab Polymer Ecomat, Changchun 130022, Jilin, Peoples R China		Huang, L (corresponding author), Univ N Carolina, Eshelman Sch Pharm, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27599 USA.	leafh@email.unc.edu	Li, Xiang/R-9392-2019; Li, Xiang/ABC-6376-2020	Li, Xiang/0000-0003-1526-6103; Liu, Yun/0000-0002-6763-496X; Huang, Leaf/0000-0002-9421-8283	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA198999]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81560575, 81760639, 81603054]; Jiangxi Province Outstanding Young Talents Program [20162BCB23034, 20171BCB23097]; Young Jinggang Scholar of Jiangxi Province [[2018]82, [2018]42]; "1050" Talents Program [[2018]82, [2018]42]; Jiangxi BaiQianWan Talents Program [2017082]; Natural Science Fund of Jiangxi Province [20171BAB215066, 20171ACB21074]; Fund for FirstRate Discipline of Chinese Materia Medica [JXSYLXKZHYA0055, JXSYLXK-ZHYA0056, JXSYLXK-ZHYA0019]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2016M602084]	The work was supported by NIH grant CA198999 (LB.), the National Natural Science Foundation of China (Nos. 81560575, 81760639, 81603054), the Jiangxi Province Outstanding Young Talents Program (20162BCB23034, 20171BCB23097), Young Jinggang Scholar of Jiangxi Province and "1050" Talents Program ([2018]82 and [2018]42, Jing Zhang), Jiangxi BaiQianWan Talents Program (2017082, Xiang Li), the Natural Science Fund of Jiangxi Province (20171BAB215066, 20171ACB21074), the Fund for FirstRate Discipline of Chinese Materia Medica (JXSYLXKZHYA0055, JXSYLXK-ZHYA0056, JXSYLXK-ZHYA0019), and a project funded by the China Postdoctoral Science Foundation (2016M602084).	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Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Science & Technology - Other Topics; Materials Science	JS9WN	WOS:000500650000027	31664821				2022-04-25	
J	Choroba, K; Machura, B; Raposo, LR; Malecki, JG; Kula, S; Pajak, M; Erfurt, K; Maroh, AM; Fernandes, AR				Choroba, Katarzyna; Machura, Barbara; Raposo, Luis R.; Malecki, Jan G.; Kula, Slawomir; Pajak, Michal; Erfurt, Karol; Maroh, Anna M.; Fernandes, Alexandra R.			Platinum(ii) complexes showing high cytotoxicity toward A2780 ovarian carcinoma cells	DALTON TRANSACTIONS			English	Article							PREFERRED HORIZONTAL DISPLACEMENTS; AROMATIC-AROMATIC INTERACTIONS; ANTICANCER ACTIVITY; METAL-COMPLEXES; DNA-BINDING; METALLOINTERCALATION REAGENTS; RUTHENIUM(II) COMPLEXES; LUMINESCENCE PROPERTIES; BIOLOGICAL EVALUATION; COPPER(II) COMPLEXES	2,6-Bis(thiazol-2-yl)pyridines functionalized with 9-anthryl (L-1), 9-phenanthryl (L-2), and 1-pyrenyl (L-3) groups were used for the preparation of [Pt(L-n)Cl]CF3SO3 (1-3). The constitution of the Pt(ii) complexes was determined by H-1 and C-13 NMR spectroscopy, HR-MS spectrometry, elemental analysis and X-ray analysis (for (1)). The electrochemical and photophysical properties of [Pt(L-n)Cl]CF3SO3 were compared with the behaviour of the Pt(ii) complexes with aryl-substituted 2,2 ':6 ',2 ''-terpyridine ligands. What is noteworthy is that the coordination ability of dtpy toward the Pt(ii) centre was investigated for the first time. All complexes were tested in vitro by MTS assay on four tumor cell lines, A2780 (ovarian carcinoma), HTC116 (colon rectal carcinoma), MCF7 (breast adenocarcinoma), and PC3 (prostate carcinoma) and on normal primary fibroblasts. Compounds (1-3) showed a dose dependent antiproliferative effect in the A2780 cell line with (3) > (2) > (1) and this loss of A2780 cell viability was due to a combination of an apoptotic cell death mechanism via mitochondria and autophagic cell death. Exposure to IC50 concentration of (2) induced an increase in the number of apoptotic nuclei and a depolarization of the mitochondrial membrane which is consistent with the induction of apoptosis while exposure to IC50 concentration of (3) showed an increase in the apoptotic nuclei with a slight hyperpolarization of the mitochondrial membrane that might indicate an initial step of apoptosis induction. The complexes (2) and (3) induce an increase in the production of intracellular ROS which is associated with the trigger of the apoptotic pathways. The ROS production was augmented by the presence of oxidants and correlated with an increase of oxygen radicals. The IC50 of (2) and (3) (4.4 mu M and 2.9 mu M, respectively) was similar to the IC50 of cisplatin (3.4 mu M) in the A2780 cell line, which together with their low cytotoxicity in normal fibroblasts, demonstrates their potential for further studies.	[Choroba, Katarzyna; Machura, Barbara; Malecki, Jan G.; Kula, Slawomir; Pajak, Michal; Maroh, Anna M.] Univ Silesia, Inst Chem, Szkolna 9, PL-10006 Katowice, Poland; [Raposo, Luis R.; Fernandes, Alexandra R.] Univ Nova Lisboa, UCIBIO, Dept Ciencias Vida, Fac Ciencias & Tecnol, Campus Caparica, P-2829516 Caparica, Portugal; [Erfurt, Karol] Silesian Tech Univ, Dept Chem Organ Technol & Petrochem, Krzywoustego 4, PL-44100 Gliwice, Poland		Maroh, AM (corresponding author), Univ Silesia, Inst Chem, Szkolna 9, PL-10006 Katowice, Poland.; Fernandes, AR (corresponding author), Univ Nova Lisboa, UCIBIO, Dept Ciencias Vida, Fac Ciencias & Tecnol, Campus Caparica, P-2829516 Caparica, Portugal.	anna.maron@us.edu.pl; ma.fernandes@fct.unl.pt	Raposo, Luís/AAX-1610-2021; Raposo, Luís R/T-3754-2017; Fernandes, Alexandra R/C-7465-2011; Malecki, Jan Grzegorz/M-4022-2017	Raposo, Luís/0000-0002-8637-346X; Raposo, Luís R/0000-0002-8637-346X; Fernandes, Alexandra R/0000-0003-2054-4438; Choroba, Katarzyna/0000-0003-0168-5753; Machura, Barbara/0000-0001-7688-6491; Kula, Slawomir/0000-0003-4520-1570; Maron, Anna Maria/0000-0001-8245-5532; Malecki, Jan Grzegorz/0000-0001-5571-3196	National Science Centre of Poland under grant MINIATURA 1 [2017/01/X/ST5/00026]; Applied Molecular Biosciences Unit-UCIBIO - FCT/MCTES [UID/Multi/04378/2019];  [PTDC/CVT/EPI/6685/2014]	This work was supported by the National Science Centre of Poland under grant MINIATURA 1 (2017/01/X/ST5/00026) and the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019). LR acknowledges project PTDC/CVT/EPI/6685/2014.	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SEP 14	2019	48	34					13081	13093		10.1039/c9dt02894c			13	Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	IU4YS	WOS:000483593600029	31411239				2022-04-25	
J	Liu, WT; Lo, YL; Hsu, C; Wu, YT; Liao, ZX; Wu, WJ; Chen, YJ; Kao, C; Chiu, CC; Wang, LF				Liu, Wangta; Lo, Yu-Lun; Hsu, Chin; Wu, Yi-Ting; Liao, Zi-Xian; Wu, Wen-Jeng; Chen, Yi-Jou; Kao, Chieh; Chiu, Chien-Chih; Wang, Li-Fang			CS-PEI/Beclin-siRNA Downregulate Multidrug Resistance Proteins and Increase Paclitaxel Therapeutic Efficacy against NSCLC	MOLECULAR THERAPY-NUCLEIC ACIDS			English	Article							CELL LUNG-CANCER; BREAST-CANCER; CO-DELIVERY; DRUG-RESISTANCE; CHONDROITIN SULFATE; COLORECTAL-CANCER; DNA-DAMAGE; AUTOPHAGY; INHIBITION; NANOPARTICLES	Paclitaxel (PTX) is a widely used chemotherapy drug; however, frequent use causes multidrug resistance (MDR), which limits the utility of PTX against advanced non-small-cell lung cancer (NSCLC). PTX-resistant subline (NCI-H23-TXR) was established in vitro by exposing NCI-H23 cells to gradually increased concentrations of PTX in culture medium. Distinct Beclin expression of autophagy level was observed between resistant NCI-H23-TXR and parental NCI-H23 cells. Beclin-small interfering RNA (siRNA) was selected to restore sensitivity of PTX against NCI-H23-TXR. Chondroitin sulfate-polyethylenimine (CS-PEI) was constructed for delivery and protection of Beclin-siRNA. To delineate the underlying molecular mechanism of Beclin knockdown, we analyzed different MDR expression proteins of two cells using western blot, and the corresponding genes were confirmed by real-time PCR. Compared with NCI-H23, NCI-H23-TXR had higher expression levels in P-glycoprotein (P-gp) and multidrug resistance protein 7 (ABCC10). Knockdown of Beclin simultaneously inhibited P-gp and ABCC10, and renewed the sensitivity of PTX against NCI-H23-TXR. Research on zebrafish embryos revealed that tumor sizes decreased in NCI-H23 tumor xenografts but remained intact in NCI-H23-TXR tumor xenografts as zebrafish were treated with 1 mu g/mL PTX. In contrast, the tumor sizes decreased in NCI-H23-TXR tumor xenografts with zebrafish pre-transfected with CS-PEI/Beclin-siRNA followed by the same treatment of PTX. The role of autophagy was associated with MDR development. This study paves the way for a new avenue of PTX in MDR-related lung cancer therapy using CS-PEI as a gene delivery carrier.	[Liu, Wangta; Chiu, Chien-Chih] Kaohsiung Med Univ, Coll Life Sci, Dept Biotechnol, 100,Shih Chuan 1st Rd, Kaohsiung 807, Taiwan; [Lo, Yu-Lun; Wu, Yi-Ting; Wang, Li-Fang] Kaohsiung Med Univ, Coll Life Sci, Dept Med & Appl Chem, 100,Shih Chuan 1st Rd, Kaohsiung 807, Taiwan; [Lo, Yu-Lun; Hsu, Chin] Kaohsiung Med Univ, Coll Med, Fac Med, Dept Physiol, Kaohsiung 807, Taiwan; [Hsu, Chin; Wu, Wen-Jeng; Chiu, Chien-Chih; Wang, Li-Fang] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung 807, Taiwan; [Liao, Zi-Xian; Wang, Li-Fang] Natl Sun Yat Sen Univ, Inst Med Sci & Technol, Kaohsiung 804, Taiwan; [Wu, Wen-Jeng] Kaohsiung Med Univ, Coll Med, Sch Med, Dept Urol, Kaohsiung 807, Taiwan; [Chen, Yi-Jou] Chang Guan Univ, Sch Med, Taoyuan 33302, Taiwan; [Kao, Chieh] I Shou Univ, Sch Med Int Students, Kaohsiung 82445, Taiwan		Chiu, CC (corresponding author), Kaohsiung Med Univ, Coll Life Sci, Dept Biotechnol, 100,Shih Chuan 1st Rd, Kaohsiung 807, Taiwan.; Wang, LF (corresponding author), Kaohsiung Med Univ, Coll Life Sci, Dept Med & Appl Chem, 100,Shih Chuan 1st Rd, Kaohsiung 807, Taiwan.	cchiu@kmu.edu.tw; lfwang@kmu.edu.tw		Lo, Yu-Lun/0000-0002-6384-3051	Ministry of Science and Technology of TaiwanMinistry of Science and Technology, Taiwan [MOST104-2314-B-037-006-MY3, MOST 106-2320-B-037-004-MY3]; Kaohsiung Medical University [KMU-DK108013]; NSYSU-KMU Joint Research Project [NSYSUKMU 107-P026]	We are grateful for the financial support from the Ministry of Science and Technology of Taiwan (grants MOST104-2314-B-037-006-MY3 and MOST 106-2320-B-037-004-MY3). This study was also supported by Kaohsiung Medical University under grant KMU-DK108013 and by the NSYSU-KMU Joint Research Project under grant NSYSUKMU 107-P026. NCI-H23 and NCI-H23-TXR cell lines were gifted from Dr. N.Y. Shih of the NHRI of Taiwan. We appreciate the experimental support of a CLSM and a TEM provided by the Center for Research Resources and Development of Kaohsiung Medical University.	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Ther.-Nucl. Acids	SEP 6	2019	17						477	490		10.1016/j.omtn.2019.06.017			14	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	JA6XF	WOS:000487984400043	31336235	gold, Green Published			2022-04-25	
J	Chen, ZH; Wang, C; Dong, H; Wang, X; Gao, F; Zhang, S; Zhang, XL				Chen, Zhihang; Wang, Chun; Dong, Hao; Wang, Xing; Gao, Feng; Zhang, Sen; Zhang, Xiaolong			Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway	MOLECULAR MEDICINE			English	Article						Colorectal cancer; Aspirin; PI3K; Akt; raptor pathway; PIK3CA mutated	A-INDUCED APOPTOSIS; PRIMARY PREVENTION; MTOR; MUTATIONS; PHOSPHORYLATION; AUTOPHAGY; DISEASE; GENE; LC3	Background Aspirin, as a non-steroidal anti-inflammatory drug, can improve the survival rate of patients with colorectal cancer, while aspirin is effective in patients with PIK3CA mutant colorectal cancer (CRC). However, the mechanism of aspirin in the treatment of PIK3CA mutated CRC patients remains unclear. Methods In this study, immunohistochemistry was used to detect the expression levels of PI3K and Raptor in colorectal cancer patients with PIK3CA mutation and PIK3CA wild-type patients. To demonstrate that aspirin has a better effect on the CRC of PIK3CA mutations in association with the PI3K/Akt/Raptor pathway, we used aspirin to treat PIK3CA mutant CRC cells (HCT-116 and RKO). Subsequently, the CCK8 assay and flow cytometry assay were used to detect the apoptosis of PIK3CA mutant CRC cells before and after aspirin use. Western blot was used to detect the changes of PI3K/Akt/Raptor-associated protein, autophagy protein microtubule associated protein 1 light chain 3 alpha (MAP1LC3A, LC3), beclin 1 (BECN1) and apoptosis protein BCL2-associated X protein/ BCL2 apoptosis regulator (Bax/Bcl2), Caspase 3 after treatment of CRC cells with PIK3CA mutation by aspirin. Results Phosphoinositide-3-kinase (PI3K) and regulatory associated protein of MTOR complex 1 (Raptor) protein expression levels were higher in PIK3CA-mutant patients than in IK3CA wild-type patients. The expression of Bax/Bcl2 increased after treatment indicates that aspirin can induce apoptosis of PIK3CA-mutant CRC cells. The expression level of MAP1LC3 (LC3) in cells increases with the concentration of aspirin demonstrates that aspirin can induce autophagy in CRC cells. After 48 h of treatment with aspirin, the phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase B1 (S6K1) was reduced, cell proliferation has been inhibited. After treatment with aspirin, as phosphorylation of PI3K and Protein kinase B (PKB, Akt) was decreased, Raptor expression was also decreased. Conclusion Aspirin can regulate the proliferation, apoptosis and autophagy of CRC cells through the PI3K/Akt/Raptor pathway, affecting PIK3CA-mutant CRC.	[Chen, Zhihang; Dong, Hao; Wang, Xing; Gao, Feng; Zhang, Sen; Zhang, Xiaolong] Guangxi Med Univ, Affiliated Hosp 1, Dept Colorectal & Anal Surg, Nanning 530021, Peoples R China; [Wang, Chun] Wuhan Univ, Dept Gastroenterol, Zhongnan Hosp, Wuhan 430000, Peoples R China		Zhang, XL (corresponding author), Guangxi Med Univ, Affiliated Hosp 1, Dept Colorectal & Anal Surg, Nanning 530021, Peoples R China.	1368913114@qq.com			Guangxi Natural Science Foundation ProgramNational Natural Science Foundation of Guangxi Province [2015GXNSFAA139185]	This work has been financially supported by Guangxi Natural Science Foundation Program (2015GXNSFAA139185).	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Med.	JAN 30	2020	26	1							14	10.1186/s10020-020-0139-5			13	Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine	KU9WD	WOS:000520074100001	32000660	gold, Green Published			2022-04-25	
J	Gibault, F; Corvaisier, M; Bailly, F; Huet, G; Melnyk, P; Cotelle, P				Gibault, Floriane; Corvaisier, Matthieu; Bailly, Fabrice; Huet, Guillemette; Melnyk, Patricia; Cotelle, Philippe			Non-Photoinduced Biological Properties of Verteporfin	CURRENT MEDICINAL CHEMISTRY			English	Article						Hippo pathway; YAP/TEAD complex; non-photoinduced therapy; oncogene; autophagy; proteotoxicity	PROTEIN-PROTEIN INTERACTION; HIPPO SIGNALING PATHWAY; YAP-TEAD; PHOTOSENSITIZER VERTEPORFIN; THERAPEUTIC TARGET; CELL-PROLIFERATION; ANTITUMOR-ACTIVITY; CANCER-CELLS; ACTIVATION; IDENTIFICATION	Background: Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last few years, YAP (TAZ), the downstream effectors of the Hippo pathway, have emerged as promising anticancer targets, as shown by several experimental lines of evidence, showing the overproduction of YAP in several cancers. However, YAP was also found to be closely connected to autophagy, mitochondria and reactive oxygen/nitrogen species. We herein, review the recent studies where VP was used without photoactivation as a YAP/TEAD inhibitor or protein oligomerization promoter, focusing on its effects on the YAP/TEAD gene targets and other biomarkers related to autophagy. Results: Since the identification of VP as YAP/TEAD inhibitor, several in vitro and in vivo studies have revealed the new potential of this molecule in different cancers, where YAP is overexpressed. However, detailed structural information about its interaction with YAP is still lacking. Concomitantly, VP was identified as autophagosome inhibitor by promoting oligomerization of p62. Moreover, VP proves to be tumor-selective proteotoxic (by oligomerization of p62, STAT3) in colorectal cancer. Knowledge on the biological properties of the only YAP inhibitor available to date is vital for its pharmacological use on cellular and animal models. Conclusion: VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.	[Gibault, Floriane; Bailly, Fabrice; Melnyk, Patricia; Cotelle, Philippe] Univ Lille, INSERM, Jean Pierre Aubert Res Ctr, Onco & NeuroChem Team,UMR S 1172, F-59000 Lille, France; [Corvaisier, Matthieu; Huet, Guillemette] Univ Lille, INSERM, Mucins Epithelial Differenciat & Carcinogenesis, Jean Pierre Aubert Res Ctr,UMR S 1172, F-59000 Lille, France		Cotelle, P (corresponding author), Fac Sci Pharmaceut & Biol, 3 Rue Prof Laguesse,BP 83, F-59006 Lille, France.	phi-lippe.cotelle@inserm.fr	Cotelle, Philippe/AAX-3905-2020	bailly, fabrice/0000-0001-9681-9309			AVELINE BM, 1995, J PHOTOCH PHOTOBIO B, V30, P161, DOI 10.1016/1011-1344(95)07174-Z; Barry ER, 2013, NATURE, V493, P106, DOI 10.1038/nature11693; Basu D, 2014, MOL CANCER THER, V13, P1457, DOI 10.1158/1535-7163.MCT-13-0918; Belzacq AS, 2001, CANCER RES, V61, P1260; Benham-Pyle BW, 2015, SCIENCE, V348, P1024, DOI 10.1126/science.aaa4559; Brodowska K, 2014, EXP EYE RES, V124, P67, DOI 10.1016/j.exer.2014.04.011; Cebola I, 2015, NAT CELL BIOL, V17, P615, DOI 10.1038/ncb3160; Chen WS, 2015, BIOCHEM BIOPH RES CO, V466, P221, DOI 10.1016/j.bbrc.2015.09.012; Chiou JF, 2010, FREE RADICAL RES, V44, P155, DOI 10.3109/10715760903380458; Ciamporcero E, 2016, ONCOGENE, V35, P1541, DOI 10.1038/onc.2015.219; Donohue E, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0114964; Donohue E, 2013, J CANCER, V4, P585, DOI 10.7150/jca.7030; Donohue E, 2011, J BIOL CHEM, V286, P7290, DOI 10.1074/jbc.M110.139915; Feng XD, 2014, CANCER CELL, V25, P831, DOI 10.1016/j.ccr.2014.04.016; Fernandez JM, 1997, J PHOTOCH PHOTOBIO B, V37, P131, DOI 10.1016/S1011-1344(96)07349-6; Gaffney CJ, 2012, GENE, V509, P215, DOI 10.1016/j.gene.2012.08.025; Garcia-Rendueles MER, 2015, CANCER DISCOV, V5, P1178, DOI 10.1158/2159-8290.CD-15-0330; Harvey KF, 2013, NAT REV CANCER, V13, P246, DOI 10.1038/nrc3458; Hau JC, 2013, CHEMBIOCHEM, V14, P1218, DOI 10.1002/cbic.201300163; Huggett MT, 2014, BRIT J CANCER, V110, P1698, DOI 10.1038/bjc.2014.95; Imajo M, 2015, NAT CELL BIOL, V17, P7, DOI 10.1038/ncb3084; Jiang N, 2015, ONCOGENE, V34, P2764, DOI 10.1038/onc.2014.206; Jiao S, 2014, CANCER CELL, V25, P166, DOI 10.1016/j.ccr.2014.01.010; Johnson R, 2014, NAT REV DRUG DISCOV, V13, P63, DOI 10.1038/nrd4161; KEENE JP, 1986, PHOTOCHEM PHOTOBIOL, V43, P117, DOI 10.1111/j.1751-1097.1986.tb09501.x; Kimura TE, 2016, J MOL CELL CARDIOL, V90, P1, DOI 10.1016/j.yjmcc.2015.11.024; Kong DL, 2015, J DRUG TARGET, V23, P125, DOI 10.3109/1061186X.2014.983522; Lai D, 2011, CANCER RES, V71, P2728, DOI 10.1158/0008-5472.CAN-10-2711; Lamar JM, 2012, P NATL ACAD SCI USA, V109, pE2441, DOI 10.1073/pnas.1212021109; Liang N, 2014, J EXP MED, V211, P2249, DOI 10.1084/jem.20140341; Liu-Chittenden Y, 2012, GENE DEV, V26, P1300, DOI 10.1101/gad.192856.112; Ma YL, 2015, INT J CANCER, V137, P2275, DOI 10.1002/ijc.29073; Mannaerts I, 2015, J HEPATOL, V63, P679, DOI 10.1016/j.jhep.2015.04.011; Mellish K. 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Med. Chem.		2016	23	11					1171	1184		10.2174/0929867323666160316125048			14	Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	DJ8YZ	WOS:000374501900006	26980565				2022-04-25	
J	Cadena-Cruz, JE; Guaman-Ortiz, LM; Romero-Benavides, JC; Bailon-Moscoso, N; Murillo-Sotomayor, KE; Ortiz-Guaman, NV; Heredia-Moya, J				Cadena-Cruz, Jose Eduardo; Guaman-Ortiz, Luis M.; Romero-Benavides, Juan Carlos; Bailon-Moscoso, Natalia; Murillo-Sotomayor, Kevin E.; Ortiz-Guaman, Nadia V.; Heredia-Moya, Jorge			Synthesis of 4,4 '-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities	BMC CHEMISTRY			English	Article						4; 4MODIFIER LETTER PRIME-(arylmethylene)bis(1H-pyrazol-5-ols); Antioxidant; Apoptosis; Autophagy	SOLID ACID CATALYST; EFFICIENT; DERIVATIVES; APOPTOSIS; EDARAVONE; REGULATORS; AUTOPHAGY; PYRAZOLE; DFT	Background Pyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer. Results 4,4MODIFIER LETTER PRIME-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4MODIFIER LETTER PRIME-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized in high to excellent yield, and pure products were isolated by simple filtration. All compounds have good radical scavenging activity, and half of them are more active than ascorbic acid used as standard. Conclusion Several derivatives proved to be cytotoxic in the RKO cell line. In particular, compound 3i proved to be a very potent scavenger with an IC50 of 6.2 +/- 0.6 mu M and exhibited an IC50 of 9.9 +/- 1.1 mu M against RKO cell. Autophagy proteins were activated as a survival mechanism, whereas the predominant pathway of death was p53-mediated apoptosis.	[Cadena-Cruz, Jose Eduardo] Univ Cent Ecuador, Fac Ciencias Quim, Quito, Ecuador; [Guaman-Ortiz, Luis M.; Bailon-Moscoso, Natalia; Murillo-Sotomayor, Kevin E.; Ortiz-Guaman, Nadia V.] Univ Tecn Particular Loja, Dept Ciencias Salud, San Cayetano Alto S-N, Loja 1101608, Ecuador; [Romero-Benavides, Juan Carlos] Univ Tecn Particular Loja, Dept Quim & Ciencias Exactas, San Cayetano Alto S-N, Loja 1101608, Ecuador; [Heredia-Moya, Jorge] Univ UTE, Fac Ciencias Salud Eugenio Espejo, Ctr Invest Biomed CENBIO, Quito 170527, Ecuador		Heredia-Moya, J (corresponding author), Univ UTE, Fac Ciencias Salud Eugenio Espejo, Ctr Invest Biomed CENBIO, Quito 170527, Ecuador.	jorgeh.heredia@ute.edu.ec	; Romero Benavides, Juan Carlos/Q-9855-2018	Heredia-Moya, Jorge/0000-0001-7620-9140; Cadena Cruz, Jose Eduardo/0000-0001-9023-7674; Romero Benavides, Juan Carlos/0000-0003-1660-1217	Corporacion Ecuatoriana para el Desarrollo de la Investigacion y la Academia (CEDIA) [CEPRA XI-2017-10]; Universidad Tecnica Particular de Loja (UTPL) [PROY_INV_QUI_2017_2222]; Universidad UTE; Universidad Central del Ecuador	This work was supported by Corporacion Ecuatoriana para el Desarrollo de la Investigacion y la Academia (CEDIA), (CEPRA XI-2017-10), Universidad Tecnica Particular de Loja (UTPL), (PROY_INV_QUI_2017_2222), Universidad UTE, and Universidad Central del Ecuador.	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JUN 3	2021	15	1							38	10.1186/s13065-021-00765-y			12	Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	SM6XY	WOS:000657746900001	34082794	Green Published, gold			2022-04-25	
J	Maiese, K				Maiese, Kenneth			WISP1: Clinical Insights for a Proliferative and Restorative Member of the CCN Family	CURRENT NEUROVASCULAR RESEARCH			English	Article						Akt; Alzheimer's; amyloid; apoptosis; autophagy; beta-catenin; bone; cancer; cardiac; caspase; CCN4; erythropoietin; fibrosis; forkhead transcription factor; FoxO3a; liver; lung; metastases; miRNA; mTOR; PRAS40; pulmonary; sirtuin; SIRT1; stem cell; WISP1; Wnt	WNT1-INDUCIBLE SIGNALING PROTEIN-1; WNT/BETA-CATENIN PATHWAY; FOCAL CEREBRAL-ISCHEMIA; HUMAN COLORECTAL-CANCER; TISSUE GROWTH-FACTOR; BETA-CATENIN; OXIDATIVE STRESS; CELL-SURVIVAL; WNT PATHWAY; STEM-CELLS	As a proliferative and restorative entity, Wnt1 inducible signaling pathway protein 1 (WISP1) is emerging as a novel target for a number of therapeutic strategies that are relevant for disorders such as traumatic injury, neurodegeneration, musculoskeletal disorders, cardiovascular disease, pulmonary compromise, and control of tumor growth as well as distant metastases. WISP1, a target of the wingless pathway Wnt1, oversees cellular mechanisms that include apoptosis, autophagy, cellular migration, stem cell proliferation, angiogenesis, immune cell modulation, and tumorigenesis. The signal transduction pathways of WISP1 are broad and involve phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), mitogen activated protein (MAP) kinase, c-Jun N-terminal kinase (JNK), caspases, forkhead transcription factors, sirtuins, c-myc, glycogen synthase kinase -3 beta (GSK-3 beta), beta-catenin, miRNAs, and the mechanistic target of rapamaycin (mTOR). Ultimately, these signal transduction pathways of WISP1 can result in varied and sometimes unpredictable outcomes especially for cell survival, tissue repair, and tumorigenesis that demand increased insight into the critical role WISP1 holds for cellular biology and clinical medicine.				wntin75@yahoo.com			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; 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, Janssen Neuroscience Award, LEARN Foundation Award, NIH NIEHS, NIH NIA, NIH NINDS, and NIH ARRA.	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Neurovasc. Res.		2014	11	4					378	389		10.2174/1567202611666140912115107			12	Clinical Neurology; Neurosciences	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology	AS2DM	WOS:000344089700011	25219658	Green Accepted			2022-04-25	
J	Huang, LN; Wang, WN; Hu, ZT; Guan, CH; Li, WZ; Jiang, XM				Huang, Lining; Wang, Weina; Hu, Zengtao; Guan, Canghai; Li, Wenzhi; Jiang, Xingming			Hypoxia and lncRNAs in gastrointestinal cancers	PATHOLOGY RESEARCH AND PRACTICE			English	Review						Hypoxia; LncRNA; Gastrointestinal cancer; Regulation; Functions	COMPETING ENDOGENOUS RNA; GASTRIC-CANCER; COLORECTAL-CANCER; NONCODING RNAS; MESSENGER-RNAS; TUMOR; METASTASIS; CELLS; CONTRIBUTES; AUTOPHAGY	Objectives: Hypoxia is a hallmark of the tumor microenvironment, and hypoxia regions are frequently found in gastrointestinal cancers, which are associated with worse patients' survival and therapy resistance. However, the potential mechanisms of hypoxic tumor microenvironment still need to be further elucidated, especially about the roles of long non-coding RNAs (lncRNAs) in hypoxic tumor regions. In recent years, a great mount of independent research showed that many lncRNAs were modulated by hypoxia, and these lncRNAs were named as "hypoxia-regulated lncRNAs". In this review, the recent developments in the expression, regulation and functions of hypoxia-regulated lncRNAs in gastrointestinal cancers were summarized. Materials and methods: In this review, we summarized and figured out recent studies concerning the expression and biological mechanisms of hypoxia-regulated lncRNAs in gastrointestinal cancers. The related studies were obtained through a systematic search of PubMed, Embase and Cochrane Library. Results: Hypoxia-regulated lncRNAs have various roles in the regulation of metabolism, autophagy, invasion and metastasis in the hypoxic microenvironment. More importantly, hypoxic-regulated lncRNAs have a variety of potential mechanisms in gastrointestinal tumors, including epigenetic, lncRNA-miRNA interaction, lncRNA-protein interactions. Conclusions: Hypoxia-regulated lncRNAs will undoubtedly be developed as targets and promote the progress in ideal therapies for gastrointestinal cancer patients.	[Huang, Lining; Hu, Zengtao; Guan, Canghai; Jiang, Xingming] Harbin Med Univ, Affiliated Hosp 2, Dept HPB Surg, 246 Xuefu Ro, Harbin 150086, Peoples R China; [Wang, Weina; Li, Wenzhi] Harbin Med Univ, Affiliated Hosp 2, Dept Anesthesiol, 246 Xuefu Ro, Harbin 150086, Peoples R China		Jiang, XM (corresponding author), Harbin Med Univ, Affiliated Hosp 2, Dept HPB Surg, 246 Xuefu Ro, Harbin 150086, Peoples R China.; Li, WZ (corresponding author), Harbin Med Univ, Affiliated Hosp 2, Dept Anesthesiol, 246 Xuefu Ro, Harbin 150086, Peoples R China.	liwz2nd@163.com; jiangxingming@hrbmu.edu.cn	Jiang, Xingming/ABA-1971-2021		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81602088]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2017M621305]; Heilongjiang Postdoctoral Science Foundation [LBH-Z16096]; Health and Family Planning Commission Research Project of Heilongjiang Province [2016-049]; HMU College Students' Innovation and Entrepreneurship Training Program [201810226105]; Innovative Science Foundation of Harbin Medical University [2016LCZX09]	This work was supported by grants from National Natural Science Foundation of China [grant numbers 81602088], China Postdoctoral Science Foundation [grant numbers 2017M621305], Heilongjiang Postdoctoral Science Foundation [grant numbers LBH-Z16096], Health and Family Planning Commission Research Project of Heilongjiang Province [grant numbers 2016-049], HMU College Students' Innovation and Entrepreneurship Training Program [grant numbers 201810226105] and Innovative Science Foundation of Harbin Medical University [grant numbers 2016LCZX09].	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Res. Pract.		2019	215	12							152687	10.1016/j.prp.2019.152687			6	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	KK1BP	WOS:000512485400003	31640897				2022-04-25	
J	Bathula, C; Roma-Rodrigues, C; Chauhan, J; Fernandes, AR; Sen, S				Bathula, Chandramohan; Roma-Rodrigues, Catarina; Chauhan, Jyoti; Fernandes, Alexandra R.; Sen, Subhabrata			Synthesis of tetrahydro-1H-indolo[2,3-b]-pyrrolo[3,2-c] quinolones via intramolecular oxidative ring rearrangement of tetrahydro-beta-bcarbolines and their biological evaluation	NEW JOURNAL OF CHEMISTRY			English	Article							OXINDOLE ALKALOIDS; COBALT COMPLEXES; IN-VIVO; APOPTOSIS; CANCER; CHLORINATION; COMMUNESINS; CYCLIZATION; NOMOFUNGIN; LIGANDS	A simple oxidative ring rearrangement of diversely substituted 1-(2-amminoaryl)-tetrahydro-b-carbolines has been developed to generate architecturally interesting tetrahydro-1H-indolo[2,3-b]pyrrolo[3,2-c] quinolones. This unique transformation involves four reaction centers (aniline, C1-carboline and C-2/C-3 of indole) and utilizes tert-butylhypochlorite as the reagent. The generic nature of the reaction was demonstrated by the synthesis of a wide variety of analogs 9a-j. A putative reaction mechanism was proposed. Cytotoxicity screening of these compounds against three human cancer cells (A2780 ovarian and HCT116 colorectal carcinoma cell lines and A549 lung adenocarcinoma cell line) revealed selective inhibition of proliferation of the A2780 human ovarian carcinoma cell line by one of the molecules 9a with an IC50 of 14 mu M. No cytotoxic activity was observed in human normal fibroblasts for concentrations up to 100 mM. Compound 9a induced hyperpolarization of the mitochondrial membrane potential of the A2780 cell line leading to an increase of reactive oxygen species (ROS) that trigger cell death via apoptosis. Interestingly, compound 9a was also able to induce cell death via autophagy. Compounds that induce apoptosis and autophagy, thus leading to cancer cells' death, are good candidates for cancer therapy.	[Bathula, Chandramohan; Chauhan, Jyoti; Sen, Subhabrata] Shiv Nadar Univ, Sch Nat Sci, Dept Chem, Gautambudh Nagar 201314, Uttar Pradesh, India; [Roma-Rodrigues, Catarina; Fernandes, Alexandra R.] Univ Nova Lisboa, Dept Ciencias Vida, UCIBIO, Fac Ciencias & Tecnol, Caparica, Portugal		Sen, S (corresponding author), Shiv Nadar Univ, Sch Nat Sci, Dept Chem, Gautambudh Nagar 201314, Uttar Pradesh, India.; Fernandes, AR (corresponding author), Univ Nova Lisboa, Dept Ciencias Vida, UCIBIO, Fac Ciencias & Tecnol, Caparica, Portugal.	ma.fernandes@fct.unl.pt; subhabrata.sen@snu.edu.in	chauhan, jyoti/O-5069-2017; Roma-Rodrigues, Catarina/S-6144-2016; Roma-Rodrigues, Catarina/AAT-5658-2021; Fernandes, Alexandra R/C-7465-2011	Roma-Rodrigues, Catarina/0000-0002-8676-6562; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Fernandes, Alexandra R/0000-0003-2054-4438; Sen, Subhabrata/0000-0002-4608-5498	Shiv Nadar University; national funds from FCT/MEC [UID/Multi/04378/2013]; ERDF under the PT Partnership Agreement [POCI-01-0145-FEDER-007728]	This work was supported by Shiv Nadar University and The Unidade de Ciencias Biomoleculares Aplicadas - UCIBIO which is financed by national funds from FCT/MEC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728).	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J	Tu, CE; Hu, Y; Zhou, PR; Guo, XX; Gu, CC; Zhang, YL; Li, AM; Liu, SD				Tu, Cheng-e; Hu, Ying; Zhou, Peirong; Guo, Xuxue; Gu, Chuncai; Zhang, Yali; Li, Aimin; Liu, Side			Lactate and TGF-beta antagonistically regulate inflammasome activation in the tumor microenvironment	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						autophagy; inflammasome; lactate; reactive oxygen species; transforming growth factor&#8208; &#946	COLORECTAL-CANCER; TRANSCRIPTION; POLARIZATION; MACROPHAGES; GROWTH; CELLS	The tumor microenvironment significantly affects tumor progression, and tumor cells can also remodel the tumor microenvironment through complex interaction. Inflammasomes are innate immune system receptors/sensors that regulate an inflammatory response mainly mediated by the nucleotide-binding oligomerization domain-like receptors in macrophages, which can also influence the formation, progression and therapeutic response of cancer. However, the effects of tumor-derived factors in the microenvironment on inflammasomes have rarely been reported. In this study, we found that lactate, as the main metabolite of tumor cells could specifically activate the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing protein 3 inflammasome through increasing the level of reactive oxygen species (ROS) in THP-1-derived macrophages. Furthermore, we showed that transforming growth factor-beta (TGF-beta), a cytokine accumulated in the tumor microenvironment, could be induced by lactate treatment in tumor cells, and in turn inhibit inflammasome activation induced by lactate and other canonical ligands in macrophages. In addition, TGF-beta might induce autophagy of macrophages in a SMAD-dependent manner, leading to ROS clearance and eventually inhibiting the activation of inflammasomes. Collectively, these results indicated that in the tumor microenvironment, tumor-derived lactate could act as a danger signal alerting innate immunity, but nevertheless tumor cells produced more TGF-beta to avoid immune surveillance.	[Tu, Cheng-e; Hu, Ying; Zhou, Peirong; Guo, Xuxue; Gu, Chuncai; Zhang, Yali; Li, Aimin; Liu, Side] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou, Peoples R China		Zhang, YL; Li, AM; Liu, SD (corresponding author), Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou, Peoples R China.	zyl41531@.163.com; Lam0725@163.com; liuside2011@163.com			Guangdong gastrointestinal disease research center [2017B020209003]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2020A1515011283]	Guangdong gastrointestinal disease research center, Grant/Award Number: 2017B020209003; Natural Science Foundation of Guangdong Province, Grant/Award Number: 2020A1515011283	Allen IC, 2010, J EXP MED, V207, P1045, DOI 10.1084/jem.20100050; Brand A, 2016, CELL METAB, V24, P657, DOI 10.1016/j.cmet.2016.08.011; Brooks GA, 2018, CELL METAB, V27, P757, DOI 10.1016/j.cmet.2018.03.008; Calon A, 2012, CANCER CELL, V22, P571, DOI 10.1016/j.ccr.2012.08.013; Colegio OR, 2014, NATURE, V513, P559, DOI 10.1038/nature13490; Dupaul-Chicoine J, 2015, IMMUNITY, V43, P751, DOI 10.1016/j.immuni.2015.08.013; Feng J, 2017, ONCOGENE, V36, P5829, DOI 10.1038/onc.2017.188; Fridlender ZG, 2009, CANCER CELL, V16, P183, DOI 10.1016/j.ccr.2009.06.017; Ghiringhelli F, 2009, NAT MED, V15, P1170, DOI 10.1038/nm.2028; Gross O, 2011, IMMUNOL REV, V243, P136, DOI 10.1111/j.1600-065X.2011.01046.x; Guido C, 2012, CELL CYCLE, V11, P3019, DOI 10.4161/cc.21384; Hahm KB, 2000, J CLIN INVEST, V105, P1057, DOI 10.1172/JCI8337; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Ivashkiv LB, 2020, NAT REV IMMUNOL, V20, P85, DOI 10.1038/s41577-019-0259-8; Kiyono K, 2009, CANCER RES, V69, P8844, DOI 10.1158/0008-5472.CAN-08-4401; Koelwyn GJ, 2017, NAT REV CANCER, V17, P620, DOI 10.1038/nrc.2017.78; Li XR, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0701-y; Moossavi M, 2018, MOL CANCER, V17, DOI 10.1186/s12943-018-0900-3; Rajamaki K, 2013, J BIOL CHEM, V288, P13410, DOI 10.1074/jbc.M112.426254; Rathinam VAK, 2016, CELL, V165, P792, DOI 10.1016/j.cell.2016.03.046; Regateiro FS, 2011, EUR J IMMUNOL, V41, P2955, DOI 10.1002/eji.201141512; Samuvel DJ, 2009, J IMMUNOL, V182, P2476, DOI 10.4049/jimmunol.0802059; Schmid SA, 2007, EXP CELL RES, V313, P2531, DOI 10.1016/j.yexcr.2007.05.016; Wilson JE, 2015, NAT MED, V21, P906, DOI 10.1038/nm.3908; Worthington JJ, 2015, IMMUNITY, V42, P903, DOI 10.1016/j.immuni.2015.04.012; Yoshida Y, 2014, IMMUNITY, V40, P187, DOI 10.1016/j.immuni.2013.11.022; Zhou L, 2008, NATURE, V453, P236, DOI 10.1038/nature06878; Zitvogel L, 2012, NAT IMMUNOL, V13, P343, DOI 10.1038/ni.2224	28	2	2	1	6	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0021-9541	1097-4652		J CELL PHYSIOL	J. Cell. Physiol.	JUN	2021	236	6					4528	4537		10.1002/jcp.30169		NOV 2020	10	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	RA5YF	WOS:000591564600001	33230810				2022-04-25	
J	Pathania, AS; Challagundla, KB				Pathania, Anup S.; Challagundla, Kishore B.			Exosomal Long Non-coding RNAs: Emerging Players in the Tumor Microenvironment	MOLECULAR THERAPY-NUCLEIC ACIDS			English	Review							CELL-DERIVED EXOSOMES; EXTRACELLULAR VESICLES; COLORECTAL-CANCER; LNCRNA; PROMOTE; INVASION; PROGRESSION; EXPRESSION; MICRORNAS; AUTOPHAGY	Recent advances in exosome biology have uncovered a significant role of exosomes in cancer and make them a determining factor in intercellular communication. Exosomes are types of extracellular vesicles that are involved in the communication between cells by exchanging various signaling molecules between the surrounding cells. Among various signaling molecules, long non-coding RNAs (lncRNAs), a type of non-coding RNA having a size of more than 200 nt in length and lacking protein-coding potential, have emerged as crucial regulators of intercellular communication. Tumor-derived exosomes containing various lncRNAs, known as exosomal lncRNAs, reprogram the microenvironment by regulating numerous cellular functions, including the regulation of gene transcription that favors cancer growth and progression, thus significantly determining the biological effects of exosomes. In addition, deregulated expression of lncRNAs is found in various human cancers and serves as a diagnostic biomarker to predict cancer type. The present review discusses the role of exosomal lncRNAs in the crosstalk between tumor cells and the surrounding cells of the microenvironment. Furthermore, we also discuss the involvement of exosomal lncRNAs within the tumor microenvironment in favoring tumor growth, metabolic reprogramming of tumor cells, and tumor-supportive autophagy. Therefore, lncRNAs can be used as a therapeutic target in the treatment of various human cancers.	[Pathania, Anup S.; Challagundla, Kishore B.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, 985870 Nebraska Med Ctr, Omaha, NE 68198 USA; [Pathania, Anup S.; Challagundla, Kishore B.] Univ Nebraska Med Ctr, Fred & Pamela Buffet Canc Ctr, 985870 Nebraska Med Ctr, Omaha, NE 68198 USA; [Challagundla, Kishore B.] Univ Nebraska Med Ctr, Childrens Hlth Res Inst, Omaha, NE 68198 USA		Challagundla, KB (corresponding author), Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, 985870 Nebraska Med Ctr, Omaha, NE 68198 USA.; Challagundla, KB (corresponding author), Univ Nebraska Med Ctr, Fred & Pamela Buffet Canc Ctr, 985870 Nebraska Med Ctr, Omaha, NE 68198 USA.	kishore.challagundla@unmc.edu	Challagundla, Kishore B./H-8189-2019	Challagundla, Kishore B./0000-0001-8654-7717	NIH/National Cancer Institute (NCI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [1K22CA197074]; Buffet Pilot & Pediatric Cancer Research Grants at the University of Nebraska Medical Center (UNMC) [LB506]; Leukemia Research Foundation [LB506]; Department of Biochemistry & Molecular Biology start-up grants	K.B.C.'s laboratory is supported in whole or part by NIH/National Cancer Institute (NCI) grant 1K22CA197074; Buffet Pilot & Pediatric Cancer Research Grants at the University of Nebraska Medical Center (UNMC), LB506 (Nebraska Department of Health and Human Services) and Leukemia Research Foundation, LB506 (Nebraska Department of Health and Human Services); and the Department of Biochemistry & Molecular Biology start-up grants. The authors would like to thank Jeffrey Patterson, University of Nebraska Medical Center (Omaha, NE, USA), for editorial assistance. Figures were prepared using EazyDraw and BioRender tools.	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Ther.-Nucl. Acids	MAR 5	2021	23						1371	1383		10.1016/j.omtn.2020.09.039		MAR 2021	13	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	RB1FJ	WOS:000631861800011	33738133	Green Published, gold			2022-04-25	
J	Saxena, M; Yeretssian, G				Saxena, Mansi; Yeretssian, Garabet			NOD-like receptors: master regulators of inflammation and cancer	FRONTIERS IN IMMUNOLOGY			English	Review						apoptosis; autophagy; colorectal cancer; innate immunity; intestinal inflammation; inflammasome; nod-like receptors; nodosome	NF-KAPPA-B; TOLL-LIKE-RECEPTOR; CASPASE RECRUITMENT DOMAIN; GENOME-WIDE ASSOCIATION; NLRP3 INFLAMMASOME; NALP3 INFLAMMASOME; MURAMYL DIPEPTIDE; CELL-DEATH; PROTEIN-KINASE; CUTTING EDGE	Cytosolic NOD-like receptors (NLRs) have been associated with human diseases including infections, cancer, and autoimmune and inflammatory disorders. These innate immune pattern recognition molecules are essential for controlling inflammatory mechanisms through induction of cytokines, chemokines, and anti-microbial genes. Upon activation, some NLRs form multi-protein complexes called inflammasomes, while others orchestrate caspase-independent nuclear factor kappa B (NE-kappa B) and mitogen activated protein kinase (MARK) signaling. Moreover, NLRs and their downstream signaling components engage in an intricate crosstalk with cell death and autophagy pathways, both critical processes for cancer development. Recently, increasing evidence has extended the concept that chronic inflammation caused by abberant NLR signaling is a powerful driver of carcinogenesis, where it abets genetic mutations, tumor growth, and progression. In this review, we explore the rapidly expanding area of research regarding the expression and functions of NLRs in different types of cancers. Furthermore, we particularly focus on how maintaining tissue homeostasis and regulating tissue repair may provide a logical platform for understanding the liaisons between the NLR-driven inflammatory responses and cancer. Finally, we outline novel therapeutic approaches that target NLR signaling and speculate how these could be developed as potential pharmaceutical alternatives for cancer treatment.	[Saxena, Mansi; Yeretssian, Garabet] Icahn Sch Med Mt Sinai, Inst Immunol, Dept Med, New York, NY 10029 USA; [Yeretssian, Garabet] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA		Yeretssian, G (corresponding author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, Clin Immunol Immunol Inst, Dept Med, 1425 Madison Ave,12-20E, New York, NY 10029 USA.	garabet.yeretssian@mssm.edu		Saxena, Mansi/0000-0001-5482-3158; Saleh, Maya/0000-0003-1538-9146	Helmsley Foundation	We thank all the Yeretssian lab members for the insightful and critical reading of the manuscript. This work was supported by the Helmsley Foundation.	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Immunol.	JUL 14	2014	5								327	10.3389/fimmu.2014.00327			16	Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Immunology	CH9SZ	WOS:000354377900001	25071785	gold, Green Published			2022-04-25	
J	Shi, CH; Wu, J; Fu, M; Zhang, BH; Wang, J; Yang, X; Chi, YP				Shi, Conghong; Wu, Jing; Fu, Min; Zhang, Baohong; Wang, Juan; Yang, Xi; Chi, Yunpeng			Ambra1 modulates starvation-induced autophagy through AMPK signaling pathway in cardiomyocytes	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Autophagy; Ambra1; Cardiomyocytes	COLORECTAL-CANCER CELLS; REGULATES AUTOPHAGY; APOPTOSIS; MTOR; CLEARANCE; RADICALS; DISEASE; INJURY; HEALTH	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 and cancer cells. However, whether Ambra1 plays an important role in the autophagy pathway in cardiomyocytes is unknown. In this study, we hypothesized that Ambra1 is an important regulator of autophagy and apoptosis in cardiomyocytes. To test this hypothesis, we confirmed autophagic activity in serum-starved cardiomyocytes by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3) localization, the presence of autophagosomes and LC3 protein levels. 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 cardiomyocytes. When Ambra1 expression was reduced by siRNA, the cardiomyocytes were more sensitive to staurosporine-induced apoptosis. In addition, co-immunoprecipitation of Ambra1 and Beclin1 demonstrated that Ambra1 and Beclin1 interact in serum-starved or rapamycin-treated cardiomyocytes, suggesting that Ambra1 regulates autophagy in cardiomyocytes by interacting with Beclin1. Finally, we determined that starvation stress-induced activation of Ambra1 contributes to the attenuation of adaptive AMP-activated protein kinase (AMPK) signaling. In conclusion, Ambra1 is a crucial regulator of autophagy and apoptosis through AMPK signaling pathway in cardiomyocytes that maintains the balance between autophagy and apoptosis. (C) 2014 Elsevier Inc. All rights reserved.	[Chi, Yunpeng] Capital Univ Med Sci, Beijing Anzhen Hosp, Beijing 100029, Peoples R China; [Shi, Conghong; Fu, Min; Zhang, Baohong; Wang, Juan] Baotou Fourth Hosp, Baoutou, Inner Mongolia, Peoples R China; [Wu, Jing] Inner Mongolia Med Univ, Affiliated Hosp, Image Sect, Hohhot, Inner Mongolia, Peoples R China; [Yang, Xi] Inner Mongolia Med Univ, Teaching & Res Sect Human Anat & Histol, Hohhot, Inner Mongolia, Peoples R China		Chi, YP (corresponding author), Capital Univ Med Sci, Beijing Anzhen Hosp, Beijing 100029, Peoples R China.	ypchiaz@163.com					Bolli R, 1999, PHYSIOL REV, V79, P609, DOI 10.1152/physrev.1999.79.2.609; Boya P, 2008, BIOCHEM SOC T, V36, P813, DOI 10.1042/BST0360813; Cheng TO, 1999, HOSP MED, V60, P456; Dutta D, 2013, AUTOPHAGY, V9, P328, DOI 10.4161/auto.22971; Fan YJ, 2013, CHIN J CANCER, V32, P121, DOI 10.5732/cjc.012.10106; Fimia GM, 2007, NATURE, V447, P1121, DOI 10.1038/nature05925; Fimia GM, 2011, AUTOPHAGY, V7, P115, DOI 10.4161/auto.7.1.14071; GOLDHABER JI, 1992, HYPERTENSION, V20, P118, DOI 10.1161/01.HYP.20.1.118; Gu W, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0090151; Harhaji-Trajkovic L, 2009, J CELL MOL MED, V13, P3644, DOI 10.1111/j.1582-4934.2009.00663.x; HESS ML, 1979, J SURG RES, V26, P175, DOI 10.1016/0022-4804(79)90097-0; Holt SV, 2011, TOXICOL PATHOL, V39, P516, DOI 10.1177/0192623310396903; Inoki K, 2012, ANNU REV PHARMACOL, V52, P381, DOI 10.1146/annurev-pharmtox-010611-134537; JEROUDI MO, 1994, AM J CARDIOL, V73, pB2, DOI 10.1016/0002-9149(94)90257-7; Kang R, 2011, CELL DEATH DIFFER, V18, P571, DOI 10.1038/cdd.2010.191; Kim J, 2011, NAT CELL BIOL, V13, P132, DOI 10.1038/ncb2152; Kundu M, 2008, BLOOD, V112, P1493, DOI 10.1182/blood-2008-02-137398; 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; Mazure NM, 2010, CURR OPIN CELL BIOL, V22, P177, DOI 10.1016/j.ceb.2009.11.015; Mizushima N, 2004, INT J BIOCHEM CELL B, V36, P2491, DOI 10.1016/j.biocel.2004.02.005; 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; Pua HH, 2009, J IMMUNOL, V182, P4046, DOI 10.4049/jimmunol.0801143; Reiter RJ, 2003, CARDIOVASC RES, V58, P10, DOI 10.1016/S0008-6363(02)00827-1; Rosenfeldt MT, 2009, EXPERT REV MOL MED, V11, DOI 10.1017/S1462399409001306; Sakoda H, 2002, AM J PHYSIOL-ENDOC M, V282, pE1239, DOI 10.1152/ajpendo.00455.2001; 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; Singh R, 2009, J CLIN INVEST, V119, P3329, DOI 10.1172/JCI39228; Srinivas V, 2009, CELLS TISSUES ORGANS, V189, P88, DOI 10.1159/000151428; Strappazzon F, 2011, EMBO J, V30, P1195, DOI 10.1038/emboj.2011.49; Todde V, 2009, BBA-MOL BASIS DIS, V1792, P3, DOI 10.1016/j.bbadis.2008.10.016; Tsujimoto Y, 2005, CELL DEATH DIFFER, V12, P1528, DOI 10.1038/sj.cdd.4401777; Zheng Hai-yang, 2012, Cancer Biology Medicine, V9, P105, DOI 10.3969/j.issn.2095-3941.2012.02.004	35	10	10	1	10	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.	SEP 26	2014	452	3					308	314		10.1016/j.bbrc.2014.08.017			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	AQ7UE	WOS:000343023900002	25117440				2022-04-25	
J	Zhang, SH; Zhou, L; Zhang, MD; Wang, YH; Wang, MQ; Du, JC; Gu, WW; Kui, FG; Li, JH; Geng, SN; Du, GJ				Zhang, Shuhui; Zhou, Lin; Zhang, Mengdi; Wang, Yuehua; Wang, Mengqi; Du, Jincheng; Gu, Wenwen; Kui, Fuguang; Li, Jiahuan; Geng, Shengnan; Du, Gangjun			Berberine Maintains the Neutrophil N1 Phenotype to Reverse Cancer Cell Resistance to Doxorubicin	FRONTIERS IN PHARMACOLOGY			English	Article						berberine; doxorubicin; neutrophil phenotype; carcinogenesis; chemotherapeutic resistance	BREAST-CANCER; PERITONEAL CARCINOMATOSIS; SYSTEMIC CHEMOTHERAPY; COLORECTAL-CANCER; APOPTOSIS; CYCLOPHOSPHAMIDE; MICROENVIRONMENT; COMBINATION; AUTOPHAGY; THERAPY	This study explores the contributions of neutrophils to chemotherapeutic resistance and berberine-regulated cancer cell sensitivity to doxorubicin (DOX). In vitro experiments, continuous DOX treatment led to the shift of HL-60 cells to N2 neutrophils and thus induced chemotherapeutic resistance. The combination treatment with DOX and 2 mu M berberine resulted in the differentiation of HL-60 cells toward N1 and therefore stimulated HL-60 cell immune clearance. Berberine increased reactive oxygen species (ROS) and decreased autophagy and therefore induced apoptosis in HL-60-N2 cells with morphological changes, but had no effect on cell viability in HL-60-N1 cells. The neutrophil-regulating efficacy of berberine was confirmed in the urethane-induced lung carcinogenic model and H22 liver cancer allograft model. Furthermore, we found that DOX-derived neutrophils had high levels of CD133 and CD309 surface expression, which prevented both chemotherapeutic sensitivity and immune rejection by self-expression of PD-L1 and surface expression of PD-1 receptor on T cells, whereas berberine could downregulate CD133 and CD309 surface expression. Finally, berberine-relevant targets and pathways were evaluated. This study first suggests an important role of berberine in regulating neutrophil phenotypes to maintain cancer cell sensitivity to DOX.	[Zhang, Shuhui; Zhou, Lin; Zhang, Mengdi; Wang, Yuehua; Wang, Mengqi; Du, Jincheng; Gu, Wenwen; Kui, Fuguang; Li, Jiahuan; Du, Gangjun] Henan Univ, Pharmaceut Coll, Inst Pharm, Kaifeng, Peoples R China; [Geng, Shengnan; Du, Gangjun] Zhengzhou Univ Ind Technol, Sch Pharm & Chem Engn, Xinzheng, Peoples R China; [Du, Jincheng] Hunan Univ Chinese Med, Chinese Med Sch, Changsha, Peoples R China		Li, JH; Du, GJ (corresponding author), Henan Univ, Pharmaceut Coll, Inst Pharm, Kaifeng, Peoples R China.; Geng, SN; Du, GJ (corresponding author), Zhengzhou Univ Ind Technol, Sch Pharm & Chem Engn, Xinzheng, Peoples R China.	jiahuan1020@126.com; 1017172540@qq.com; 10200029@vip.henu.edu.cn			Natural Science Foundation of Henan Province [182300410310]; Postgraduate Education Reform Project of Henan Province [hnyjs2015kc24]; Postgraduate Education Innovation and Quality Improvement Project of Henan University [SYL18060136, SYL18060137, SYL19060140, SYL19060139]	Natural Science Foundation of Henan Province (No. 182300410310). Postgraduate Education Reform Project of Henan Province (No. hnyjs2015kc24). Postgraduate Education Innovation and Quality Improvement Project of Henan University (No. SYL18060136, SYL18060137, SYL19060140 and SYL19060139).	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Pharmacol.	JAN 29	2020	10								1658	10.3389/fphar.2019.01658			15	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	KM7BY	WOS:000514296000001	32063859	Green Published, gold			2022-04-25	
J	Wang, KS; Chan, CK; Hidayat, AFA; Wong, YH; Kadir, HA				Wang, Kar Suen; Chan, Chim Kei; Hidayat, Ahmad Fadhlurrahman Ahmad; Wong, Yau Hsiung; Kadir, Habsah Abdul			Clinacanthus nutans induced reactive oxygen species-dependent apoptosis and autophagy in HCT116 human colorectal cancer cells	PHARMACOGNOSY MAGAZINE			English	Article						Apoptosis; autophagy; Clinacanthus nutans; colorectal cancer; reactive oxygen species	LUPEOL INHIBITS PROLIFERATION; OXIDATIVE STRESS; DEATH; ROS; GENERATION; NECROSIS; LC3	Background: Clinacanthus nutans (Burm.f.) Lindau is a medicinal herb that is conventionally used for the treatment of skin rashes, insect bites, snake bites, diabetes, and cancer. Objective: Our study aims to investigate the apoptosis- and autophagy-inducing effects of C. nutans in HCT116 human colorectal cancer cells. Materials and Methods: Cytotoxicity of ethanol extract, hexane, ethyl acetate, and aqueous fractions of C. nutans against various cancer cell lines was determined via MTT assay. Apoptosis assays including annexin V, mito-ID, and Hoechst 33342/propidium iodide staining were carried out. The level of intracellular reactive oxidative species was determined using flow cytometry. Western blot analysis was carried out to assess the protein expression in C. nutans ethyl acetate fraction (CNEAF)-treated HCT116 cells. Results: CNEAF was found to exert the strongest cytotoxic effect against HCT116 cells (IC50 =48.81 1.44 mg/mL). CNEAF-induced apoptosis was evidenced by nuclear morphological alterations, phosphatidylserine externalization, dissipation of mitochondrial membrane potential, and elevation of intracellular reactive oxygen species (ROS) level. Dissipation of mitochondrial membrane potential was attributed to the upregulation of Bax and Bak accompanied by downregulation of Bcl-2 and Bcl-xL, leading to caspase-3, -9, -8, and -10 activation. Interestingly, an upregulation of death receptor 5 was detected, suggesting involvement of intrinsic and extrinsic pathways. In addition, the occurrence of autophagy by CNEAF was supported by LC-3 accumulation and p62 degradation. The reduction of intracellular ROS level by N-acetylcysteine showed that the apoptosis and autophagy induced by CNEAF is ROS dependent. Conclusions: CNEAF induced ROS-dependent apoptosis and autophagy on HCT116 cells. Abbreviations used: CNEAF: Clinacanthus nutans ethyl acetate fraction; ROS: Reactive oxygen species; PS: Phosphatidylserine; NAC:N-Acetyl Cysteine; Bax: Bcl-2-associated X; Bcl-2: B-cell lymphoma 2; DR-5: Death receptor 5 Bak: Bcl-2-antagonist/killer 1; Bcl-xL: B-cell lymphoma-extra large.	[Wang, Kar Suen; Chan, Chim Kei; Hidayat, Ahmad Fadhlurrahman Ahmad; Kadir, Habsah Abdul] Univ Malaya, Inst Biol Sci, Fac Sci, Kuala Lumpur 50603, Malaysia; [Wong, Yau Hsiung] Taylors Univ Lakeside Campus, Sch Liberal Art & Sci, Dept Math & Comp Sci, Subang Jaya, Selangor Darul, Malaysia		Kadir, HA (corresponding author), Univ Malaya, Inst Biol Sci, Fac Sci, Kuala Lumpur 50603, Malaysia.	habsah@um.edu.my	Hsiung, Wong Yau/AAC-7291-2022	Hsiung, Wong Yau/0000-0001-8050-1064			Alam A., 2016, CLINACANTHUS NUTANS, V9, P402, DOI DOI 10.1016/j.apjtm.2016.03.011; Arullappan S, 2014, TROP J PHARM RES, V13, P1455, DOI 10.4314/tjpr.v13i9.11; Ashkenazi A, 2008, CYTOKINE GROWTH F R, V19, P325, DOI 10.1016/j.cytogfr.2008.04.001; Awad AB, 2007, PHYTOMEDICINE, V14, P747, DOI 10.1016/j.phymed.2007.01.003; Awan A.J., 2014, INT J PHARM PHARM SC, V10, P44; Baskar AA, 2010, BMC COMPLEM ALTERN M, V10, DOI 10.1186/1472-6882-10-24; Bjorkoy G, 2005, J CELL BIOL, V171, P603, DOI 10.1083/jcb.200507002; Bold RJ, 1997, SURG ONCOL, V6, P133, DOI 10.1016/S0960-7404(97)00015-7; Brunk UT, 1997, FREE RADICAL BIO MED, V23, P616, DOI 10.1016/S0891-5849(97)00007-5; Bursch W, 2000, ANN NY ACAD SCI, V926, P1, DOI 10.1111/j.1749-6632.2000.tb05594.x; Chen L, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2016.234; Chen Y, 2008, CELL DEATH DIFFER, V15, P171, DOI 10.1038/sj.cdd.4402233; Duan P, 2016, TOXICOLOGY, V341, P28, DOI 10.1016/j.tox.2016.01.004; Edinger AL, 2004, CURR OPIN CELL BIOL, V16, P663, DOI 10.1016/j.ceb.2004.09.011; Edlich F, 2016, CELL DEATH BIOL DIS, P69, DOI 10.1007/978-1-4939-3612-0_4; Fan TJ, 2005, ACTA BIOCH BIOPH SIN, V37, P719, DOI 10.1111/j.1745-7270.2005.00108.x; Feng YC, 2014, CELL RES, V24, P24, DOI 10.1038/cr.2013.168; Ferlay J, 2015, INT J CANCER, V136, pE359, DOI 10.1002/ijc.29210; Fong SY, 2016, BMC COMPLEM ALTERN M, V16, DOI 10.1186/s12906-016-1348-x; Fulda S, 2015, SEMIN CELL DEV BIOL, V39, P20, DOI 10.1016/j.semcdb.2015.01.006; Kabeya Y, 2004, J CELL SCI, V117, P2805, DOI 10.1242/jcs.01131; Kiffin R, 2006, ANTIOXID REDOX SIGN, V8, P152, DOI 10.1089/ars.2006.8.152; Klionsky DJ, 2007, NAT REV MOL CELL BIO, V8, P931, DOI 10.1038/nrm2245; KOOPMAN G, 1994, BLOOD, V84, P1415, DOI 10.1182/blood.V84.5.1415.1415; Levine B, 2005, J CLIN INVEST, V115, P2679, DOI 10.1172/JCI26390; Li L, 2012, FREE RADICAL BIO MED, V53, P1399, DOI 10.1016/j.freeradbiomed.2012.07.011; Liu Y, 2016, CYTOTECHNOLOGY, V68, P123, DOI 10.1007/s10616-014-9763-7; Liu Y, 2015, N-S ARCH PHARMACOL, V388, P295, DOI 10.1007/s00210-014-1071-4; Lu YP, 2016, EUR J PHARMACOL, V771, P130, DOI 10.1016/j.ejphar.2015.12.026; Meijer AJ, 2004, BIOCHEM BIOPH RES CO, V313, P397, DOI 10.1016/j.bbrc.2003.07.012; Paglin S, 2001, CANCER RES, V61, P439; Park KW, 2014, INT J ONCOL, V44, P1309, DOI 10.3892/ijo.2014.2281; Pelicano H, 2004, DRUG RESIST UPDATE, V7, P97, DOI 10.1016/j.drup.2004.01.004; Pongmuangmul S, 2016, ASIAN PAC J TROP BIO, V6, P192, DOI 10.1016/j.apjtb.2015.12.014; Rauth S, 2016, MOL CELL BIOCHEM, V417, P97, DOI 10.1007/s11010-016-2717-y; Sakdarat S, 2009, BIOORGAN MED CHEM, V17, P1857, DOI 10.1016/j.bmc.2009.01.059; Saleem M, 2009, CARCINOGENESIS, V30, P808, DOI 10.1093/carcin/bgp044; Simon HU, 2000, APOPTOSIS, V5, P415, DOI 10.1023/A:1009616228304; Tan ML, 2009, PHARM RES-DORDR, V26, P1547, DOI 10.1007/s11095-009-9895-1; Tanida I, 2004, INT J BIOCHEM CELL B, V36, P2503, DOI 10.1016/j.biocel.2004.05.009; Tarapore RS, 2013, MOL NUTR FOOD RES, V57, P1950, DOI 10.1002/mnfr.201300155; Temraz S, 2014, CRIT REV ONCOL HEMAT, V89, P217, DOI 10.1016/j.critrevonc.2013.08.015; Trachootham D, 2009, NAT REV DRUG DISCOV, V8, P579, DOI 10.1038/nrd2803; Tsujimoto Y, 1998, GENES CELLS, V3, P697, DOI 10.1046/j.1365-2443.1998.00223.x; Tuntiwachwuttikul P, 2004, CHEM PHARM BULL, V52, P27, DOI 10.1248/cpb.52.27; von Holtz RL, 1998, NUTR CANCER, V32, P8, DOI 10.1080/01635589809514709; Wei MC, 2000, GENE DEV, V14, P2060; Yahaya R., 2015, INT J PHARMACOGN PHY, V7, P1244; Yian ShimSiang, 2013, International Journal of Integrative Biology, V14, P7; Yong YK, 2013, EVID-BASED COMPL ALT, V2013, DOI 10.1155/2013/462751	50	5	6	1	11	WOLTERS KLUWER MEDKNOW PUBLICATIONS	MUMBAI	WOLTERS KLUWER INDIA PVT LTD , A-202, 2ND FLR, QUBE, C T S  NO 1498A-2 VILLAGE MAROL, ANDHERI EAST, MUMBAI, 400059, INDIA	0973-1296	0976-4062		PHARMACOGN MAG	Pharmacogn. Mag.	JAN-MAR	2019	15	60					87	97		10.4103/pm.pm_299_17			11	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	HI7BR	WOS:000456610600013					2022-04-25	
J	Podralska, M; Ciesielska, S; Kluiver, J; van den Berg, A; Dzikiewicz-Krawczyk, A; Slezak-Prochazka, I				Podralska, Marta; Ciesielska, Sylwia; Kluiver, Joost; van den Berg, Anke; Dzikiewicz-Krawczyk, Agnieszka; Slezak-Prochazka, Izabella			Non-Coding RNAs in Cancer Radiosensitivity: MicroRNAs and lncRNAs as Regulators of Radiation-Induced Signaling Pathways	CANCERS			English	Review						non-coding RNA; miRNA; lncRNA; circRNA; radiation response; radiotherapy	CELL LUNG-CANCER; NASOPHARYNGEAL CARCINOMA RADIORESISTANCE; HUMAN COLORECTAL-CANCER; STRAND BREAK REPAIR; DNA-DAMAGE RESPONSE; ENHANCES RADIOSENSITIVITY; PROSTATE-CANCER; IONIZING-RADIATION; DOWN-REGULATION; GASTRIC-CANCER	Radiotherapy is a cancer treatment that applies high doses of ionizing radiation to induce cell death, mainly by triggering DNA double-strand breaks. The outcome of radiotherapy greatly depends on radiosensitivity of cancer cells, which is determined by multiple proteins and cellular processes. In this review, we summarize current knowledge on the role of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in determining the response to radiation. Non-coding RNAs modulate ionizing radiation response by targeting key signaling pathways, including DNA damage repair, apoptosis, glycolysis, cell cycle arrest, and autophagy. Additionally, we indicate miRNAs and lncRNAs that upon overexpression or inhibition alter cellular radiosensitivity. Current data indicate the potential of using specific non-coding RNAs as modulators of cellular radiosensitivity to improve outcome of radiotherapy.	[Podralska, Marta; Dzikiewicz-Krawczyk, Agnieszka] Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland; [Ciesielska, Sylwia] Silesian Tech Univ, Dept Syst Biol & Engn, Fac Automat Control Elect & Comp Sci, PL-44100 Gliwice, Poland; [Kluiver, Joost; van den Berg, Anke] Univ Groningen, Univ Med Ctr, Dept Pathol & Med Biol, NL-9700 RB Groningen, Netherlands; [Slezak-Prochazka, Izabella] Silesian Tech Univ, Ctr Biotechnol, PL-44100 Gliwice, Poland		Dzikiewicz-Krawczyk, A (corresponding author), Polish Acad Sci, Inst Human Genet, PL-60479 Poznan, Poland.; Slezak-Prochazka, I (corresponding author), Silesian Tech Univ, Ctr Biotechnol, PL-44100 Gliwice, Poland.	marta.podralska@igcz.poznan.pl; sylwia.ciesielska@polsl.pl; j.l.kluiver@umcg.nl; a.van.den.berg01@umcg.nl; marta.podralska@igcz.poznan.pl; izabella.slezak-prochazka@polsl.pl	Kluiver, Joost/G-6406-2014; van den Berg, Anke/H-1718-2011; Slezak-Prochazka, Izabella/F-7674-2019	Kluiver, Joost/0000-0001-7650-2937; Podralska, Marta/0000-0001-9720-7881; van den Berg, Anke/0000-0002-8894-2638; Slezak-Prochazka, Izabella/0000-0002-0707-2213; Ciesielska, Sylwia/0000-0002-1051-0632; Dzikiewicz-Krawczyk, Agnieszka/0000-0001-7633-2114	National Science Centre, PolandNational Science Centre, Poland [2017/27/B/NZ1/00877, 2015/19/B/ST7/02984, 2015/19/D/NZ1/03443]	This research was funded by the National Science Centre, Poland, grants number 2017/27/B/NZ1/00877 to AD-K and MP, 2015/19/B/ST7/02984 to SC and 2015/19/D/NZ1/03443 to IS-P.	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J	Kim, EK; Jang, M; Song, MJ; Kim, D; Kim, Y; Jang, HH				Kim, Eun-Kyung; Jang, MinGyeong; Song, Min-Jeong; Kim, Dongwoo; Kim, Yosup; Jang, Ho Hee			Redox-Mediated Mechanism of Chemoresistance in Cancer Cells	ANTIOXIDANTS			English	Review						reactive oxygen species; antioxidant proteins; chemoresistance; oxaliplatin; 5-Fluorouracil	ENDOPLASMIC-RETICULUM-STRESS; EPITHELIAL-MESENCHYMAL TRANSITION; MANGANESE SUPEROXIDE-DISMUTASE; OXYGEN SPECIES ROS; NADPH OXIDASE 2; DRUG-RESISTANCE; COLORECTAL-CANCER; 5-FLUOROURACIL RESISTANCE; PANCREATIC-CANCER; OXIDATIVE STRESS	Cellular reactive oxygen species (ROS) status is stabilized by a balance of ROS generation and elimination called redox homeostasis. ROS is increased by activation of endoplasmic reticulum stress, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family members and adenosine triphosphate (ATP) synthesis of mitochondria. Increased ROS is detoxified by superoxide dismutase, catalase, and peroxiredoxins. ROS has a role as a secondary messenger in signal transduction. Cancer cells induce fluctuations of redox homeostasis by variation of ROS regulated machinery, leading to increased tumorigenesis and chemoresistance. Redox-mediated mechanisms of chemoresistance include endoplasmic reticulum stress-mediated autophagy, increased cell cycle progression, and increased conversion to metastasis or cancer stem-like cells. This review discusses changes of the redox state in tumorigenesis and redox-mediated mechanisms involved in tolerance to chemotherapeutic drugs in cancer.	[Kim, Eun-Kyung; Jang, MinGyeong; Song, Min-Jeong; Jang, Ho Hee] Gachon Univ, Coll Med, Dept Biochem, Incheon 21999, South Korea; [Kim, Dongwoo; Kim, Yosup; Jang, Ho Hee] Gachon Univ, Dept Hlth Sci & Technol, GAIHST, Incheon 21999, South Korea		Jang, HH (corresponding author), Gachon Univ, Coll Med, Dept Biochem, Incheon 21999, South Korea.; Jang, HH (corresponding author), Gachon Univ, Dept Hlth Sci & Technol, GAIHST, Incheon 21999, South Korea.	ekkim@gachon.ac.kr; apnea4001@naver.com; neptune6nrg@hanmail.net; cd0575@naver.com; youandkys@naver.com; hhjang@gachon.ac.kr		Jang, Ho Hee/0000-0003-0314-8230	National Research Foundation of Korea (NRF) - Korea governmentNational Research Foundation of Korea [NRF-2017R1D1A1B03035550]; National Research Foundation of Korea (NRF)National Research Foundation of Korea; Center for Women In Science, Engineering and Technology (WISET) - Ministry of Science, ICT & Future Planning of Korea (MSIP) under the Program for Returners into RD	This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2017R1D1A1B03035550) to E.-K.K., and by the National Research Foundation of Korea (NRF) and the Center for Women In Science, Engineering and Technology (WISET) Grant funded by the Ministry of Science, ICT & Future Planning of Korea (MSIP) under the Program for Returners into R&D to M.J.	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J	Jiang, LH; Zhang, HD; Tang, JH				Jiang, Lin-hong; Zhang, He-da; Tang, Jin-hai			MiR-30a: A Novel Biomarker and Potential Therapeutic Target for Cancer	JOURNAL OF ONCOLOGY			English	Review							EPITHELIAL-MESENCHYMAL TRANSITION; CELL LUNG-CANCER; ALTERED MICRORNA EXPRESSION; WNT/BETA-CATENIN PATHWAY; DOWN-REGULATION; COLORECTAL-CANCER; MATRIX METALLOPROTEINASES; SIGNALING PATHWAY; POOR-PROGNOSIS; TUMOR-GROWTH	MicroRNAs (miRNAs) are small, highly conserved noncoding RNAs molecules, consisting of 18-25 nucleotides that regulate gene expression by binding to complementary binding sites within the 3' untranslated region (3'UTR) of target mRNAs. MiRNAs have been involved in regulating gene expression and diverse physiological and pathological processes. Several studies have reported that miR-30a, situated on chromosome 6q.13, is produced by an intronic transcriptional unit. Moreover, miR-30a has demonstrated its role in biological processes, including inhibiting proliferation and metastasis in many tumors, autophagy in chronic myelogenous leukemia, and regulating TGF-b1-induced epithelial-mesenchymal transition. However, based on the pathogenetic relationship between miR-30a and cancer in tumorigenesis, we believe that miR-30a may serve as tumor promising biomarker. Moreover, it would offer a therapeutic target for the treatment of cancer.	[Jiang, Lin-hong] Xuzhou Med Univ, Dept Oncol, Xuzhou, Jiangsu, Peoples R China; [Jiang, Lin-hong] Xuzhou Infect Dis Hosp, Xuzhou, Jiangsu, Peoples R China; [Zhang, He-da] Southeast Univ, Sch Med, Dept Gen Surg, Nanjing, Jiangsu, Peoples R China; [Tang, Jin-hai] Nanjing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Nanjing, Jiangsu, Peoples R China		Tang, JH (corresponding author), Nanjing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Nanjing, Jiangsu, Peoples R China.	jhtang@njmu.edu.cn			National Key Research and Development Program of China [2016YFC0905900]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20151579]	This research was supported by the National Key Research and Development Program of China (no. 2016YFC0905900) and Natural Science Foundation of Jiangsu Province (no. BK20151579).	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Oncol.		2018	2018								5167829	10.1155/2018/5167829			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GQ8CL	WOS:000441977800001	30158978	Green Published, gold, Green Submitted			2022-04-25	
J	Skalka, N; Caspi, M; Lahav-Ariel, L; Loh, YP; Hirschberg, K; Rosin-Arbesfeld, R				Skalka, N.; Caspi, M.; Lahav-Ariel, L.; Loh, Y. P.; Hirschberg, K.; Rosin-Arbesfeld, R.			Carboxypeptidase E (CPE) inhibits the secretion and activity of Wnt3a	ONCOGENE			English	Article							CELL-PROLIFERATION; COLORECTAL-CANCER; PATHWAY; STRESS; NEUROPROTECTION; EXPRESSION; ENDOCRINE; AUTOPHAGY; SURVIVAL; NEURONS	The Wnt pathway has essential roles in cell proliferation, cell fate determination and tumorigenesis by regulating the expression of a wide range of target genes. As a core signaling cascade, the canonical Wnt pathway is regulated at different levels by numerous proteins. We have previously shown that carboxypeptidase E (CPE) is a novel regulator of the canonical Wnt signaling pathway. Here, we show that CPE and the Wnt3a ligand are co-secreted from cells. We show that although the C'-terminal Lys residue of Wnt3a is critical for its activity and is important for the effect of CPE on the Wnt pathway, CPE does not execute its effect by removing this Wnt3a residue. Interestingly, CPE through its N'-terminal sequence, forms aggregates with Wnt3a and possible endoplasmic reticulum (ER) stress leading to its loss of function. Together, our current results provide a mechanistic insight into the way CPE regulates the canonical Wnt signaling pathway.	[Skalka, N.; Caspi, M.; Lahav-Ariel, L.; Rosin-Arbesfeld, R.] Tel Aviv Univ, Sackler Sch Med, Dept Clin Microbiol & Immunol, IL-69978 Tel Aviv, Israel; [Loh, Y. P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Neurobiol, Program Dev Neurosci, NIH, Bethesda, MD USA; [Hirschberg, K.] Tel Aviv Univ, Sackler Sch Med, Dept Pathol, Tel Aviv, Israel		Rosin-Arbesfeld, R (corresponding author), Tel Aviv Univ, Sackler Sch Med, Dept Clin Microbiol & Immunol, IL-69978 Tel Aviv, Israel.	arina@post.tau.ac.il			Rising Tide Foundation for Clinical Cancer Research; Gateway for Cancer Research Foundation; Israel Science FoundationIsrael Science Foundation [20120016]; 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) [ZIAHD000056] Funding Source: NIH RePORTER	This work was supported by Rising Tide Foundation for Clinical Cancer Research, by the Gateway for Cancer Research Foundation and by the Israel Science Foundation (Grant no. 20120016).	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J	Berger, MD; Yamauchi, S; Cao, S; Hanna, DL; Sunakawa, Y; Schirripa, M; Matsusaka, S; Yang, DY; Groshen, S; Zhang, W; Ning, Y; Okazaki, S; Miyamoto, Y; Suenaga, M; Lonardi, S; Cremolini, C; Falcone, A; Heinemann, V; Loupakis, F; Stintzing, S; Lenz, HJ				Berger, Martin D.; Yamauchi, Shinichi; Cao, Shu; Hanna, Diana L.; Sunakawa, Yu; Schirripa, Marta; Matsusaka, Satoshi; Yang, Dongyun; Groshen, Susan; Zhang, Wu; Ning, Yan; Okazaki, Satoshi; Miyamoto, Yuji; Suenaga, Mitsukuni; Lonardi, Sara; Cremolini, Chiara; Falcone, Alfredo; Heinemann, Volker; Loupakis, Fotios; Stintzing, Sebastian; Lenz, Heinz-Josef			Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials	EUROPEAN JOURNAL OF CANCER			English	Article						Autophagy; Hypertension; Colorectal cancer; Single-nucleotide polymorphism; Bevacizumab-associated toxicity; FOLFIRI/bevacizumab	PLUS BEVACIZUMAB; INHIBITION; STRESS; PROGRESSION; SENESCENCE; APOPTOSIS	Purpose: The most frequent bevacizumab-related side-effects are hypertension, proteinuria, bleeding and thromboembolism. To date, there is no biomarker that predicts anti-VEGF-associated toxicity. As autophagy inhibits angiogenesis, we hypothesised that single-nucleotide polymorphisms (SNPs) within autophagy-related genes may predict bevacizumab-mediated toxicity in patients with metastatic colorectal cancer (mCRC). Patients and methods: Patients with mCRC treated with first-line FOLFIRI and bevacizumab in two phase III randomised trials, namely the TRIBE trial (n = 219, discovery cohort) and the FIRE-3 trial (n = 234, validation cohort) were included in this study. Patients receiving treatment with FOLFIRI and cetuximab (FIRE-3, n = 204) served as a negative control. 12 SNPs in eight autophagy-related genes (ATG3/5/8/13, beclin 1, FIP200, unc-51-like kinase 1, UVRAG) were analysed by PCR-based direct sequencing. Results: The FIP200 rs1129660 variant showed significant associations with hypertension in the TRIBE cohort. Patients harbouring any G allele of the FIP200 rs1129660 SNP showed a significantly lower rate of grade 2-3 hypertension compared with the A/A genotype (3% versus 15%, odds ratio [OR] 0.17; 95% confidence interval [CI], 0.02-0.73; P = 0.009). Similarly, G allele carriers of the FIP200 rs1129660 SNP were less likely to develop grade 2-3 hypertension than patients with an A/A genotype in the FIRE-3 validation cohort (9% versus 20%, OR 0.43; 95% CI, 0.14-1.11; P =0.077), whereas this association could not be observed in the control cohort (12% versus 9%, OR 1.40; 95% CI, 0.45-4.04; P = 0.60). Conclusion: This is the first report demonstrating that polymorphisms in the autophagy-related FIP200 gene may predict hypertension in patients with mCRC treated with FOLFIRI and bevacizumab. (C) 2017 Elsevier Ltd. All rights reserved.	[Berger, Martin D.; Yamauchi, Shinichi; Hanna, Diana L.; Sunakawa, Yu; Schirripa, Marta; Matsusaka, Satoshi; Zhang, Wu; Ning, Yan; Okazaki, Satoshi; Miyamoto, Yuji; Suenaga, Mitsukuni; Lenz, Heinz-Josef] Univ Southern Calif, Div Med Oncol, Norris Comprehens Canc Ctr, Keck Sch Med, 1441 Eastlake Ave, Los Angeles, CA 90033 USA; [Cao, Shu; Yang, Dongyun; Groshen, Susan; Lenz, Heinz-Josef] Univ Southern Calif, Dept Prevent Med, Norris Comprehens Canc Ctr, Keck Sch Med, 1441 Eastlake Ave, Los Angeles, CA 90033 USA; [Heinemann, Volker; Stintzing, Sebastian] Univ Munich LMU, Dept Med Oncol, Marchioninistr 15, D-81377 Munich, Germany; [Heinemann, Volker; Stintzing, Sebastian] Univ Munich LMU, Ctr Comprehens Canc, Marchioninistr 15, D-81377 Munich, Germany; [Schirripa, Marta; Lonardi, Sara; Loupakis, Fotios] IRCCS, Oncol Med 1, Ist Oncol Veneto, Via Gattamelata 64, I-35128 Padua, Italy; [Cremolini, Chiara; Falcone, Alfredo] Azienda Osped Univ Pisana, Ist Toscano Tumori, UO Oncol Med, Via Roma 67, I-56126 Pisa, Italy		Lenz, HJ (corresponding author), Univ Southern Calif, Div Med Oncol, Norris Comprehens Canc Ctr, Keck Sch Med, 1441 Eastlake Ave, Los Angeles, CA 90033 USA.	lenz@med.usc.edu	Lonardi, Sara/F-4228-2014; Berger, Martin D./AAR-4415-2021; Cremolini, Chiara/AAC-1889-2019; Loupakis, Fotios/I-7243-2012; Yang, Dongyun/M-2579-2019; Schirripa, Marta/F-3688-2017; Berger, Martin D./AAS-1238-2021; Stintzing, Sebastian/I-4538-2016	Lonardi, Sara/0000-0002-7593-8138; Loupakis, Fotios/0000-0001-9651-0395; Yang, Dongyun/0000-0003-0736-4977; Schirripa, Marta/0000-0001-8316-4411; Berger, Martin D./0000-0001-9224-7104; Stintzing, Sebastian/0000-0002-3297-5801; Falcone, Alfredo/0000-0001-5840-2529; CREMOLINI, CHIARA/0000-0002-0520-4841; Miyamoto, Yuji/0000-0003-3948-5044	Swiss Cancer League [BIL KLS-3334-02-2014]; Werner and Hedy Berger-Janser Foundation for Cancer Research; National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA014089]; Gloria Borges WunderGlo Project; Dhont Family Foundation; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [S2606]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA014089] Funding Source: NIH RePORTER	Martin D. Berger received a grant from the Swiss Cancer League (BIL KLS-3334-02-2014) and the Werner and Hedy Berger-Janser Foundation for Cancer Research. This work was partly supported by the National Cancer Institute (grant number P30CA014089), the Gloria Borges WunderGlo Project and the Dhont Family Foundation. Y. Miyamoto received a grant from the Japan Society for the Promotion of Science (S2606).	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J. Cancer	MAY	2017	77						13	20		10.1016/j.ejca.2017.02.020			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	EV7BS	WOS:000401929900003	28347919	Green Accepted			2022-04-25	
J	Lin, YM; Chen, CI; Hsiang, YP; Hsu, YC; Cheng, KC; Chien, PH; Pan, HL; Lu, CC; Chen, YJ				Lin, Yueh-Ming; Chen, Chih-I; Hsiang, Yi-Ping; Hsu, Yung-Chia; Cheng, Kung-Chuan; Chien, Pei-Hsuan; Pan, Hsiao-Lin; Lu, Chien-Chang; Chen, Yun-Ju			Chrysin Attenuates Cell Viability of Human Colorectal Cancer Cells through Autophagy Induction Unlike 5-Fluorouracil/Oxaliplatin	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						CRC; chrysin; chemotherapy; autophagy; ROS	FLAVONOID CHRYSIN; CROSS-TALK; RESISTANCE; OXALIPLATIN; EXPRESSION; BIOMARKERS; MICRORNAS; TOXICITY	Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), western blotting, fluorescence microscopy, and reactive oxygen species (ROS) production were assayed. We found that chrysin exhibited similar inhibition of cell viability as the 5-FU combination in a panel of human CRC cells. Furthermore, the results showed that chrysin significantly increased the levels of LC3-II, an autophagy-related marker, in CRC cells, which was not observed with the 5-FU combination. More importantly, blockage of autophagy induction restored chrysin-attenuated CRC cell viability. Further mechanistic analysis revealed that chrysin, not the 5-FU combination, induced ROS generation, and in turn, inhibited the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Collectively, these results imply that chrysin may be a potential replacement for the 5-FU and oxaliplatin combination to achieve antitumor activity through autophagy for CRC treatment in the future.	[Lin, Yueh-Ming; Cheng, Kung-Chuan; Lu, Chien-Chang] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Div Colorectal Surg, Kaohsiung 833, Taiwan; [Lin, Yueh-Ming; Cheng, Kung-Chuan; Lu, Chien-Chang] Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan; [Chen, Chih-I] E Da Hosp, Dept Surg, Div Colon & Rectal Surg, Kaohsiung 824, Taiwan; [Chen, Chih-I; Chen, Yun-Ju] I Shou Univ, Sch Med Int Students, Kaohsiung 824, Taiwan; [Hsiang, Yi-Ping] E Da Hosp, Dept Pharm, Kaohsiung 824, Taiwan; [Hsu, Yung-Chia; Chen, Yun-Ju] E Da Canc Hosp, Dept Pharm, Kaohsiung 824, Taiwan; [Chien, Pei-Hsuan; Pan, Hsiao-Lin; Chen, Yun-Ju] E Da Hosp, Dept Med Res, Kaohsiung 824, Taiwan		Lu, CC (corresponding author), Kaohsiung Chang Gung Mem Hosp, Dept Surg, Div Colorectal Surg, Kaohsiung 833, Taiwan.; Lu, CC (corresponding author), Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan.; Chen, YJ (corresponding author), I Shou Univ, Sch Med Int Students, Kaohsiung 824, Taiwan.; Chen, YJ (corresponding author), E Da Canc Hosp, Dept Pharm, Kaohsiung 824, Taiwan.; Chen, YJ (corresponding author), E Da Hosp, Dept Med Res, Kaohsiung 824, Taiwan.	porta2005@gmail.com; jimmyee0901@gmail.com; ed108228@edah.org.tw; ed108840@edah.org.tw; topguncheng@gmail.com; peihsuan68@gmail.com; dkiyh@yahoo.com.tw; doctor.lu@msa.hinet.net; yjchen0326@isu.edu.tw		Chen, Chih-I/0000-0002-5311-6889	Ministry of Science and Technology, R.O.C. [MOST 105-2320-B-214-005]; E-Da Hospital [EDPJ104070, EDPJ105083]	This work was supported by grants from the Ministry of Science and Technology, R.O.C. (MOST 105-2320-B-214-005), and E-Da Hospital (EDPJ104070 and EDPJ105083).	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J. Mol. Sci.	JUN	2018	19	6							1763	10.3390/ijms19061763			12	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	GK8UZ	WOS:000436506600218	29899208	Green Published, Green Submitted, gold			2022-04-25	
J	Tian, Y; Gong, GY; Ma, LL; Wang, ZQ; Song, D; Fang, MY				Tian, Ye; Gong, Guan-Yu; Ma, Liang-Liang; Wang, Zhuo-Qun; Song, Dan; Fang, Mei-Yun			Anti-cancer effects of Polyphyllin I: An update in 5 years	CHEMICO-BIOLOGICAL INTERACTIONS			English	Review						Traditional medicine; Polyphyllin I; Cancer; Inflammation	D INDUCES APOPTOSIS; BREAST-CANCER CELLS; HUMAN GLIOMA-CELLS; PARIS-POLYPHYLLA; CYCLE ARREST; COLORECTAL-CANCER; GROWTH-INHIBITION; SIGNALING PATHWAY; STEROIDAL SAPONIN; PHASE ARREST	Chong-lou, the rhizome of Paris polyphylla, has been used in herbal regimes to treat parotitis, mastitis and certain malignant tumors for thousands of years in traditional medicine. Polyphyllin I (PPI) is the main bioactive component in Paris polyphylla. Recent studies of PPI in various types of cancers have shown that PPI may exert a broad spectrum of anti-tumor effects, including inducing cell cycle arrest, inducing cell apoptosis, inducing autophagy, anti-angiogenesis, sensitizing tumors to chemotherapy, and participating in the modulation of inflammatory and immune response. Along with the growing research interest in PPI as well as accumulation of experimental evidences, this review periodically summarized the recent advances in regard to PPI's anti-tumor propensities in various cancers and the underlying mechanisms for future prospective research.	[Tian, Ye] Xian Med Univ, Dept Nephrol & Endocrinol, Affiliated Hosp 2, Xian 710038, Peoples R China; [Gong, Guan-Yu] Dalian Univ, Inst Translat Med, Affiliated Zhongshan Hosp, Dalian 116001, Peoples R China; [Ma, Liang-Liang] Dalian Med Univ, Dept Hematol, Affiliated Hosp 1, Dalian 116021, Peoples R China; [Wang, Zhuo-Qun] Cent Hosp Zibo, Dept Oncol, Zibo 255036, Peoples R China; [Song, Dan] Dalian Med Univ, Dept Oncol, Affiliated Hosp 1, Dalian 116021, Peoples R China; [Fang, Mei-Yun] Dalian Univ, Dept Hematol, Affiliated Zhongshan Hosp, 6 Jiefang St, Dalian 116001, Peoples R China		Fang, MY (corresponding author), Dalian Univ, Dept Hematol, Affiliated Zhongshan Hosp, 6 Jiefang St, Dalian 116001, Peoples R China.	646603350@qq.com; dlfangmeiyun@sina.com	Gong, Guanyu/ABA-1935-2021	Gong, Guanyu/0000-0002-5791-0916			Al Sawah E, 2015, J CANCER RES CLIN, V141, P237, DOI 10.1007/s00432-014-1797-x; Ballweg R, 2018, BIOPHYS J, V115, P2250, DOI 10.1016/j.bpj.2018.10.025; Chan JYW, 2011, J ETHNOPHARMACOL, V137, P64, DOI 10.1016/j.jep.2011.04.021; 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Interact.	JAN 25	2020	316								108936	10.1016/j.cbi.2019.108936			8	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	KN4NM	WOS:000514815400024	31870841				2022-04-25	
J	Cheng, L; Han, T; Zhang, ZY; Yi, PJ; Zhang, CH; Zhang, SF; Peng, WJ				Cheng, Lin; Han, Tong; Zhang, Zheyu; Yi, Pengji; Zhang, Chunhu; Zhang, Sifang; Peng, Weijun			Identification and Validation of Six Autophagy-related Long Non-coding RNAs as Prognostic Signature in Colorectal Cancer	INTERNATIONAL JOURNAL OF MEDICAL SCIENCES			English	Article						Autophagy; colorectal cancer; long non-coding RNA; prognostic signature	MTOR PATHWAY; VEGF; P53; ACTIVATION; THERAPY; DISEASE; HEALTH; UCA1; DRAM	Colorectal cancer (CRC) is a commonly occurring tumour with poor prognosis. Autophagy-related long non-coding RNAs (lncRNAs) have received much attention as biomarkers for cancer prognosis and diagnosis. However, few studies have focused on their prognostic predictive value specifically in CRC. This research aimed to construct a robust autophagy-related lncRNA prognostic signature for CRC. Autophagy-related lncRNAs from The Cancer Genome Atlas database were screened using univariate Cox, LASSO, and multivariate Cox regression analyses, and the resulting key lncRNAs were used to establish a prognostic risk score model. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression of several lncRNAs in cancer tissues from CRC patients and in normal tissues adjacent to the cancer tissues. A prognostic signature comprising lncRNAs AC125603.2, LINC00909, AC016876.1, MIR210HG, AC009237.14, and LINC01063 was identified in patients with CRC. A graphical nomogram based on the autophagy-related lncRNA signature was developed to predict CRC patients' 1-, 3-, and 5-year survival. Overall survival in patients with low risk scores was significantly better than in those with high risk scores (P < 0.0001); a similar result was obtained in an internal validation sample. The nomogram was shown to be suitable for clinical use and gave correct predictions. The 1- and 3-year values of the area under the receiver operating characteristic curve were 0.797 and 0.771 in the model sample, and 0.656 and 0.642 in the internal validation sample, respectively. The C-index values for the verification samples and training samples were 0.756 (95% CI = 0.668-0.762) and 0.715 (95% CI = 0.683-0.829), respectively. Gene set enrichment analysis showed that the six autophagy-related lncRNAs were greatly enriched in CRC-related signalling pathways, including p53 and VEGF signalling. The qRT-PCR results showed that the expression of lncRNAs in CRC was higher than that in adjacent tissues, consistent with the expression trends of lncRNAs in the CRC data set. In summary, we established a signature of six autophagy-related lncRNAs that could effectively guide clinical prediction of prognosis in patients with CRC. This lncRNA signature has significant clinical implications for improving the prediction of outcomes and, with further prospective validation, could be used to guide tailored therapy for CRC patients.	[Cheng, Lin; Zhang, Zheyu; Yi, Pengji; Zhang, Sifang; Peng, Weijun] Cent South Univ, Xiangya Hosp 2, Dept Integrated Tradit Chinese & Western Med, Changsha 410011, Hunan, Peoples R China; [Han, Tong] Cent South Univ, Xiangya Hosp 2, Dept Gen Surg, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China; [Zhang, Chunhu] Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha 410008, Hunan, Peoples R China		Zhang, SF; Peng, WJ (corresponding author), Cent South Univ, Xiangya Hosp 2, Dept Integrated Tradit Chinese & Western Med, Changsha 410011, Hunan, Peoples R China.	sifangzhang2005@csu.edu.cn; pengweijun87@csu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81273722]; Hunan Provincial Natural Science Foundation of ChinaNatural Science Foundation of Hunan Province [2018JJ2595]; Research projects of traditional Chinese medicine of Hunan Province [2020012]	This work was supported by the National Natural Science Foundation of China (No. 81273722),Hunan Provincial Natural Science Foundation of China (No. 2018JJ2595), and Research projects of traditional Chinese medicine of Hunan Province (No. 2020012).	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J. Med. Sci.		2021	18	1					88	98		10.7150/ijms.49449			11	Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine	OP2JW	WOS:000587910700010	33390777	gold, Green Published			2022-04-25	
J	Shu, YH; Yuan, HH; Xu, MT; Hong, YT; Gao, CC; Wu, ZP; Han, HT; Sun, X; Gao, RL; Yang, SF; Li, SX; Tian, JK; Zhang, JB				Shu, Yu-han; Yuan, Hua-hua; Xu, Meng-ting; Hong, Ye-ting; Gao, Cheng-cheng; Wu, Zhi-pan; Han, Hao-te; Sun, Xin; Gao, Rui-lan; Yang, Si-fu; Li, Shou-xin; Tian, Jing-kui; Zhang, Jian-bin			A novel Diels-Alder adduct of mulberry leaves exerts anticancer effect through autophagy-mediated cell death	ACTA PHARMACOLOGICA SINICA			English	Article						Guangsangon E; autophagy; ER stress; respiratory cancer	COLORECTAL-CANCER; OXIDATIVE STRESS; APOPTOSIS; ACTIVATION; INJURY	Guangsangon E (GSE) is a novel Diels-Alder adduct isolated from leaves ofMorus albaL, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP-LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as "autophagy-mediated cell death." Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.	[Shu, Yu-han; Yuan, Hua-hua; Xu, Meng-ting; Gao, Cheng-cheng; Wu, Zhi-pan; Han, Hao-te; Li, Shou-xin; Tian, Jing-kui] Zhejiang Univ, Coll Biomed Engn & Instrument Sci, Hangzhou 310058, Peoples R China; [Shu, Yu-han; Zhang, Jian-bin] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Clin Res Inst, Peoples Hosp, Hangzhou 310014, Peoples R China; [Hong, Ye-ting] Hangzhou Med Coll, Hangzhou 310053, Peoples R China; [Sun, Xin; Yang, Si-fu] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Dept Oncol, Peoples Hosp, Hangzhou 310014, Peoples R China; [Gao, Rui-lan] Zhejiang Chinese Med Univ, Dept Hematol, Affiliated Hosp 1, Hangzhou 310006, Peoples R China; [Li, Shou-xin; Tian, Jing-kui] Zhejiang Univ, Zhejiang Malaysia Joint Res Ctr Tradit Med, Key Lab Biomed Engn, Minist Educ, Hangzhou 310058, Peoples R China		Tian, JK (corresponding author), Zhejiang Univ, Coll Biomed Engn & Instrument Sci, Hangzhou 310058, Peoples R China.; Zhang, JB (corresponding author), Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Clin Res Inst, Peoples Hosp, Hangzhou 310014, Peoples R China.; Tian, JK (corresponding author), Zhejiang Univ, Zhejiang Malaysia Joint Res Ctr Tradit Med, Key Lab Biomed Engn, Minist Educ, Hangzhou 310058, Peoples R China.	tjk@zju.edu.cn; zhangjianbin@hmc.edu.cn			National Science and Technology Major Project of China [2019ZX09301004]; Zhejiang Provincial Science and Technology Planning Project [2016C04005]; Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program; Zhejiang Provincial Qianjiang Talents Program; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LR18H160002]; Traditional Chinese Medicine Scientific Research Fund Project of Zhejiang Province [2018ZB010]; Zhejiang Provincial Program in Medicine and Health Sciences and Technology [2018253645, 2018KY223]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81703907]	This work was supported by the National Science and Technology Major Project of China (2019ZX09301004), Zhejiang Provincial Science and Technology Planning Project (2016C04005) to JKT; Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program, Zhejiang Provincial Qianjiang Talents Program, Zhejiang Provincial Natural Science Foundation (LR18H160002), Traditional Chinese Medicine Scientific Research Fund Project of Zhejiang Province (2018ZB010), Zhejiang Provincial Program in Medicine and Health Sciences and Technology (2018253645) to JBZ; National Natural Science Foundation of China (81703907) to XS; Zhejiang Provincial Program in Medicine and Health Sciences and Technology (2018KY223) to SFY.	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Sin.	MAY	2021	42	5					780	790		10.1038/s41401-020-0492-5		AUG 2020	11	Chemistry, Multidisciplinary; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	RQ2FF	WOS:000560981000001	32814819				2022-04-25	
J	Tang, B; Wang, K; Jia, YP; Zhu, P; Fang, Y; Zhang, ZJ; Mao, XH; Li, Q; Zeng, DZ				Tang, Bin; Wang, Kun; Jia, Yin-ping; Zhu, Pan; Fang, Yao; Zhang, Zhu-jun; Mao, Xu-hu; Li, Qian; Zeng, Dong-zhu			Fusobacterium nucleatum-Induced Impairment of Autophagic Flux Enhances the Expression of Proinflammatory Cytokines via ROS in Caco-2 Cells	PLOS ONE			English	Article							EPITHELIAL-CELLS; VACUOLATING CYTOTOXIN; COLORECTAL-CANCER; INFLAMMATION; GENERATION; INFECTION; PATHWAY; DISEASE; MECHANISMS; MICROBIOTA	Fusobacterium nucleatum (F. nucleatum) plays a critical role in gastrointestinal inflammation. However, the exact mechanism by which F. nucleatum contributes to inflammation is unclear. In the present study, it was revealed that F. nucleatum could induce the production of proinflammatory cytokines (IL- 8, IL- 1 beta and TNF-alpha) and reactive oxygen species (ROS) in Caco-2 colorectal) adenocarcinoma cells. Furthermore, ROS scavengers (NAC or Tiron) could decrease the production of proinflammatory cytokines during F. nucleatum infection. In addition, we observed that autophagy is impaired in Caco-2 cells after F. nucleatum infection. The production of proinflammatory cytokines and ROS induced by F. nucleatum was enhanced with either autophagy pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (ATG5 or ATG12) in Caco-2 cells. Taken together, these results indicate that F. nucleatum-induced impairment of autophagic flux enhances the expression of proinflammatory cytokines via ROS in Caco-2 Cells.	[Tang, Bin; Wang, Kun; Jia, Yin-ping; Zhu, Pan; Fang, Yao; Zhang, Zhu-jun; Mao, Xu-hu; Li, Qian] Third Mil Med Univ, Southwest Hosp, Dept Clin Microbiol & Immunol, Chongqing, Peoples R China; [Tang, Bin; Wang, Kun; Jia, Yin-ping; Zhu, Pan; Fang, Yao; Zhang, Zhu-jun; Mao, Xu-hu; Li, Qian] Third Mil Med Univ, Coll Med Lab Sci, Chongqing, Peoples R China; [Zeng, Dong-zhu] Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing, Peoples R China; [Zeng, Dong-zhu] Third Mil Med Univ, Southwest Hosp, Ctr Minimal Invas Gastrointestinal Surg, Chongqing, Peoples R China; [Tang, Bin] Emei Sanat PLA Rocket Force, Emeishan, Peoples R China		Li, Q (corresponding author), Third Mil Med Univ, Southwest Hosp, Dept Clin Microbiol & Immunol, Chongqing, Peoples R China.; Li, Q (corresponding author), Third Mil Med Univ, Coll Med Lab Sci, Chongqing, Peoples R China.; Zeng, DZ (corresponding author), Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing, Peoples R China.; Zeng, DZ (corresponding author), Third Mil Med Univ, Southwest Hosp, Ctr Minimal Invas Gastrointestinal Surg, Chongqing, Peoples R China.	liqianjane@163.com; zdz1140@163.com	bin, tang/AAK-9399-2020	bin, tang/0000-0002-1762-3883	National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81301482, 81501796]; project of medical science and technology for training youth scholars of PLA [14QNP054]	This work was supported by a grant from National Natural Science Foundation of China (NSFC, 81301482 and 81501796), and the project of medical science and technology for training youth scholars of PLA (14QNP054).; This work was supported by Grant Nos. 81301482 (for B.T.) and 81501796 (for Q.L.) from National Natural Science Foundation of China (NSFC,), and the project of medical science and technology for training youth scholars of PLA (14QNP054) (for B.T.).	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J	Benigno, SJ; Oyong, G; Licayan, JJ; Sumayao, R				Benigno, Sol Joaquin; Oyong, Glenn; Licayan, Josafat John; Sumayao, Rodolfo, Jr.			Antidesma bunius aqueous crude extract promotes cell death via modulation of redox-sensitive and autophagy-associated genes in HCT 116 human-derived colorectal cancer cells	ARCHIVES OF BIOLOGICAL SCIENCES			English	Article						Antidesma bunius; colorectal cancer; oxidative stress; antioxidants; autophagy; mitochondria	ANTIOXIDANT ACTIVITIES	Antidesma bunius fruit was previously shown to exhibit antioxidant properties, but its anticancer activities remain underexplored. We hypothesized that the phytochemicals in this fruit can influence mitochondrial integrity and can modulate stress-responsive genes in cancer cells. The present study investigated the effects of A. bunius fruit aqueous crude extract (A. bunius ACE) on the viability, redox status, and mitochondrial transmembrane potential (MTP) using a colorectal cancer cell line, HCT 116. The expression of key genes associated with oxidative stress and autophagy was also determined. Treatment of cells with A. bunius ACE resulted in a similar to 27% reduction in viability, coupled with a marked decrease in oxidative stress index by similar to 59%. This was accompanied by the upregulation of NRF2 and NRF2-dependent genes. MTP increased similar to 3-fold in response to A. bunius ACE. The expression of BECLIN1, ATG5, and LC3 genes also increased. Our results indicate that the phytochemicals in A. bunius fruits enhance mitochondrial integrity and modulate the expression of stress-responsive genes, which may be responsible for the mitigation of oxidative stress in cancer cells. These alterations may be involved in the cascade of events leading to cancer cell death effected by A. bunius.	[Benigno, Sol Joaquin; Licayan, Josafat John; Sumayao, Rodolfo, Jr.] De La Salle Univ, Chem Dept, 2401 Taft Ave, Manila 0922, Philippines; [Oyong, Glenn] De La Salle Univ, Ctr Nat Sci & Ecol Res CENSER, 2401 Taft Ave, Manila 0922, Philippines		Sumayao, R (corresponding author), De La Salle Univ, Chem Dept, 2401 Taft Ave, Manila 0922, Philippines.	rodolfo.sumayao@dlsu.edu.ph	Oyong, Glenn/A-6142-2019	Oyong, Glenn/0000-0001-8224-9034	De La Salle University Research Fellowship Program	This study was supported by the De La Salle University Research Fellowship Program.	Bakar A, 2016, EVID-BASED COMPL ALT, V2016; Barcelo J. 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Sci.		2020	72	3					433	443		10.2298/ABS200703037B			11	Biology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics	OJ4NI	WOS:000583939900014		gold			2022-04-25	
J	Brunel, A; Begaud, G; Auger, C; Durand, S; Battu, S; Bessette, B; Verdier, M				Brunel, Aude; Begaud, Gaelle; Auger, Clement; Durand, Stephanie; Battu, Serge; Bessette, Barbara; Verdier, Mireille			Autophagy and Extracellular Vesicles, Connected to rabGTPase Family, Support Aggressiveness in Cancer Stem Cells	CELLS			English	Review						rab family; autophagy; extracellular vesicles; cancer stem cells	GLIOMA-INITIATING CELLS; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER; COLORECTAL-CANCER; MULTIVESICULAR BODIES; DYNAMIC EQUILIBRIUM; ENDOTHELIAL-CELLS; EXOSOME SECRETION; PROGENITOR CELLS; PROSTATE-CANCER	Even though cancers have been widely studied and real advances in therapeutic care have been made in the last few decades, relapses are still frequently observed, often due to therapeutic resistance. Cancer Stem Cells (CSCs) are, in part, responsible for this resistance. They are able to survive harsh conditions such as hypoxia or nutrient deprivation. Autophagy and Extracellular Vesicles (EVs) secretion are cellular processes that help CSC survival. Autophagy is a recycling process and EVs secretion is essential for cell-to-cell communication. Their roles in stemness maintenance have been well described. A common pathway involved in these processes is vesicular trafficking, and subsequently, regulation by Rab GTPases. In this review, we analyze the role played by Rab GTPases in stemness status, either directly or through their regulation of autophagy and EVs secretion.	[Brunel, Aude; Begaud, Gaelle; Auger, Clement; Durand, Stephanie; Battu, Serge; Bessette, Barbara; Verdier, Mireille] Univ Limoges, Fac Med, GEIST Inst, EA 3842,CAPTuR, 2 Rue Dr Marcland, F-87025 Limoges, France		Verdier, M (corresponding author), Univ Limoges, Fac Med, GEIST Inst, EA 3842,CAPTuR, 2 Rue Dr Marcland, F-87025 Limoges, France.	aude.brunel@unilim.fr; gaelle.begaud@unilim.fr; clement.auger@unilim.fr; stephanie.durand@unilim.fr; serge.battu@unilim.fr; barbara.bessette@unilim.fr; mireille.verdier@unilim.fr		Bessette, Barbara/0000-0001-6673-3694; DURAND, Stephanie/0000-0003-2434-9429; Auger, Clement/0000-0001-5260-535X; Begaud, Gaelle/0000-0003-4771-8979; VERDIER, Mireille/0000-0002-8162-4856	La Ligue contre le cancer, comite de la Haute-Vienne	This research was funded by La Ligue contre le cancer, comite de la Haute-Vienne.	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J	Schaaf, MBE; Keulers, TG; Vooijs, MA; Rouschop, KMA				Schaaf, Marco B. E.; Keulers, Tom G.; Vooijs, Marc A.; Rouschop, Kasper M. A.			LC3/GABARAP family proteins: autophagy-(un) related functions	FASEB JOURNAL			English	Article						cancer; ATG7; Atg8 orthologues; autophagosome	RECEPTOR-ASSOCIATED PROTEIN; GABA(A) RECEPTOR; AUTOPHAGOSOME BIOGENESIS; SKELETAL-MUSCLE; MEMBRANE-FUSION; ANTIBACTERIAL AUTOPHAGY; REGULATES AUTOPHAGY; GLYCOGEN-METABOLISM; COLORECTAL-CANCER; PLASMA-MEMBRANE	From yeast to mammals, autophagy is an important mechanism for sustaining cellular homeostasis through facilitating the degradation and recycling of aged and cytotoxic components. During autophagy, cargo is captured in double-membraned vesicles, the autophagosomes, and degraded through lysosomal fusion. In yeast, autophagy initiation, cargo recognition, cargo engulfment, and vesicle closure is Atg8 dependent. In higher eukaryotes, Atg8 has evolved into the LC3/GABARAP protein family, consisting of 7 family proteins [LC3A(2 splice variants), LC3B, LC3C, GABARAP, GABARAPL1, and GABARAPL2]. LC3B, the most studied family protein, is associated with autophagosome development and maturation and is used to monitor autophagic activity. Given the high homology, the other LC3/GABARAP family proteins are often presumed to fulfill similar functions. Nevertheless, substantial evidence shows that the LC3/GABARAP family proteins are unique in function and important in autophagy-independent mechanisms. In this review, we discuss the current knowledge and functions of the LC3/GABARAP family proteins. We focus on processing of the individual family proteins and their role in autophagy initiation, cargo recognition, vesicle closure, and trafficking, a complex and tightly regulated process that requires selective presentation and recruitment of these family proteins. In addition, functions unrelated to autophagy of the LC3/GABARAP protein family members are discussed.-Schaaf, M. B. E., Keulers, T. G, Vooijs, M. A., Rouschop, K. M. A. LC3/GABARAP family proteins: autophagy-(un) related functions.	[Schaaf, Marco B. E.; Keulers, Tom G.; Vooijs, Marc A.; Rouschop, Kasper M. A.] Maastricht Univ, Med Ctr, Dept Radiat Oncol, Maastro Lab,GROW Sch Oncol & Dev Biol, Maastricht, Netherlands		Rouschop, KMA (corresponding author), Maastricht Univ, Med Ctr, Univ Singel 50,Room 3-318, NL-6200 MD Maastricht, Netherlands.	kasper.rouschop@maastrichtuniversity.nl	Vooijs, Marc/K-3522-2019	Rouschop, Kasper/0000-0002-4208-5415	Dutch Cancer Society (KWF)KWF Kankerbestrijding [UM 2012-5506, 2015-7735]; Worldwide Cancer Research Award [16-0265]; European Research Council under the European Union's Seventh Framework Programme (FP)/ERC GrantEuropean Research Council (ERC) [617060]	The authors apologize to researchers whose work could not be included due to the extensive field of autophagy. This work was supported by the Dutch Cancer Society (KWF) Grants UM 2012-5506 and 2015-7735 (to K.R.), Worldwide Cancer Research Award 16-0265 (to K.R.), and European Research Council under the European Union's Seventh Framework Programme (FP) 2007-2013/ERC Grant Agreement 617060 (to M.V.).	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DEC	2016	30	12					3961	3978		10.1096/fj.201600698R			18	Biochemistry & Molecular Biology; Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology	EC5UG	WOS:000388201500005	27601442		Y	N	2022-04-25	
J	Renga, G; Oikonomou, V; Stincardini, C; Pariano, M; Borghi, M; Costantini, C; Bartoli, A; Garaci, E; Goldstein, AL; Romani, L				Renga, Giorgia; Oikonomou, Vasilis; Stincardini, Claudia; Pariano, Marilena; Borghi, Monica; Costantini, Claudio; Bartoli, Andrea; Garaci, Enrico; Goldstein, Allan L.; Romani, Luigina			Thymosin 4 limits inflammation through autophagy	EXPERT OPINION ON BIOLOGICAL THERAPY			English	Review						Autophagy; chronic granulomatous disease; inflammation; thymosin 4	CHRONIC GRANULOMATOUS-DISEASE; INTEGRIN-LINKED KINASE; LC3-ASSOCIATED PHAGOCYTOSIS; ASPERGILLUS-FUMIGATUS; COLORECTAL-CARCINOMA; IFN-GAMMA; REPAIR; INFLAMMASOMES; IMMUNITY; ACTIN	Introduction: Thymosin 4 (T4) is a thymic hormone with multiple and different intracellular and extracellular activities affecting wound healing, inflammation, fibrosis and tissue regeneration. As the failure to resolve inflammation leads to uncontrolled inflammatory pathology which underlies many chronic diseases, the endogenous pathway through which T4 may promote inflammation resolution becomes of great interest. In this review, we discuss data highlighting the efficacy of T4 in resolving inflammation by restoring autophagy.Areas covered: The authors provide an overview of the T4's anti-inflammatory properties in several pathologies and provide preliminary evidence on the ability of T4 to resolve inflammation via the promotion of non-canonical autophagy associated with the activation of the DAP kinase anti-inflammatory function.Expert opinion: Based on its multitasking activity in various animal studies, including tissue repair and prevention of chronic inflammation, T4 may represent a potential, novel treatment for inflammatory diseases associated with defective autophagy.	[Renga, Giorgia; Oikonomou, Vasilis; Stincardini, Claudia; Pariano, Marilena; Borghi, Monica; Costantini, Claudio; Bartoli, Andrea; Romani, Luigina] Univ Perugia, Dept Expt Med, I-06132 Perugia, Italy; [Garaci, Enrico] Univ San Raffaele, Rome, Italy; [Garaci, Enrico] IRCCS San Raffaele, Rome, Italy; [Goldstein, Allan L.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, Washington, DC 20052 USA		Renga, G (corresponding author), Univ Perugia, Dept Expt Med, I-06132 Perugia, Italy.	rengagiorgia@gmail.com	Oikonomou, Vasileios/ABC-7703-2021; Romani, Luigina/O-9987-2018; GARACI, ENRICO/AAB-3349-2021	Oikonomou, Vasileios/0000-0002-7553-0159; Renga, Giorgia/0000-0002-9762-6493; pariano, marilena/0000-0002-9896-171X; Romani, Luigina/0000-0002-1356-525X; Borghi, Monica/0000-0002-6337-5999; Costantini, Claudio/0000-0002-1433-7830	European Research CouncilEuropean Research Council (ERC)European Commission [ERC-2011-AdG-293714]	This study was supported by the European Research Council (ERC-2011-AdG-293714 to LR). The data contained in this paper were presented at the 5th International Symposium on Thymosins in Health and Disease, Washington DC, USA, November 15-17, 2017.	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Biol. Ther.		2018	18			1			171	175		10.1080/14712598.2018.1473854			5	Biotechnology & Applied Microbiology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Research & Experimental Medicine	GP1QR	WOS:000440592000025	30063848				2022-04-25	
J	Zhang, H; Wei, PT; Lv, WW; Han, XT; Yang, JH; Qin, SF				Zhang, Han; Wei, Pengtao; Lv, Wenwei; Han, Xingtao; Yang, Jinhui; Qin, Shuaifeng			Long noncoding RNA lnc-DILC stabilizes PTEN and suppresses clear cell renal cell carcinoma progression	CELL AND BIOSCIENCE			English	Article						Ubiquitination; PTEN; WWP2; USP11	PROMOTES; CANCER; GROWTH; PHOSPHORYLATION; METASTASIS; EXPRESSION; AUTOPHAGY; INVASION; PROTEIN; CERNA	Background: Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are crucial regulators affecting the progression of human cancers. Recently, lncRNA downregulated in liver cancer stem cells (lnc-DILC) was identified to function as a tumor suppressor inhibiting the tumorigenesis and metastasis in liver cancer and colorectal cancer. However, to date, little is known about the functional roles of lnc-DILC in modulating malignant phenotypes of clear cell renal cell carcinoma (ccRCC) cells. Methods: lnc-DILC expression in human ccRCC tissues was detected by qRT-PCR. Overexpression and knockdown experiments were carried out to determine the effects of lnc-DILC on ccRCC cell proliferation, migration and invasion. To reveal the underlying mechanisms of lnc-DILC functions in ccRCC cells. RNA immunoprecipitation, RNA pull-down, in vivo ubiquitination, co-immunoprecipitation and western blot assays were performed. Results: Here, we identified that lnc-DILC levels were dramatically downregulated in ccRCC tissues. Loss of lncDILC expression was correlated with larger tumor size, advanced tumor grade and lymph node metastasis, and also predicted worse prognosis in patients with ccRCC. Functionally, knockdown and overexpression experiments demonstrated that lnc-DILC inhibited cell proliferation, migration and invasion in ccRCC cells. Mechanistic investigation revealed that lnc-DILC bound to tumor suppressor PTEN and suppressed its degradation. lnc-DILC repressed the PTEN ubiquitination through blocking the interaction between PTEN and E3 ubiquitin ligase WWP2 and recruiting the deubiquitinase USP11 to PTEN. Moreover, we demonstrated that PTEN-AKT signaling was crucial for lnc-DILC-mediated suppressive effects. Conclusions: In summary, our research revealed a novel mechanism by which lnc-DILC regulates PTEN stability via WWP2 and USP11, and shed light on potential therapeutic strategies by the restoration of lnc-DILC expression in patients with ccRCC.	[Zhang, Han; Wei, Pengtao; Lv, Wenwei; Han, Xingtao; Yang, Jinhui; Qin, Shuaifeng] Luoyang Cent Hosp, Urol Dept, 288 Zhongzhou Rd, Luoyang 471000, Henan, Peoples R China		Zhang, H (corresponding author), Luoyang Cent Hosp, Urol Dept, 288 Zhongzhou Rd, Luoyang 471000, Henan, Peoples R China.	zhanghanlyh@163.com			Clinical study on anatomic adrenalectomy through abdomen pathway Grant [1301070A-5]	The research was supported by Clinical study on anatomic adrenalectomy through abdomen pathway Grant (No: 1301070A-5).	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OCT 2	2019	9	1							81	10.1186/s13578-019-0345-4			13	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	JF2GA	WOS:000491202700001	31592114	Green Published, gold			2022-04-25	
J	Lin, GG; Andrejeva, G; Te Fong, ACW; Hill, DK; Orton, MR; Parkes, HG; Koh, DM; Robinson, SP; Leach, MO; Eykyn, TR; Chung, YL				Lin, Gigin; Andrejeva, Gabriela; Te Fong, Anne-Christine Wong; Hill, Deborah K.; Orton, Matthew R.; Parkes, Harry G.; Koh, Dow-Mu; Robinson, Simon P.; Leach, Martin O.; Eykyn, Thomas R.; Chung, Yuen-Li			Reduced Warburg Effect in Cancer Cells Undergoing Autophagy: Steady-State H-1-MRS and Real-Time Hyperpolarized C-13-MRS Studies	PLOS ONE			English	Article							TUMOR RESPONSE; BREAST; PYRUVATE; LACTATE; INHIBITOR; INDUCTION; PROSTATE; RECOVERY; SURVIVAL; BRAIN	Autophagy is a highly regulated, energy dependent cellular process where proteins, organelles and cytoplasm are sequestered in autophagosomes and digested to sustain cellular homeostasis. We hypothesized that during autophagy induced in cancer cells by i) starvation through serum and amino acid deprivation or ii) treatment with PI-103, a class I PI3K/mTOR inhibitor, glycolytic metabolism would be affected, reducing flux to lactate, and that this effect may be reversible. We probed metabolism during autophagy in colorectal HT29 and HCT116 Bax knock-out cells using hyperpolarized C-13-magnetic resonance spectroscopy (MRS) and steady-state H-1-MRS. 24 hr PI103-treatment or starvation caused significant reduction in the apparent forward rate constant (k(PL)) for pyruvate to lactate exchange compared with controls in HT29 (100 mu M PI-103: 82%, p = 0.05) and HCT116 Bax-ko cells (10 mu M PI-103: 53%, p = 0.05; 20 mu M PI-103: 42%, p<0.0001; starvation: 52%, p<0.001), associated with reduced lactate excretion and intracellular lactate in all cases, and unchanged lactate dehydrogenase (LDH) activity and increased NAD+/NADH ratio following PI103 treatment or decreased LDH activity and unchanged NAD+/NADH ratio following starvation. After 48 hr recovery from PI103 treatment, k(PL) remained below control levels in HT29 cells (74%, p = 0.02), and increased above treated values, but remained below 24 hr vehicle-treated control levels in HCT116 Bax-ko cells (65%, p = 0.004) both were accompanied by sustained reduction in lactate excretion, recovery of NAD+/NADH ratio and intracellular lactate. Following recovery from starvation, k(PL) was significantly higher than 24 hr vehicle-treated controls (140%, p = 0.05), associated with increased LDH activity and total cellular NAD(H). Changes in k(PL) and cellular and excreted lactate provided measureable indicators of the major metabolic processes accompanying starvation-and drug-induced autophagy. The changes are reversible, returning towards and exceeding control values on cellular recovery, which potentially identifies resistance. k(PL) (hyperpolarized C-13-MRS) and lactate (H-1-MRS) provide useful biomarkers for the autophagic process, enabling non-invasive monitoring of the Warburg effect.	[Lin, Gigin; Andrejeva, Gabriela; Te Fong, Anne-Christine Wong; Hill, Deborah K.; Orton, Matthew R.; Parkes, Harry G.; Koh, Dow-Mu; Robinson, Simon P.; Leach, Martin O.; Eykyn, Thomas R.; Chung, Yuen-Li] Canc Res UK, Sutton, Surrey, England; [Lin, Gigin; Andrejeva, Gabriela; Te Fong, Anne-Christine Wong; Hill, Deborah K.; Orton, Matthew R.; Parkes, Harry G.; Koh, Dow-Mu; Robinson, Simon P.; Leach, Martin O.; Eykyn, Thomas R.; Chung, Yuen-Li] Inst Canc Res, Div Radiotherapy & Imaging, EPSRC Canc Imaging Ctr, Sutton, Surrey, England; [Lin, Gigin; Andrejeva, Gabriela; Te Fong, Anne-Christine Wong; Hill, Deborah K.; Orton, Matthew R.; Parkes, Harry G.; Koh, Dow-Mu; Robinson, Simon P.; Leach, Martin O.; Eykyn, Thomas R.; Chung, Yuen-Li] Royal Marsden Hosp, Sutton, Surrey, England; [Lin, Gigin] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp Linkou, Dept Med Imaging & Intervent, Taoyuan, Taiwan; [Eykyn, Thomas R.] St Thomas Hosp, Rayne Inst, Kings Coll London, Div Imaging Sci & Biomed Engn, London SE1 7EH, England		Leach, MO (corresponding author), Canc Res UK, Sutton, Surrey, England.	Martin.Leach@icr.ac.uk; ylichung@icr.ac.uk	Chung, Yuen-Li/K-2269-2019; leach, martin o/C-2248-2008; Parkes, Harold G/I-7412-2012; Lin, Gigin/A-2676-2017; Eykyn, Thomas/J-3284-2016	Chung, Yuen-Li/0000-0003-0807-1658; leach, martin o/0000-0002-0756-5368; Lin, Gigin/0000-0001-7246-1058; Eykyn, Thomas/0000-0003-1768-3808; Robinson, Simon/0000-0003-4101-7274; Andrejeva, Gabriela/0000-0002-3508-7682; Parkes, Harold/0000-0003-4981-864X; Hill, Deborah/0000-0002-6441-5489; Koh, Dow-Mu/0000-0001-7654-8011	Cancer Research UKCancer Research UK; EPSRC Cancer Imaging CentreUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC); MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC); Department of Health (England) [C1060/A10334]; NHS; Chang Gung Medical Foundation (Taiwan) [CMRPG370443, CMRPG3B1922]; Cancer Research UKCancer Research UK [16464] 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 [1100738] Funding Source: researchfish; National Institute for Health ResearchNational Institute for Health Research (NIHR) [NF-SI-0512-10162] Funding Source: researchfish; EPSRCUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [EP/H046526/1] Funding Source: UKRI	The authors acknowledge the support received from the Cancer Research UK and EPSRC Cancer Imaging Centre in association with the MRC and Department of Health (England) grant C1060/A10334, also NHS funding to the NIHR Biomedical Research Centre, MRC-funded studentship, also Chang Gung Medical Foundation (Taiwan) grants CMRPG370443 and CMRPG3B1922. MOL is an NIHR Senior Investigator. The authors also thank Alice Warley at the King's College London Centre for Ultrastructural Imaging (CUI) for assistance with electron microscopy. 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	Cioccoloni, G; Soteriou, C; Websdale, A; Wallis, L; Zulyniak, MA; Thorne, JL				Cioccoloni, Giorgia; Soteriou, Chrysa; Websdale, Alex; Wallis, Lewis; Zulyniak, Michael A.; Thorne, James L.			Phytosterols and phytostanols and the hallmarks of cancer in model organisms: A systematic review and meta-analysis	CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION			English	Review						Phytosterol; phytostanol; cancer; neoplasm; cancer hallmarks; molecular mechanism	BETA-SITOSTEROL GLUCOSIDE; CELL PROLIFERATION; TUMOR-FORMATION; BREAST-CANCER; IN-VITRO; GROWTH; RISK; APOPTOSIS; AUTOPHAGY; MICE	Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products whose intake is inversely associated with incidence and prognosis of several cancers. Randomized cancer prevention trials in humans are unfeasible due to time and cost yet the cellular processes and signaling cascades that underpin anti-cancer effects of these phytochemicals have been explored extensively in vitro and in preclinical in vivo models. Here we have performed an original systematic review, meta-analysis, and qualitative interpretation of literature published up to June 2020. MEDLINE, Scopus, and hand-searching identified 408 unique records that were screened leading to 32 original articles that had investigated the effects of phytosterols or phytostanols on cancer biology in preclinical models. Data was extracted from 22 publications for meta-analysis. Phytosterols were most commonly studied and found to reduce primary and metastatic tumor burden in all cancer sites evaluated. Expression of pAKT, and markers of metastasis (alkaline phosphatase, matrix metalloproteases, epithelial to mesenchymal transcription factors, lung and brain colonization), angiogenesis (vascular endothelial growth factor, CD31), and proliferation (Ki67, proliferating cell nuclear antigen) were consistently reduced by phytosterol treatment in breast and colorectal cancer. Very high dose treatment (equivalent to 0.2-1 g/kg body weight not easily achievable through diet or supplementation in humans) was associated with adverse events including poor gut health and intestinal adenoma development. Phytosterols and phytostanols are already clinically recommended for cardiovascular disease risk reduction, and represent promising anti-cancer agents that could be delivered in clinic and to the general population at low cost, with a well understood safety profile, and now with a robust understanding of mechanism-of-action.	[Cioccoloni, Giorgia; Soteriou, Chrysa; Websdale, Alex; Wallis, Lewis; Zulyniak, Michael A.; Thorne, James L.] Univ Leeds, Food Sci & Nutr, Leeds LS2 9JT, W Yorkshire, England		Thorne, JL (corresponding author), Univ Leeds, Food Sci & Nutr, Leeds LS2 9JT, W Yorkshire, England.	j.l.thorne@leeds.ac.uk		Websdale, Alex/0000-0002-6147-933X; Soteriou, Chrysa/0000-0002-2808-1215; Zulyniak, Michael/0000-0003-4944-5521; Wallis, Lewis/0000-0001-5800-3245; Cioccoloni, Giorgia/0000-0003-0102-9182; Thorne, James/0000-0002-3037-8528	Breast Cancer Action [3T57/9R17-02]; University of Leeds	GC is supported by a research grant from Breast Cancer Action (3T57/9R17-02). CS and AW are supported by doctoral scholarships from the University of Leeds.	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J	Bobbili, MR; Mader, RM; Grillari, J; Dellago, H				Bobbili, Madhusudhan Reddy; Mader, Robert M.; Grillari, Johannes; Dellago, Hanna			OncomiR-17-5p: alarm signal in cancer?	ONCOTARGET			English	Review						miRNA; miR-17-5p; biomarker; cancer	TUMOR-SUPPRESSOR GENE; MIR-17-92 CLUSTER; MICRORNA EXPRESSION; CELL-PROLIFERATION; HEPATOCELLULAR-CARCINOMA; NONCODING RNAS; GASTRIC-CANCER; MOLECULAR MARKERS; MYELOID-LEUKEMIA; MATURE MIR-17-5P	Soon after microRNAs entered the stage as novel regulators of gene expression, they were found to regulate -and to be regulated by- the development, progression and aggressiveness of virtually all human types of cancer. Therefore, miRNAs in general harbor a huge potential as diagnostic and prognostic markers as well as potential therapeutic targets in cancer. The miR-17-92 cluster was found to be overexpressed in many human cancers and to promote unrestrained cell growth, and has therefore been termed onco-miR-1. In addition, its expression is often dysregulated in many other diseases. MiR-17-5p, its most prominent member, is an essential regulator of fundamental cellular processes like proliferation, autophagy and apoptosis, and its deficiency is neonatally lethal in the mouse. Many cancer types are associated with elevated miR-17-5p expression, and the degree of overexpression might correlate with cancer aggressiveness and responsiveness to chemotherapeutics - suggesting miR-17-5p to be an alarm signal. Liver, gastric or colorectal cancers are examples where miR-17-5p has been observed exclusively as an oncogene, while, in other cancer types, like breast, prostate and lung cancer, the role of miR-17-5p is not as clear-cut, and it might also act as tumor-suppressor. However, in all cancer types studied so far, miR-17-5p has been found at elevated levels in the circulation. In this review, we therefore recapitulate the current state of knowledge about miR-17-5p in the context of cancer, and suggest that elevated miR-17-5p levels in the plasma might be a sensitive and early alarm signal for cancer ('alarmiR'), albeit not a specific alarm for a specific type of tumor.	[Bobbili, Madhusudhan Reddy; Grillari, Johannes] BOKU Univ Nat Resources & Life Sci, Dept Biotechnol, Vienna, Austria; [Grillari, Johannes; Dellago, Hanna] BOKU Univ Nat Resources & Life Sci, Dept Biotechnol, Christian Doppler Lab Biotechnol Skin Aging, Vienna, Austria; [Mader, Robert M.] Med Univ Vienna, Comprehens Canc Ctr, Dept Med 1, Vienna, Austria; [Grillari, Johannes] Evercyte GmbH, Vienna, Austria; [Dellago, Hanna] TAmiRNA GmbH, Vienna, Austria		Grillari, J (corresponding author), BOKU Univ Nat Resources & Life Sci, Dept Biotechnol, Vienna, Austria.	johannes.grillari@boku.ac.at	Grillari, Johannes/B-2967-2011	Grillari, Johannes/0000-0001-5474-6332; Mader, Robert/0000-0003-3017-8240	BioToP 'Biomolecular technology of proteins' PhD Programme; Austrian Science Funds (FWF) ProjectAustrian Science Fund (FWF) [W1224]; Christian Doppler Society; Austrian Federal Ministry of Economy, Family and Youth; National Foundation for Research, Technology and Development; FP7 EU project Frailomic; FP7 EU project Sybil	This work was funded by the BioToP 'Biomolecular technology of proteins' PhD Programme, Austrian Science Funds (FWF) Project W1224, and the Christian Doppler Society. The financial support by the Austrian Federal Ministry of Economy, Family and Youth, the National Foundation for Research, Technology and Development as well as the FP7 EU projects Frailomic and Sybil are also gratefully acknowledged.	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J	Zhen, HC; Li, GX; Zhao, PF; Zhang, Y; Wang, J; Yu, JX; Cao, BW				Zhen, Hongchao; Li, Guangxin; Zhao, Pengfei; Zhang, Ying; Wang, Jing; Yu, Junxian; Cao, Bangwei			Raltitrexed Enhances the Antitumor Effect of Apatinib in Human Esophageal Squamous Carcinoma Cells via Akt and Erk Pathways	ONCOTARGETS AND THERAPY			English	Article						raltitrexed; apatinib; antitumor; ESCC; Akt; Erk	ENDOTHELIAL GROWTH-FACTOR; SALVAGE TREATMENT; CANCER-CELL; PHASE-III; INHIBITOR; APOPTOSIS; CARDIOTOXICITY; PROLIFERATION; CHEMOTHERAPY; EFFICACY	Objective: Apatinib has been proved effective in the treatment of advanced gastric cancer and a variety of solid tumors. Raltitrexed is emerging as a promising alternative for treating advanced colorectal cancer in China. This work aims to study the combinatory antitumor effect of apatinib and raltitrexed on human esophageal squamous carcinoma cells (ESCC). Materials and Methods: Two VEGFR-2-positive human ESCC lines, KYSE-30 and TE-1, were treated with apatinib or raltitrexed, or both, then the cell proliferation rate was measured by MTS assay; cell migration and invasion were studied by transwell assays; cell apoptosis rate was determined by flow cytometry; cellular autophagy level affected was analyzed by Western blot analysis; finally, quantitative polymerase chain reaction (qPCR) was used to monitor transcription and Western blot was performed to check phosphorylation of apoptotic proteins after treatment. Results: Both apatinib and raltitrexed significantly inhibited KYSE-30 and TE-1 cell proliferation in a dose-dependent manner. Treatment with both drugs showed enhanced inhibitory effects on cell proliferation, migration, and invasiveness compared with apatinib monotherapy. Apoptosis percentages in both cell lines were also remarkably increased by the combined treatment. Moreover, the combination of apatinib and raltitrexed down-regulated mRNA level of the anti-apoptotic protein Bcl-2, while up-regulated pro-apoptotic protein PARP, Bax, and caspase-3 transcription. Western blot analysis showed that phosphorylation levels of Erk, Akt, and invasiveness-associated protein matrix metalloproteinases-9 (MMP-9) were decreased in the combination group. Conclusion: Taken together, these results indicate that raltitrexed enhances the antitumor effects of apatinib on human ESCC cells by down-regulating phosphorylation of Akt and Erk, implying a combination of raltitrexed and apatinib might be an effective option for treating esophageal squamous cell carcinoma patients.	[Zhen, Hongchao; Zhao, Pengfei; Zhang, Ying; Wang, Jing; Cao, Bangwei] Capital Med Univ, Beijing Friendship Hosp, Ctr Canc, 95 Yong An Rd, Beijing 100050, Peoples R China; [Li, Guangxin] Tsinghua Univ, Beijing Tsinghua Changgung Hosp, Sch Clin Med, Radiat Oncol, Beijing 102218, Peoples R China; [Yu, Junxian] Capital Med Univ, Beijing Friendship Hosp, Dept Pharm, Beijing 100050, Peoples R China		Cao, BW (corresponding author), Capital Med Univ, Beijing Friendship Hosp, Ctr Canc, 95 Yong An Rd, Beijing 100050, Peoples R China.	oncology@ccmu.edu.cn			Research Foundation of Beijing Friendship Hospital, Capital Medical University [yyqdkt2017-19]; Digestive Medical Coordinated Development Center of Beijing Hospitals Authority [XXT01]; Beijing key clinical specialist project funding (2018-2020); pilot project of clinical collaboration with traditional Chinese medicine and western medicine in major refractory disease-esophageal cancer [2019-ZX-005]	This work was supported by Grants from the Research Foundation of Beijing Friendship Hospital, Capital Medical University (No.yyqdkt2017-19); the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (to Bangwei Cao, No. XXT01); the Beijing key clinical specialist project funding (2018-2020); the pilot project of clinical collaboration with traditional Chinese medicine and western medicine in major refractory disease-esophageal cancer (to Bangwei Cao, No. 2019-ZX-005).	Adlung L, 2017, MOL SYST BIOL, V13, DOI 10.15252/msb.20167258; Asati V, 2016, EUR J MED CHEM, V109, P314, DOI 10.1016/j.ejmech.2016.01.012; Barillari G, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21124526; Candido S, 2016, BBA-MOL CELL RES, V1863, P438, DOI 10.1016/j.bbamcr.2015.08.010; Ding WX, 2019, CANCER CELL INT, V19, DOI 10.1186/s12935-019-0752-y; Ewald F, 2015, J CANCER, V6, P1195, DOI 10.7150/jca.12452; Frezzetti D, 2016, J CELL PHYSIOL, V231, P1514, DOI 10.1002/jcp.25243; Gou MM, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-22302-z; Hicklin DJ, 2005, J CLIN ONCOL, V23, P1011, DOI 10.1200/JCO.2005.06.081; Hu LJ, 2019, ONCOL LETT, V17, P1609, DOI 10.3892/ol.2018.9803; Hu XC, 2014, BMC CANCER, V14, DOI 10.1186/1471-2407-14-820; JACKMAN AL, 1995, EUR J CANCER, V31A, P1277, DOI 10.1016/0959-8049(95)00166-G; Kelly C, 2013, EUR J CANCER, V49, P2303, DOI 10.1016/j.ejca.2013.03.004; Kosmas C, 2008, J CANCER RES CLIN, V134, P75, DOI 10.1007/s00432-007-0250-9; Li F, 2017, ONCOTARGET, V8, P64471, DOI 10.18632/oncotarget.16293; Li HX, 2016, MED SCI MONITOR, V22, DOI 10.12659/MSM.899950; Li JQ, 2017, ONCOTARGETS THER, V10, P3965, DOI 10.2147/OTT.S132756; Li J, 2016, J CLIN ONCOL, V34, P1448, DOI 10.1200/JCO.2015.63.5995; Liang LJ, 2018, ONCOTARGETS THER, V11, P5821, DOI 10.2147/OTT.S174429; Lieto E, 2008, ANN SURG ONCOL, V15, P69, DOI 10.1245/s10434-007-9596-0; Luz Caio Cesar Floriano, 2018, Asian Pac J Cancer Prev, V19, P171; Ma YJ, 2020, BIOSCI BIOTECH BIOCH, V84, P743, DOI 10.1080/09168451.2019.1709789; McCubrey JA, 2007, BBA-MOL CELL RES, V1773, P1263, DOI 10.1016/j.bbamcr.2006.10.001; Pan WT, 2015, SCI REP-UK, V5, DOI 10.1038/srep11833; Parkin DM, 2005, CA-CANCER J CLIN, V55, P74, DOI 10.3322/canjclin.55.2.74; Planting A, 2005, EUR J CANCER, V41, P93, DOI 10.1016/j.ejca.2004.09.022; Qiu HF, 2018, CELL CYCLE, V17, P1235, DOI 10.1080/15384101.2018.1471315; Reni M, 2006, BRIT J CANCER, V94, P785, DOI 10.1038/sj.bjc.6603026; Saif MW, 2009, EXPERT OPIN DRUG SAF, V8, P191, DOI [10.1517/14740330902733961, 10.1517/14740330902733961 ]; Song ZB, 2017, ONCOTARGETS THER, V10, P1821, DOI 10.2147/OTT.S113435; Tian S, 2011, CANCER SCI, V102, P1374, DOI 10.1111/j.1349-7006.2011.01939.x; van Meerbeeck JP, 2005, J CLIN ONCOL, V23, P6881, DOI 10.1200/JCO.20005.14.589; Wei L, 2020, ONCOTARGETS THER, V13, P2459, DOI 10.2147/OTT.S238348; Wu J, 2018, ONCOTARGETS THER, V11, P2685, DOI 10.2147/OTT.S157129; Wu J, 2018, BIOMED PHARMACOTHER, V100, P176, DOI 10.1016/j.biopha.2018.01.140; Xu WW, 2015, ONCOTARGET, V6, P1790, DOI 10.18632/oncotarget.2781; Xue S, 2014, MOL MED REP, V10, P1927, DOI 10.3892/mmr.2014.2438; Yamazaki T, 2020, NAT IMMUNOL, V21, P1160, DOI 10.1038/s41590-020-0751-0; Yang L, 2017, INT J ONCOL, V51, P378, DOI 10.3892/ijo.2017.4015; Yang LG, 2018, ONCOTARGETS THER, V11, P5333, DOI 10.2147/OTT.S175507; Yang YS, 2017, ONCOTARGET, V8, P43397, DOI 10.18632/oncotarget.14762; Yu WC, 2018, MEDICINE, V97, DOI 10.1097/MD.0000000000009704; Zhao HW, 2016, ONCOL RES, V23, P237, DOI 10.3727/096504016X14562725373671	43	0	0	0	0	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2020	13						12325	12339		10.2147/OTT.S276125			15	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	PB9HH	WOS:000596622800005	33293826	Green Published, gold			2022-04-25	
J	Li, RG; Deng, H; Liu, XH; Chen, ZY; Wan, SS; Wang, L				Li, Ren-Gui; Deng, Huan; Liu, Xiu-Heng; Chen, Zhi-yuan; Wan, Shan-shan; Wang, Lei			Histone Methyltransferase G9a Promotes the Development of Renal Cancer through Epigenetic Silencing of Tumor Suppressor Gene SPINK5	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY			English	Article							PROTEIN EXPRESSION; COLORECTAL-CANCER; DNA METHYLATION; PROLIFERATION; METASTASIS; INHIBITOR; AUTOPHAGY; INVASION; PATHWAY; TARGET	Background. Renal cell carcinoma (RCC) accounts for approximately 2-3% of malignant tumors in adults, while clear cell renal cell carcinoma accounts for 70-85% of kidney cancer cases, with an increasing incidence worldwide. G9a is the second histone methyltransferase found in mammals, catalyzing lysine and histone methylation. It regulates gene transcription by catalyzing histone methylation and interacting with transcription factors to alter the tightness of histone-DNA binding. The main purpose of this study is to explore the role and mechanism of G9a in renal cell carcinoma. Methods. Firstly, we investigated the expression of G9a in 80 clinical tissues and four cell lines. Then, we explored the effect of G9a-specific inhibitor UNC0638 on proliferation, apoptosis, migration, and invasion of two renal cancer cell lines (786-O, SN12C). In order to study the specific mechanism, G9a knocking down renal cancer cell line was constructed by lentivirus. Finally, we identified the downstream target genes of G9a using ChIP experiments and rescue experiments. Results. The results showed that the specific G9a inhibitor UNC0638 significantly inhibited the proliferation, migration, and invasion of kidney cancer in vivo and in vitro; similar results were obtained after knocking down G9a. Meanwhile, we demonstrated that SPINK5 was one of the downstream target genes of G9a through ChIP assay and proved that G9a downregulate the expression of SPINK5 by methylation of H3K9me2. Therefore, targeting G9a might be a new approach to the treatment of kidney cancer. Conclusion. G9a was upregulated in renal cancer and could promote the development of renal cancer in vitro and in vivo. Furthermore, we identified SPINK5 as one of the downstream target genes of G9a. Therefore, targeting G9a might be a new treatment for kidney cancer.	[Li, Ren-Gui; Liu, Xiu-Heng; Chen, Zhi-yuan; Wang, Lei] Wuhan Univ, Dept Urol, Renmin Hosp, Wuhan, Peoples R China; [Li, Ren-Gui; Deng, Huan] Chongqing Univ, Canc Hosp, Chongqing, Peoples R China; [Deng, Huan] Wuhan Univ, Dept Gastroenterol, Renmin Hosp, Wuhan, Peoples R China; [Wan, Shan-shan] Wuhan Univ, Dept Ophthalmol, Renmin Hosp, Wuhan, Peoples R China		Wang, L (corresponding author), Wuhan Univ, Dept Urol, Renmin Hosp, Wuhan, Peoples R China.; Wan, SS (corresponding author), Wuhan Univ, Dept Ophthalmol, Renmin Hosp, Wuhan, Peoples R China.	2012302180010@whu.edu.cn; huangdeng@whu.edu.cn; drliuxh@126.com; 176023442@qq.com; ophwss@whu.edu.cn; drwanglei@whu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972408, 82000639]; Application and Basic Research Project of Wuhan City [2018060401011321]; Innovation Project of Medical School of Wuhan University [TFZZ2018017]	We thank Dr. Huan Deng for the assistance in statistical analysis. This study was supported by the National Natural Science Foundation of China (No. 81972408, No. 82000639), Application and Basic Research Project of Wuhan City (No. 2018060401011321), and Innovation Project of Medical School of Wuhan University (TFZZ2018017).	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Cell. Longev.	JUL 14	2021	2021								6650781	10.1155/2021/6650781			16	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	TT7LV	WOS:000680527100004	34336110	gold, Green Published			2022-04-25	
J	Wu, CS; Wu, SY; Chen, HC; Chu, CA; Tang, HH; Liu, HS; Hong, YR; Huang, CYF; Huang, GC; Su, CL				Wu, Chi-Shivan; Wu, Shan-Ying; Chen, Hsin-Chih; Chu, Chien-An; Tang, Han-Hsuan; Liu, Hsiao-Sheng; Hong, Yi-Ren; Huang, Chi-Ying F.; Huang, Guan-Cheng; Su, Chun-Li			Curcumin functions as a MEK inhibitor to induce a synthetic lethal effect on KRAS mutant colorectal cancer cells receiving targeted drug regorafenib	JOURNAL OF NUTRITIONAL BIOCHEMISTRY			English	Article						Curcumin; Regorafenib; Synthetic lethality; Chemosensitivity; MEK inhibition; FDA-approved anticancer drugs	NF-KAPPA-B; GENE-EXPRESSION; MOLECULAR-MECHANISMS; RAS; APOPTOSIS; AURORA; CHEMOSENSITIVITY; SUPPRESSION; ACTIVATION; PATHWAY	Curcumin, a major yellow pigment and spice in turmeric and curry, has been demonstrated to have an anticancer effect in human clinical trials. Mutation of KRAS has been shown in 35%-45% of colorectal cancer, and regorafenib has been approved by the US FDA to treat patients with colorectal cancer. Synthetic lethality is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. Here, we reveal that curcumin significantly enhanced the growth inhibition of regorafenib in human colorectal cancer HCT 116 cells (KRAS mutant) to a greater extent than in human colorectal cancer HT-29 cells (KRAS wild-type), producing an additive or synergistic effect in HCT 116 cells and causing an antagonistic effect in HT-29 cells. Flow cytometric analysis showed that the addition of curcumin elevated apoptosis and greatly increased autophagy in HCT 116 cells but not in HT-29 cells. Mechanistically, curcumin behaved like MEK-specific inhibitor (U0126) to enhance regorafenib-induced growth inhibition, apoptosis and autophagy in HCT 116 cells. Our data suggest that curcumin may target one more gene other than mutant KRAS to enhance regorafenib-induced growth inhibition (synthetic lethality) in colorectal cancer HCT 116 cells, indicating a possible role of curcumin in regorafenib-treated KRAS mutant colorectal cancer. (C) 2019 Elsevier Inc. All rights reserved.	[Wu, Chi-Shivan; Wu, Shan-Ying; Chen, Hsin-Chih; Su, Chun-Li] Natl Taiwan Normal Univ, Dept Human Dev & Family Studies, Taipei 106, Taiwan; [Wu, Shan-Ying; Tang, Han-Hsuan; Su, Chun-Li] Natl Taiwan Normal Univ, Sch Life Sci, Grad Program Nutr Sci, 162,Sec 1,He Ping East Rd, Taipei 106, Taiwan; [Chu, Chien-An; Liu, Hsiao-Sheng] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 701, Taiwan; [Liu, Hsiao-Sheng] Natl Cheng Kung Univ, Coll Med, Ctr Infect Dis, Tainan 701, Taiwan; [Liu, Hsiao-Sheng] Natl Cheng Kung Univ, Coll Med, Signaling Res Ctr, Tainan 701, Taiwan; [Hong, Yi-Ren] Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung 807, Taiwan; [Hong, Yi-Ren; Huang, Chi-Ying F.] Kaohsiung Med Univ, Dept Biochem, Coll Med, Kaohsiung 807, Taiwan; [Huang, Chi-Ying F.] Natl Yang Ming Univ, Inst Biopharmaceut Sci, 155,Sec 2,Linong St, Taipei 112, Taiwan; [Huang, Guan-Cheng] Yuans Gen Hosp, Dept Internal Med, Div Hematooncol, 162 Cheng Kung 1st Rd, Kaohsiung 802, Taiwan		Su, CL (corresponding author), Natl Taiwan Normal Univ, Sch Life Sci, Grad Program Nutr Sci, 162,Sec 1,He Ping East Rd, Taipei 106, Taiwan.; Huang, CYF (corresponding author), Natl Yang Ming Univ, Inst Biopharmaceut Sci, 155,Sec 2,Linong St, Taipei 112, Taiwan.; Huang, GC (corresponding author), Yuans Gen Hosp, Dept Internal Med, Div Hematooncol, 162 Cheng Kung 1st Rd, Kaohsiung 802, Taiwan.	cyhuang5@ym.edu.tw; guanchenghuang@yahoo.com.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; Tang, Han-Hsuan/0000-0002-9034-3597; Wu, Shan-Ying/0000-0003-2380-5760; Liu, Hsiao-Sheng/0000-0003-0576-7203; Hong, Yi-Ren/0000-0001-5470-6090	National Science Council, TaiwanMinistry of Science and Technology, Taiwan [101-2313-B-003-002-MY3]; Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [MOST 104-2320-B-003-007, 105-2320-B-003-003, 106-2320-B-003-006-MY3]; National Taiwan Normal University, Taiwan [10502, 10602]; Yuan's General Hospital [RG15-003, YGH 17-002]	This work was supported by grants from the National Science Council, Taiwan (101-2313-B-003-002-MY3); the Ministry of Science and Technology, Taiwan (MOST 104-2320-B-003-007, 105-2320-B-003-003 and 106-2320-B-003-006-MY3); National Taiwan Normal University, Taiwan (10502 and 10602); and Yuan's General Hospital (RG15-003 and YGH 17-002).	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Nutr. Biochem.	DEC	2019	74								108227	10.1016/j.jnutbio.2019.108227			13	Biochemistry & Molecular Biology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Nutrition & Dietetics	JY4GN	WOS:000504375400005	31675556				2022-04-25	
J	Liang, JX; Ning, Z; Gao, W; Ling, J; Wang, AM; Luo, HF; Liang, Y; Yan, Q; Wang, ZY				Liang, Jin-Xiao; Ning, Zhen; Gao, Wei; Ling, Jun; Wang, A-Man; Luo, Hai-Feng; Liang, Yong; Yan, Qiu; Wang, Zhong-Yu			Ubiquitin-specific protease 22-induced autophagy is correlated with poor prognosis of pancreatic cancer	ONCOLOGY REPORTS			English	Article						autophagy; LC3; pancreatic cancer; prognosis; ubiquitin-specific protease 22	COLORECTAL-CANCER; THERAPY FAILURE; CELL-DEATH; INHIBITION; EXPRESSION; USP22; TRANSCRIPTION; CHEMOTHERAPY; GEMCITABINE; PROGRESSION	Ubiquitin-specific protease 22 (USP22) is a component of the transcription regulatory histone acetylation complex SAGA, which broadly regulates gene transcription and correlates with cancer progression, metastasis and prognosis. Autophagy is a cell pathway with dual functions that promotes cell survival or death. However, it is not known whether USP22 can regulate autophagy in pancreatic cancer. In the present study, we first identified that USP22 was overexpressed in a large number of pancreatic cancer patient samples, concomitant with the increased expression of LC3, a marker of autophagy. Statistical analysis revealed that the increase in USP22 and autophagy was positively correlated with poor prognosis of pancreatic cancer patients. Further investigation using a human pancreatic cancer cell (Panc-1) identified that the overexpression of USP22 increased the processing of LC3 into the active form LC3-II and the number of autophagosomes, thus leading to enhanced autophagy. Activation of ERK1/2 kinase rather than AKT1 by USP22 was found to be one of the mechanisms promoting LC3 processing. USP22-induced autophagy was also found to enhance cell proliferation and resistance to starvation and chemotherapeutic drugs in Panc-1 cells, therefore expressing an overall effect that promotes cell survival. Collectively, the present study demonstrated a new function of USP22 that induces autophagy, thus leading to the poor prognosis of pancreatic cancer.	[Liang, Jin-Xiao] Zhejiang Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China; [Ning, Zhen; Wang, A-Man; Luo, Hai-Feng; Wang, Zhong-Yu] Dalian Med Univ, Affiliated Hosp 1, Dalian 116011, Liaoning, Peoples R China; [Gao, Wei; Yan, Qiu] Dalian Med Univ, Dept Biochem & Mol Biol, Dalian 116011, Liaoning, Peoples R China; [Ling, Jun] Commonwealth Med Coll, Dept Basic Sci, Scranton, PA 18509 USA; [Liang, Yong] Taizhou Univ, Sch Med, Dept Clin Med, Taizhou 318000, Zhejiang, Peoples R China		Wang, ZY (corresponding author), Dalian Med Univ, Affiliated Hosp 1, 222 Zhongshan Rd, Dalian 116011, Liaoning, Peoples R China.	yanqiudalian@gmail.com; wangzhongyudl@gmail.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30870719]; Dalian Municipal Science and Technology Foundation [2011E15SF114]	This study was supported by grants from the National Natural Science Foundation of China (no. 30870719), and the Dalian Municipal Science and Technology Foundation (no. 2011E15SF114).	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Rep.	DEC	2014	32	6					2726	2734		10.3892/or.2014.3508			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AT4JE	WOS:000344904900055	25241857	Bronze			2022-04-25	
J	Shan, CY; Hui, WQ; Li, HW; Wang, Z; Guo, CL; Peng, RK; Gu, J; Chen, YC; Ouyang, Q				Shan, Changyu; Hui, Wenqi; Li, Hongwei; Wang, Zheng; Guo, Chunling; Peng, Ruikun; Gu, Jing; Chen, Yingchun; Ouyang, Qin			Discovery of Novel Autophagy Inhibitors and Their Sensitization Abilities for Vincristine-Resistant Esophageal Cancer Cell Line Eca109/VCR	CHEMMEDCHEM			English	Article						autophagy inhibitors; drug-resistant cancer cell lines; molecular docking	COLORECTAL-CANCER; RECURRENCE; HYDROXYCHLOROQUINE; COMBINATION; DISSECTION; ACTIVATION; PROGNOSIS; PROTEIN; POTENT; TRIAL	Resistance phenomena, especially acquired drug resistance, have been severely hampering the application of chemotherapeutics during cancer chemotherapy. Autophagy plays a role in maintaining the survival of cancer cells and might mediate resistance to chemotherapy drugs. Herein, a new series of 5-amino-2-ether-benzamide derivatives were synthesized and evaluated as autophagy inhibitors. Selected from 14 synthesized compounds as lead autophagy inhibitor, N-(cyclohexylmethyl)-5-(((cyclohexylmethyl)amino)methyl)-2-((4-(trifluoromethyl)benzyl)oxy)benzamide (4 d) showed the most obvious effect of LC3B protein conversion. Further, its autophagy inhibition, evaluated by using transmission electron microscopy and confocal microscopy, showed that the fusion of autophagosomes and lysosomes in the final stage of autophagic flux was suppressed. We also found that 4 d could enhance the chemosensitivity of vincristine in vincristine-resistant esophageal cancer cell line Eca109/VCR in a synergistic, associative manner. Moreover, a computational study showed that 4 d might bind with p62-zz to inhibit autophagy. We also found 4 d to be relatively less cytotoxic to normal cells versus cancer cells than the reported p62-zz inhibitor.	[Shan, Changyu; Hui, Wenqi; Li, Hongwei; Guo, Chunling; Peng, Ruikun; Gu, Jing; Chen, Yingchun; Ouyang, Qin] Third Mil Med Univ, Dept Pharmaceut Chem, Chongqing 400038, Peoples R China; [Hui, Wenqi] Xian Fifth Hosp, Dept Pharm, Xian 710082, Shanxi, Peoples R China; [Wang, Zheng] Sichuan Univ Sci & Engn, Coll Chem & Environm Engn, Zigong 643000, Sichuan, Peoples R China		Ouyang, Q (corresponding author), Third Mil Med Univ, Dept Pharmaceut Chem, Chongqing 400038, Peoples R China.	ouyangq@tmmu.edu.cn			National Key R&D program of China [2018YFA0507900]; Chongqing Young Top Talents Training Plan	We are grateful for the financial support from the National Key R&D program of China (2018YFA0507900) and Chongqing Young Top Talents Training Plan.	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J	Zhang, J; Yang, ZZ; Dong, J				Zhang, Jing; Yang, Zuozhang; Dong, Jian			P62: An emerging oncotarget for osteolytic metastasis	JOURNAL OF BONE ONCOLOGY			English	Review						P62/SQSTM1; Bone metastasis; Cancer; Osteoclasts; Autophagy	TRANSCRIPTION FACTOR NRF2; TUMOR-ASSOCIATED ANTIGENS; PAGETS-DISEASE; OXIDATIVE STRESS; PROTEIN P62; DNA VACCINE; SELECTIVE AUTOPHAGY; COLORECTAL-CANCER; BREAST-CANCER; CELL-DEATH	Bone metastasis occurs in the majority of late-stage tumors with poor prognosis. It is mainly classified as osteoblastic metastasis and osteolytic metastasis. The pathogenesis of osteolytic metastasis is a "vicious cycle" between tumor cells and bone cells (primarily the osteoclasts), which is mediated by secretory factors. The P62 adapter protein is a versatile multitasker between tumor cells and bone cells. The overexpression of P62 has been detected among a variety of tumors, playing positive roles in both tumorigenesis and metastasis. Moreover, P62 is an important modulator of the osteoclastogenesis pathway. Therefore, the ability of P62 to modulate tumors and osteoclasts suggests that it may be a feasible oncotarget for bone metastasis, especially for osteolytic metastasis. Recent research has shown that a P62 DNA vaccine triggered effective anti-tumor, anti-metastatic and anti-osteoporotic activities. Growing lines of evidence point to P62 as an emerging oncotarget for osteolytic metastasis. In this review, we outline the different roles of P62 in tumor cells and osteoclasts, focusing on the P62-related signaling pathway in key steps of osteolytic metastasis, including tumorigenesis, metastasis and osteoclastogenesis. Finally, we discuss the newest observations on P62 as an oncotarget for osteolytic metastasis treatment. (C) 2016 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license.	[Zhang, Jing; Yang, Zuozhang; Dong, Jian] Kunming Med Univ, Tumor Hosp Yunnan Prov, Bone & Soft Tissue Tumors Res Ctr Yunnan Prov, Affiliated Hosp 3,Dept Orthopaed, Kunming 650118, Yunnan, Peoples R China; [Dong, Jian] Stem Cell Therapy Tech Clin Transformat & Basic R, Kunming 650118, Yunnan, Peoples R China		Dong, J (corresponding author), Kunming Med Univ, Tumor Hosp Yunnan Prov, Bone & Soft Tissue Tumors Res Ctr Yunnan Prov, Affiliated Hosp 3,Dept Orthopaed, Kunming 650118, Yunnan, Peoples R China.	nmlimit@sina.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81302343/H1624]; Joint Special Funds for the Department of Science and Technology of Yunnan Province - Kunming Medical University [2014FB0 592014FB067]	This research was supported in part by Grants (no. 81302343/H1624) from the National Natural Science Foundation of China, a Grant (no. 2014FB0 592014FB067) from the Joint Special Funds for the Department of Science and Technology of Yunnan Province - Kunming Medical University.	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J	Gupta, SC; Kismali, G; Aggarwal, BB				Gupta, Subash C.; Kismali, Gorkem; Aggarwal, Bharat B.			Curcumin, a component of turmeric: From farm to pharmacy	BIOFACTORS			English	Review						autophagy; cancer stem cells; curcumin; microRNA	CANCER STEM-CELLS; ADVANCED PANCREATIC-CANCER; EPITHELIAL OVARIAN-CANCER; LUNG ADENOCARCINOMA CELLS; I CLINICAL-TRIAL; COLORECTAL-CANCER; BRAIN-TUMORS; ORAL BIOAVAILABILITY; MIR-21 EXPRESSION; MOLECULAR TARGETS	Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. 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J	Itahana, Y; Itahana, K				Itahana, Yoko; Itahana, Koji			Emerging Roles of p53 Family Members in Glucose Metabolism	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						p53; p63; p73; p53 mutant; glucose metabolism; glycolysis; mitochondria; autophagy; diabetes; cancer	TUMOR-SUPPRESSOR P53; PENTOSE-PHOSPHATE PATHWAY; PANCREATIC BETA-CELLS; MITOCHONDRIAL-DNA DEPLETION; COLORECTAL-CANCER CELLS; BASE EXCISION-REPAIR; LI-FRAUMENI-SYNDROME; FATTY LIVER-DISEASE; WILD-TYPE P53; MUTANT P53	Glucose is the key source for most organisms to provide energy, as well as the key source for metabolites to generate building blocks in cells. The deregulation of glucose homeostasis occurs in various diseases, including the enhanced aerobic glycolysis that is observed in cancers, and insulin resistance in diabetes. Although p53 is thought to suppress tumorigenesis primarily by inducing cell cycle arrest, apoptosis, and senescence in response to stress, the non-canonical functions of p53 in cellular energy homeostasis and metabolism are also emerging as critical factors for tumor suppression. Increasing evidence suggests that p53 plays a significant role in regulating glucose homeostasis. Furthermore, the p53 family members p63 and p73, as well as gain-of-function p53 mutants, are also involved in glucose metabolism. Indeed, how this protein family regulates cellular energy levels is complicated and difficult to disentangle. This review discusses the roles of the p53 family in multiple metabolic processes, such as glycolysis, gluconeogenesis, aerobic respiration, and autophagy. We also discuss how the dysregulation of the p53 family in these processes leads to diseases such as cancer and diabetes. Elucidating the complexities of the p53 family members in glucose homeostasis will improve our understanding of these diseases.	[Itahana, Yoko; Itahana, Koji] Duke NUS Med Sch, Canc & Stem Cell Biol Program, 8 Coll Rd, Singapore 169857, Singapore		Itahana, K (corresponding author), Duke NUS Med Sch, Canc & Stem Cell Biol Program, 8 Coll Rd, Singapore 169857, Singapore.	yoko.itahana@duke-nus.edu.sg; koji.itahana@duke-nus.edu.sg			Duke-NUS Signature Programme Block Grant; Singapore Ministry of Health's National Medical Research CouncilNational Medical Research Council, Singapore [NMRC/OFIRG/15nov049/2016]; Singapore Ministry of Education Academic Research FundMinistry of Education, Singapore [MOE2013-T2-2-123, MOE2017-T2-1-081]	We thank Angela Andersen, Life Science Editors for editorial assistance. We acknowledge the funding supports from Duke-NUS Signature Programme Block Grant, the Singapore Ministry of Health's National Medical Research Council grants (NMRC/OFIRG/15nov049/2016 to K.I.) and Singapore Ministry of Education Academic Research Fund Tier 2 grants (MOE2013-T2-2-123 and MOE2017-T2-1-081 to K.I.).	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J	Dezelak, M; Repnik, K; Koder, S; Ferkolj, I; Potocnik, U				Dezelak, Matjaz; Repnik, Katja; Koder, Silvo; Ferkolj, Ivan; Potocnik, Uros			A Prospective Pharmacogenomic Study of Crohn's Disease Patients during Routine Therapy with Anti-TNF- Drug Adalimumab: Contribution of ATG5, NFKB1, and CRP Genes to Pharmacodynamic Variability	OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY			English	Article							C-REACTIVE PROTEIN; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; INFLIXIMAB THERAPY; CLINICAL-RESPONSE; ASSOCIATION ANALYSIS; COLORECTAL-CANCER; PREDICT RESPONSE; AUTOPHAGY; POLYMORPHISMS	Crohn's disease is often treated with the anti-tumor necrosis factor- drug adalimumab. However, about 20%-40% of patients do not display adequate therapeutic response. We prospectively evaluated, during a routine therapy of Crohn's disease patients, the candidate autophagy-related genes ATG12 and ATG5 and the inflammation-related genes NFKB1, NFKBIA, and CRP as potential predictors of adalimumab treatment response (pharmacodynamics). The associations of haplotypes and SNPs in these genes with response to drug therapy, biochemical parameters, and body mass were determined at baseline and after 4, 12, 20, and 30 weeks of therapy. Association analysis showed that haplotypes defined with the SNPs rs9373839 and rs510432 in ATG5 gene were significantly associated with positive response to therapy (p<0.002). In addition, allele C and genotypes CC and CT of the rs1130864 in the CRP gene were positively associated with therapeutic response (p<0.002). To the best of our knowledge, this is the first report that supports the association of SNPs in ATG5 and CRP genes with response to adalimumab therapy in Crohn's disease. Further study of these biological pathways in larger and independent clinical samples is warranted as novel streams of research on precision medicine and diagnostics for Crohn's disease.	[Dezelak, Matjaz; Repnik, Katja; Potocnik, Uros] Univ Maribor, Fac Med, Ctr Human Mol Genet & Pharmacogen, Taborska Ulica 8, SLO-2000 Maribor, Slovenia; [Repnik, Katja; Potocnik, Uros] Univ Maribor, Lab Biochem Mol Biol & Genom, Fac Chem & Chem Engn, SLO-2000 Maribor, Slovenia; [Koder, Silvo] Univ Med Ctr Maribor, Maribor, Slovenia; [Ferkolj, Ivan] Univ Med Ctr Ljubljana, Ljubljana, Slovenia		Potocnik, U (corresponding author), Univ Maribor, Fac Med, Ctr Human Mol Genet & Pharmacogen, Taborska Ulica 8, SLO-2000 Maribor, Slovenia.	uros.potocnik@um.si	Dezelak, Matjaz/H-3935-2011	Dezelak, Matjaz/0000-0002-9298-4582	Slovenian Research AgencySlovenian Research Agency - Slovenia [P3-0067]	The authors thank Alojz Tapajner for technical support in statistical analysis. This study was financially supported by Slovenian Research Agency (grant P3-0067).	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J	Baek, SH; Jang, YK				Baek, Seung-Heon; Jang, Yeun-Kyu			AMBRA1 Negatively Regulates the Function of ALDH1B1, a Cancer Stem Cell Marker, by Controlling Its Ubiquitination	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						colorectal cancer stem cell; E3 ubiquitin ligase; substrate receptor; noncanonical ubiquitination	AUTOPHAGY; PARKIN	Activating molecule in Beclin-1-regulated autophagy (AMBRA1), a negative regulator of tumorigenesis, is a substrate receptor of the ubiquitin conjugation system. ALDH1B1, an aldehyde dehydrogenase, is a cancer stem cell (CSC) marker that is required for carcinogenesis via upregulation of the beta-catenin pathway. Although accumulating evidence suggests a role for ubiquitination in the regulation of CSC markers, the ubiquitination-mediated regulation of ALDH1B1 has not been unraveled. While proteome analysis has suggested that AMBRA1 and ALDH1B1 can interact, their interaction has not been validated. Here, we show that AMBRA1 is a negative regulator of ALDH1B1. The expression of ALDH1B1-regulated genes, including PTEN, CTNNB1 (beta-catenin), and CSC-related beta-catenin target genes, is inversely regulated by AMBRA1, suggesting a negative regulatory role of AMBRA1 in the expression of ALDH1B1-regulated genes. We found that the K27- and K33-linked ubiquitination of ALDH1B1 is mediated via the cooperation of AMBRA1 with other E3 ligases, such as TRAF6. Importantly, ubiquitination site mapping revealed that K506, K511, and K515 are important for the K27-linked ubiquitination of ALDH1B1, while K33-linked ubiquitination occurs at K506. A ubiquitination-defective mutant of ALDH1B1 increased the self-association ability of ALDH1B1, suggesting a negative correlation between the ubiquitination and self-association of ALDH1B1. Together, our findings indicate that ALDH1B1 is negatively regulated by AMBRA1-mediated noncanonical ubiquitination.	[Baek, Seung-Heon; Jang, Yeun-Kyu] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Syst Biol, Seoul 03722, South Korea; [Baek, Seung-Heon; Jang, Yeun-Kyu] Yonsei Univ, BK21 Yonsei Educ & Res Ctr Biosyst, Seoul 03722, South Korea		Jang, YK (corresponding author), Yonsei Univ, Coll Life Sci & Biotechnol, Dept Syst Biol, Seoul 03722, South Korea.; Jang, YK (corresponding author), Yonsei Univ, BK21 Yonsei Educ & Res Ctr Biosyst, Seoul 03722, South Korea.	baeksh9505@naver.com; ykjang@yonsei.ac.kr		Baek, SeungHeon/0000-0003-1793-1576	National Research Foundation of Korea (NRF) - Korean government (MSIT)National Research Foundation of Korea [2019R1A2C1009907]; Brain Korea 21 (BK21) FOUR program	This work was supported in part by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2019R1A2C1009907). In addition, S.H.B. and Y.K.J. were supported in part by the Brain Korea 21 (BK21) FOUR program.	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J. Mol. Sci.	NOV	2021	22	21							12079	10.3390/ijms222112079			17	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	WZ9KP	WOS:000720278700001	34769507	Green Published, gold			2022-04-25	
J	Khan, MZI; Law, HKW				Khan, Md Zahirul Islam; Law, Helen Ka Wai			Cancer Susceptibility Candidate 9 (CASC9) Promotes Colorectal Cancer Carcinogenesis via mTOR-Dependent Autophagy and Epithelial-Mesenchymal Transition Pathways	FRONTIERS IN MOLECULAR BIOSCIENCES			English	Article						cancer susceptibility candidate 9; long non-coding RNA; colorectal cancer; autophagy; epithelial-mesenchymal transition	LONG NONCODING RNA; PROLIFERATION; PROGRESSION; CELLS; CONTRIBUTES; METASTASIS; INHIBITION; ACTIVATION; APOPTOSIS; GROWTH	Background Colorectal cancer (CRC) is the third most common cancer worldwide. Many recent studies have demonstrated that different long non-coding RNAs (lncRNAs) are involved in the initiation, advancement, and metastasis of many cancers including CRC. Cancer susceptibility candidate 9 (CASC9) is an lncRNA that has been reported in many cancers, but its role in CRC is poorly understood. In this study, we aimed to examine the expression of CASC9 in CRC cell lines and to determine the mechanism of action of CASC9 in CRC carcinogenesis. Methods The expression of CASC9 in CRC tissues was compared with normal samples from publicly available datasets in The Cancer Genome Atlas (TCGA) and The Encyclopedia of RNA Interactomes (ENCORI). CASC9 expression was further verified in four CRC cell lines (DLD1, HT-29, SW480, and HCT-116) and normal colorectal cell line (CCD-112CoN) by real-time quantitative polymerase chain reaction (RT-qPCR). After gene silencing in HCT-116 and SW480, Cell Counting Kit-8 assay, clonogenic assay, and wound healing assay were performed to evaluate cell proliferation, viability, and migration index of cells. Western blotting was used to explore the key pathways involved. Results CASC9 was significantly upregulated as analyzed from both public datasets TCGA and ENCORI where its overexpression was associated with poor survival of CRC patients. Similarly, CASC9 was significantly overexpressed in the CRC cell lines compared with normal cells studied. The silencing of CASC9 in HCT-116 and SW480 attenuated cell proliferation and migration significantly. Furthermore, pathways investigations showed that silencing of CASC9 significantly induced autophagy, promoted AMP-activated protein kinase (AMPK) phosphorylation, inhibited mTOR and AKT signaling pathways, and altered epithelial-mesenchymal transition (EMT) marker protein expression. Conclusion We demonstrated that silencing of CASC9 contributes to the reduced CRC cell proliferation and migration by regulating autophagy and AKT/mTOR/EMT signaling. Therefore, CASC9 plays an important role in carcinogenesis, and its expression may act as a prognostic biomarker and a potential therapeutic target of CRC management.	[Khan, Md Zahirul Islam; 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		Islam Khan, Md Zahirul/0000-0001-7048-2613	Internal Institutional Research Fund from The Hong Kong Polytechnic University [P0031318-UAHS]; Hong Kong Polytechnic UniversityHong Kong Polytechnic University; Departmental Seeding Fund from The Hong Kong Polytechnic University [P0031318-UAHS]	This project was partially supported by the research grant to HL including Departmental Seeding Fund and Internal Institutional Research Fund (P0031318-UAHS) and Postgraduate studentship from The Hong Kong Polytechnic University for MI.	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Mol. Biosci.	MAY 4	2021	8								627022	10.3389/fmolb.2021.627022			12	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	SD2SC	WOS:000651219600001	34017854	Green Published, gold			2022-04-25	
J	Amin, A; Bajbouj, K; Koch, A; Gandesiri, M; Schneider-Stock, R				Amin, Amr; Bajbouj, Khuloud; Koch, Adrian; Gandesiri, Muktheshwar; Schneider-Stock, Regine			Defective Autophagosome Formation in p53-Null Colorectal Cancer Reinforces Crocin-Induced Apoptosis	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						autophagy; autophagosome; apoptosis; crocin; colorectal cancer; p53	CELL-DEATH; MONITORING AUTOPHAGY; P53; SAFFRON; INDUCTION; P21; CONTRIBUTES; CORDYCEPIN; MUTATION; THERAPY	Crocin, a bioactive molecule of saffron, inhibited proliferation of both HCT116 wild-type and HCT116 p53-/- cell lines at a concentration of 10 mM. Flow cytometric analysis of cell cycle distribution revealed that there was an accumulation of HCT116 wild-type cells in G1 (55.9%, 56.1%) compared to the control (30.4%) after 24 and 48 h of crocin treatment, respectively. However, crocin induced only mild G2 arrest in HCT116 p53-/- after 24 h. Crocin induced inefficient autophagy in HCT116 p53-/- cells, where crocin induced the formation of LC3-II, which was combined with a decrease in the protein levels of Beclin 1 and Atg7 and no clear p62 degradation. Autophagosome formation was not detected in HCT116 p53-/- after crocin treatment predicting a nonfunctional autophagosome formation. There was a significant increase of p62 after treating the cells with Bafilomycin A1 (Baf) and crocin compared to crocin exposure alone. Annexin V staining showed that Baf-pretreatment enhanced the induction of apoptosis in HCT116 wild-type cells. Baf-exposed HCT116 p53-/- cells did not, however, show any enhancement	[Amin, Amr; Bajbouj, Khuloud] United Arab Emirates Univ, Coll Sci, Dept Biol, Al Ain 15551, U Arab Emirates; [Amin, Amr] Cairo Univ, Fac Sci, Dept Zool, Cairo 12613, Egypt; [Bajbouj, Khuloud] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA; [Koch, Adrian; Gandesiri, Muktheshwar; Schneider-Stock, Regine] Univ Erlangen Nurnberg, Inst Pathol, D-91054 Erlangen, Germany		Amin, A (corresponding author), United Arab Emirates Univ, Coll Sci, Dept Biol, Al Ain 15551, U Arab Emirates.	a.amin@uaeu.ac.ae; khuloud@hotmail.de; adrian.koch@uk-erlangen.de; mukthi_14@yahoo.com; regine.schneider-stock@uk-erlangen.de	Amin, Amr/I-2137-2019	Amin, Amr/0000-0001-8888-1102	Emirates Foundation [2009-079]; National Research Foundation [U-IRCA 2012-21832]; UPAR; Terry Fox Foundation	This study was funded by Emirates Foundation Grant (No. 2009-079) and in part by National Research Foundation Grant (No. U-IRCA 2012-21832), UPAR 2013 and the Terry Fox Foundation 2013 for Amr Amin. We also thank Ala'a Al-Hrout at UAE and Moustafa Abdalla at MSU for their technical assistance formatting the figures.	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J	Zhang, P; Holowatyj, AN; Roy, T; Pronovost, SM; Marchetti, M; Liu, HB; Ulrich, CM; Edgar, BA				Zhang, Peng; Holowatyj, Andreana N.; Roy, Taylor; Pronovost, Stephen M.; Marchetti, Marco; Liu, Hanbin; Ulrich, Cornelia M.; Edgar, Bruce A.			An SH3PX1-Dependent Endocytosis-Autophagy Network Restrains Intestinal Stem Cell Proliferation by Counteracting EGFR-ERK Signaling	DEVELOPMENTAL CELL			English	Article							ISLAND METHYLATOR PHENOTYPE; SORTING NEXIN; MICROSATELLITE INSTABILITY; DROSOPHILA; TRAFFICKING; MAINTENANCE; RECEPTOR; MIDGUT; REGENERATION; DEGRADATION	The effect of intracellular vesicle trafficking on stem-cell behavior is largely unexplored. We screened the Drosophila sorting nexins (SNXs) and discovered that one, SH3PX1, profoundly affects gut homeostasis and lifespan. SH3PX1 restrains intestinal stem cell (ISC) division through an endocytosis-autophagy network that includes Dynamin, Rab5, Rab7, Atg1, 5, 6, 7, 8a, 9, 12, 16, and Syx17. Blockages in this network stabilize ligand-activated EGFRs, recycling them via Rab11-dependent endosomes to the plasma membrane. This hyperactivated ERK, calcium signaling, and ER stress, autonomously stimulating ISC proliferation. The excess divisions induced epithelial stress, Yki activity, and Upd3 and Rhomboid production in enterocytes, catalyzing feedforward ISC hyperplasia. Similarly, blocking autophagy increased ERK activity in human cells. Many endocytosis-autophagy genes are mutated in cancers, most notably those enriched in microsatellite instable-high and KRAS-wild-type colorectal cancers. Disruptions in endocytosis and autophagy may provide an alternative route to RAS-ERK activation, resulting in EGFR-dependent cancers.	[Zhang, Peng; Holowatyj, Andreana N.; Roy, Taylor; Pronovost, Stephen M.; Marchetti, Marco; Liu, Hanbin; Ulrich, Cornelia M.; Edgar, Bruce A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA; [Zhang, Peng; Roy, Taylor; Pronovost, Stephen M.; Marchetti, Marco; Liu, Hanbin; Edgar, Bruce A.] Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84112 USA; [Holowatyj, Andreana N.; Ulrich, Cornelia M.] Univ Utah, Dept Populat Hlth Sci, Salt Lake City, UT 84112 USA; [Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA		Edgar, BA (corresponding author), Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.; Edgar, BA (corresponding author), Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84112 USA.	bruce.edgar@hci.utah.edu			Huntsman Cancer Foundation; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 GM124434, P30 CA042014, U01 CA206110, R01 CA189184, R01 CA211705]; NIH/National Human Genome Research InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [T32 HG008962]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [U01CA206110, R01CA189184, R01CA211705, P30CA042014, R01CA207371] Funding Source: NIH RePORTER; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [T32HG008962] 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) [R01GM124434] Funding Source: NIH RePORTER	We thank X. Lin, H. Kn ae velsrud, A. Rodal, D. Strutt, U. Banerjee, N. Perrimon, H. Jasper, J. Dixon, and X. Yang for fly stocks and antibodies. This work was supported by the Huntsman Cancer Foundation (to B.A.E. and C.M.U.) and grants from the National Institutes of Health (R01 GM124434 to B.A.E.; P30 CA042014 to B.A.E. and C.M.U.; U01 CA206110, R01 CA189184, and R01 CA211705 to C.M.U.). A.N.H. was supported by the NIH/National Human Genome Research Institute (T32 HG008962).	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Cell	MAY 20	2019	49	4					574	+		10.1016/j.devcel.2019.03.029			21	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	HY7HE	WOS:000468303700010	31006650	Bronze, Green Accepted			2022-04-25	
J	Coronel-Hernandez, J; Salgado-Garcia, R; Cantu-De Leon, D; Jacobo-Herrera, N; Millan-Catalan, O; Delgado-Waldo, I; Campos-Parra, AD; Rodriguez-Morales, M; Delgado-Buenrostro, NL; Perez-Plasencia, C				Coronel-Hernandez, Jossimar; Salgado-Garcia, Rebeca; Cantu-De Leon, David; Jacobo-Herrera, Nadia; Millan-Catalan, Oliver; Delgado-Waldo, Izamary; Campos-Parra, Alma D.; Rodriguez-Morales, Miguel; Delgado-Buenrostro, Norma L.; Perez-Plasencia, Carlos			Combination of Metformin, Sodium Oxamate and Doxorubicin Induces Apoptosis and Autophagy in Colorectal Cancer Cells via Downregulation HIF-1 alpha	FRONTIERS IN ONCOLOGY			English	Article						HIF-1 alpha; autophagy; ULK1; mir-26a; AKT; proliferation	NEGATIVE BREAST-CANCER; HYPOXIA; INHIBITION; EXPRESSION; MIR-26A; AKT; PROLIFERATION; INVOLVEMENT; DEPRIVATION; PANITUMUMAB	Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide in both sexes. Current therapies include surgery, chemotherapy, and targeted therapy; however, prolonged exposure to chemical agents induces toxicity in patients and drug resistance. So, we implemented a therapeutic strategy based on the combination of doxorubicin, metformin, and sodium oxamate called triple therapy (Tt). We found that Tt significantly reduced proliferation by inhibiting the mTOR/AKT pathway and promoted apoptosis and autophagy in CRC derived cells compared with doxorubicin. Several autophagy genes were assessed by western blot; ULK1, ATG4, and LC3 II were overexpressed by Tt. Interestingly, ULK1 was the only one autophagy-related protein gradually overexpressed during Tt administration. Thus, we assumed that there was a post-transcriptional mechanism mediating by microRNAs that regulate UKL1 expression during autophagy activation. Through bioinformatics approaches, we ascertained that ULK1 could be targeted by mir-26a, which is overexpressed in advanced stages of CRC. In vitro experiments revealed that overexpression of mir-26a decreased significantly ULK1, mRNA, and protein expression. Contrariwise, the Tt recovered ULK1 expression by mir-26a decrease. Due to triple therapy repressed mir-26a expression, we hypothesized this drug combination could be involved in mir-26a transcription regulation. Consequently, we analyzed the mir-26a promoter sequence and found two HIF-1 alpha transcription factor recognition sites. We developed two different HIF-1 alpha stabilization models. Both showed mir-26a overexpression and ULK1 reduction in hypoxic conditions. Immunoprecipitation experiments were performed and HIF-1 alpha enrichment was observed in mir-26a promoter. Surprisingly, Tt diminished HIF-1 alpha detection and restored ULK1 mRNA expression. These results reveal an important regulation mechanism controlled by the signaling that activates HIF-1 alpha and that in turn regulates mir-26a transcription.	[Coronel-Hernandez, Jossimar; Perez-Plasencia, Carlos] UNAM, FES Iztacala, Unidad Biomed, Lab Genom Func, Tlalnepantla, Mexico; [Coronel-Hernandez, Jossimar; Salgado-Garcia, Rebeca; Cantu-De Leon, David; Millan-Catalan, Oliver; Delgado-Waldo, Izamary; Campos-Parra, Alma D.; Rodriguez-Morales, Miguel; Perez-Plasencia, Carlos] Inst Nacl Cancerol, Lab Genomica, Tlalpan, Mexico; [Jacobo-Herrera, Nadia] INCMNSZ, Unidad Bioquimca, Tlalpan, Mexico; [Delgado-Buenrostro, Norma L.] UNAM, FES IZTACALA, Lab Toxicol, Unidad Biomed, Tlalnepantla, Mexico		Perez-Plasencia, C (corresponding author), UNAM, FES Iztacala, Unidad Biomed, Lab Genom Func, Tlalnepantla, Mexico.; Perez-Plasencia, C (corresponding author), Inst Nacl Cancerol, Lab Genomica, Tlalpan, Mexico.	carlos.pplas@gmail.com	Rodriguez, Miguel/AGY-0751-2022; Jacobo-Herrera, Nadia/AGG-8009-2022	Rodriguez, Miguel/0000-0002-4302-1069; Jacobo-Herrera, Nadia/0000-0002-1026-3774; Delgado-Waldo, Izamary/0000-0002-3688-9775	CONACYTConsejo Nacional de Ciencia y Tecnologia (CONACyT) [402278]; COMECYT [2019ND0005-11]; UNAMUniversidad Nacional Autonoma de Mexico [PAPIIT-IN231420]	JC-H is a doctoral student from Programa de Doctorado en Ciencias Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM) and received fellowship 402278 from CONACYT and 2019ND0005-11 from COMECYT. This study was supported by UNAM PAPIIT-IN231420 research funds granted to CP-P.	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Oncol.	MAY 26	2021	11								594200	10.3389/fonc.2021.594200			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	SO6MK	WOS:000659084500001	34123772	Green Published, gold			2022-04-25	
J	Shen, CY; Yang, C; Xia, B; You, ML				Shen, Chongyang; Yang, Chuan; Xia, Bing; You, Mingliang			Long non-coding RNAs: Emerging regulators for chemo/immunotherapy resistance in cancer stem cells	CANCER LETTERS			English	Article						lncRNA; CSCs; Chemo/immunotherapy; Chemoresistance; Cancer immunotherapy resistance	EPITHELIAL-MESENCHYMAL TRANSITION; PREDICTS POOR-PROGNOSIS; HLA-G EXPRESSION; LUNG-CANCER; COLORECTAL-CANCER; PROSTATE-CANCER; PROMOTES; AUTOPHAGY; HOTAIR; CHEMOSENSITIVITY	Cancer stem cells (CSCs) are a small subpopulation of tumor cells critical for tumor development. Their unique abilities, such as self-renewal, have resulted in tumor resistance to various cancer treatments, including traditional chemotherapy and latest immunotherapy. CSCs-targeting therapy is a promising treatment to overcome the therapeutic resistances to different tumors. However, despite their significance, the regulatory mechanism generating therapy-resistant CSCs is still obscure. Long non-coding RNAs (lncRNAs) are key regulators in various biological processes, including cell proliferation, apoptosis, migration, and invasion. Recent studies have revealed that lncRNAs play an important role in the therapeutic resistance of CSCs. Here we summarize the latest studies on the regulatory role of lncRNAs in sustaining the stemness of CSCs, and discuss the associated mechanisms behind these behavior changes in CSCs-related chemo- and immune-resistance. Future research implications are also discussed, shedding light on the potential CSCs-targeted strategies to break through the resistance of current therapies.	[Shen, Chongyang] Chengdu Univ Tradit Chinese Med, Basic Med Sch, Chengdu 611137, Peoples R China; [Shen, Chongyang] Anhui Univ Chinese Med, Key Lab Xinan Med, Minist Educ, Hefei 230038, Anhui, Peoples R China; [Yang, Chuan] Sichuan Univ, Dept Resp & Crit Care Med, West China Hosp, Clin Res Ctr Resp Dis, Chengdu 610041, Peoples R China; [Yang, Chuan] Sichuan Univ, Frontiers Sci Ctr Dis Related Mol Network, Lab Pulm Immunol & Inflammat, Chengdu 610041, Peoples R China; [Xia, Bing] Hangzhou Canc Hosp, Dept Radiat Oncol, Key Lab Clin Canc Pharmacol & Toxicol Res Zhejian, Hangzhou 310002, Peoples R China; [You, Mingliang] Hangzhou Canc Hosp, Hangzhou Canc Inst, Key Lab Clin Canc Pharmacol & Toxicol Res Zhejian, Hangzhou 310002, Peoples R China		You, ML (corresponding author), Hangzhou Canc Hosp, Hangzhou Canc Inst, Key Lab Clin Canc Pharmacol & Toxicol Res Zhejian, Hangzhou 310002, Peoples R China.	youml@zjhealth.org		Yang, Chuan/0000-0003-0725-7207	Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province [2020E10021]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81603478]; Key research program of science technology department of Sichuan province [2019YFS0317, 2020YFQ004]; Sichuan Youth Science and Technology Innovation Research Team of Experimental Formulology [2020JDTD0022]; Sichuan National (International) High-end Talents Introduction Project [SYZ202069]	This work was supported by Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province (2020E10021), National Natural Science Foundation of China (81603478), Key research program of science technology department of Sichuan province (2019YFS0317,2020YFQ004), Sichuan Youth Science and Technology Innovation Research Team of Experimental Formulology (2020JDTD0022), Sichuan National (International) High-end Talents Introduction Project in 2020 (SYZ202069). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.	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MAR 1	2021	500						244	252		10.1016/j.canlet.2020.11.010		JAN 2021	9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	PR4II	WOS:000607200800023	33242560				2022-04-25	
J	Mastorci, K; Montico, B; Fae, DA; Sigalotti, L; Ponzoni, M; Inghirami, G; Dolcetti, R; Dal Col, J				Mastorci, Katy; Montico, Barbara; Fae, Damiana A.; Sigalotti, Luca; Ponzoni, Maurilio; Inghirami, Giorgio; Dolcetti, Riccardo; Dal Col, Jessica			Phospholipid scramblase 1 as a critical node at the crossroad between autophagy and apoptosis in mantle cell lymphoma	ONCOTARGET			English	Article						mantle cell lymphoma; phospholipid scramblase 1; autophagy; apoptosis; interferon-alpha	COLORECTAL-CANCER; CYCLIN D1; GENE-EXPRESSION; MOLECULAR-BASIS; RETINOIC ACID; RESISTANCE; BORTEZOMIB; INHIBITION; EFFICACY; REVEALS	Mantle cell lymphoma (MCL) is an aggressive haematological malignancy in which the response to therapy can be limited by aberrantly activated molecular and cellular pathways, among which autophagy was recently listed. Our study shows that the 9-cis-retinoic acid (RA)/Interferon(IFN)-beta combination induces protective autophagy in MCL cell lines and primary cultures reducing the extent of drug-induced apoptosis. The treatment significantly up-regulates phospholipid scramblase 1 (PLSCR1), a protein which bi-directionally flips lipids across membranes. In particular, RA/IFN-beta combination concomitantly increases PLSCR1 transcription and controls PLSCR1 protein levels via lysosomal degradation. Herein we describe a new function for PLSCR1 as negative regulator of autophagy. Indeed, PLSCR1 overexpression reduced MCL cell susceptibility to autophagy induced by RA/IFN-beta, serum deprivation or mTOR pharmacological inhibition. Moreover, PLSCR1 can bind the ATG12/ATG5 complex preventing ATG16L1 recruitment and its full activation, as indicated by co-immunoprecipitation experiments. The combination of doxorubicin or bortezomib with RA/IFN-beta strengthened PLSCR1 up-regulation and enhanced apoptosis, as a likely consequence of the blockade of RA/IFN-beta-induced autophagy. Immunohistochemical analysis of 32 MCL biopsies revealed heterogeneous expression of PLSCR1 and suggests its possible implication in the response to anticancer therapies, especially to drugs promoting protective autophagy.	[Mastorci, Katy; Montico, Barbara; Fae, Damiana A.; Sigalotti, Luca; Dolcetti, Riccardo; Dal Col, Jessica] IRCCS Natl Canc Inst, Dept Translat Res, Canc Bioimmunotherapy Unit, Ctr Riferimento Oncol, Aviano, PN, Italy; [Ponzoni, Maurilio] Univ Vita Salute San Raffaele, Pathol Unit, Milan, Italy; [Ponzoni, Maurilio] Ist Sci San Raffaele, Unit Lymphoid Malignancies, Milan, Italy; [Inghirami, Giorgio] Univ Turin, Dept Pathol, Turin, Italy; [Inghirami, Giorgio] Univ Turin, CeRMS, Turin, Italy; [Dolcetti, Riccardo] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia		Dal Col, J (corresponding author), IRCCS Natl Canc Inst, Dept Translat Res, Canc Bioimmunotherapy Unit, Ctr Riferimento Oncol, Aviano, PN, Italy.	jdalcol@cro.it	Dolcetti, Riccardo/O-3832-2015; Montico, Barbara/AAB-8942-2020; Dal Col, Jessica/ABD-9479-2020; Sigalotti, Luca/AAC-2926-2020; , Dal Col Jessica/AAC-4852-2020	Dolcetti, Riccardo/0000-0003-1625-9853; Montico, Barbara/0000-0001-6783-2969; Dal Col, Jessica/0000-0002-0042-2161; Sigalotti, Luca/0000-0002-1436-2358; 	Italian Association for Cancer ResearchFondazione AIRC per la ricerca sul cancro [MFAG 11729, 14257]; "CRO Intramural Bench to Bedside" Grant; Italian Foundation for Cancer ResearchFondazione AIRC per la ricerca sul cancro	This study was supported by: Italian Association for Cancer Research (My First Grant MFAG 11729 to JDC, and contract 14257 to RD), "CRO Intramural Bench to Bedside" Grant 2012 (to RD). KM was supported by an Italian Foundation for Cancer Research fellowship.	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J	Zhang, J; Song, QQ; Wu, MN; Zheng, WJ				Zhang, Jie; Song, Qianqian; Wu, Mengna; Zheng, Wenjie			The Emerging Roles of Exosomes in the Chemoresistance of Hepatocellular Carcinoma	CURRENT MEDICINAL CHEMISTRY			English	Review						Hepatocellular carcinoma; chemoresistance; exosome; tumor microenvironment; epithelial-mesenchymal transition; cancer stem cell	TO-MESENCHYMAL TRANSITION; BINDING CASSETTE TRANSPORTER; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; STEM-CELLS; P-GLYCOPROTEIN; CANCER CELLS; TUMOR MICROENVIRONMENT; POTENTIAL BIOMARKERS; COLORECTAL-CANCER	Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with a leading incidence of cancer-related mortality worldwide. Despite the progress of treatment options, there remains low efficacy for patients with intermediate-advanced HCC, due to tumor metastasis, recurrence and chemoresistance. Increasing evidence suggests that exosomes in the tumor microenvironment (TME), along with other extracellular vesicles (EVs) and cytokines, contribute to the drug chemosensitivity of cancer cells. Exosomes, the intercellular communicators in various biological activities, have shown to play important roles in HCC progression. This review summarizes the underlying associations between exosomes and chemoresistance of HCC cells. The exosomes derived from distinct cell types mediate the drug resistance by regulating drug efflux, epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) properties, autophagic phenotypes, as well as the immune response. In summary, TME-related exosomes can be a potential target to reverse chemoresistance and a candidate biomarker of drug efficacy in HCC patients.	[Zhang, Jie] Nantong Univ, Dept Chemotherapy, Affiliated Hosp, 20 Xisi Rd, Nantong 226001, Jiangsu, Peoples R China; [Zhang, Jie; Wu, Mengna; Zheng, Wenjie] Nantong Univ, Res Ctr Clin Med, Affiliated Hosp, 20 Xisi Rd, Nantong 226001, Jiangsu, Peoples R China; [Song, Qianqian] Wake Forest Sch Med, Dept Radiol, One Med Ctr Blvd, Winston Salem, NC 27157 USA		Zheng, WJ (corresponding author), Nantong Univ, Res Ctr Clin Med, Affiliated Hosp, 20 Xisi Rd, Nantong 226001, Jiangsu, Peoples R China.	zwj007008009@163.com		Zheng, Wenjie/0000-0001-5987-5272; zheng, wenjie/0000-0002-3073-4596	National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81702419]; Jiangsu Graduate innovation [KYCX17_1934]; Nan-tong Health and Family Planning Commission [WQ2016083]	This study has been supported by grants from the National Natural Science Foundation (81702419), Jiangsu Graduate innovation (KYCX17_1934), and Nan-tong Health and Family Planning Commission (WQ2016083).	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Med. Chem.		2021	28	1					93	109		10.2174/0929867327666200130103206			17	Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	QC1RB	WOS:000614610300007	32000636				2022-04-25	
J	Qu, JS; Luo, MY; Zhang, JW; Han, F; Hou, NN; Pan, RY; Sun, XD				Qu, Junsheng; Luo, Moyi; Zhang, Jingwen; Han, Fang; Hou, Ningning; Pan, Ruiyan; Sun, Xiaodong			A paradoxical role for sestrin 2 protein in tumor suppression and tumorigenesis	CANCER CELL INTERNATIONAL			English	Review						Sestrin 2; Cancer; Tumor suppressor; Tumorigenesis	ENDOPLASMIC-RETICULUM STRESS; SIGNALING PATHWAY; DRUG-RESISTANCE; UP-REGULATION; CANCER; MTOR; INDUCTION; APOPTOSIS; AUTOPHAGY; EXPRESSION	Sestrin 2, a highly conserved stress-induced protein, participates in the pathological processes of metabolic and age-related diseases. This p53-inducible protein also regulates cell growth and metabolism, which is closely related to malignant tumorigenesis. Sestrin 2 was reported to regulate various cellular processes, such as tumor cell proliferation, invasion and metastasis, apoptosis, anoikis resistance, and drug resistance. Although sestrin 2 is associated with colorectal, lung, liver, and other cancers, sestrin 2 expression varies among different types of cancer, and the effects and mechanisms of action of this protein are also different. Sestrin 2 was considered a tumor suppressor gene in most studies, whereas conflicting reports considered sestrin 2 an oncogene. Thus, this review aims to examine the literature regarding sestrin 2 in various cancers, summarize its roles in suppression and tumorigenesis, discuss potential mechanisms in the regulation of cancer, and provide a basis for follow-up research and potential cancer treatment development.	[Qu, Junsheng; Zhang, Jingwen; Hou, Ningning; Sun, Xiaodong] Weifang Med Univ, Affiliated Hosp, Dept Endocrinol & Metab, 2428 Yuhe Rd, Weifang 261031, Shandong, Peoples R China; [Luo, Moyi] Weifang Med Univ, Sch Clin Med, Weifang, Peoples R China; [Luo, Moyi; Zhang, Jingwen; Sun, Xiaodong] Weifang Med Univ, Affiliated Hosp, Clin Res Ctr, Weifang, Peoples R China; [Han, Fang] Weifang Med Univ, Affiliated Hosp, Dept Pathol, Weifang, Peoples R China; [Pan, Ruiyan] Weifang Med Univ, Sch Pharm, Weifang, Peoples R China		Sun, XD (corresponding author), Weifang Med Univ, Affiliated Hosp, Dept Endocrinol & Metab, 2428 Yuhe Rd, Weifang 261031, Shandong, Peoples R China.; Pan, RY (corresponding author), Weifang Med Univ, Sch Pharm, Weifang, Peoples R China.	panry@wfmc.edu.cn; xiaodong.sun@wfmc.edu.cn	Sun, Xiaodong/Q-8284-2018	Sun, Xiaodong/0000-0001-7775-2823; Han, Fang/0000-0002-8743-8763; Zhang, Jingwen/0000-0002-6064-1374; Hou, Ningning/0000-0002-3813-8465	Natural Science Foundation of Shandong ProvinceNatural Science Foundation of Shandong Province [ZR2019BH036, ZR2020MH106]; Science and Technology Development Project of Weifang [2018YX058]; PhD Foundation of Weifang Medical University [20217-03]	This work was supported by the Natural Science Foundation of Shandong Province (ZR2019BH036, ZR2020MH106), the Science and Technology Development Project of Weifang (2018YX058), the PhD Foundation of Weifang Medical University and the public domestic visiting program of Weifang Medical University (20217-03).	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NOV 16	2021	21	1							606	10.1186/s12935-021-02317-9			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	WY5NK	WOS:000719325200001	34784907	Green Published, gold			2022-04-25	
J	Chow, MJ; Alfiean, M; Pastorin, G; Gaiddon, C; Ang, WH				Chow, Mun Juinn; Alfiean, Mohammad; Pastorin, Giorgia; Gaiddon, Christian; Ang, Wee Han			Apoptosis-independent organoruthenium anticancer complexes that overcome multidrug resistance: self-assembly and phenotypic screening strategies	CHEMICAL SCIENCE			English	Article							CELL-DEATH; DRUG DISCOVERY; TUMOR RESISTANCE; CANCER-CELLS; AUTOPHAGY; INDUCERS; STRESS	Multidrug resistance is a major impediment to chemotherapy and limits the efficacies of conventional anticancer drugs. A strategy to bypass multidrug resistance is to develop new drug candidates capable of inducing apoptosis-independent programmed cell death. However, cellular pathways implicated in alternative programmed cell death are not well-elucidated and multifactorial, making a target-based discovery approach a challenge. Here, we show that a coordination-directed three-component assembly and phenotypic screening strategy could be employed as a viable alternative for the identification of apoptosis-independent organoruthenium anticancer agents. Through an on-plate synthesis and screening of 195 organoruthenium complexes against apoptosis-sensitive and -resistant cancers, we identified two apoptosis-independent hits. Subsequent validation of the two hits showed a lack of induction of apoptotic biomarkers, a caspase-independent activity and an equal efficacy in both apoptosis-sensitive and -resistant colorectal cancers. This validated their apoptosis-independent modes-of-action, paving the way as potential candidates for the treatment of highly-refractory cancer phenotypes.	[Chow, Mun Juinn; Ang, Wee Han] Natl Univ Singapore, Dept Chem, 3 Sci Dr 3, Singapore 117543, Singapore; [Alfiean, Mohammad] Nanyang Polytech, Sch Chem & Life Sci, Singapore, Singapore; [Pastorin, Giorgia] Natl Univ Singapore, Dept Pharm, 3 Sci Dr 3, Singapore 117543, Singapore; [Pastorin, Giorgia; Ang, Wee Han] NUS Grad Sch Integrat Sci & Engn, Singapore, Singapore; [Gaiddon, Christian] Univ Strasbourg, Strasbourg, France; [Gaiddon, Christian] INSERM, U1113, 3 Ave Moliere, F-67200 Strasbourg, France		Chow, MJ; Ang, WH (corresponding author), Natl Univ Singapore, Dept Chem, 3 Sci Dr 3, Singapore 117543, Singapore.; Ang, WH (corresponding author), NUS Grad Sch Integrat Sci & Engn, Singapore, Singapore.	a0037979@u.nus.edu; chmawh@nus.edu.sg	Ang, Wee Han/L-2249-2013; Chow, Mun Juinn/D-8847-2016; Gaiddon, Christian/F-7321-2012; Chow, Mun Juinn/N-3882-2019	Ang, Wee Han/0000-0003-2027-356X; Chow, Mun Juinn/0000-0002-0812-9226; Gaiddon, Christian/0000-0003-4315-3851; Chow, Mun Juinn/0000-0002-0812-9226; Pastorin, Giorgia/0000-0002-2568-0626	Ministry of Education; National University of SingaporeNational University of Singapore [R143-000-680-114]; Ligue contre le CancerLigue nationale contre le cancer; COSTEuropean Cooperation in Science and Technology (COST) [CM1105]; Accociation pour la Recherche contre le Cancer (ARC)	The authors gratefully acknowledge financial support from Ministry of Education and the National University of Singapore (R143-000-680-114) and Ligue contre le Cancer, COST CM1105, Accociation pour la Recherche contre le Cancer (ARC). The authors also thank Associate Professor Han-ming Shen (NUS) for providing the HCT116 and HCT116 p53<SUP>-/-</SUP> cell lines and CMMAC for performing elemental analysis and ICP-OES experiments.	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Sci.	MAY 1	2017	8	5					3641	3649		10.1039/c7sc00497d			9	Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	ET8MH	WOS:000400553000041	30155208	gold, Green Published			2022-04-25	
J	Guo, KB; Feng, YQ; Zheng, XE; Sun, LT; Wasan, HS; Ruan, SM; Shen, MH				Guo, Kaibo; Feng, Yuqian; Zheng, Xueer; Sun, Leitao; Wasan, Harpreet S.; Ruan, Shanming; Shen, Minhe			Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors	FRONTIERS IN ONCOLOGY			English	Review						epithelial-to-mesenchymal transition; metastasis; chemoresistance; cancer cell stemness; resveratrol	SIGNALING PATHWAY; COLORECTAL-CANCER; GASTRIC-CANCER; NADPH OXIDASE; UP-REGULATION; EMT; INHIBITION; RESISTANCE; AUTOPHAGY; CELLS	Epithelial-to-mesenchymal transition (EMT), a complicated program through which polarized epithelial cells acquire motile mesothelial traits, is regulated by tumor microenvironment. EMT is involved in tumor progression, invasion and metastasis via reconstructing the cytoskeleton and degrading the tumor basement membrane. Accumulating evidence shows that resveratrol, as a non-flavonoid polyphenol, can reverse EMT and inhibit invasion and migration of human tumors via diverse mechanisms and signaling pathways. In the present review, we will summarize the detailed mechanisms and pathways by which resveratrol and its analogs (e.g. Triacetyl resveratrol, 3,5,4'-Trimethoxystilbene) might regulate the EMT process in cancer cells to better understand their potential as novel anti-tumor agents. Resveratrol can also reverse chemoresistance via EMT inhibition and improvement of the antiproliferative effects of conventional treatments. Therefore, resveratrol and its analogs have the potential to become novel adjunctive agents to inhibit cancer metastasis, which might be partly related to their blocking of the EMT process.	[Guo, Kaibo; Feng, Yuqian; Zheng, Xueer; Sun, Leitao; Ruan, Shanming; Shen, Minhe] Zhejiang Chinese Med Univ, First Clin Med Coll, Hangzhou, Peoples R China; [Sun, Leitao; Ruan, Shanming; Shen, Minhe] Zhejiang Chinese Med Univ, Dept Med Oncol, Affiliated Hosp 1, Hangzhou, Peoples R China; [Wasan, Harpreet S.] Imperial Coll Healthcare NHS Trust, Dept Canc Med, Hammersmith Hosp, London, England		Ruan, SM; Shen, MH (corresponding author), Zhejiang Chinese Med Univ, First Clin Med Coll, Hangzhou, Peoples R China.; Ruan, SM; Shen, MH (corresponding author), Zhejiang Chinese Med Univ, Dept Med Oncol, Affiliated Hosp 1, Hangzhou, Peoples R China.	shanmingruan@zcmu.edu.cn; shenminhe@zcmu.edu.cn	Ruan, Shanming/S-3999-2018; Guo, Kaibo/AAT-7116-2021	Ruan, Shanming/0000-0003-1061-5255; Guo, Kaibo/0000-0002-6348-9785	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81573902]; Zhejiang provincial TCM scientific research fund project [2019ZQ015]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2017M612040, 2018T110610]; Top ten thousand talents program of Zhejiang Province [2019-97]; Zhejiang Provincial Project for the key discipline of Traditional Chinese Medicine [2017-XKA09]; Science and technology innovation activity plan and new seedling of college students in Zhejiang Province [2019R410001]	National Natural Science Foundation of China (81573902); Zhejiang provincial TCM scientific research fund project (2019ZQ015); China Postdoctoral Science Foundation (2017M612040; 2018T110610); Top ten thousand talents program of Zhejiang Province (SR, no.2019-97, http://www.zjzzgz.gov.cn/); Zhejiang Provincial Project for the key discipline of Traditional Chinese Medicine (YG, no,2017-XKA09, http://www.zjwjw.gov.cn/); Science and technology innovation activity plan and new seedling of college students in Zhejiang Province (2019R410001).	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Oncol.	APR 16	2021	11								644134	10.3389/fonc.2021.644134			16	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	RV0PR	WOS:000645540300001	33937049	Green Published, gold			2022-04-25	
J	Chan, YT; Cheung, F; Zhang, C; Fu, BW; Tan, HY; Norimoto, H; Wang, N; Feng, YB				Chan, Yau-Tuen; Cheung, Fan; Zhang, Cheng; Fu, Bowen; Tan, Hor-Yue; Norimoto, Hisayoshi; Wang, Ning; Feng, Yibin			Ancient Chinese Medicine Herbal Formula Huanglian Jiedu Decoction as a Neoadjuvant Treatment of Chemotherapy by Improving Diarrhea and Tumor Response	FRONTIERS IN PHARMACOLOGY			English	Article						Huanglian Jiedu decoction; chemotherapy-induced diarrhea; 5-fluorouracil; irinotecan; tumor response	GASTROINTESTINAL TOXICITY; IRINOTECAN; CANCER; 5-FLUOROURACIL; REGENERATION; AUTOPHAGY; MODULATOR; INJURY; RATS	Background Diarrhea is a major gastrointestinal complication in cancer patients receiving chemotherapy. Prognosis and treatment of chemotherapy-induced diarrhea (CID) remain unsatisfactory. This study aims to explore the potential of an ancient Chinese Medicine herbal formula Huanglian Jiedu Decoction (HLJDD) as an adjuvant treatment on CID. Method HLJDD extract was prepared by GMP manufacturing standard with quality and stability being checked. 5-fluorouracil (5-Fu) and irinotecan (CPT-11)-induced diarrhea model in mice was established and pre-, co- and post-treatment of HLJDD was implemented. Mechanism of action was explored by detecting related protein expression. In addition, the effect of HLJDD on diarrhea and tumor response induced by clinical regimens FOLFOX and FOLFIRI was measured in murine orthotopic colorectal cancer model. Results HLJDD exhibited consistency in quality and stability after 24-month storage. Pre-treatment of HLJDD, but not co-treatment or post-treatment, could significantly improve the diarrhea score, body weight loss and intestinal damage in 5-Fu- and CPT-11-treated mice. Pre-treatment of HLJDD reduced cell apoptosis in the intestine of chemotherapy-treated mice, and promoted renewal of intestinal cell wall. CD44 was predicted as the potential target of HLJDD-containing compounds in CID. HLJDD pre-treatment induced presentation of CD44-postive cells in the intestine of chemotherapy-treated mice, and initiated expression of stemness-associated genes. Transcriptional products of the downstream Wnt signaling of CD44 were elevated. Furthermore, pre-treatment of HLJDD could significantly improve the tumor response of clinical chemotherapy regimens FOLFOX and FOLFIRI in orthotopic colorectal cancer, and reduce diarrhea and intestinal damage. Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response.	[Chan, Yau-Tuen; Cheung, Fan; Zhang, Cheng; Fu, Bowen; Tan, Hor-Yue; Wang, Ning; Feng, Yibin] Univ Hong Kong, Li Ka Shing Fac Med, Sch Chinese Med, Pokfulam, Hong Kong, Peoples R China; [Norimoto, Hisayoshi] PuraPharm Int HK Ltd, Shatin, Hong Kong, Peoples R China		Feng, YB (corresponding author), Univ Hong Kong, Li Ka Shing Fac Med, Sch Chinese Med, Pokfulam, Hong Kong, Peoples R China.	yfeng@hku.hk			Research Grant Council, HKSARHong Kong Research Grants Council [RGC GRF 17152116]; Commissioner for Innovation Technology, HKSAR [ITS/091/16FX]; Health and Medical Research Fund (HMRF) [15162961, 16172751]	This study was supported by Research Grant Council, HKSAR (Project code: RGC GRF 17152116), Commissioner for Innovation Technology, HKSAR (Project code: ITS/091/16FX), and Health and Medical Research Fund (HMRF, project code: 15162961 and 16172751).	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Pharmacol.	MAR 10	2020	11								252	10.3389/fphar.2020.00252			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	LC8QQ	WOS:000525597800001	32210825	Green Published, gold			2022-04-25	
J	Zeng, KX; Chen, XX; Xu, M; Liu, XX; Hu, XX; Xu, T; Sun, HL; Pan, YQ; He, BS; Wang, SK				Zeng, Kaixuan; Chen, Xiaoxiang; Xu, Mu; Liu, Xiangxiang; Hu, Xiuxiu; Xu, Tao; Sun, Huiling; Pan, Yuqin; He, Bangshun; Wang, Shukui			CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7	CELL DEATH & DISEASE			English	Article							CIRCULAR RNA; EXPRESSION; MICRORNA-7; ABUNDANT; AUTOPHAGY; MIGRATION; REVEALS; GLUCOSE; CELLS	Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] - 2.75, 95% confidence interval [CI] 1.74-6.51, p = 0.009). Functionally, knockdown of circHIPK3 markedly inhibited CRC cells proliferation, migration, invasion, and induced apoptosis in vitro and suppressed CRC growth and metastasis in vivo. Mechanistically, by using biotinylated-circHIPK3 probe to perform RNA pull-down assay in CRC cells, we identified miR7 was the only one microRNA that was abundantly pulled down by circHIPK3 in both HCT116 and HT29 cells and these interactions were also confirmed by biotinylated miR-7 pull-down and dual-luciferase reporter assays. Overexpression of miR-7 mimicked the effect of circHIPK3 knockdown on CRC cells proliferation, migration, invasion, and apoptosis. Furthermore, ectopic expression of circHIPK3 effectively reversed miR-7-induced attenuation of malignant phenotypes of CRC cells by increasing the expression levels of miR-7 targeting proto-oncogenes (FAK, IGF1R, EGFR, YY1). Remarkably, the combination of circHIPK3 silencing and miR-7 overexpression gave a better effect on tumor suppression both in vitro and in vivo than did circHIPK3 knockdown or miR-7 overexpression alone. Taken together, our data indicate that circHIPK3 may have considerable potential as a prognostic biomarker in CRC, and support the notion that therapeutic targeting of the c-Myb/circHIPK3/miR-7 axis may be a promising treatment approach for CRC patients.	[Zeng, Kaixuan; Chen, Xiaoxiang; Xu, Mu; Liu, Xiangxiang; Hu, Xiuxiu; Xu, Tao; Sun, Huiling; Pan, Yuqin; He, Bangshun; Wang, Shukui] Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing 210006, Jiangsu, Peoples R China; [Zeng, Kaixuan; Chen, Xiaoxiang; Wang, Shukui] Southeast Univ, Sch Med, Nanjing 210009, Peoples R China		Wang, SK (corresponding author), Nanjing Med Univ, Nanjing Hosp 1, Gen Clin Res Ctr, Nanjing 210006, Jiangsu, Peoples R China.; Wang, SK (corresponding author), Southeast Univ, Sch Med, Nanjing 210009, Peoples R China.	sk_wang@njmu.edu.cn			National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472027, 81501820]; Key Project of Science and Technology Development of Nanjing Medicine [ZDX16005]	This project was supported by grants from the National Nature Science Foundation of China (Nos. 81472027, 81501820) to S.W. and Y.P.; Key Project of Science and Technology Development of Nanjing Medicine (ZDX16005). Innovation team of Jiangsu provincial health-strengthening engineering by science and education to S.W.	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MAR 16	2018	9								417	10.1038/s41419-018-0454-8			15	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	FZ7BY	WOS:000427755700005	29549306	gold, Green Published	Y	N	2022-04-25	
J	Chen, XR; Zhang, L; Ding, SP; Lei, QF; Fang, WJ				Chen, Xuerui; Zhang, Li; Ding, Shiping; Lei, Qunfang; Fang, Wenjun			Cisplatin combination drugs induce autophagy in HeLa cells and interact with HSA via electrostatic binding affinity	RSC ADVANCES			English	Article							COLORECTAL-CANCER CELLS; HUMAN SERUM-ALBUMIN; INDUCED APOPTOSIS; SILVER NANOPARTICLES; ANTITUMOR-ACTIVITY; IN-VITRO; INHIBITION; DEATH; CYTOTOXICITY; PATHWAY	Cisplatin, as a significant chemotherapeutic drug for the treatment of cancers, was combined with rapamycin (RAPA), an autophagy inducer, or 3-methyladenine (3-MA), an autophagy inhibitor, and these cisplatin combination drugs were tested with HeLa cells to explore their specific effects on autophagy by cell viability assay, mitochondria membrane potential (MMP) determination, transmission electron microscopic (TEM) observation, dansylcadaverine (MDC) staining, and western blotting analysis. Results revealed that cisplatin combination drugs enhanced formation of autophagosomes, and morphological and biochemical markers of autophagy in HeLa cells can be clearly determined with the formation of enlarged acidic vesicles and conversion of light chain 3 (LC3) protein. Cisplatin combination drugs induce stronger effects on autophagy than either of the components does. Combination drug-induced autophagy inhibits the growth of HeLa cell in a dose-dependent manner and subsequently sensitizes the cells to apoptosis and cell death. Furthermore, interactions between cisplatin combination drugs and human serum albumin (HSA) were investigated under fluorescence, synchronous fluorescence, and circular dichroism analysis. Results suggest that cisplatin combination drugs can bind to HSA and induce conformation and microenvironmental changes of HSA via electrostatic binding affinity. These investigations can provide useful and fundamental information, which could be used in cytotoxic chemotherapy to dramatically increase efficacy in pharmaceutical and biotechnology fields.	[Chen, Xuerui; Zhang, Li; Lei, Qunfang; Fang, Wenjun] Zhejiang Univ, Dept Chem, Hangzhou 310027, Zhejiang, Peoples R China; [Ding, Shiping] Zhejiang Univ, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China		Lei, QF; Fang, WJ (corresponding author), Zhejiang Univ, Dept Chem, Hangzhou 310027, Zhejiang, Peoples R China.	qflei@zju.edu.cn; fwjun@zju.edu.cn		Chen, Xuerui/0000-0003-2945-6311	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21473157]	This work was supported by the National Natural Science Foundation of China (No. 21473157).	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J	Li, XH; Ma, L; Huang, K; Wei, YL; Long, SD; Liu, QY; Zhang, DQ; Wu, SY; Wang, WR; Yang, G; Zhou, HG; Yang, C				Li, Xiaohe; Ma, Ling; Huang, Kai; Wei, Yuli; Long, Shida; Liu, Qinyi; Zhang, Deqiang; Wu, Shuyang; Wang, Wenrui; Yang, Guang; Zhou, Honggang; Yang, Cheng			Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-beta 1 Signaling Pathway	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						pulmonary fibrosis; regorafenib; myofibroblasts; TGF-&#946; 1 signaling pathway		Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-beta 1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-beta 1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-beta 1 signaling pathway.	[Li, Xiaohe; Ma, Ling; Huang, Kai; Wei, Yuli; Long, Shida; Liu, Qinyi; Zhang, Deqiang; Wu, Shuyang; Wang, Wenrui; Yang, Guang; Zhou, Honggang; Yang, Cheng] Nankai Univ, Coll Pharm, State Key Lab Med Chem Biol, Tianjin 300353, Peoples R China; [Li, Xiaohe; Ma, Ling; Huang, Kai; Wei, Yuli; Long, Shida; Liu, Qinyi; Zhang, Deqiang; Wu, Shuyang; Wang, Wenrui; Yang, Guang; Zhou, Honggang; Yang, Cheng] Nankai Univ, Tianjin Key Lab Mol Drug Res, Tianjin 300353, Peoples R China; [Li, Xiaohe; Ma, Ling; Zhou, Honggang; Yang, Cheng] Tianjin Int Joint Acad Biomed, Tianjin Key Lab Mol Drug Res, Tianjin 300457, Peoples R China		Yang, G; Zhou, HG; Yang, C (corresponding author), Nankai Univ, Coll Pharm, State Key Lab Med Chem Biol, Tianjin 300353, Peoples R China.; Yang, G; Zhou, HG; Yang, C (corresponding author), Nankai Univ, Tianjin Key Lab Mol Drug Res, Tianjin 300353, Peoples R China.; Zhou, HG; Yang, C (corresponding author), Tianjin Int Joint Acad Biomed, Tianjin Key Lab Mol Drug Res, Tianjin 300457, Peoples R China.	lixiaohe908@163.com; mal930602@163.com; kaihuang0819@163.com; weiyuli2021@126.com; starlongsd@163.com; jiukn365@126.com; 13345278851@163.com; shuyang_wu@163.com; wwr15641208039@163.com; Guang.yang@nankai.edu.cn; honggang.zhou@nankai.edu.cn; cheng.yang@nankai.edu.cn		Liu, Qinyi/0000-0001-5439-7849	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82072660, 82070060, 82000073]	This study was supported by The National Natural Science Foundation of China (grants 82072660, 82070060, 82000073).	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J. Mol. Sci.	FEB	2021	22	4							1985	10.3390/ijms22041985			17	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	QP4GS	WOS:000623795300001	33671452	Green Published, gold			2022-04-25	
J	Li, B; Huang, QL; Wei, GH				Li, Bo; Huang, Qilai; Wei, Gong-Hong			The Role of HOX Transcription Factors in Cancer Predisposition and Progression	CANCERS			English	Review						HOX; cancer susceptibility; risk SNP; coding mutation; regulatory SNP; mechanism	LONG NONCODING RNA; GENETIC SUSCEPTIBILITY LOCI; GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; BREAST-CANCER; COLORECTAL-CANCER; GERMLINE MUTATION; OVARIAN-CANCER; MALIGNANT PROGRESSION; EPIGENETIC REGULATION	Homeobox (HOX) transcription factors, encoded by a subset of homeodomain superfamily genes, play pivotal roles in many aspects of cellular physiology, embryonic development, and tissue homeostasis. Findings over the past decade have revealed that mutations in HOX genes can lead to increased cancer predisposition, and HOX genes might mediate the effect of many other cancer susceptibility factors by recognizing or executing altered genetic information. Remarkably, several lines of evidence highlight the interplays between HOX transcription factors and cancer risk loci discovered by genome-wide association studies, thereby gaining molecular and biological insight into cancer etiology. In addition, deregulated HOX gene expression impacts various aspects of cancer progression, including tumor angiogenesis, cell autophagy, proliferation, apoptosis, tumor cell migration, and metabolism. In this review, we will discuss the fundamental roles of HOX genes in cancer susceptibility and progression, highlighting multiple molecular mechanisms of HOX involved gene misregulation, as well as their potential implications in clinical practice.	[Li, Bo; Huang, Qilai] Shandong Univ, Sch Life Sci, Shandong Prov Key Lab Anim Cell & Dev Biol, Qingdao 266237, Shandong, Peoples R China; [Wei, Gong-Hong] Univ Oulu, Bioctr Oulu, Fac Biochem & Mol Med, SF-90220 Oulu, Finland		Huang, QL (corresponding author), Shandong Univ, Sch Life Sci, Shandong Prov Key Lab Anim Cell & Dev Biol, Qingdao 266237, Shandong, Peoples R China.; Wei, GH (corresponding author), Univ Oulu, Bioctr Oulu, Fac Biochem & Mol Med, SF-90220 Oulu, Finland.	libo1051@163.com; qlhuang@sdu.edu.cn; gonghong.wei@oulu.fi	; Huang, Qilai/B-4725-2015	Wei, Gong-Hong/0000-0001-6546-9334; Huang, Qilai/0000-0002-4252-3980	Shandong Provincial Natural Science Foundation, ChinaNatural Science Foundation of Shandong Province [ZR2016CM50]; Academy of FinlandAcademy of Finland; Finnish Cancer Foundation; Jane and Aatos Erkkos Foundation	This work was supported by the grants Shandong Provincial Natural Science Foundation, China, ZR2016CM50, the Academy of Finland, the Finnish Cancer Foundation, and the Jane and Aatos Erkkos Foundation.	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J	Flanigan, PM; Aghi, MK				Flanigan, Patrick M.; Aghi, Manish K.			Adaptation to antiangiogenic therapy in neurological tumors	CELLULAR AND MOLECULAR LIFE SCIENCES			English	Review						Resistance; Adaptive; Glioblastoma; Bevacizumab; Pericytes; Bone marrow; Autophagy	ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; ANTI-ANGIOGENIC THERAPY; CELL-SURVIVAL; COLORECTAL-CANCER; PROGENITOR CELLS; BLOOD-VESSELS; GLIOMA GROWTH; STEM-CELLS; PDGF-B	Because tumors require a vascular supply for their survival and growth, angiogenesis is considered an important therapeutic target in most human cancers including cancer of the central nervous system. Antiangiogenic therapy has focused on inhibitors of the vascular endothelial growth factor (VEGF) signaling pathway. VEGF pathway-targeted drugs have shown therapeutic efficacy in several CNS tumors and have been tried most frequently in glioblastoma. These therapies, however, have been less effective than anticipated as some patients do not respond to therapy and some receive only modest benefit. Underlying this suboptimal response are multiple mechanisms of drug resistance involving changes in both tumor cells and their microenvironment. In this review, we discuss the multiple proposed mechanisms by which neurological tumors evolve to become resistant to antiangiogenic therapies. A better understanding of these mechanisms, their context, and their interplay will likely facilitate improvements in pharmacological strategies for the targeted treatment of neurological tumors.	[Flanigan, Patrick M.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA; [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurol Surg, Calif Ctr Pituitary Disorders, San Francisco, CA 94143 USA		Aghi, MK (corresponding author), Univ Calif San Francisco, Dept Neurol Surg, Calif Ctr Pituitary Disorders, San Francisco, CA 94143 USA.	aghim@neurosurg.ucsf.edu		Flanigan, Patrick/0000-0002-3611-8575	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1 R01 NS079697]; 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) [R01NS079697] Funding Source: NIH RePORTER	This work was supported by funding to M.K.A.'s laboratory from the NIH (1 R01 NS079697).	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Mol. Life Sci.	AUG	2015	72	16					3069	3082		10.1007/s00018-015-1916-0			14	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	CN0EX	WOS:000358088000005	25943307	Green Accepted			2022-04-25	
J	Stramucci, L; Pranteda, A; Stravato, A; Amoreo, CA; Pennetti, A; Diodoro, MG; Bartolazzi, A; Milella, M; Bossi, G				Stramucci, Lorenzo; Pranteda, Angelina; Stravato, Arianna; Amoreo, Carla Azzurra; Pennetti, Annarita; Diodoro, Maria Grazia; Bartolazzi, Armando; Milella, Michele; Bossi, Gianluca			MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer	CELL DEATH & DISEASE			English	Article							P38 MAPK; TUMOR-SUPPRESSOR; PROTEIN-KINASES; BREAST-CANCER; IN-VITRO; P38-DELTA; P38-ALPHA; ISOFORMS; IDENTIFICATION; INHIBITION	Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and understanding its underlying molecular mechanisms is crucial for the development of therapeutic strategies. The mitogen-activated protein kinase-kinase 3 (MKK3) is a specific activator of p38 MAP kinases (p38 MAPKs), which contributes to the regulation of several cellular functions, such as proliferation, differentiation, apoptosis as well as response to drugs. At present, the exact MKK3/p38 MAPK pathway contribution in cancer is heavily debated because of its pleiotropic function. In this work, we retrospectively explored the prognostic and pathobiologic relevance of MKK3 in a cohort of CRC patients and assessed MKK3 molecular functions in a panel of CRC lines and colonocytes primary cultures. We found increased MKK3 levels in late-stage CRC patients which correlated with shorter overall survival. Herein, we report that the MKK3 targeting by inducible RNA interference univocally exerts antitumor effects in CRC lines but not in primary colonocytes. While MKK3 depletion per se affects growth and survival by induction of sustained autophagy and death in some CRC lines, it potentiates response to chemotherapeutic drug 5-fluorouracil (5-FU) in all of the tested CRC lines in vitro. Here, we demonstrate for the first time that in CRC the MKK3 specifically activates p38delta MAPK isoform to sustain prosurvival signaling and that such effect is exacerbated upon 5-FU challenge. Indeed, p38delta MAPK silencing recapitulates MKK3 depletion effects in CRC cells in vitro and in vivo. Overall, our data identified a molecular mechanism through which MKK3 supports proliferation and survival signaling in CRC, further supporting MKK3 as a novel and extremely attractive therapeutic target for the development of promising strategies for the management of CRC patients.	[Stramucci, Lorenzo; Pranteda, Angelina; Stravato, Arianna; Bossi, Gianluca] IRCCS Regina Elena NCI, Lab Med Phys & Expert Syst, Dept Diagnost Res & Technol Innovat, I-00144 Rome, Italy; [Stramucci, Lorenzo; Pranteda, Angelina; Stravato, Arianna; Bossi, Gianluca] IRCCS Regina Elena NCI, Oncogen & Epigenet Unit, Dept Diagnost Res & Technol Innovat, I-00144 Rome, Italy; [Amoreo, Carla Azzurra; Pennetti, Annarita; Diodoro, Maria Grazia] IRCCS Regina Elena NCI, Dept Pathol, I-00144 Rome, Italy; [Bartolazzi, Armando] St Andrea Hosp, Pathol Res Lab, I-00189 Rome, Italy; [Milella, Michele] IRCCS Regina Elena NCI, Med Oncol 1, I-00144 Rome, Italy; [Milella, Michele] Univ Verona, Dept Med, Oncol Sect, Sch Med,Verona Univ Hosp Trust, I-37134 Verona, Italy		Bossi, G (corresponding author), IRCCS Regina Elena NCI, Lab Med Phys & Expert Syst, Dept Diagnost Res & Technol Innovat, I-00144 Rome, Italy.; Bossi, G (corresponding author), IRCCS Regina Elena NCI, Oncogen & Epigenet Unit, Dept Diagnost Res & Technol Innovat, I-00144 Rome, Italy.	gianluca.bossi@ifo.gov.it	Milella, Michele/ABH-8606-2020; Bossi, Gianluca/B-9394-2017; Bossi, Gianluca/ABH-6846-2020	Bossi, Gianluca/0000-0002-2947-1063; Bossi, Gianluca/0000-0002-2947-1063	AIRCFondazione AIRC per la ricerca sul cancro [IG 2016-ID. 18449]; "Alice triangi" Pezcoller-Foundation fellowship; Italian Ministry of HealthMinistry of Health, Italy	The research leading to these results has received funding from AIRC under IG 2016-ID. 18449 project-P.I. Bossi Gianluca. LS was supported by "Alice triangi" Pezcoller-Foundation fellowship. B.G. was supported by 5 x 1000 funds from Italian Ministry of Health (years 2011, 2012 and 2016). Results published here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.	Adams M, 2016, BIOORG MED CHEM LETT, V26, P1086, DOI 10.1016/j.bmcl.2015.11.054; Anaya J, 2016, PEERJ COMPUT SCI, DOI 10.7717/peerj-cs.67; Baldari S, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2014.591; Benson AB, 2017, J NATL COMPR CANC NE, V15, P370, DOI 10.6004/jnccn.2017.0036; Bertero L, 2018, VIRCHOWS ARCH, V472, P519, DOI 10.1007/s00428-017-2276-y; Bossi G, 2016, AGING-US, V8, P1; Boyle DS, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0103091; Bracht K, 2010, BRIT J CANCER, V103, P340, DOI 10.1038/sj.bjc.6605780; Brancho D, 2003, GENE DEV, V17, P1969, DOI 10.1101/gad.1107303; Chen JH, 2007, ACS CHEM BIOL, V2, P329, DOI 10.1021/cb700025j; Corre I, 2017, ONCOTARGET, V8, P55684, DOI 10.18632/oncotarget.18264; Cuenda A, 2017, TRENDS BIOCHEM SCI, V42, P431, DOI 10.1016/j.tibs.2017.02.008; de la Cruz-Morcillo MA, 2012, ONCOGENE, V31, P1073, DOI 10.1038/onc.2011.321; De Nicola GF, 2013, NAT STRUCT MOL BIOL, V20, P1182, DOI 10.1038/nsmb.2668; del Reino P, 2014, CANCER RES, V74, P6150, DOI 10.1158/0008-5472.CAN-14-0870; DERIJARD B, 1995, SCIENCE, V267, P682, DOI 10.1126/science.7839144; Engelberg D, 2004, SEMIN CANCER BIOL, V14, P271, DOI 10.1016/j.semcancer.2004.04.006; Escos A, 2016, FRONT CELL DEV BIOL, V4, DOI 10.3389/fcell.2016.00031; Galan-Moya EM, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0028406; Germani A, 2014, CANCER LETT, V344, P110, DOI 10.1016/j.canlet.2013.10.035; Giafis N, 2006, CANCER RES, V66, P6763, DOI 10.1158/0008-5472.CAN-05-3699; Guma M, 2012, ARTHRITIS RHEUM-US, V64, P2887, DOI 10.1002/art.34489; Gurtner A, 2010, J BIOL CHEM, V285, P14160, DOI 10.1074/jbc.M109.094813; Hall Michael J, 2018, Am Soc Clin Oncol Educ Book, V38, P220, DOI 10.1200/EDBK_200961; Han JH, 1997, FEBS LETT, V403, P19, DOI 10.1016/S0014-5793(97)00021-5; Huth HW, 2016, CELL SIGNAL, V28, P1283, DOI 10.1016/j.cellsig.2016.05.009; Junttila MR, 2007, ONCOGENE, V26, P5267, DOI 10.1038/sj.onc.1210332; Keshet Y, 2010, METHODS MOL BIOL, V661, P3, DOI 10.1007/978-1-60761-795-2_1; Kuma Y, 2005, J BIOL CHEM, V280, P19472, DOI 10.1074/jbc.M414221200; Kwong J, 2013, MOL CELL BIOL, V33, P3780, DOI 10.1128/MCB.00784-13; Liu JL, 2018, J CELL BIOCHEM, V119, P8472, DOI 10.1002/jcb.27073; Loesch M, 2010, J BIOL CHEM, V285, P15149, DOI 10.1074/jbc.M110.105429; MacNeil AJ, 2014, CANCER RES, V74, P162, DOI 10.1158/0008-5472.CAN-13-1310; Mittelstadt PR, 2005, CELL CYCLE, V4, P1189, DOI 10.4161/cc.4.9.2043; Patnaik A, 2016, CLIN CANCER RES, V22, P1095, DOI 10.1158/1078-0432.CCR-15-1718; Remy G, 2010, CELL SIGNAL, V22, P660, DOI 10.1016/j.cellsig.2009.11.020; Steelman LS, 2016, CURR PHARM DESIGN, V22, P2358, DOI 10.2174/1381612822666160304151011; Stramucci L, 2018, CANCERS, V10, DOI 10.3390/cancers10050131; Svensson C, 2011, BIOCHEM BIOPH RES CO, V406, P488, DOI 10.1016/j.bbrc.2011.02.083; Tsai MS, 2012, MOL CANCER THER, V11, P561, DOI 10.1158/1535-7163.MCT-11-0684; Yoshida T, 2002, J CLIN MICROBIOL, V40, P105, DOI 10.1128/JCM.40.1.105-110.2002; Zhang CL, 2018, J CELL SCI, V131, DOI 10.1242/jcs.216671; Zou X, 2017, CANCER LETT, V384, P19, DOI 10.1016/j.canlet.2016.10.008	43	14	14	1	2	NATURE PUBLISHING GROUP	LONDON	MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	2041-4889			CELL DEATH DIS	Cell Death Dis.	NOV 6	2019	10								842	10.1038/s41419-019-2083-2			13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	JP0OF	WOS:000497970800002	31695024	Green Published, gold			2022-04-25	
J	Zhang, J; Chu, DK; Kawamura, T; Tanaka, K; He, SX				Zhang, Juan; Chu, Dake; Kawamura, Takuji; Tanaka, Kiyohito; He, Shuixiang			GRIM-19 repressed hypoxia-induced invasion and EMT of colorectal cancer by repressing autophagy through inactivation of STAT3/HIF-1 signaling axis	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						colorectal cancer; epithelial-mesenchymal transition; GRIM-19; invasion; STAT3; HIF-1 signaling	EPITHELIAL-MESENCHYMAL TRANSITION; DOWN-REGULATION; CELL-DEATH; EXPRESSION; STAT3; PROLIFERATION; SWITCH	Hypoxia leads to cancer progression and promotes the metastatic potential of cancer cells. Thereby, the aim of the present study was to investigate the detailed effects of gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) in colorectal cancer (CRC) cell lines under hypoxia conditions and explore the potential molecular mechanisms. Here, we observed that GRIM-19 expression was downregulated in several CRC cell lines as well as in HCT116 and Caco-2 cells under a hypoxic microenvironment. Additionally, the introduction of GRIM-19 obviously suppressed cell invasive ability and epithelial-mesenchymal transition (EMT) through modulating EMT markers as reflected by the upregulation of E-cadherin along with the downregulation of vimentin and N-cadherin under hypoxic conditions. Moreover, the addition of GRIM-19 repressed hypoxia-induced autophagy through modulating autophagy associated proteins as reflected by the downregulation of LC3-II/LC3-I ratio and Beclin-1 expression, as well as the increased of p62 expression. Interestingly, overexpression of GRIM-19 markedly ameliorated the accumulation of HIF-1 triggered by hypoxia accompanied by an inhibition of vascular endothelial growth factor (VEGF) production and phospho-signal transducer and activator of transcription 3(p-STAT3) expression. Further data demonstrated that GRIM-19 have a negative feedback effect on the expression of HIF-1. Mechanistically, re-expression of HIF-1 completely reversed the inhibitory effects of GRIM-19 on hypoxia-induced invasion and EMT. Taken all data together, our findings established that GRIM-19 suppresses hypoxia-triggered invasion and EMT by inhibiting hypoxia-induced autophagy through inactivation HIF-1/STAT3 signaling pathway, indicating that GRIM-19 may serve as a potential predictive factor and therapeutic target for CRC treatment.	[Zhang, Juan; Chu, Dake; He, Shuixiang] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Gastroenterol, Yan Tower West Rd 277, Xian 710061, Shaanxi, Peoples R China; [Kawamura, Takuji; Tanaka, Kiyohito] Kyoto Second Red Cross Hosp, Dept Gastroenterol, Kyoto 6028026, Japan		He, SX (corresponding author), Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Gastroenterol, Yan Tower West Rd 277, Xian 710061, Shaanxi, Peoples R China.; Tanaka, K (corresponding author), Kyoto Second Red Cross Hosp, Dept Gastroenterol, Kyoto 6028026, Japan.	seijin7705@gmail.com; dyyyjxk@mail.xjtu.edu.cn	Kawamura, Takuji/AAT-4380-2020	Kawamura, Takuji/0000-0002-1155-3116	Xi'an Science and Technology Planning Project [201805094YX2SF28]	This research was supported by Xi'an Science and Technology Planning Project (201805094YX2SF28).	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Cell. Physiol.	AUG	2019	234	8					12800	12808		10.1002/jcp.27914			9	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	HX2SA	WOS:000467240800058	30537081				2022-04-25	
J	Jin, KT; Lu, ZB; Lv, JQ; Zhang, JG				Jin, Ke-Tao; Lu, Ze-Bei; Lv, Jie-Qing; Zhang, Jun-Gang			The role of long non-coding RNAs in mediating chemoresistance by modulating autophagy in cancer	RNA BIOLOGY			English	Review						Cancer; LncRNAs; metastasis; chemoresistance; autophagy	EPITHELIAL-MESENCHYMAL TRANSITION; GASTRIC-CANCER; COLORECTAL-CANCER; MULTIDRUG-RESISTANCE; DOWN-REGULATION; OVARIAN-CANCER; CISPLATIN-RESISTANCE; CELL-PROLIFERATION; BLADDER-CANCER; UP-REGULATION	Cancer is a complex process in which protein-coding and non-coding genes play essential roles. Long noncoding RNAs (lncRNAs), as a subclass of noncoding genes, are implicated in various cancer processes including growth, proliferation, metastasis, and angiogenesis. Due to presence in body fluids such as blood and urine, lncRNAs have become novel biomarkers in cancer detection, diagnosis, progression, and therapy response. Remarkably, increasing evidence has verified that lncRNAs play essential roles in chemoresistance by targeting different signalling pathways. Autophagy, a highly conserved process in response to environmental stresses such as starvation and hypoxia, plays a paradoxical role in inducing resistance or sensitivity to chemotherapy agents. In this regard, we reviewed chemoresistance, the role of lncRNAs in cancer, and the role of lncRNAs in chemoresistance by modulating autophagy.	[Jin, Ke-Tao; Lv, Jie-Qing] Zhejiang Univ, Shaoxing Peoples Hosp, Dept Colorectal Surg, Sch Med, Shaoxing, Zhejiang, Peoples R China; [Lu, Ze-Bei; Zhang, Jun-Gang] Hangzhou Med Coll, Key Lab Tumor Mol Diag & Individualized Med Zheji, Zhejiang Prov Peoples Hosp, Peoples Hosp, Hangzhou, Zhejiang, Peoples R China; [Zhang, Jun-Gang] Hangzhou Med Coll, Hepatobiliary & Pancreat Surg, Zhejiang Prov Peoples Hosp, Peoples Hosp, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China		Zhang, JG (corresponding author), Hangzhou Med Coll, Hepatobiliary & Pancreat Surg, Zhejiang Prov Peoples Hosp, Peoples Hosp, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China.	zjg2sy1@163.com			Zhejiang Provincial Science and Technology Projects [LGF18H160041, LGD19H160001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772537, 81374014, 81502482]; Zhejiang Provincial Research Projects of Medical and Healthy Industries [2017KY193, 2017KY210]	This work was supported by the [Zhejiang Provincial Science and Technology Projects] under Grant [Nos. LGF18H160041 to LJQ, LGD19H160001 to JKT]; [National Natural Science Foundation of China] under Grant [Nos. 81772537 to JKT; 81374014 to JKT; 81502482 to JGZ]; and [Zhejiang Provincial Research Projects of Medical and Healthy Industries] under Grant [Nos. 2017KY193 and 2017KY210 to JGZ].	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DEC 1	2020	17	12					1727	1740		10.1080/15476286.2020.1737787		MAR 2020	14	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	OY4PW	WOS:000519901500001	32129701	Green Published, Bronze			2022-04-25	
J	Yin, X; Zhang, N; Di, W				Yin, Xia; Zhang, Ning; Di, Wen			Regulation of LC3-Dependent Protective Autophagy in Ovarian Cancer Cells by Protein Phosphatase 2A	INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER			English	Article						Protein phosphatase 2A; Cisplatin; Apoptosis; Protective autophagy; Ovarian cancer	PPP2R1B GENE; SUBUNIT INTERACTION; COLORECTAL CANCERS; CISPLATIN THERAPY; P38 MAPK; PP2A; MUTATIONS; DEPHOSPHORYLATION; PHOSPHORYLATION; SUPPRESSION	Objective: Protein phosphatase 2A (PP2A) is a target for cisplatin, which is a widely used platinum drug to treat various cancer, including ovarian cancer. However, to date, the exact role of PP2A in chemoresistance to cisplatin-centered ovarian cancer therapy is not clear. Methods and Materials: To analyze the function of PP2A in cisplatin-resistant ovarian cancer cells, we derived A2780/cisplatin (CDDP), which is resistant to cisplatin, from A2780 cell line. Western blotting was used to detect the expression of PP2A, autophagy, and apoptosis markers. Results: The expression of PP2A catalytic subunit, (PP2Ac) was reduced in A2780/CDDP as well as in cisplatin-resistant patients' tissues compared with A2780 and cisplatin-sensitive patients. In the A2780 cells, cisplatin induced both apoptosis and autophagy. Interestingly, however, the autophagy inhibitor 3-methyladenine increased the cell death induced by diamindichloridoplatin (DDP), which suggested the protective function of autophagy in DDP-induced cell death. Knocking down of PP2A promoted autophagy but suppressed DDP-induced apoptosis and cell death. In contrast, overexpression of PP2Ac or reinduction of the activity of PP2A by FTY720 decreased autophagy but increased cell death induced by DDP. Our experiments demonstrated that apoptosis suppressed by the knocking down of PP2Ac can be reversed by the administration of 3-methyladenine. The elevated accumulation of microtubule-associated protein 1 light chain 3-II and the decline of the autophagy substrate p62 were also observed in PP2Ac-small interfering RNA transfected cells. However, overexpression of PP2Ac suppressed the accumulation of microtubule-associated protein 1 light chain 3-II and restored p62. Conclusions: Taken together, our results showed that protective autophagy regulated by PP2Ac is at least part of the mechanism to how certain ovarian cancers are resistant to cisplatin. Prospective studies are necessary to determine the detailed mechanism of how PP2Ac regulates autophagy in chemoresistant patients.	[Yin, Xia; Zhang, Ning; Di, Wen] Shanghai Jiao Tong Univ, Renji Hosp, Dept Obstet & Gynecol, Sch Med, Shanghai 200127, Peoples R China		Di, W (corresponding author), Shanghai Jiao Tong Univ, Renji Hosp, Dept Obstet & Gynecol, Sch Med, Peoples Republic China E mail diwen163 163 com T, Shanghai 200127, Peoples R China.	diwen163@163.com	ZHANG, NING/C-8105-2015	Zhang, Ning/0000-0001-6306-4819	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81072137]	This work was supported by grants from the National Natural Science Foundation of China (No. 81072137).	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J. Gynecol. Cancer	MAY	2013	23	4					630	641		10.1097/IGC.0b013e3182892cee			12	Oncology; Obstetrics & Gynecology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Obstetrics & Gynecology	132MB	WOS:000318071300009	23518861				2022-04-25	
J	Li, H; Meng, XX; Zhang, L; Zhang, BJ; Liu, XY; Fu, WW; Tan, HS; Lao, YZ; Xu, HX				Li, Hui; Meng, Xiao-xiao; Zhang, Li; Zhang, Bao-jun; Liu, Xin-yu; Fu, Wen-wei; Tan, Hong-sheng; Lao, Yuan-zhi; Xu, Hong-xi			Oblongifolin C and guttiferone K extracted from Garcinia yunnanensis fruit synergistically induce apoptosis in human colorectal cancer cells in vitro	ACTA PHARMACOLOGICA SINICA			English	Article						Garcinia yunnanensis Hu; oblongifolin C; guttiferone K; colorectal cancer; HCT116 cells; apoptosis; autophagy; ROS; JNK	DRUG-COMBINATION; AUTOPHAGY; COMPOUND; BENZOPHENONES; STRESS; DEATH	Oblongifolin C (OC) and guttiferone K (GUTK) are two anticancer compounds extracted from Garcinia yunnanensis Hu, but they act by different mechanisms. In this study we investigated whether a combination of OC and GUTK (1:1 molar ratio) could produce synergistic anticancer effects against human colorectal cancer cells in vitro. For comparison, we also examined the anticancer efficacy of ethanol extracts from G yunnanensis fruit, which contain OC and GUTK up to 5%. Compared to OC and GUTK alone, the combination of OC and GUTK as well as the ethanol extracts more potently inhibited the cancer cell growth with IC50 values of 3.4 mu mol/L and 3.85 mu g/mL, respectively. Furthermore, OC and GUTK displayed synergistic inhibition on HCT116 cells: co-treatment with OC and GUTK induced more prominent apoptosis than treatment with either drug alone. Moreover, the combination of OC and GUTK markedly increased cleavage of casapse-3 and PARP, and enhanced cellular ROS production and increased JNK protein phosphorylation. In addition, the combination of OC and GUTK exerted stronger effects under nutrient-deprived conditions than in complete medium, suggesting that autophagy played an essential role in regulating OC- and GUTK-mediated cell death. OC and GUTK are the main components that contribute to the anticancer activity of G yunnanensis and the compounds have apoptosis-inducing effects in HCT116 cells in vitro.	[Li, Hui; Meng, Xiao-xiao; Zhang, Li; Zhang, Bao-jun; Liu, Xin-yu; Fu, Wen-wei; Tan, Hong-sheng; Lao, Yuan-zhi; Xu, Hong-xi] Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China; [Li, Hui; Meng, Xiao-xiao; Zhang, Li; Zhang, Bao-jun; Liu, Xin-yu; Fu, Wen-wei; Tan, Hong-sheng; Lao, Yuan-zhi; Xu, Hong-xi] Shanghai Coll TCM New Drug Discovery, Engn Res Ctr, Shanghai 201203, Peoples R China		Lao, YZ; Xu, HX (corresponding author), Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China.; Lao, YZ; Xu, HX (corresponding author), Shanghai Coll TCM New Drug Discovery, Engn Res Ctr, Shanghai 201203, Peoples R China.	laurence_ylao@163.com; xuhongxi88@gmail.com	Fu, Wenwei/AAD-6756-2020; Zhang, Li/AAD-5917-2020; tan, Hongsheng/AAD-5830-2020; Xu, Hongxi/AAC-2799-2020; , Yuanzhi/D-3936-2015	Xu, Hongxi/0000-0001-6238-4511; , Yuanzhi/0000-0002-7803-4484	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81173485, 81273403]; Natural Science Foundation of ShanghaiNatural Science Foundation of Shanghai [14ZR1441300]	This work was supported by the National Natural Science Foundation of China (No 81173485 and 81273403) and the Natural Science Foundation of Shanghai (No 14ZR1441300).	Anholeti MC, 2015, AN ACAD BRAS CIENC, V87, P289, DOI 10.1590/0001-3765201520140564; [Anonymous], 2004, GUID IND BOT DRUG PR; Chou TC, 2006, PHARMACOL REV, V58, P621, DOI 10.1124/pr.58.3.10; Chou TC, 2010, CANCER RES, V70, P440, DOI 10.1158/0008-5472.CAN-09-1947; Date AA, 2016, DRUG DISCOV TODAY, V21, P333, DOI 10.1016/j.drudis.2015.10.019; DeSantis CE, 2014, CA-CANCER J CLIN, V64, P252, DOI 10.3322/caac.21235; Farooqi AA, 2014, MAR DRUGS, V12, P5408, DOI 10.3390/md12115408; Feng C, 2012, INT J CANCER, V131, P1445, DOI 10.1002/ijc.27365; Ferlay J, 2015, INT J CANCER, V136, pE359, DOI 10.1002/ijc.29210; Filomeni G, 2015, CELL DEATH DIFFER, V22, P377, DOI 10.1038/cdd.2014.150; Goldar Samira, 2015, Asian Pac J Cancer Prev, V16, P2129; Guo XQ, 2015, CHEM-BIOL INTERACT, V235, P27, DOI 10.1016/j.cbi.2015.04.009; Kan WLT, 2013, INT J CANCER, V132, P707, DOI 10.1002/ijc.27694; Kim GT, 2014, INT J MOL MED, V33, P863, DOI 10.3892/ijmm.2014.1658; Lao YZ, 2014, AUTOPHAGY, V10, P736, DOI 10.4161/auto.28034; Liu EY, 2012, J CELL SCI, V125, P2349, DOI 10.1242/jcs.093708; Nash KM, 2015, INTEGR MED INSIGHTS, V10, P1, DOI 10.4137/IMI.S25054; Ouyang L, 2012, CELL PROLIFERAT, V45, P487, DOI 10.1111/j.1365-2184.2012.00845.x; Ovadje P, 2015, EVID-BASED COMPL ALT, V2015, DOI 10.1155/2015/751348; Romano B, 2014, PHYTOMEDICINE, V21, P631, DOI 10.1016/j.phymed.2013.11.006; van Beek TA, 2009, J CHROMATOGR A, V1216, P2002, DOI 10.1016/j.chroma.2009.01.013; Wang XY, 2015, SCI REP-UK, V5, DOI 10.1038/srep10293; Wu M, 2015, PHYTOMEDICINE, V22, P902, DOI 10.1016/j.phymed.2015.06.008; Wu SB, 2014, NAT PROD REP, V31, P1158, DOI 10.1039/c4np00027g; Wu Z. Y., 1991, FLORA OF YUNNAN; Xu G, 2008, J AGR FOOD CHEM, V56, P11144, DOI 10.1021/jf802690g	26	14	14	3	19	ACTA PHARMACOLOGICA SINICA	SHANGHAI	294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA	1671-4083	1745-7254		ACTA PHARMACOL SIN	Acta Pharmacol. Sin.	FEB	2017	38	2					252	263		10.1038/aps.2016.101			12	Chemistry, Multidisciplinary; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Pharmacology & Pharmacy	EJ2AY	WOS:000393013400010	27840412	Bronze, Green Published			2022-04-25	
J	Liu, J; Ren, YJ; Hou, YL; Zhang, CQ; Wang, B; Li, XR; Sun, R; Liu, J				Liu, Jing; Ren, Yanjun; Hou, Yinglong; Zhang, Caiqing; Wang, Bei; Li, Xiaorui; Sun, Rong; Liu, Ju			Dihydroartemisinin Induces Endothelial Cell Autophagy through Suppression of the Akt/mTOR Pathway	JOURNAL OF CANCER			English	Article						Dihydroartemisinin; Autophagy; HUVEC; Akt; MTOR	COLORECTAL-CANCER CELLS; SIGNALING PATHWAYS; MAMMALIAN TARGET; ANGIOGENESIS; INHIBITION; APOPTOSIS; PHOSPHORYLATION; PROLIFERATION; ARTESUNATE; INDUCTION	Aims: Dihydroartemisinin (DHA), a derivative of artemisinin, suppresses angiogenesis by regulating endothelial cell phenotypes. In this study, we investigated the effect of DHA on endothelial cell autophagy and the underlying mechanisms. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with DHA. Formation of autophagosomes in HUVECs was observed by fluorescence microscope after pcDNA3.1-green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) plasmids transfection. Dichlorofluorescein diacetate (DCFH-DA) staining was used to detect intracellular reactive oxygen species (ROS). Western blot was performed to detect the protein levels of LC3, p62, beclin 1, autophagy-related protein (Atg) 5, p-Akt (protein kinase B), p-mTOR (mammalian target of rapamycin), p-4E-BP1 (eukaryotic translation initiation factor 4E-binding protein 1), and p-p70S6K (p70 ribosomal S6 kinase). Results: DHA increased LC3-II and the number of fluorescent GFP-LC3 puncta in HUVECs. Silencing ATG5 by siRNA interference attenuated DHA-induced LC3-II elevation. DHA enhanced ROS production, but pretreatment with antioxidant N-acety-l-cysteine (NAC) failed to reduce DHA-induced autophagy in HUVECs. Pretreatment with PD98059, SP600125 and SB203580, the inhibitors of ERK, JNK, and p38 MAPK, did not reverse autophagy in DHA-treated HUVECs. DHA significantly reduced phosphorylation of Akt, mTOR, p70S6K, 4E-BP1 in HUVECs. Rapamycin, an mTOR antagonist, compromised DHA-induced autophagy. Conclusion: DHA induces autophagy in HUVECs by inhibition of the Akt/mTOR pathway	[Liu, Jing; Liu, Ju] Shandong First Med Univ, Hosp 1, Shandong Prov Qianfoshan Hosp, Lab Microvasc Med,Med Res Ctr, Jinan, Shandong, Peoples R China; [Ren, Yanjun] Shandong First Med Univ, Hosp 1, Shandong Prov Qianfoshan Hosp, Dept Orthopaed, Jinan, Shandong, Peoples R China; [Hou, Yinglong] Shandong First Med Univ, Hosp 1, Shandong Prov Qianfoshan Hosp, Dept Cardiol, Jinan, Shandong, Peoples R China; [Zhang, Caiqing] Shandong First Med Univ, Hosp 1, Shandong Prov Qianfoshan Hosp, Dept Resp Med, Jinan, Shandong, Peoples R China; [Wang, Bei] Shandong First Med Univ, Hosp 1, Shandong Prov Qianfoshan Hosp, Dept Ultrasound, Jinan, Shandong, Peoples R China; [Li, Xiaorui] Shandong First Med Univ & Shandong Acad Med Sci, Grad Sch, Jinan, Shandong, Peoples R China; [Sun, Rong] Shandong Univ, Adv Med Res Inst, Jinan, Shandong, Peoples R China; [Sun, Rong] Shandong Univ, Hosp 2, Jinan, Shandong, Peoples R China		Liu, J (corresponding author), Shandong First Med Univ, Hosp 1, Shandong Prov Qianfoshan Hosp, Med Res Ctr, 16766 Jingshi Rd, Jinan 250014, Shandong, Peoples R China.	ju.liu@sdu.edu.cn	Liu, Ju/Q-6319-2016	Liu, Ju/0000-0001-9932-2613	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81700319]; Traditional Chinese Medicine Research Projects of Shandong Province [2015-285]; National Fundamental Research Program of China [2009CB522802]; Shandong Taishan Scholarship; Science and Technology Development Plan of Shandong Province [2016GSF121037]	This work was supported by grants from National Natural Science Foundation of China (81700319), the Traditional Chinese Medicine Research Projects of Shandong Province (no. 2015-285), the National Fundamental Research Program of China (2009CB522802), the Shandong Taishan Scholarship (R.S and J.L) and the Science and Technology Development Plan of Shandong Province (2016GSF121037).	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Cancer		2019	10	24					6057	6064		10.7150/jca.33704			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	JE7YF	WOS:000490906300017	31762815	Green Published, gold			2022-04-25	
J	Bagherian, A; Roudi, B; Masoudian, N; Mirzaei, H				Bagherian, Ali; Roudi, Bostan; Masoudian, Nahid; Mirzaei, Hamed			Anti-glioblastoma effects of nanomicelle-curcumin plus erlotinib	FOOD & FUNCTION			English	Article							KAPPA-B; CELL-PROLIFERATION; COLORECTAL-CANCER; DOWN-REGULATION; LUNG-CANCER; CYCLIN D1; IN-VITRO; GROWTH; EGFR; ANGIOGENESIS	Glioblastoma (GBM), one of the most significant brain neoplasms, is characterized by high metastasis and recurrence. Crossing the blood-brain barrier is one of the main therapeutic obstacles, seriously hampering therapeutic agents entering the brain. This research investigated the co-delivery of erlotinib and curcumin via nanomicelles for enhancing anti-GBM treatment in vitro. For this purpose, curcumin and nanomicelle-curcumin (50 mu M) were investigated alone and also with erlotinib (50 mu M) in U87 glioblastoma cells. The cell viability of U87 cells after exposure to curcumin/nanomicelle curcumin/erlotinib and their combinations was measured by CCK-8 assay. The expression of the Wnt signaling-related genes was measured by qRT-PCR assay. The altered expression of NF-kB and proteins associated with angiogenesis, apoptosis, and autophagy were investigated by western blot assay. Compared with the control, all treatments reduced the viability of U87 glioblastoma cells. Furthermore, the level of proteins related to angiogenesis and Wnt pathway-associated genes in the nanomicelle-curcumin + erlotinib group were significantly decreased compared to the curcumin, erlotinib, and control groups. Each treatment regulated autophagy and apoptosis-associated proteins. Total phospho-NF-kappa B (p65) and total NF-kappa B (p65) declined in each treatment at the protein levels. Overall, nanomicelle-curcumin alone or combined with erlotinib showed anti-GBM activity in the U87 cell line by regulating the signaling pathways in GBM pathogenesis and thus may be a promising nanodrug candidate for application in the field of GBM therapy.	[Bagherian, Ali; Roudi, Bostan; Masoudian, Nahid] Islamic Azad Univ, Damghan Branch, Dept Biol, Fac Sci, Damghan, Iran; [Mirzaei, Hamed] Kashan Univ Med Sci, Inst Basic Sci, Res Ctr Biochem & Nutr Metab Dis, Kashan, Iran; [Mirzaei, Hamed] Kashan Univ Med Sci, Student Res Comm, Kashan, Iran		Masoudian, N (corresponding author), Islamic Azad Univ, Damghan Branch, Dept Biol, Fac Sci, Damghan, Iran.; Mirzaei, H (corresponding author), Kashan Univ Med Sci, Inst Basic Sci, Res Ctr Biochem & Nutr Metab Dis, Kashan, Iran.; Mirzaei, H (corresponding author), Kashan Univ Med Sci, Student Res Comm, Kashan, Iran.	nahidmasoudian@yahoo.com; h.mirzaei2002@gmail.com		mirzaei, hamed/0000-0002-9399-8281	Islamic Azad University, Damghan Branch, Damghan, IranIslamic Azad University	This study was a part of thesis that was supported from Islamic Azad University, Damghan Branch, Damghan, Iran.	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NOV 1	2021	12	21					10926	10937		10.1039/d1fo01611c		OCT 2021	12	Biochemistry & Molecular Biology; Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Food Science & Technology	WP8NF	WOS:000707177900001	34647945				2022-04-25	
J	Miranda-Goncalves, V; Cardoso-Carneiro, D; Valbom, I; Cury, FP; Silva, VA; Granja, S; Reis, RM; Baltazar, F; Martinho, O				Miranda-Goncalves, Vera; Cardoso-Carneiro, Diana; Valbom, Ines; Cury, Fernanda Paula; Silva, Viviane Aline; Granja, Sara; Reis, Rui M.; Baltazar, Fatima; Martinho, Olga			Metabolic alterations underlying Bevacizumab therapy in glioblastoma cells	ONCOTARGET			English	Article						anti-angiogenic therapy; Bevacizumab; glioblastoma; glycolytic metabolism	ANTI-ANGIOGENIC THERAPY; ENDOTHELIAL GROWTH-FACTOR; COLORECTAL-CANCER CELLS; PHASE-II TRIAL; IN-VIVO; ANTIANGIOGENIC THERAPY; ADJUVANT TEMOZOLOMIDE; GLYCOLYTIC PHENOTYPE; RADIATION-THERAPY; INDUCED AUTOPHAGY	Anti-VEGF therapy with Bevacizumab is approved for glioblastoma treatment, however, it is known that tumors acquired resistance and eventually became even more aggressive and infiltrative after treatment. In the present study we aimed to unravel the potential cellular mechanisms of resistance to Bevacizumab in glioblastoma in vitro models. Using a panel of glioblastoma cell lines we found that Bevacizumab is able to block the secreted VEGF by the tumor cells and be internalized to the cytoplasm, inducing cytotoxicity in vitro. We further found that Bevacizumab increases the expression of hypoxic HIF-1 alpha and CAIX) and glycolytic markers GLUT1 and MCT1), leading to higher glucose uptake and lactate production. Furthermore, we showed that part of the consumed glucose by the tumor cells can be stored as glycogen, hampering cell dead following Bevacizumab treatment. Importantly, we found that this change on the glycolytic metabolism occurs independently of hypoxia and before mitochondrial impairment or autophagy induction. Finally, the combination of Bevacizumab with glucose uptake inhibitors decreased in vivo tumor growth and angiogenesis and shift the expression of glycolytic proteins. In conclusion, we reported that Bevacizumab is able to increase the glucose metabolism on cancer cells by abrogating autocrine VEGF in vitro. Define the effects of anti-angiogenic drugs at the cellular level can allow us to discover ways to revert acquired resistance to this therapeutic approaches in the future.	[Miranda-Goncalves, Vera; Cardoso-Carneiro, Diana; Valbom, Ines; Granja, Sara; Reis, Rui M.; Baltazar, Fatima; Martinho, Olga] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, Braga, Portugal; [Miranda-Goncalves, Vera; Cardoso-Carneiro, Diana; Valbom, Ines; Granja, Sara; Reis, Rui M.; Baltazar, Fatima; Martinho, Olga] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal; [Cury, Fernanda Paula; Silva, Viviane Aline; Reis, Rui M.; Martinho, Olga] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil		Martinho, O (corresponding author), Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Campus Gualtar, Braga, Portugal.; Martinho, O (corresponding author), ICVS 3Bs PT Govt Associate Lab, Braga, Portugal.; Martinho, O (corresponding author), Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil.	olgamartinho@med.uminho.pt	Granja, Sara/AAE-7136-2021; Martinho, Olga/B-9695-2009; Reis, Rui Manuel/B-1744-2018; Sara, Granja C/T-6442-2018; Silva, Viviane A O/O-1772-2015; F, Baltazar/A-8720-2010; Reis, Rui Manuel/AAD-6470-2020	Granja, Sara/0000-0001-8717-6751; Martinho, Olga/0000-0002-3221-0403; Reis, Rui Manuel/0000-0002-9639-7940; Sara, Granja C/0000-0001-8717-6751; F, Baltazar/0000-0002-1770-4544; Reis, Rui Manuel/0000-0002-9639-7940; Silva, Viviane A O/0000-0001-5919-5242; Miranda-Goncalves, Vera/0000-0002-4231-5532	Northern Portugal Regional Operational Programme (NORTE), under the Portugal, through the European Regional Development Fund (FEDER) [NORTE-01-0145-FEDER-000013]; Competitiveness Factors Operational Programme (COMPETE); Foundation for Science and Technology (FCT)Portuguese Foundation for Science and TechnologyEuropean Commission [POCI-01-0145-FEDER-007038]; Brazilian MCTI/CNPq [73/2013]; Fundacao para a Ciencia e Tecnologia (FCT), PortugalPortuguese Foundation for Science and Technology [SFRH/BD/51997/2012]; FAPESP fellowshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2014/03684-0]; BEPE - Bolsa Estagio de Pesquisa no Exterior [2015/02691-6]; FCT, PortugalPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BPD/108351/2015]	This study was partially developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and through the Competitiveness Factors Operational Programme (COMPETE), by Portuguese funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038, and by Brazilian MCTI/CNPq No 73/2013. VMG was recipient from a PhD fellowship (SFRH/BD/51997/2012) from Fundacao para a Ciencia e Tecnologia (FCT), Portugal. FC was recipient of a master FAPESP fellowship (no 2014/03684-0) and "BEPE - Bolsa Estagio de Pesquisa no Exterior" (no 2015/02691-6). OM is recipient of a post-doc fellowship (SFRH/BPD/108351/2015) from FCT, Portugal.	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J	Hernandez-Borrero, LJ; Zhang, SL; Lulla, A; Dicker, DT; El-Deiry, WS				Hernandez-Borrero, Liz J.; Zhang, Shengliang; Lulla, Amriti; Dicker, David T.; El-Deiry, Wafik S.			CB002, a novel p53 tumor suppressor pathway-restoring small molecule induces tumor cell death through the pro-apoptotic protein NOXA	CELL CYCLE			English	Article						apoptosis; autophagy; mutant p53 degradation; NOXA; p53 pathway restoration; ubiquitin proteasome system	MUTANT P53; CANCER-CELLS; OPPORTUNITIES; RESTORATION; ACTIVATION; AUTOPHAGY; GAIN; ATG5; DRUG; P73	P53 tumor suppressor gene mutations occur in the majority of human cancers and contribute to tumor development, progression and therapy resistance. Direct functional restoration of p53 as a transcription factor has been difficult to achieve in the clinic. We performed a functional screen using a bioluminescence-based transcriptional read-out to identify small molecules that restore the p53 pathway in mutant p53-bearing cancer cells. We identified CB002, as a candidate that restores p53 function in mutant p53-expressing colorectal cancer cells and without toxicity to normal human fibroblasts. Cells exposed to CB002 show increased expression of endogenous p53 target genes NOXA, DR5, and p21 and cell death which occurs by 16hours, as measured by cleaved caspases or PARP. Stable knockdown of NOXA completely abrogates PARP cleavage and reduces sub-G1 content, implicating NOXA as the key mediator of cell death induction by CB002. Moreover, CB002 decreases the stability of mutant p53 in RXF393 cancer cells and an exogenously expressed R175H p53 mutant in HCT116 p53-null cells. R175H p53 expression was rescued by addition of proteasome inhibitor MG132 to CB002, suggesting a role for ubiquitin-mediated degradation of the mutant protein. In summary, CB002, a p53 pathway-restoring compound that targets mutant p53 for degradation and induces tumor cell death through NOXA, may be further developed as a cancer therapeutic.	Fox Chase Canc Ctr, Dept Med Oncol, Lab Translat Oncol & Expt Canc Therapeut, 7701 Burholme Ave, Philadelphia, PA 19111 USA; Fox Chase Canc Ctr, Mol Therapeut Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA		El-Deiry, WS (corresponding author), 333 Cottman Ave,P2035, Philadelphia, PA 19111 USA.	wafik.eldeiry@gmail.com	Lulla, Amriti R./AAI-4167-2020; El-Deiry, Wafik/AAJ-6080-2020	El-Deiry, Wafik/0000-0002-9577-8266	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [N01-CN43302-WA-17, N01-CN43302- WA-27, R01 CA176289]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA176289] Funding Source: NIH RePORTER	This work was supported by NIH grants N01-CN43302-WA-17, N01-CN43302- WA-27, and R01 CA176289 (W.S.E-D.). W.S.E-D. is an American Cancer Society (ACS) Research Professor.	Boeckler FM, 2008, P NATL ACAD SCI USA, V105, P10360, DOI 10.1073/pnas.0805326105; Bykov VJN, 2002, NAT MED, V8, P282, DOI 10.1038/nm0302-282; DITTMER D, 1993, NAT GENET, V4, P42, DOI 10.1038/ng0593-42; Garufi A, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.217; Hong B, 2014, CANCER RES, V74, P1153, DOI 10.1158/0008-5472.CAN-13-0955; Hong B, 2014, CURR DRUG TARGETS, V15, P80, DOI 10.2174/1389450114666140106101412; Lang GA, 2004, CELL, V119, P861, DOI 10.1016/j.cell.2004.11.006; Li D, 2011, CELL DEATH DIFFER, V18, P1904, DOI 10.1038/cdd.2011.71; Liu YL, 2014, ONCOTARGET, V5, P11237; Mizushima N, 2007, AUTOPHAGY, V3, P542, DOI 10.4161/auto.4600; Muller PAJ, 2014, CANCER CELL, V25, P304, DOI 10.1016/j.ccr.2014.01.021; Nishida Y, 2009, NATURE, V461, P654, DOI 10.1038/nature08455; North S, 2002, MOL CARCINOGEN, V33, P181, DOI 10.1002/mc.10038; Oshima Y, 2007, CANCER BIOL THER, V6, P1058, DOI 10.4161/cbt.6.7.4320; Pant V, 2014, GENE DEV, V28, P1739, DOI 10.1101/gad.247452.114; Parrales A, 2015, FRONT ONCOL, V5, DOI 10.3389/fonc.2015.00288; Pyo JO, 2005, J BIOL CHEM, V280, P20722, DOI 10.1074/jbc.M413934200; Riley T, 2008, NAT REV MOL CELL BIO, V9, P402, DOI 10.1038/nrm2395; Takimoto R, 2002, CANCER BIOL THER, V1, P47, DOI 10.4161/cbt.1.1.41; Vakifahmetoglu-Norberg H, 2013, GENE DEV, V27, P1718, DOI 10.1101/gad.220897.113; Wang WG, 2006, P NATL ACAD SCI USA, V103, P11003, DOI 10.1073/pnas.0604507103; Yousefi S, 2006, NAT CELL BIOL, V8, P1124, DOI 10.1038/ncb1482; Yu X, 2010, CANCER CELL, V21, P614; Zhang SL, 2015, CANCER RES, V75, P3842, DOI 10.1158/0008-5472.CAN-13-1079	24	7	8	1	3	TAYLOR & FRANCIS INC	PHILADELPHIA	530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA	1538-4101	1551-4005		CELL CYCLE	Cell Cycle		2018	17	5					557	567		10.1080/15384101.2017.1346762			11	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	GE0VN	WOS:000430934900005	28749203	Green Published, Bronze			2022-04-25	
J	Podolski-Renic, A; Bosze, S; Dinic, J; Kocsis, L; Hudecz, F; Csampai, A; Pesic, M				Podolski-Renic, Ana; Bosze, Szilvia; Dinic, Jelena; Kocsis, Laszlo; Hudecz, Ferenc; Csampai, Antal; Pesic, Milica			Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel	METALLOMICS			English	Article							COLLATERAL SENSITIVITY; IN-VITRO; ANTIPROLIFERATIVE ACTIVITY; AUTOPHAGY; SUPEROXIDE; BREAST	Recently, we demonstrated that ferrocene-containing compounds with a cinchona moiety displayed marked anticancer activity. Here we report on the effects of the most promising isomers encompassing quinine-(compounds 4 and 5) and quinidine-epimers (compounds 6 and 7)-synthesized using improved methods providing controlled diastereoselectivity-in three different human multidrug resistant (MDR) cancer cell lines and their sensitive counterparts (non-small cell lung carcinoma NCI-H460/R/NCI-H460, colorectal carcinoma DLD1-TxR/DLD1 and glioblastoma U87-TxR/U87). We observed that the presence of the MDR phenotype did not diminish the activity of the compounds suggesting that ferrocene quinine-and quinidine-epimers are not substrates for P-glycoprotein, which has been indicated as a major mechanism of MDR in the cell lines used. Considering that metal-based anticancer agents mainly act by increasing ROS production, we investigated the potential of ferrocene-quinidine epimers to generate ROS. We found that 6 and 7 more readily increased ROS production and induced mitochondrial damage in MDR cancer cells. According to cell death analysis, 6 and 7 were more active against MDR cancer cells showing collateral sensitivity. In addition, our data suggest that these compounds could act as inhibitors of autophagy. Importantly, simultaneous treatments of 6 and 7 with paclitaxel (PTX) increased the sensitivity of MDR cancer cells to PTX. In conclusion, the ferrocene-quinidine epimers, besides being selective towards MDR cancer cells, could also possess potential to overcome PTX resistance.	[Podolski-Renic, Ana; Dinic, Jelena; Pesic, Milica] Univ Belgrade, Dept Neurobiol, Inst Biol Res Sinisa Stankovic IBISS, Belgrade, Serbia; [Bosze, Szilvia; Hudecz, Ferenc] Eotvos Lorand Univ, MTA ELTE Res Grp Peptide Chem, Budapest, Hungary; [Kocsis, Laszlo; Hudecz, Ferenc] Eotvos Lorand Univ, Dept Organ Chem, Budapest, Hungary; [Csampai, Antal] Eotvos Lorand Univ, Dept Inorgan Chem, Budapest, Hungary		Pesic, M (corresponding author), Univ Belgrade, Dept Neurobiol, Inst Biol Res Sinisa Stankovic IBISS, Belgrade, Serbia.	camala@ibiss.bg.ac.rs	Kocsis, László/AAB-3683-2019; Bosze, Szilvia/X-1368-2019; Pešić, Milica/I-4727-2019	Kocsis, László/0000-0002-0277-5374; Bosze, Szilvia/0000-0001-9555-699X; Pešić, Milica/0000-0002-9045-8239; Podolski-Renic, Ana/0000-0001-7412-3685; Dinic, Jelena/0000-0003-3371-2381	Ministry of Education, Science and Technological Development of the Republic of Serbia [III41031]; Hungarian National Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K104385]	This research was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. III41031) and by a grant from the Hungarian National Research Fund (OTKA K104385). This work was performed within the framework of COST Actions CM1106 (Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells) and CM1407 (Challenging organic syntheses inspired by nature from natural products chemistry to drug discovery).	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J	Fricker, M; O'Prey, J; Tolkovsky, AM; Ryan, KM				Fricker, M.; O'Prey, J.; Tolkovsky, A. M.; Ryan, K. M.			Phosphorylation of Puma modulates its apoptotic function by regulating protein stability	CELL DEATH & DISEASE			English	Article						Puma; phosphorylation; protein stability	COLORECTAL-CANCER CELLS; BH3-ONLY PROTEINS; BCL-2 FAMILY; DEPENDENT APOPTOSIS; INDUCE APOPTOSIS; DEATH; BAX; P53; AUTOPHAGY; BINDING	Puma is a potent BH3-only protein that antagonises anti-apoptotic Bcl-2 proteins, promotes Bax/Bak activation and has an essential role in multiple apoptotic models. Puma expression is normally kept very low, but can be induced by several transcription factors including p53, p73, E2F1 and FOXO3a, whereby it can induce an apoptotic response. As Puma can to bind and inactivate all anti-apoptotic members of the Bcl-2 family, its activity must be tightly controlled. We report here, for the first time, evidence that Puma is subject to post-translational control through phosphorylation. We show that Puma is phosphorylated at multiple sites, with the major site of phosphorylation being serine 10. Replacing serine 10 with alanine causes reduced Puma turnover and enhanced cell death. Interestingly, Puma turnover occurs through the proteasome, and substitution of serine 10 causes elevated Puma levels independently of macroautophagy, Bcl-2 family member binding, caspase activity and apoptotic death. We conclude, therefore, that phosphorylation of Puma at serine 10 promotes Puma turnover, represses Puma's cell death potential and promotes cell survival. Owing to the highly pro-apoptotic nature of Puma, these studies highlight an important additional regulatory step in the determination of cellular life or death. Cell Death and Disease (2010) 1, e59; doi:10.1038/cddis.2010.38; published online 29 July 2010	[Fricker, M.; O'Prey, J.; Ryan, K. M.] Beatson Inst Canc Res, Tumour Cell Death Lab, Glasgow G61 1BD, Lanark, Scotland; [Fricker, M.; Tolkovsky, A. M.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England; [Tolkovsky, A. M.] Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB2 OPY, England		Ryan, KM (corresponding author), Beatson Inst Canc Res, Tumour Cell Death Lab, Garscube Estate,Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.	mf309@cam.ac.uk; k.ryan@beatson.gla.ac.uk	FRICKER, MICHAEL/ABE-2316-2021	Fricker, Michael/0000-0002-8587-1774; Ryan, Kevin M./0000-0002-1059-9681	Cancer Research UKCancer Research UK; Association for International Cancer Research; Wellcome TrustWellcome TrustEuropean Commission; BBSRC (University of Cambridge)UK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC)University of Cambridge; Cancer Research UK (Beatson Institute)Cancer Research UK	We thank Noboru Mizushima, Craig Thompson, Andy Villunger, Stanley Korsmeyer, Bert Vogelstein and Karen Vousden for reagents and members of the Tumour Cell Death Laboratory for critical reading of the paper. Work in the Tumour Cell Death Laboratory is supported by Cancer Research UK and the Association for International Cancer Research. Work in the Tolkovsky Laboratory was supported by the Wellcome Trust. MF was the recipient of a BBSRC research studentship (University of Cambridge) and was supported by Cancer Research UK as a post-doctoral fellow (Beatson Institute).	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JUL	2010	1								e59	10.1038/cddis.2010.38			9	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	665VP	WOS:000283064100007	21364664	Green Published, gold			2022-04-25	
J	Zhou, CF; Yi, CH; Yi, YX; Qin, WY; Yan, YN; Dong, XY; Zhang, XW; Huang, Y; Zhang, R; Wei, J; Ali, DW; Michalak, M; Chen, XZ; Tang, JF				Zhou, Cefan; Yi, Changhua; Yi, Yongxiang; Qin, Wenying; Yan, Yanan; Dong, Xueying; Zhang, Xuewen; Huang, Yuan; Zhang, Rui; Wei, Jie; Ali, Declan William; Michalak, Marek; Chen, Xing-Zhen; Tang, Jingfeng			LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/beta-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes	MOLECULAR CANCER			English	Article						PVT1; Gemcitabine resistance; Autophagy; miR-619-5p; Wnt/beta-catenin	NONCODING RNA PVT1; COLORECTAL-CANCER; INDUCED APOPTOSIS; BREAST-CANCER; CHEMORESISTANCE; AXIS; DEGRADATION; PROGRESSION; EXPRESSION; COMPLEX	Background: Pancreatic cancer is one of the most lethal malignancies and has an extremely poor diagnosis and prognosis. The development of resistance to gemcitabine is still a major challenge. The long noncoding RNA PVT1 was reported to be involved in carcinogenesis and chemoresistance; however, the mechanism by which PVT1 regulates the sensitivity of pancreatic cancer to gemcitabine remains poorly understood. Methods: The viability of pancreatic cancer cells was assessed by MTT assay in vitro and xenograft tumor formation assay in vivo. The expression levels of PVT1 and miR-619-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting analysis and qRT-PCR were performed to assess the protein and mRNA levels of Pygo2 and ATG14, respectively. Autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of PVT1 were further investigated by gain- and loss-of-function assays in vitro. Results: In the present study, we demonstrated that PVT1 was up-regulated in gemcitabine-resistant pancreatic cancer cell lines. Gain- and loss-of-function assays revealed that PVT1 impaired sensitivity to gemcitabine in vitro and in vivo. We further found that PVT1 up-regulated the expression of both Pygo2 and ATG14 and thus regulated Wnt/beta-catenin signaling and autophagic activity to overcome gemcitabine resistance through sponging miR-619-5p. Moreover, we discovered three TCF/LEF binding elements (TBEs) in the promoter region of PVT1, and activation of Wnt/beta-catenin signaling mediated by the up-regulation of Pygo2 increased PVT1 expression by direct binding to the TBE region. Furthermore, PVT1 was discovered to interact with ATG14, thus promoting assembly of the autophagy specific complex I (PtdIns3K-C1) and ATG14-dependent class III PtdIns3K activity. Conclusions: These data indicate that PVT1 plays a critical role in the sensitivity of pancreatic cancer to gemcitabine and highlight its potential as a valuable target for pancreatic cancer therapy.	[Zhou, Cefan; Qin, Wenying; Yan, Yanan; Dong, Xueying; Zhang, Xuewen; Huang, Yuan; Zhang, Rui; Tang, Jingfeng] Hubei Univ Technol, Natl 111 Ctr Cellular Regulat & Mol Pharmaceut, Key Lab Fermentat Engn, Minist Educ, 28 NanLi Rd, Wuhan 430068, Hubei, Peoples R China; [Yi, Changhua; Yi, Yongxiang; Wei, Jie] Southeast Univ, Nanjing Clin Med Ctr Infect Dis, Affiliated Hosp 2, Hosp Nanjing 2, Nanjing, Peoples R China; [Ali, Declan William] Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada; [Michalak, Marek] Univ Alberta, Dept Biochem, Edmonton, AB, Canada; [Chen, Xing-Zhen] Univ Alberta, Fac Med & Dent, Dept Physiol, Membrane Prot Dis Res Grp, Edmonton, AB, Canada		Tang, JF (corresponding author), Hubei Univ Technol, Natl 111 Ctr Cellular Regulat & Mol Pharmaceut, Key Lab Fermentat Engn, Minist Educ, 28 NanLi Rd, Wuhan 430068, Hubei, Peoples R China.	Jingfeng_hut@163.com		Zhou, Cefan/0000-0003-0680-3843	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31701228, 31871420, 31871176]; Wuhan Science and Technology Project [2019020701011475]	This work was supported by the National Natural Science Foundation of China (31701228 to C.F.Z., 31871420 to J.F.T., 31871176 to X.Z.C.), Wuhan Science and Technology Project (2019020701011475 to J.F.T).	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Cancer	JUL 29	2020	19	1							118	10.1186/s12943-020-01237-y			24	Biochemistry & Molecular Biology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Oncology	MX1FJ	WOS:000557472000001	32727463	gold, Green Published			2022-04-25	
J	Ren, BJ; Zhou, ZW; Zhu, DJ; Ju, YL; Wu, JH; Ouyang, MZ; Chen, XW; Zhou, SF				Ren, Bao-Jun; Zhou, Zhi-Wei; Zhu, Da-Jian; Ju, Yong-Le; Wu, Jin-Hao; Ouyang, Man-Zhao; Chen, Xiao-Wu; Zhou, Shu-Feng			Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						alisertib; colorectal cancer; cell cycle; programmed cell death; EMT	TO-MESENCHYMAL TRANSITION; INVESTIGATIONAL AURORA KINASE; SIGNALING PATHWAYS; CANCER; INHIBITOR; PHOSPHORYLATION; PROTEIN; DEATH; PI3K/AKT/MTOR; CHEMOTHERAPY	Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G2/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5 1 AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.	[Ren, Bao-Jun; Zhu, Da-Jian; Ju, Yong-Le; Wu, Jin-Hao; Ouyang, Man-Zhao; Chen, Xiao-Wu] Southern Med Univ, Shunde Peoples Hosp 1, Dept Gastrointestinal Surg, Guangzhou 528300, Guangdong, Peoples R China; [Ren, Bao-Jun; Zhou, Zhi-Wei; Zhou, Shu-Feng] Univ S Florida, Coll Med, Dept Pharmaceut Sci, 12901 Bruce B Downs Blvd,MDC 30, Tampa, FL 33612 USA		Chen, XW (corresponding author), Southern Med Univ, Shunde Peoples Hosp 1, Dept Gastrointestinal Surg, Guangzhou 528300, Guangdong, Peoples R China.; Zhou, SF (corresponding author), Univ S Florida, Coll Med, Dept Pharmaceut Sci, 12901 Bruce B Downs Blvd,MDC 30, Tampa, FL 33612 USA.	rbjsdyy@outlook.com; zzhou1@health.usf.edu; zdjsdyy@outlook.com; jylsdyy@outlook.com; wjhsdyy@outlook.com; oymzsdyy@outlook.com; cxwsdyy@outlook.com; szhou@health.usf.edu	Ouyang, Manzhao/U-2758-2017; Zhou, Shu-Feng/E-3166-2013	Zhou, Shu-Feng/0000-0002-5542-6119	College of Pharmacy, University of South Florida, Tampa, Florida, USA	The authors appreciate the financial support from the Startup Fund of the College of Pharmacy, University of South Florida, Tampa, Florida 33612, USA. Zhi-Wei Zhou is a holder of a postdoctoral scholarship from the College of Pharmacy, University of South Florida, Tampa, Florida 33612, USA.	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J. Mol. Sci.	JAN	2016	17	1							41	10.3390/ijms17010041			34	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	DK0DW	WOS:000374583800039	26729093	Green Published, gold, Green Submitted			2022-04-25	
J	Kordestani, N; Rudbari, HA; Fernandes, AR; Raposo, LR; Luz, A; Baptista, PV; Bruno, G; Scopelliti, R; Fateminia, Z; Micale, N; Tumanov, N; Wouters, J; Kajani, AA; Bordbar, AK				Kordestani, Nazanin; Rudbari, Hadi Amiri; Fernandes, Alexandra R.; Raposo, Luis R.; Luz, Andre; Baptista, Pedro, V; Bruno, Giuseppe; Scopelliti, Rosario; Fateminia, Zohreh; Micale, Nicola; Tumanov, Nikolay; Wouters, Johan; Kajani, Abolghasem Abbasi; Bordbar, Abdol-Khalegh			Copper(ii) complexes with tridentate halogen-substituted Schiff base ligands: synthesis, crystal structures and investigating the effect of halogenation, leaving groups and ligand flexibility on antiproliferative activities	DALTON TRANSACTIONS			English	Article							CU(II) COMPLEXES; CELL APOPTOSIS; DNA-BINDING; CYTOTOXICITY; SALICYLALDEHYDE; SPECTROSCOPY	To investigate the effect of different halogen substituents and leaving groups and the flexibility of ligands on the anticancer activity of copper complexes, sixteen copper(ii) complexes with eight different tridentate Schiff-base ligands containing pyridine and 3,5-halogen-substituted phenol moieties were synthesized and characterized by spectroscopic methods. Four of these complexes were also characterized by X-ray crystallography. The cytotoxicity of the complexes was determined in three different tumor cell lines (i.e. the A2780 ovarian, HCT116 colorectal and MCF7 breast cancer cell line) and in a normal primary fibroblast cell line. Complexes were demonstrated to induce a higher loss of cell viability in the ovarian carcinoma cell line (A2780) with respect to the other two tumor cell lines, and therefore the biological mechanisms underlying this loss of viability were further investigated. Complexes with ligand L-1 (containing a 2-pycolylamine-type motif) were more cytotoxic than complexes with L-2 (containing a 2-(2-pyridyl)ethylamine-type motif). The loss of cell viability in A2780 tumor cells was observed in the order Cu(Cl-2-L-1)NO3 > Cu(Cl-2-L-1)Cl > Cu(Br-2-L-1)Cl > Cu(BrCl-L-1)Cl. All complexes were able to induce reactive oxygen species (ROS) that could be related to the loss of cell viability. Complexes Cu(BrCl-L-1)Cl and Cu(Cl-2-L-1)NO3 were able to promote A2780 cell apoptosis and autophagy and for complex Cu(BrCl-L-1)Cl the increase in apoptosis was due to the intrinsic pathway. Cu(Cl-2-L-1)Cl and Cu(Br-2-L-1)Cl complexes lead to cellular detachment allowing to correlate with the results of loss of cell viability. Despite the ability of the Cu(BrCl-L-1)Cl complex to induce programmed cell death in A2780 cells, its therapeutic window turned out to be low making the Cu(Cl-2-L-1)NO3 complex the most promising candidate for additional biological applications.	[Kordestani, Nazanin; Rudbari, Hadi Amiri; Fateminia, Zohreh; Bordbar, Abdol-Khalegh] Univ Isfahan, Dept Chem, Esfahan 8171673111, Iran; [Fernandes, Alexandra R.; Raposo, Luis R.; Luz, Andre; Baptista, Pedro, V] Univ Nova Lisboa, Fac Ciencias & Tecnol, UCIBIO, Dept Ciencias Vida, P-2829516 Caparica, Portugal; [Bruno, Giuseppe; Micale, Nicola] Univ Messina, Dept Chem Biol Pharmaceut & Environm Sci, Viale Ferdinando Stagno Alcontres 31, I-98166 Messina, Italy; [Scopelliti, Rosario] Ecole Polytech Fed Lausanne EPFL, Inst Sci Ingn Chim, CH-1015 Lausanne, Switzerland; [Tumanov, Nikolay; Wouters, Johan] Univ Namur, Dept Chem, Namur Inst Struct Matter, B-5000 Namur, Belgium; [Kajani, Abolghasem Abbasi] Isfahan Univ Med Sci, Appl Physiol Res Ctr, Cardiovasc Res Inst, Esfahan 8174673461, Iran; [Bordbar, Abdol-Khalegh] Univ Calif Berkeley, Calif Inst Quantitat Biosci QB3, Berkeley, CA 94720 USA		Rudbari, HA (corresponding author), Univ Isfahan, Dept Chem, Esfahan 8171673111, Iran.; Fernandes, AR (corresponding author), Univ Nova Lisboa, Fac Ciencias & Tecnol, UCIBIO, Dept Ciencias Vida, P-2829516 Caparica, Portugal.	hamiri1358@gmail.com; ma.fernandes@fct.unl.pt	Raposo, Luís/AAX-1610-2021; Kordestani, Nazanin/AAP-9585-2021; Raposo, Luís R/T-3754-2017; rudbari, Hadi Amiri/G-8030-2011; Fernandes, Alexandra/C-7465-2011; Baptista, Pedro/A-1237-2009	Raposo, Luís/0000-0002-8637-346X; Kordestani, Nazanin/0000-0001-5108-920X; Raposo, Luís R/0000-0002-8637-346X; rudbari, Hadi Amiri/0000-0002-3020-8596; Scopelliti, Rosario/0000-0001-8161-8715; Luz, Andre/0000-0001-7764-9033; MICALE, Nicola/0000-0002-9294-6033; Fernandes, Alexandra/0000-0003-2054-4438; Baptista, Pedro/0000-0001-5255-7095	Research Council of the University of Isfahan; national funds from FCT/MCTESPortuguese Foundation for Science and Technology [UIDB/04378/2020]	The authors are grateful to the Research Council of the University of Isfahan for financial support of this work. This work was supported by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT/MCTES (UIDB/04378/2020).	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MAR 21	2021	50	11					3990	4007		10.1039/d0dt03962d			18	Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	RA7LQ	WOS:000631597500026	33650599				2022-04-25	
J	Kapuy, O; Makk-Merczel, K; Szarka, A				Kapuy, Orsolya; Makk-Merczel, Kinga; Szarka, Andras			Therapeutic Approach of KRAS Mutant Tumours by the Combination of Pharmacologic Ascorbate and Chloroquine	BIOMOLECULES			English	Article						cancer; Warburg effect; mutant KRAS; PKM2; GLUT1; autophagy; chloroquine; ascorbate; systems biology	COLORECTAL-CANCER CELLS; AEROBIC GLYCOLYSIS; UP-REGULATION; METABOLISM; PKM2; AUTOPHAGY; DYNAMICS; PROMOTES; MTORC1; ACCUMULATION	The Warburg effect has been considered a potential therapeutic target to fight against cancer progression. In KRAS mutant cells, PKM2 (pyruvate kinase isozyme M2) is hyper-activated, and it induces GLUT1 expression; therefore, KRAS has been closely involved in the initiation of Warburg metabolism. Although mTOR (mammalian target of rapamycin), a well-known inhibitor of autophagy-dependent survival in physiological conditions, is also activated in KRAS mutants, many recent studies have revealed that autophagy becomes hyper-active in KRAS mutant cancer cells. In the present study, a mathematical model was built containing the main elements of the regulatory network in KRAS mutant cancer cells to explore the further possible therapeutic strategies. Our dynamical analysis suggests that the downregulation of KRAS, mTOR and autophagy are crucial in anti-cancer therapy. PKM2 has been assumed to be the key switch in the stress response mechanism. We predicted that the addition of both pharmacologic ascorbate and chloroquine is able to block both KRAS and mTOR pathways: in this case, no GLUT1 expression is observed, meanwhile autophagy, essential for KRAS mutant cancer cells, is blocked. Corresponding to our system biological analysis, this combined pharmacologic ascorbate and chloroquine treatment in KRAS mutant cancers might be a therapeutic approach in anti-cancer therapies.	[Kapuy, Orsolya; Szarka, Andras] Semmelweis Univ, Inst Biochem & Mol Biol, Dept Mol Biol, H-1428 Budapest, Hungary; [Makk-Merczel, Kinga; Szarka, Andras] Budapest Univ Technol & Econ, Dept Appl Biotechnol & Food Sci, Lab Biochem & Mol Biol, H-1111 Budapest, Hungary; [Makk-Merczel, Kinga; Szarka, Andras] Budapest Univ Technol & Econ, Fac Chem Technol & Biotechnol, Biotechnol Model Lab, Szent Gellert Ter 4, H-1111 Budapest, Hungary		Szarka, A (corresponding author), Semmelweis Univ, Inst Biochem & Mol Biol, Dept Mol Biol, H-1428 Budapest, Hungary.; Szarka, A (corresponding author), Budapest Univ Technol & Econ, Dept Appl Biotechnol & Food Sci, Lab Biochem & Mol Biol, H-1111 Budapest, Hungary.; Szarka, A (corresponding author), Budapest Univ Technol & Econ, Fac Chem Technol & Biotechnol, Biotechnol Model Lab, Szent Gellert Ter 4, H-1111 Budapest, Hungary.	kapuy.orsolya@med.semmelweis-univ.hu; makkmerczel@mail.bme.hu; szarka.andras@vbk.bme.hu		Szarka, Andras/0000-0001-6594-254X	National Research, Development and Innovation Fund of Hungary [K 123752, 129593, FK 134267, 2018-1.2.1-NKP-2018-00005]	This work was financially supported by the National Research, Development and Innovation Fund of Hungary under Grant K 123752 and 129593, FK 134267, 2018-1.2.1-NKP-2018-00005 and by the BME-Biotechnology FIKP grant.	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J	Maddalena, F; Sisinni, L; Lettini, G; Condelli, V; Matassa, DS; Piscazzi, A; Amoroso, MR; La Torre, G; Esposito, F; Landriscina, M				Maddalena, Francesca; Sisinni, Lorenza; Lettini, Giacomo; Condelli, Valentina; Matassa, Danilo Swann; Piscazzi, Annamaria; Amoroso, Maria Rosaria; La Torre, Giuseppe; Esposito, Franca; Landriscina, Matteo			Resistance to paclitxel in breast carcinoma cells requires a quality control of mitochondrial antiapoptotic proteins by TRAP1	MOLECULAR ONCOLOGY			English	Article						TRAP1; Paclitaxel; Apoptosis; ER stress; Drug resistance; Breast carcinoma	HUMAN COLORECTAL-CANCER; ENDOPLASMIC-RETICULUM-STRESS; CHAPERONE TRAP1; ER CHAPERONE; GRP78; APOPTOSIS; SORCIN; ACTIVATION; BIOMARKERS; AUTOPHAGY	TRAP1 is a mitochondrial antiapoptotic protein up-regulated in several human malignancies. However, recent evidences suggest that TRAP1 is also localized in the endoplasmic reticulum (ER) where it is involved in ER stress protection and protein quality control of tumor cells. Based on the mechanistic link between ER stress, protection from apoptosis and drug resistance, we questioned whether these novel roles of TRAP1 are relevant for its antiapoptotic function. Here, we show for the first time that: i) TRAP1 expression is increased in about 50% of human breast carcinomas (BC), and ii) the ER stress protecting activity of TRAP1 is conserved in human tumors since TRAP1 is co-upregulated with the ER stress marker, BiP/Grp78. Notably, ER-associated TRAP1 modulates mitochondrial apoptosis by exerting a quality control on 18 kDa Sorcin, a TRAP1 mitochondrial client protein involved in TRAP1 cytoprotective pathway. Furthermore, this TRAP1 function is relevant in favoring resistance to paclitaxel, a microtubule stabilizing/ER stress inducer agent widely used in BC therapy. Indeed, the transfection of a TRAP1 deletion mutant, whose localization is restricted to the ER, in shTRAP1 cells enhances the expression of mitochondrial Sorcin and protects from apoptosis induced by ER stress agents and paclitaxel. Furthermore, BC cells adapted to paclitaxel or ER stress inducers share common resistance mechanisms: both cell models exhibit cross-resistance to single agents and the inhibition of TRAP1 by siRNAs or gamitrinib, a mitochondria-directed HSP90 family inhibitor, in paclitaxel-resistant cells rescues the sensitivity to paclitaxel. These results support the hypothesis that ER-associated TRAP1 is responsible for an extramitochondrial control of apoptosis and, therefore, an interference of ER stress adaptation through TRAP1 inhibition outside of mitochondria may be considered a further compartment-specific molecular approach to rescue drug-resistance. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.	[Maddalena, Francesca; Sisinni, Lorenza; Lettini, Giacomo; Condelli, Valentina] Referral Canc Ctr Basilicata, IRCCS, Lab Preclin & Translat Res, Rionero In Vulture, PZ, Italy; [Matassa, Danilo Swann; Amoroso, Maria Rosaria; Esposito, Franca] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy; [Piscazzi, Annamaria; Landriscina, Matteo] Univ Foggia, Dept Med & Surg Sci, Clin Oncol Unit, I-71100 Foggia, Italy; [La Torre, Giuseppe] Referral Canc Ctr Basilicata, IRCCS, Unit Gen Surg, Rionero In Vulture, PZ, Italy		Landriscina, M (corresponding author), Univ Foggia, Dipartimento Sci Med & Chirurg, Viale Pinto 1, I-71100 Foggia, Italy.	franca.esposito@unina.it; m.landriscina@unifg.it	Matassa, Danilo Swann/K-1596-2016; La Torre, Giuseppe/AAI-6866-2020; Lettini, Giacomo/K-5391-2018; MADDALENA, FRANCESCA/J-9983-2016; Condelli, Valentina/K-1426-2016; Sisinni, Lorenza/K-7543-2016; Landriscina, Matteo/K-1092-2016; Esposito, Franca/K-2024-2016	Matassa, Danilo Swann/0000-0002-4259-9221; La Torre, Giuseppe/0000-0002-1233-2040; MADDALENA, FRANCESCA/0000-0003-4859-885X; Condelli, Valentina/0000-0003-4552-2980; Sisinni, Lorenza/0000-0002-8159-8109; Esposito, Franca/0000-0001-9340-6875; Landriscina, Matteo/0000-0003-0591-9799; Amoroso, Maria Rosaria/0000-0002-8982-0616	Associazione Italiana per la Ricerca sul Cancro (AIRC)Fondazione AIRC per la ricerca sul cancro [IG13128]; Italian Ministry of HealthMinistry of Health, Italy [GR-2010-2310057, E66110000220001]	Our special thanks to Professor John Credico for proofreading the manuscript and suggesting stylistic improvements. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC, IG13128) to M.L. and F.E. and from the Italian Ministry of Health (Giovani Ricercatori GR-2010-2310057 E66110000220001) to FM.	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Oncol.	OCT	2013	7	5					895	906		10.1016/j.molonc.2013.04.009			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	234TW	WOS:000325668200004	23735188	Green Published, hybrid			2022-04-25	
J	Cai, H; Scott, E; Kholghi, A; Andreadi, C; Rufini, A; Karmokar, A; Britton, RG; Horner-Glister, E; Greaves, P; Jawad, D; James, M; Howells, L; Ognibene, T; Malfatti, M; Goldring, C; Kitteringham, N; Walsh, J; Viskaduraki, M; West, K; Miller, A; Hemingway, D; Steward, WP; Gescher, AJ; Brown, K				Cai, Hong; Scott, Edwina; Kholghi, Abeer; Andreadi, Catherine; Rufini, Alessandro; Karmokar, Ankur; Britton, Robert G.; Horner-Glister, Emma; Greaves, Peter; Jawad, Dhafer; James, Mark; Howells, Lynne; Ognibene, Ted; Malfatti, Michael; Goldring, Christopher; Kitteringham, Neil; Walsh, Joanne; Viskaduraki, Maria; West, Kevin; Miller, Andrew; Hemingway, David; Steward, William P.; Gescher, Andreas J.; Brown, Karen			Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice	SCIENCE TRANSLATIONAL MEDICINE			English	Article							ACCELERATOR MASS-SPECTROMETRY; PROSTATE-CANCER; BETA-CAROTENE; COLORECTAL-CANCER; AGENT RESVERATROL; CLINICAL-TRIAL; APC(MIN/+); SUPPLEMENTATION; MECHANISMS; MOUSE	Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a lack of information on the optimal dose prohibits rationally designed trials to assess efficacy. To challenge the assumption that "more is better," we compared the pharmacokinetics and activity of a dietary dose with an intake 200 times higher. The dose-response relationship for concentrations generated and the metabolite profile of [C-14]-resveratrol in colorectal tissue of cancer patients helped us to define clinically achievable levels. In Apc(Min) mice (a model of colorectal carcinogenesis) that received a high-fat diet, the low resveratrol dose suppressed intestinal adenoma development more potently than did the higher dose. Efficacy correlated with activation of adenosine monophosphate-activated protein kinase (AMPK) and increased expression of the senescence marker p21. Nonlinear dose responses were observed for AMPK and mechanistic target of rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and senescence. In human colorectal tissues exposed to low dietary concentrations of resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The expression of the cytoprotective NAD(P) H dehydrogenase, quinone 1 (NQO1) enzyme was also increased in tissues from cancer patients participating in our [C-14]-resveratrol trial. These findings warrant a revision of developmental strategies for diet-derived agents designed to achieve cancer chemoprevention.	[Cai, Hong; Scott, Edwina; Kholghi, Abeer; Andreadi, Catherine; Rufini, Alessandro; Karmokar, Ankur; Britton, Robert G.; Horner-Glister, Emma; Greaves, Peter; Jawad, Dhafer; James, Mark; Howells, Lynne; Steward, William P.; Gescher, Andreas J.; Brown, Karen] Univ Leicester, Dept Canc Studies, Canc Chemoprevent Grp, Leicester LE2 7LX, Leics, England; [Ognibene, Ted; Malfatti, Michael] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA; [Goldring, Christopher; Kitteringham, Neil; Walsh, Joanne] Univ Liverpool, Dept Pharmacol & Therapeut, MRC, Ctr Drug Safety Sci, Liverpool L69 3GE, Merseyside, England; [Viskaduraki, Maria] Univ Leicester, Bioinformat & Biostat Support Hub, Leicester LE1 9HN, Leics, England; [West, Kevin; Miller, Andrew; Hemingway, David] Univ Hosp Leicester NHS Trust, Leicester LE1 5WW, Leics, England		Brown, K (corresponding author), Univ Leicester, Dept Canc Studies, Canc Chemoprevent Grp, Leicester LE2 7LX, Leics, England.	kb20@le.ac.uk		Brown, Karen/0000-0002-5217-1501; Walsh, Joanne/0000-0002-5109-2019	Cancer Research UKCancer Research UK [C325/A13101]; Libyan government through Benghazi University; NIH National Centre for Research Resources, Biomedical Technology ProgramUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P41RR13461]; Cancer Research UKCancer Research UK [13101] Funding Source: researchfish; NATIONAL CENTER FOR RESEARCH RESOURCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [P41RR013461] 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) [P41GM103483] Funding Source: NIH RePORTER	This work was supported by Cancer Research UK (C325/A13101) with assistance from the Leicester Experimental Cancer Medicine Centre (C325/A15575, Cancer Research UK/UK Department of Health). A. Kholghi was funded by a studentship from the Libyan government through Benghazi University. AMS analysis was performed at the Research Resource for Biomedical AMS Laboratory, operated at LLNL, and supported by the NIH National Centre for Research Resources, Biomedical Technology Program grant #P41RR13461.	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Transl. Med.	JUL 29	2015	7	298							298ra117	10.1126/scitranslmed.aaa7619			12	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	CN9AZ	WOS:000358739300003	26223300	Green Submitted, Green Accepted			2022-04-25	
J	Chen, PH; Liu, AJ; Ho, KH; Chiu, YT; Lin, ZHA; Lee, YT; Shih, CM; Chen, KC				Chen, Peng-Hsu; Liu, Ann-Jeng; Ho, Kuo-Hao; Chiu, Ya-Ting; Lin, Zhe-Harn Anne; Lee, Yi-Ting; Shih, Chwen-Ming; Chen, Ku-Chung			microRNA-199a/b-5p enhance imatinib efficacy via repressing WNT2 signaling-mediated protective autophagy in imatinib-resistant chronic myeloid leukemia cells	CHEMICO-BIOLOGICAL INTERACTIONS			English	Article						Imatinib resistance; Autophagy; miR-199a-5p; miR-199b-5p; WNT2; Chronic myeloid leukemia (CML)	BCR-ABL; LUNG-CANCER; COLORECTAL-CANCER; CML; PATHWAY; INHIBITION; DEGRADATION; ACTIVATION; PROTEIN; GENES	Imatinib (IM) is a first-line therapeutic drug for chronic myeloid leukemia (CML), a hematological disease. Mutations in the BCR-ABL domain increase formation of IM resistance in CML. However, not all patients are BCR-ABL domain-mutant dependent. Investigating non-mutant mechanisms in the development of acquired IM resistance is a critical issue. We explored the mechanisms which influence IM efficacy and resistance in CML. Higher protective autophagy was identified in IM-resistant K562 (K562R) cells. Inhibition of autophagy by the inhibitors, chloroquine and 3-methyladenine, enhanced IM's efficacy in K562R cells. In addition, microRNA (miR)-199a/b-5p were downregulated in K562R cells compared to parent cells. Overexpression of miR-199a/b-5p reduced autophagy and induced cell apoptosis, resulting in enhanced IM's efficacy in K562R cells. Moreover, expression levels of the Wingless-type MMTV integration site family member 2 (WNT2), a positive regulator of autophagy, were significantly higher in K562R cells, and it was validated as a direct target gene of miR-199a/b5p. Overexpressions of miR-199a/b-5p inhibited WNT2 downstream signaling. Furthermore, overexpression and knockdown of WNT2 influenced autophagy formation and CML drug sensitivity to IM. Overexpression of WNT2 could also reverse miR-199a/b-5p-enhanced IM efficacy in K562R cells. These results emphasized that miR-199a/b-5p inhibited autophagy via repressing WNT2 signaling and might provide novel therapeutic strategies for future IM-resistant CML therapy and drug development.	[Chen, Peng-Hsu; Ho, Kuo-Hao; Chiu, Ya-Ting; Lee, Yi-Ting; Shih, Chwen-Ming; Chen, Ku-Chung] Taipei Med Univ, Grad Inst Med Sci, Coll Med, Taipei, Taiwan; [Chen, Peng-Hsu; Ho, Kuo-Hao; Chiu, Ya-Ting; Lee, Yi-Ting; Shih, Chwen-Ming; Chen, Ku-Chung] Taipei Med Univ, Sch Med, Dept Biochem & Mol Cell Biol, Coll Med, Taipei, Taiwan; [Liu, Ann-Jeng] Taipei City Hosp, Dept Neurosurg, Ren Ai Branch, Taipei, Taiwan; [Lin, Zhe-Harn Anne] Taipei Med Univ, Sch Med, Coll Med, Taipei, Taiwan		Shih, CM; Chen, KC (corresponding author), Taipei Med Univ, Dept Biochem & Mol Cell Biol, 250 Wu Hsing St, Taipei 11031, Taiwan.	cmshih@tmu.edu.tw; kuchung@tmu.edu.tw		Chiu, wendy/0000-0002-7438-3556	Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [MOST 106-2320-B-038-051-MY3]; Taipei City Government [105XDAA00013]; Taipei City Hospital Ren-Ai Branch [TPCH-106-020]; Taipei Medical University [106-1200-008-110]	This work was supported by the Ministry of Science and Technology, Taiwan contract grant no.: MOST 106-2320-B-038-051-MY3 [https://www.most.gov.tw/] (to Ku-Chung Chen); Taipei City Government contract grant no.: 105XDAA00013 [http://english.gov.taipei/] (to Ann-Jeng Liu); Taipei City Hospital Ren-Ai Branch contract grant no.: TPCH-106-020 [http://tcgwww.taipei.gov.tw] (to Ann-Jeng Liu); and Taipei Medical University contract grant no.: 106-1200-008-110 [http://www.tmu.edu.tw] (to Chwen-Ming Shih). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.	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Interact.	AUG 1	2018	291						144	151		10.1016/j.cbi.2018.06.006			8	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology	GM6UH	WOS:000438310700018	29890129				2022-04-25	
J	Tran, PHL; Wang, T; Yin, W; Tran, TTD; Nguyen, TNG; Lee, BJ; Duan, W				Tran, Phuong H. L.; Wang, Tao; Yin, Wang; Tran, Thao T. D.; Nguyen, Tuong N. G.; Lee, Beom-Jin; Duan, Wei			Aspirin-loaded nanoexosomes as cancer therapeutics	INTERNATIONAL JOURNAL OF PHARMACEUTICS			English	Article						Exosome; Aspirin; Breast cancer; Colorectal cancer; Cancer stem cell	STEM-CELLS; TARGETED DELIVERY; EXOSOMES; CARRIERS; APTAMER; ACID; DOXORUBICIN; STABILITY; AUTOPHAGY	The long history of discovery and recently encouraging studies of the anti-cancer effect of aspirin promise a closer step to widely used aspirin-based medication in cancer therapy. To resolve the poor water-solubility of aspirin and low encapsulation efficiency of exosomes for further developing a new delivery of aspirin as anticancer treatment, our nanoamorphous exosomal delivery platform was established. In this study, the anti-tumour effects of nanoamorphous aspirin-loaded exosomes with exosomes derived from breast and colorectal cancer cells, were comprehensively studied using both in vitro and in vivo models. These exosomes displayed enhanced cellular uptake via both clathrin-dependent and -independent endocytosis pathways, and significantly improved cytotoxicity of aspirin to breast and colorectal cancer cells, accompanied by the enhanced apoptosis and autophagy. Remarkably, this nanoamorphous exosomal platform endowed aspirin with the unprecedented cancer stem cell eradication capacity. Further animal study demonstrated that this developed exosomal system was able to efficiently deliver aspirin to in vivo tumours. The active targeting of these exosomes to tumour was further improved by conjugating an aptamer specifically targeting EpCAM protein. Hence, this nanoamorphous structured exosome system effectively transformed aspirin into a potential cancer stem cell killer with distinguished properties for clinical translation.	[Tran, Phuong H. L.; Yin, Wang; Nguyen, Tuong N. G.; Duan, Wei] Deakin Univ, Sch Med, Waurn Ponds, Vic 3216, Australia; [Tran, Phuong H. L.; Yin, Wang; Nguyen, Tuong N. G.; Duan, Wei] Deakin Univ, Ctr Mol & Med Res, Waurn Ponds, Vic 3216, Australia; [Wang, Tao] Zhengzhou Univ, Sch Nursing, Zhengzhou 450001, Henan, Peoples R China; [Wang, Tao] Murdoch Univ, Ctr Comparat Genom, Perth, WA 6150, Australia; [Tran, Thao T. D.] Ton Duc Thang Univ, Dept Management Sci & Technol Dev, Ho Chi Minh City, Vietnam; [Tran, Thao T. D.] Ton Duc Thang Univ, Fac Pharm, Ho Chi Minh City, Vietnam; [Lee, Beom-Jin] Ajou Univ, Coll Pharm, Suwon 16499, South Korea		Tran, PHL; Duan, W (corresponding author), Deakin Univ, Sch Med, Waurn Ponds, Vic 3216, Australia.; Tran, PHL; Duan, W (corresponding author), Deakin Univ, Ctr Mol & Med Res, Waurn Ponds, Vic 3216, Australia.	phuong.tran1@deakin.edu.au; wei.duan@deakin.edu.au	Tran, Thao/A-5591-2011	Tran, Thao/0000-0003-2885-5134; Wang, Tao/0000-0002-9623-8800	Australian Research Council's Discovery Early Career Researcher AwardAustralian Research Council [DE160100900]	Dr. Phuong Ha Lien Tran is the recipient of Australian Research Council's Discovery Early Career Researcher Award (project number DE160100900).	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J. Pharm.	DEC 15	2019	572								118786	10.1016/j.ijpharm.2019.118786			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	JS4WU	WOS:000500308000044	31669214				2022-04-25	
J	Cao, H; Li, ZL; Zhou, D; Wan, LD; Yu, D; Zhang, J; Xu, EP; Zhang, DD; Lai, MD				Cao, Hui; Li, Zhenli; Zhou, Dan; Wan, Ledong; Yu, Dan; Zhang, Jing; Xu, Enping; Zhang, Dandan; Lai, Maode			ATG16L1 rs2241880 polymorphism predicts unfavorable clinical outcomes for colorectal cancer patients in the Chinese population	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY			English	Article						ATG16L1; SNP; rs2241880; colorectal cancer; survival	GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; JAPANESE POPULATION; AUTOPHAGY; CYTOKINES; VARIANTS; T300A; PATHOGENESIS; DEGRADATION	Numerous studies have shown that the single-nucleotide polymorphism (SNP) rs2241880 (Thr300Ala) of autophagy related 16-like 1 (ATG16L1) is strongly associated with development of Crohn's disease, which represents a risk factor for colorectal cancer (CRC). To date, the role of ATG16L1 rs2241880 polymorphism in CRC remains unclear. In this study, we aim to determine if the rs2241880 SNP is correlated with the risk of developing CRC and to investigate the prognostic value of this SNP in patients with CRC in the Chinese population. No significant association was found between the ATG16L1 genotypes and clinicopathological parameters. We observed that ATG16L1 rs2241880 was not associated with the risk of CRC. However, compared to those with AA and AG genotypes, CRC patients carrying the GG genotype at ATG16L1 showed a marginal trend to be diagnosed with CRC at younger age (recessive model) (P=0.067). Besides, overall median follow-up time was significantly decreased in patients with the GG genotype (recessive model) (P=0.027). Kaplan-Meier survival analysis exhibited that patients carrying the GG genotype of rs2241880 had worse overall survival than those with the AA and AG genotype (P<0.001). In multivariate analyses, rs2241880 GG genotype was revealed as an independent prognostic marker for overall survival (HR=4.70, P<0.001). These results suggest that GG genotype of rs2241880 may predict unfavorable outcome of patients with colorectal cancer. Further investigations are required to explore the role and mechanism of the polymorphism rs2241880 at ATG16L1 in colorectal cancer.	[Cao, Hui; Li, Zhenli; Zhou, Dan; Wan, Ledong; Yu, Dan; Zhang, Jing; Xu, Enping; Zhang, Dandan; Lai, Maode] Zhejiang Univ, Sch Med, Dept Pathol, Hangzhou 310058, Zhejiang, Peoples R China; [Cao, Hui; Li, Zhenli; Zhou, Dan; Wan, Ledong; Yu, Dan; Zhang, Jing; Xu, Enping; Zhang, Dandan; Lai, Maode] Key Lab Dis Prote Zhejiang Prov, Hangzhou 310058, Zhejiang, Peoples R China; [Zhou, Dan] Zhejiang Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Hangzhou 310058, Zhejiang, Peoples R China		Lai, MD (corresponding author), Zhejiang Univ, Sch Med, Dept Pathol, Hangzhou 310058, Zhejiang, Peoples R China.	lmp@zju.edu.cn	wan, ledong/J-8445-2017		National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81101640/81572716]; 111 projectMinistry of Education, China - 111 Project [B13026]	This work was funded by National Natural Science Foundation of China (81101640/81572716) and the 111 project (B13026).	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J. Clin. Exp. Pathol.		2016	9	8					8586	8595					10	Oncology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pathology	EA5IR	WOS:000386653400098					2022-04-25	
J	Silva, DF; Vidal, FCB; Santos, D; Costa, MCP; Morgado-Diaz, JA; Nascimento, MDSB; de Moura, RS				Silva, Dulcelena Ferreira; Branco Vidal, Flavia Castello; Santos, Debora; Pires Costa, Maria Celia; Morgado-Diaz, Jose Andres; Soares Brandao Nascimento, Maria do Desterro; de Moura, Roberto Soares			Cytotoxic effects of Euterpe oleracea Mart. in malignant cell lines	BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE			English	Article						Anticancer; Euterpe oleracea mart.; MC Gamma-7; Phytochemicals; Chemopreventive	BREAST-CANCER CELLS; AUTOPHAGOSOME FORMATION; ACAI; INDUCTION; APOPTOSIS; RAT; ANTHOCYANINS; PREVENTION; STRESS; FRUIT	Background: Euterpe oleracea Mart., a plant from the Amazon region, is commonly known as acai or jucara; it has high nutritional value and elevated levels of lipids, proteins, and minerals. Acai is an abundant and much consumed fruit by the Amazon local population, and studies have demonstrated that it is rich in phytochemicals with antioxidant, anti-inflammatory, and anticancer activities. Therefore, the aim of this study was to test this plant for anticancer activity in different human malignant cell lines. Methods: Cell lines derived from breast and colorectal adenocarcinomas were treated with 10, 20, and 40 mu g/mL of bark, seed, and total acai fruit hydroalcoholic extracts for 24 and 48 h. After treatment, cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and cell morphological features were observed by light and transmission electron microscopy. The type of cell death was also evaluated. The data were analyzed statistically by one-way analysis of variance (ANOVA), followed by Dunnett's or Tukey's post hoc tests, as appropriate. Results: We observed that of all the cell lines tested, MCF-7 was the only line that responded to acai treatment. The extracts caused significant reduction (p < 0.01) in cell viability and altered cell morphological features by inducing the appearance of autophagic vacuoles, as observed by transmission electron microscopy. Furthermore, increased expression of LC3BII, a protein marker of autophagosome formation, was observed by western blotting. Caspase Glo (TM) assays and morphologic observations by DAPI nuclear staining and transmission electron microscopy did not indicate any apoptotic events. Conclusions: The present study demonstrated that acai possesses antitumorigenic potential in the MCF-7 cell line. Further studies are needed to identify the compound (s) responsible for this cytotoxic activity and the molecular target in the cell. This discovery of the anticancer potential of acai may help in the development of chemopreventive drugs and may have therapeutic effects in the treatment of breast cancer.	[Silva, Dulcelena Ferreira; Branco Vidal, Flavia Castello] Univ Fed Maranhao, Dept Morphol, BR-65020140 Sao Luis, Maranhao, Brazil; [Branco Vidal, Flavia Castello; Soares Brandao Nascimento, Maria do Desterro] Univ Fed Maranhao, Tumors & DNA Bank Maranhao, BR-65020140 Sao Luis, Maranhao, Brazil; [Santos, Debora; Pires Costa, Maria Celia] Univ Estadual Maranhao, Dept Biol & Chem, Maranhao, Brazil; [Morgado-Diaz, Jose Andres] Natl Canc Inst, Struct Biol Lab, Div Cell Biol, Rio De Janeiro, Brazil; [Soares Brandao Nascimento, Maria do Desterro] Univ Fed Maranhao, Dept Pathol, BR-65020140 Sao Luis, Maranhao, Brazil; [de Moura, Roberto Soares] Univ Estado Rio De Janeiro, Dept Pharmacol, Lab Pharmacol & Psychobiol, Rio De Janeiro, Brazil		Vidal, FCB (corresponding author), Univ Fed Maranhao, Dept Morphol, Rua Coelho Neto 311, BR-65020140 Sao Luis, Maranhao, Brazil.	flavidal@hotmail.com	Morgado-Diaz, Jose A./A-9649-2010; Santos, Débora S./P-9188-2014; Vidal, Flavia/AAX-6843-2021; do Desterro Soares Brandão Nascimento, Maria/S-7024-2019	Santos, Débora S./0000-0003-0659-4711; Vidal, Flavia/0000-0002-4721-6824; do Desterro Soares Brandão Nascimento, Maria/0000-0003-2783-362X	Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Ministerio da Saude, Brasil; Fundacao de Amparo a Pesquisa e ao Desenvolvimento Cientifico e Tecnologico do Estado do Maranhao (FAPEMA)	This study was supported by grants from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Ministerio da Saude, Brasil, and Fundacao de Amparo a Pesquisa e ao Desenvolvimento Cientifico e Tecnologico do Estado do Maranhao (FAPEMA). We are grateful to Dr. Marcelo for the preparation of acai extracts and Simone Fernandes for sample processing for TEM observations.	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Altern. Med.	MAY 29	2014	14								175	10.1186/1472-6882-14-175			9	Integrative & Complementary Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine	AI4UR	WOS:000336860800001	24886139	Green Published, gold			2022-04-25	
J	Moghadasi, M; Alivand, M; Fardi, M; Moghadam, KS; Solali, S				Moghadasi, Maryam; Alivand, Mohammadreza; Fardi, Masoumeh; Moghadam, Kobra Shojaei; Solali, Saeed			Emerging molecular functions of microRNA-124: Cancer pathology and therapeutic implications	PATHOLOGY RESEARCH AND PRACTICE			English	Review						microRNA; Cancer; Drug; Target therapy; Leukemia	EPITHELIAL-MESENCHYMAL TRANSITION; INHIBITS CELL-PROLIFERATION; WNT/BETA-CATENIN PATHWAY; NONCODING RNA; DOWN-REGULATION; MULTIDRUG-RESISTANCE; COLORECTAL-CANCER; ESOPHAGEAL CANCER; INDUCED APOPTOSIS; BRAIN METASTASIS	MicroRNAs are characterized as small, single-stranded, non-coding RNA molecules that bind to their target mRNA to prevent protein synthesis. MicroRNAs regulate various normal processes; however, they are aberrantly regulated in many cancers. They control the expression of various genes, including cancer-related genes. This causes microRNAs to be considered as a good target for further investigations for designing novel therapeutic strategies. Since miR124 is known for some time already, it has a tumor-suppressing role in various cancers. Numerous studies indicate its definite roles in malignant processes such as epithelial-to-mesenchymal transition, cell cycle arrest, metastasis, cancer stem cell formation and induction of apoptosis. However, some studies have indicated a dual role for miR-124 in oncogenic processes like autophagy and multi-drug resistance. In this article, we will review recent researches on the biological functions and clinical implications of miR-124. Subsequently, we will discuss future perspectives in terms of the roles of this miRNA in cancers.	[Moghadasi, Maryam] Tabriz Univ Med Sci, Student Res Comm, Tabriz, Iran; [Moghadasi, Maryam; Fardi, Masoumeh; Moghadam, Kobra Shojaei] Tabriz Univ Med Sci, IRC, Tabriz, Iran; [Alivand, Mohammadreza] Tabriz Univ Med Sci, Dept Med Genet, Tabriz, Iran; [Solali, Saeed] Tabriz Univ Med Sci, Mol Med Res Ctr, Tabriz, Iran; [Solali, Saeed] Tabriz Univ Med Sci, Fac Med, Dept Immunol, Div Hematol & Transfus Med, Tabriz, Iran		Solali, S (corresponding author), Tabriz Univ Med Sci, Fac Med, Dept Immunol, Div Hematol & Transfus Med, Tabriz, Iran.	ssolali@gmail.com					Acloque H, 2009, J CLIN INVEST, V119, P1438, DOI 10.1172/JCI38019; Arend RC, 2013, GYNECOL ONCOL, V131, P772, DOI 10.1016/j.ygyno.2013.09.034; Awasthi R, 2018, DRUG DELIV TRANSL RE, V8, P97, DOI 10.1007/s13346-017-0440-1; Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; Cai QQ, 2017, SCI REP-UK, V7, DOI 10.1038/srep40733; Cai WL, 2018, MOL CANCER, V17, DOI 10.1186/s12943-017-0746-0; Chen SM, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0128472; 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Res. Pract.		2020	216	3							152827	10.1016/j.prp.2020.152827			8	Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Pathology	KW1QS	WOS:000520946600001	31983567				2022-04-25	
J	Ahmadi, M; Amiri, S; Pecic, S; Machaj, F; Rosik, J; Los, MJ; Alizadeh, J; Mahdian, R; Rosa, SCD; Schaafsma, D; Shojaei, S; Madrakian, T; Zeki, AA; Ghavami, S				Ahmadi, Mazaher; Amiri, Shayan; Pecic, Stevan; Machaj, Filip; Rosik, Jakub; Los, Marek J.; Alizadeh, Javad; Mahdian, Reza; Rosa, Simone C. da Silva; Schaafsma, Dedmer; Shojaei, Shahla; Madrakian, Tayyebeh; Zeki, Amir A.; Ghavami, Saeid			Pleiotropic effects of statins: A focus on cancer	BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE			English	Review						Mevalonate cascade; Prenylation; Apoptosis; Cancer therapy; Autophagy; Chemotherapy	HMG-COA REDUCTASE; LOVASTATIN-INDUCED APOPTOSIS; COENZYME-A REDUCTASE; ENDOTHELIAL-CELL MIGRATION; DRUG-DRUG INTERACTIONS; IN-VITRO; MEVALONATE PATHWAY; GROWTH-FACTOR; LUNG-CANCER; COLORECTAL-CANCER	The statin drugs (`statins') potently inhibit hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase by competitively blocking the active site of the enzyme. Statins decrease de novo cholesterol biosynthesis and thereby reduce plasma cholesterol levels. Statins exhibit "pleiotropic" properties that are independent of their lipidlowering effects. For example, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. Furthermore, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling. However, whether statins have clinically meaningful anti-cancer effects remains an area of active investigation. Both preclinical and clinical studies on the potential mechanisms of action of statins in several cancers have been reviewed in the literature. Considering the contradictory data on their efficacy, we present an up-to-date summary of the pleiotropic effects of statins in cancer therapy and review their impact on different malignancies. We also discuss the synergistic anti-cancer effects of statins when combined with other more conventional anti-cancer drugs to highlight areas of potential therapeutic development.	[Ahmadi, Mazaher; Madrakian, Tayyebeh] Bu Ali Sina Univ, Fac Chem, Dept Analyt Chem, Hamadan, Hamadan, Iran; [Amiri, Shayan] St Boniface Gen Hosp, Div Neurodegenerat Disorders, Albrechtsen Res Ctr, R4046-351 Tache Ave, Winnipeg, MB R2H 2A6, Canada; [Amiri, Shayan] Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada; [Pecic, Stevan] Calif State Univ Fullerton, Dept Chem & Biochem, Fullerton, CA 92634 USA; [Machaj, Filip; Rosik, Jakub; Alizadeh, Javad; Rosa, Simone C. da Silva; Ghavami, Saeid] Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Human Anat & Cell Sci, Winnipeg, MB, Canada; [Machaj, Filip; Rosik, Jakub] Pomeranian Med Univ, Dept Pathol, Szczecin, Poland; [Los, Marek J.] Silesian Tech Univ, Biotechnol Ctr, Gliwice, Poland; [Alizadeh, Javad] Univ Manitoba, Children Hosp Res Inst Manitoba, Biol Breathing Theme, Winnipeg, MB, Canada; [Mahdian, Reza] Pasteur Inst Iran, Biotechnol Res Ctr, Mol Med Dept, Tehran, Iran; [Schaafsma, Dedmer] Sci Impact, Winnipeg, MB, Canada; [Zeki, Amir A.] Univ Calif Davis, UC Davis Lung Ctr, Davis Sch Med, Div Pulm Crit Care & Sleep Med, Davis, CA 95616 USA; [Ghavami, Saeid] Shiraz Univ Med Sci, Hlth Policy Res Ctr, Inst Hlth, Shiraz, Iran; [Ghavami, Saeid] Univ Manitoba, Res Inst Oncol & Hematol, Canc Care Manitoba, Winnipeg, MB, Canada; [Shojaei, Shahla] Univ Manitoba, Coll Pharm, Rady Fac Hlth Sci, Winnipeg, MB, Canada; [Zeki, Amir A.] Vet Affairs Med Ctr, Mather, CA USA		Ghavami, S (corresponding author), Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Human Anat & Cell Sci, Winnipeg, MB, Canada.	saeid.ghavami@umanitoba.ca	Pecic, Stevan/E-3578-2018; Madrakian, Tayyebeh/C-2780-2018; Ahmadi, Mazaher/C-2568-2018; Rosik, Jakub/P-6960-2018	Pecic, Stevan/0000-0002-3706-8768; Madrakian, Tayyebeh/0000-0002-6876-7633; Ahmadi, Mazaher/0000-0001-9969-170X; Rosik, Jakub/0000-0001-7377-4566; da Silva Rosa, Simone C./0000-0002-3732-3781	NIEHS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [P30 ES023513] Funding Source: Medline		Abdel-Rahman O, 2019, CLIN TRANSL ONCOL, V21, P810, DOI 10.1007/s12094-018-1992-3; 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Biophys. Acta-Mol. Basis Dis.	DEC 1	2020	1866	12							165968	10.1016/j.bbadis.2020.165968			17	Biochemistry & Molecular Biology; Biophysics; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics; Cell Biology	OU7QZ	WOS:000591721000034	32927022	Bronze			2022-04-25	
J	Chen, HY; He, LJ; Li, SQ; Zhang, YJ; Huang, JH; Qin, HX; Wang, JL; Li, QY; Yang, DL				Chen, He-ying; He, Liu-jun; Li, Shi-qiang; Zhang, Ya-jun; Huang, Jiu-hong; Qin, Hong-xia; Wang, Juan-li; Li, Qian-yin; Yang, Dong-lin			A Derivate of Benzimidazole-Isoquinolinone Induces SKP2 Transcriptional Inhibition to Exert Anti-Tumor Activity in Glioblastoma Cells	MOLECULES			English	Article						compound-7g; glioblastoma; SKP2; E2F-1; cell cycle; autophagic flux	CANCER; AUTOPHAGY; TARGET; DEGRADATION; EXPRESSION; CYCLE	We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells. The inhibitor selectively downregulated F-box protein SKP2 expression and upregulated cell cycle inhibitor p27, and then resulted in G1 cell cycle arrest. Mechanism analysis revealed that compound-7g also provokes the down-regulation of E2F-1, which acts as a transcriptional factor of SKP2. Further results indicated that compound-7g induced an increase of LC3B-II and p62, which causes a suppression of fusion between autophagosome and lysosome. Moreover, compound-7g mediated autophagic flux blockage promoted accumulation of ubiquitinated proteins and then led to endoplasmic reticulum stress. Our study thus demonstrated that pharmacological inactivation of E2F-1-SKP2-p27 axis is a promising target for restricting cancer progression.	[Chen, He-ying; Li, Qian-yin] Chongqing Med Univ, Coll Lab Med, Div Mol Nephrol, Chongqing 400016, Peoples R China; [Chen, He-ying; Li, Qian-yin] Chongqing Med Univ, Coll Lab Med, Creat Training Ctr Undergraduates, Minist Educ,Key Lab Lab Med Diagnost, Chongqing 400016, Peoples R China; [Chen, He-ying; He, Liu-jun; Li, Shi-qiang; Zhang, Ya-jun; Huang, Jiu-hong; Qin, Hong-xia; Wang, Juan-li; Yang, Dong-lin] Chongqing Univ Arts & Sci, Chongqing Engn Lab Targeted & Innovat Therapeut, Chongqing Key Lab Kinase Modulators Innovat Med, IATTI, 319 Honghe Ave, Chongqing 402160, Peoples R China; [Chen, He-ying] Chongqing Med Univ, Undergrad Class 2016 Entry Coll Lab Med, Chongqing 400016, Peoples R China		Li, QY (corresponding author), Chongqing Med Univ, Coll Lab Med, Div Mol Nephrol, Chongqing 400016, Peoples R China.; Li, QY (corresponding author), Chongqing Med Univ, Coll Lab Med, Creat Training Ctr Undergraduates, Minist Educ,Key Lab Lab Med Diagnost, Chongqing 400016, Peoples R China.; Yang, DL (corresponding author), Chongqing Univ Arts & Sci, Chongqing Engn Lab Targeted & Innovat Therapeut, Chongqing Key Lab Kinase Modulators Innovat Med, IATTI, 319 Honghe Ave, Chongqing 402160, Peoples R China.	liqianyin@cqmu.edu.cn; dlyang09@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81802549]; Chongqing Research Program of Basic Research and Frontier Technology [cstc2016jcyjA0534, cstc2018jcyjAX0219]; Chongqing Education commission Project of China [KJQN201801304, KJZH17129, KJ1711284, KJ1711287, KJ1601123]; Scientific Research Foundation of the Chongqing University of Arts and Sciences [R2015BX03, 2017RBX11, 2017ZBX05, 2017ZBX07, 2017ZBX08, 2017ZBX10]	This research was funded by National Natural Science Foundation of China (81802549), Chongqing Research Program of Basic Research and Frontier Technology (cstc2016jcyjA0534 and cstc2018jcyjAX0219), Chongqing Education commission Project of China (KJQN201801304, KJZH17129, KJ1711284, KJ1711287 and KJ1601123) and the Scientific Research Foundation of the Chongqing University of Arts and Sciences (R2015BX03, 2017RBX11, 2017ZBX05, 2017ZBX07, 2017ZBX08 and 2017ZBX10).	Chan CH, 2014, CELL CYCLE, V13, P679, DOI 10.4161/cc.27853; Chu IM, 2008, NAT REV CANCER, V8, P253, DOI 10.1038/nrc2347; Hao ZL, 2015, FRONT BIOSCI-LANDMRK, V20, P474, DOI 10.2741/4320; He LJ, 2018, BIOORGAN MED CHEM, V26, P3899, DOI 10.1016/j.bmc.2018.06.010; Huenga DY, 2017, J NUTR BIOCHEM, V41, P109, DOI 10.1016/j.jnutbio.2016.12.008; Jung D, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-20531-w; Kawaguchi Y, 2003, CELL, V115, P727, DOI 10.1016/S0092-8674(03)00939-5; Kurland JF, 2004, CANCER CELL, V5, P305, DOI 10.1016/S1535-6108(04)00091-1; Lee JY, 2010, EMBO J, V29, P969, DOI 10.1038/emboj.2009.405; Lee Y, 2016, CURR MED CHEM, V23, P2363, DOI 10.2174/0929867323666160510122624; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Liu KP, 2018, J MOL CELL BIOL, V10, P205, DOI 10.1093/jmcb/mjy012; Liu YY, 2016, J NEURO-ONCOL, V128, P217, DOI 10.1007/s11060-016-2107-z; Lu WF, 2015, ONCOTARGET, V6, P771, DOI 10.18632/oncotarget.2718; Lu ZL, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms4463; Luo J, 2015, TUMOR BIOL, V36, P5119, DOI 10.1007/s13277-015-3164-1; Mizushima N, 2010, CELL, V140, P313, DOI 10.1016/j.cell.2010.01.028; Reichert M, 2007, CANCER RES, V67, P4149, DOI 10.1158/0008-5472.CAN-06-4484; Salon C, 2007, ONCOGENE, V26, P6927, DOI 10.1038/sj.onc.1210499; Sathornsumetee S, 2007, CANCER-AM CANCER SOC, V110, P13, DOI 10.1002/cncr.22741; Shin HJR, 2016, NATURE, V534, P553, DOI 10.1038/nature18014; Stupp R, 2005, NEW ENGL J MED, V352, P987, DOI 10.1056/NEJMoa043330; Wang HB, 2010, CELL CYCLE, V9, P1021, DOI 10.4161/cc.9.5.10916; Wang ZW, 2014, NAT REV CANCER, V14, P233, DOI 10.1038/nrc3700; Wei Z, 2013, CELL SIGNAL, V25, P931, DOI 10.1016/j.cellsig.2013.01.011; Wen PY, 2008, NEW ENGL J MED, V359, P492, DOI 10.1056/NEJMra0708126; Wu HB, 2017, BIOCHEM BIOPH RES CO, V484, P304, DOI 10.1016/j.bbrc.2017.01.108; Yang CC, 2015, BREAST CANCER-BASIC, V9, P13, DOI 10.4137/BCBCR.S30101; Yeh CT, 2010, HEPATOLOGY, V52, P1922, DOI 10.1002/hep.23898; Zhang L, 2006, ONCOGENE, V25, P2615, DOI 10.1038/sj.onc.1209286	30	8	8	3	10	MDPI	BASEL	ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND		1420-3049		MOLECULES	Molecules	AUG	2019	24	15							2722	10.3390/molecules24152722			12	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	IS9AP	WOS:000482441100045	31357480	Green Submitted, Green Published, gold			2022-04-25	
J	Huang, DQ; Qiu, SW; Ge, RG; He, L; Li, M; Li, Y; Peng, Y				Huang, Daquan; Qiu, Shuwei; Ge, Ruiguang; He, Lei; Li, Mei; Li, Yi; Peng, Ying			miR-340 suppresses glioblastoma multiforme	ONCOTARGET			English	Article						glioblastoma multiforme; miR-340; ROCK1; biomarker	GLIOMA-CELLS; COLORECTAL-CANCER; MALIGNANT GLIOMAS; INITIATING CELLS; STRUCTURAL BASIS; BRAIN-TUMORS; BONE-MARROW; STEM-CELLS; DIFFERENTIATION; INHIBITION	Deregulation of microRNAs (miRs) contributes to tumorigenesis. Down-regulation of miR-340 is observed in multiple types of cancers. However, the biological function of miR-340 in glioblastoma multiforme (GBM) remains largely unknown. In the present study, we demonstrated that expression of miR-340 was downregulated in both glioma cell lines and tissues. Survival of GBM patients with high levels of miR-340 was significantly extended in comparison to patients expressing low miR-340 levels. Biological functional experiments showed that the restoration of miR-340 dramatically inhibited glioma cell proliferation, induced cell-cycle arrest and apoptosis, suppressed cell motility and promoted autophagy and terminal differentiation. Mechanistic studies disclosed that, miR-340 over-expression suppressed several oncogenes including p-AKT, EZH2, EGFR, BMI1 and XIAP. Furthermore, ROCK1 was validated as a direct functional target miR-340 and silencing of ROCK1 phenocopied the anti-tumor effect of mR-340. Our findings indicate an important role of miR-340 as a glioma killer, and suggest a potential prognosis biomarker and therapeutic target for GBM.	[Huang, Daquan; Qiu, Shuwei; He, Lei; Li, Mei; Li, Yi; Peng, Ying] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China; [Huang, Daquan; Peng, Ying] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510275, Guangdong, Peoples R China; [Ge, Ruiguang] Sun Yat Sen Univ, Coll Life Sci, Minist Educ, Key Lab Gene Engn, Guangzhou 510275, Guangdong, Peoples R China; [Ge, Ruiguang] Sun Yat Sen Univ, Coll Life Sci, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China		Peng, Y (corresponding author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China.	docpengy123@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272197, 81402065]; Culture program for Key project of National Natural Science Foundation of China of Sun Yat-Sen University [10ykjc26]; International Collaboration Program of Universities in Guangdong province [2012gjhz001]; Science & Technique Plan fund of Guangdong Province [2013B021800098]; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University [KLB09001]; Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013]163]	This work was supported by National Natural Science Foundation of China (No. 81272197 to Y. Peng and No. 81402065 to S. Qiu) and Culture program for Key project of National Natural Science Foundation of China of Sun Yat-Sen University (No. 10ykjc26 to Y. Peng), International Collaboration Program of Universities in Guangdong province (2012gjhz001) to Y. Peng, and the Science & Technique Plan fund of Guangdong Province (2013B021800098) to M. Li, Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University and Grant [2013]163 from Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology.	Abdouh M, 2009, J NEUROSCI, V29, P8884, DOI 10.1523/JNEUROSCI.0968-09.2009; Babae N, 2014, ONCOTARGET, V5, P6687, DOI 10.18632/oncotarget.2235; Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; Bruggeman SWM, 2007, CANCER CELL, V12, P328, DOI 10.1016/j.ccr.2007.08.032; Campos B, 2010, CLIN CANCER RES, V16, P2715, DOI 10.1158/1078-0432.CCR-09-1800; Chai JJ, 2001, CELL, V104, P769, DOI 10.1016/S0092-8674(01)00272-0; Das S, 2013, ONCOGENE, V32, P2927, DOI 10.1038/onc.2012.311; Dong H, 2010, BMC SYST BIOL, V4, DOI 10.1186/1752-0509-4-163; Dontula Ranadheer, 2013, Genes Cancer, V4, P285, DOI 10.1177/1947601913500141; Du Y, 2010, DIFFERENTIATION, V79, P84, DOI 10.1016/j.diff.2009.10.003; Fernandez S, 2014, ONCOGENE, V0; Frankel LB, 2011, EMBO J, V30, P4628, DOI 10.1038/emboj.2011.331; Gaur A, 2007, CANCER RES, V67, P2456, DOI 10.1158/0008-5472.CAN-06-2698; Godlewski J, 2008, CANCER RES, V68, P9125, DOI 10.1158/0008-5472.CAN-08-2629; Guerau-de-Arellano M, 2011, BRAIN, V134, P3575, DOI 10.1093/brain/awr262; Gurkar AU, 2013, NAT COMMUN, V4, DOI 10.1038/ncomms3189; Hosono Y, 2012, EMBO J, V31, P481, DOI 10.1038/emboj.2011.416; Huang X, 2013, EMBO J, V32, P2204, DOI 10.1038/emboj.2013.133; Hwang HW, 2006, BRIT J CANCER, V94, P776, DOI 10.1038/sj.bjc.6603023; Karsy Michael, 2012, Genes Cancer, V3, P3, DOI 10.1177/1947601912448068; Lee J, 2008, CANCER CELL, V13, P69, DOI 10.1016/j.ccr.2007.12.005; Li J, 2010, AM J PATHOL, V176, P699, DOI 10.2353/ajpath.2010.090502; Li Y, 2007, P NATL ACAD SCI USA, V104, P13438, DOI 10.1073/pnas.0701990104; Liu X, 2014, J MOL HISTOL, V45, P707, DOI 10.1007/s10735-014-9594-z; Lock FE, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0008190; Naumann U, 2007, GENE THER, V14, P147, DOI 10.1038/sj.gt.3302845; Oellers P, 2009, GLIA, V57, P499, DOI 10.1002/glia.20777; Omuro A, 2013, JAMA-J AM MED ASSOC, V310, P1842, DOI 10.1001/jama.2013.280319; Piccirillo SGM, 2006, NATURE, V444, P761, DOI 10.1038/nature05349; Qiu SW, 2013, BBA-MOL BASIS DIS, V1832, P1697, DOI 10.1016/j.bbadis.2013.05.015; Qiu SW, 2013, J TRANSL MED, V11, DOI 10.1186/1479-5876-11-10; Riedl SJ, 2001, CELL, V104, P791, DOI 10.1016/S0092-8674(02)02036-6; Riento K, 2003, NAT REV MOL CELL BIO, V4, P446, DOI 10.1038/nrm1128; Samuel MS, 2011, CANCER CELL, V19, P776, DOI 10.1016/j.ccr.2011.05.008; Shiozaki EN, 2003, MOL CELL, V11, P519, DOI 10.1016/S1097-2765(03)00054-6; Sun Y, 2012, ONCOL REP, V28, P1346, DOI 10.3892/or.2012.1958; Suva ML, 2009, CANCER RES, V69, P9211, DOI 10.1158/0008-5472.CAN-09-1622; Swartling FJ, 2015, CELL TISSUE RES, V359, P225, DOI 10.1007/s00441-014-2046-y; Takeyama H, 2014, MOL CANCER THER, V13, P976, DOI 10.1158/1535-7163.MCT-13-0571; Van Meir EG, 2010, CA-CANCER J CLIN, V60, P166, DOI 10.3322/caac.20069; Vigil D, 2012, CANCER RES, V72, P5338, DOI 10.1158/0008-5472.CAN-11-2373; Wang GY, 2004, J BIOL CHEM, V279, P13205, DOI 10.1074/jbc.M311427200; Wen PY, 2008, NEW ENGL J MED, V359, P492, DOI 10.1056/NEJMra0708126; Wu ZS, 2011, CANCER-AM CANCER SOC, V117, P2842, DOI 10.1002/cncr.25860; Xu XT, 2012, HEPATO-GASTROENTEROL, V59, P2523, DOI 10.5754/hge12147; Zhang H, 2010, ONCOGENE, V29, P937, DOI 10.1038/onc.2009.406; Zhang X, 2013, CURR MED CHEM, V20, P1974, DOI 10.2174/0929867311320150004; Zhou X, 2013, BIOCHEM BIOPH RES CO, V437, P653, DOI 10.1016/j.bbrc.2013.07.033; Zhuang WZ, 2011, INT J CANCER, V129, P2720, DOI 10.1002/ijc.25975	49	67	71	2	10	IMPACT JOURNALS LLC	ORCHARD PARK	6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA	1949-2553			ONCOTARGET	Oncotarget	APR 20	2015	6	11					9257	9270		10.18632/oncotarget.3288			14	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	CN9NB	WOS:000358774600058	25831237	Green Published, gold			2022-04-25	
J	He, F; Zhang, C; Chen, XL; Luo, J; Tie, HT; Li, Q; Wu, QC				He, Feng; Zhang, Cheng; Chen, Xiaolong; Luo, Jun; Tie, Hongtao; Li, Qiang; Wu, Qingchen			FBXL20 promotes cell proliferation and metastasis through activating Wnt/beta-catenin signaling pathway in esophageal cancer	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE			English	Article						FBXL20; esophageal cancer; Wnt/beta-catenin; cell cycle arrest; proliferation; migration	UBIQUITIN LIGASE; TUMOR-SUPPRESSOR; GROWTH; FBXW7; FBW7	Previous studies have demonstrated that FBXL20 can promote tumor progression in human colorectal adenocarcinoma. Additionally, FBXL20, acts as a checkpoint of p53, controls autophagy and receptor degradation. These studies suggest that FBXL20 is involved in several cancer progression. However, the role of FBXL20 in esophageal cancer remains unknown. The present study demonstrated that the expression of FBXL20 in esophageal cancer tissue was significantly higher than its expression in adjacent tissues. In vitro studies, silencing FBXL20 expression by lentiviral vector shRNA induced G0/G1 cell cycle arrest, and inhibited the proliferation, migration and invasion ability of esophageal cancer cells through Wnt/beta-catenin signaling pathway. In addition, FBXL20 silencing could increase the apoptosis of esophageal cancer cells. In summary, this study demonstrated that FBXL20 was an oncogenic gene, which could promote proliferation, migration, invasion, and G0/G1 cell cycle arrest via activating Wnt/beta-catenin signaling pathway and induce apoptosis in esophageal cancer. Therefore, FBXL20 might serve as a potential tumor marker and therapeutic target for esophageal cancer.	[He, Feng; Zhang, Cheng; Chen, Xiaolong; Luo, Jun; Tie, Hongtao; Li, Qiang; Wu, Qingchen] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, 1 Youyi Rd, Chongqing 400016, Peoples R China; [He, Feng; Chen, Xiaolong] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing 400016, Peoples R China		Wu, QC (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, 1 Youyi Rd, Chongqing 400016, Peoples R China.	qcwucq@163.com	Tie, Hongtao/X-7863-2019	Tie, Hongtao/0000-0003-1058-6407	Key Scientific Research Project of Chongqing Municipal Bureau of Health [2012-1-015]	The present study was supported by grant from the Key Scientific Research Project of Chongqing Municipal Bureau of Health (grant No. 2012-1-015).	Bengoechea-Alonso MT, 2010, ONCOGENE, V29, P5322, DOI 10.1038/onc.2010.278; Blanco MJ, 2002, ONCOGENE, V21, P3241, DOI 10.1038/sj.onc.1205416; Cheng YB, 2012, CANCER METAST REV, V31, P75, DOI 10.1007/s10555-011-9330-z; EILERS M, 1991, EMBO J, V10, P133, DOI 10.1002/j.1460-2075.1991.tb07929.x; Ferlay J, 2010, INT J CANCER, V127, P2893, DOI 10.1002/ijc.25516; Gu ZD, 2005, AM J GASTROENTEROL, V100, P1835, DOI 10.1111/j.1572-0241.2005.50018.x; Hershko DD, 2008, CANCER-AM CANCER SOC, V112, P1415, DOI 10.1002/cncr.23317; Iwatsuki M, 2010, INT J CANCER, V126, P1828, DOI 10.1002/ijc.24879; Jin JP, 2004, GENE DEV, V18, P2573, DOI 10.1101/gad.1255304; Jung P, 2008, P NATL ACAD SCI USA, V105, P15046, DOI 10.1073/pnas.0801773105; Lepage C, 2008, AM J GASTROENTEROL, V103, P2694, DOI 10.1111/j.1572-0241.2008.02191.x; Li SJ, 2016, AM J TRANSL RES, V8, P597; Mir R, 2016, ONCOGENE, V35, P1679, DOI 10.1038/onc.2015.232; Nakayama KI, 2006, NAT REV CANCER, V6, P369, DOI 10.1038/nrc1881; Ougolkov AV, 2002, GASTROENTEROLOGY, V122, P60, DOI 10.1053/gast.2002.30306; Peter C., 2003, NEW ENGL J MED, V249, P2241; Polette M, 2004, CRIT REV ONCOL HEMAT, V49, P179, DOI 10.1016/j.critrevonc.2003.10.008; SHERR CJ, 1995, TRENDS BIOCHEM SCI, V20, P187, DOI 10.1016/S0968-0004(00)89005-2; Tian XR, 2011, J BIOMED BIOTECHNOL, DOI 10.1155/2011/567305; Tsai JH, 2013, GENE DEV, V27, P2192, DOI 10.1101/gad.225334.113; Vinnedge LMP, 2015, ONCOGENE, V34, P2325, DOI 10.1038/onc.2014.173; Welcker M, 2008, NAT REV CANCER, V8, P83, DOI 10.1038/nrc2290; Wu PX, 2015, EXP MOL PATHOL, V98, P360, DOI 10.1016/j.yexmp.2015.03.015; Xiao J, 2015, GENE DEV, V29, P184, DOI 10.1101/gad.252528.114; Zhang YW, 2013, WORLD J GASTROENTERO, V19, P5598, DOI 10.3748/wjg.v19.i34.5598; Zhao S, 2015, ONCOGENE, V34, P5069, DOI 10.1038/onc.2014.429; Zhu JJ, 2014, ONCOL LETT, V7, P2185, DOI 10.3892/ol.2014.2031; Zhu JJ, 2012, ONCOL REP, V28, P2290, DOI 10.3892/or.2012.2065; Zhu JR, 2016, SCI REP-UK, V6, DOI 10.1038/srep21549	29	1	2	0	4	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	5					7796	7805					10	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	EW1ZA	WOS:000402294200047					2022-04-25	
J	Spanou, E; Kalisperati, P; Pateras, IS; Papalampros, A; Barbouti, A; Tzioufas, AG; Kotsinas, A; Sougioultzis, S				Spanou, Evagelia; Kalisperati, Polyxeni; Pateras, Ioannis S.; Papalampros, Alexandros; Barbouti, Alexandra; Tzioufas, Athanasios G.; Kotsinas, Athanassios; Sougioultzis, Stavros			Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR) and Inflammation: Focus on the Gastrointestinal (GI) Tract	FRONTIERS IN GENETICS			English	Review						toll-like receptors (TLRs); nod-like receptors (NLRs); DNA damage response (DDR); single nucleotide polymorphism (SNP); mutation; inflammation and tumorigenesis	TOLL-LIKE RECEPTORS; HELICOBACTER-PYLORI; GASTRIC-CANCER; COLORECTAL-CANCER; INNATE IMMUNITY; GENOMIC INSTABILITY; 3020INSC MUTATION; CROHNS-DISEASE; LUNG-CANCER; POLYMORPHISMS	The fundamental role of human Toll-like receptors (TLRs) and NOD-like receptors (NLRs), the two most studied pathogen recognition receptors (PRRs), is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR/NLR gene mutations and susceptibility to inflammatory, autoimmune, and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms. We briefly review the impact of TLR4 and NOD1/NOD2 and their genetic variability in the process of inflammation, tumorigenesis and DNA repair, focusing in the gastrointestinal tract. We also review the available data on new therapeutic strategies utilizing TLR/NLR agonists and antagonists for cancer, allergic diseases, viral infections and vaccine development against both infectious diseases and cancer.	[Spanou, Evagelia; Kalisperati, Polyxeni; Sougioultzis, Stavros] Univ Athens, Laikon Gen Hosp, Gastroenterol Div, Dept Pathophysiol, Athens, Greece; [Pateras, Ioannis S.; Kotsinas, Athanassios] Univ Athens, Dept Histol & Embryol, Athens, Greece; [Papalampros, Alexandros] Univ Athens, Laikon Gen Hosp, Dept Surg 1, Athens, Greece; [Barbouti, Alexandra] Univ Ioannina, Dept Anat Histol Embryol, Ioannina, Greece; [Tzioufas, Athanasios G.] Univ Athens, Laikon Gen Hosp, Dept Pathophysiol, Athens, Greece		Kotsinas, A (corresponding author), Univ Athens, Dept Histol & Embryol, Athens, Greece.	akotsin@med.uoa.gr	TZIOUFAS, ATHANASIOS G/A-1690-2008	BARBOUTI, ALEXANDRA/0000-0001-6730-359X	NKUA SARG [12128, 8916]	This work was supported by NKUA SARG grants 12128, 8916.	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Genet.	MAY 29	2017	8								65	10.3389/fgene.2017.00065			10	Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Genetics & Heredity	EW7ZN	WOS:000402737700001	28611823	Green Published, gold			2022-04-25	
J	Phang, JM; Donald, SP; Pandhare, J; Liu, YM				Phang, James M.; Donald, Steven P.; Pandhare, Jui; Liu, Yongmin			The metabolism of proline, a stress substrate, modulates carcinogenic pathways	AMINO ACIDS			English	Article; Proceedings Paper	2nd International Symposium on Proline Metabolism in Health and Disease	SEP 10-11, 2007	Frederick, MD			proline oxidase; proline dehydrogenase; mTOR; PPAR gamma; apoptosis; bioenergetics	ACTIVATED-RECEPTOR-GAMMA; MATRIX METALLOPROTEINASES; COLORECTAL-CANCER; PPAR-GAMMA; OXIDASE; GENE; APOPTOSIS; COLLAGEN; OXYGEN; INTERCONVERSIONS	The resurgence of interest in tumor metabolism has led investigators to emphasize the metabolism of proline as a "stress substrate" and to suggest this pathway as a potential anti-tumor target. Proline oxidase, a.k.a. proline dehydrogenase (POX/PRODH), catalyzes the first step in proline degradation and uses proline to generate ATP for survival or reactive oxygen species for programmed cell death. POX/PRODH is induced by p53 under genotoxic stress and initiates apoptosis by both mitochondrial and death receptor pathways. Furthermore, POX/PRODH is induced by PPAR gamma and its pharmacologic ligands, the thiazolidinediones. The anti-tumor effects of PPAR gamma may be critically dependent on POX/PRODH. In addition, it is upregulated by nutrient stress through the mTOR pathway to maintain ATP levels. We propose that proline is made available as a stress substrate by the degradation of collagen in the microenvironmental extracellular matrix by matrix metalloproteinases. In a manner analogous to autophagy, this proline-dependent process for bioenergetics from collagen in extracellular matrix can be designated "ecophagy".	[Phang, James M.; Donald, Steven P.; Pandhare, Jui] NCI, Ctr Canc Res, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA; [Liu, Yongmin] NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA		Phang, JM (corresponding author), NCI, Ctr Canc Res, Comparat Carcinogenesis Lab, Bldg 538,Room 115, Frederick, MD 21702 USA.	phang@mail.ncifcrf.gov		Pandhare, Jui/0000-0002-0356-064X	NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIABC010743, Z01BC010746, Z01BC010744] Funding Source: NIH RePORTER; Intramural NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA Funding Source: Medline; NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [N01-CO-12400] Funding Source: Medline		ADAMS E, 1980, ANNU REV BIOCHEM, V49, P1005, DOI 10.1146/annurev.bi.49.070180.005041; 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Conference Proceedings Citation Index - Science (CPCI-S)	Biochemistry & Molecular Biology	355NE	WOS:000259714800006	18401543	Green Submitted			2022-04-25	
J	Zhao, HB; Xu, XG; Lei, SZ; Shao, DY; Jiang, CM; Shi, JL; Zhang, YW; Liu, L; Lei, SZ; Sun, H; Huang, QS				Zhao, Haobin; Xu, Xiaoguang; Lei, Shuzhen; Shao, Dongyan; Jiang, Chunmei; Shi, Junling; Zhang, Yawen; Liu, Li; Lei, Shuzhen; Sun, Hui; Huang, Qingsheng			Iturin A-like lipopeptides from Bacillus subtilis trigger apoptosis, paraptosis, and autophagy in Caco-2 cells	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						anticancer; apoptosis; autophagy; endoplasmic reticulum stress; iturin; lipopeptide; paraptosis	CANCER-CELLS; ER STRESS; CA2+ OVERLOAD; SURFACTIN; ACTIVATION; INDUCTION; MEMBRANE; PATHWAY; INVOLVEMENT; DYSFUNCTION	This study revealed that iturin A-like lipopeptides produced by Bacillus subtillis induced both paraptosis and apoptosis in heterogeneous human epithelial colorectal adenocarcinoma (Caco-2) cells. Autophagy was simultaneously induced in Caco-2 cells treated with iturin A-like lipopeptides at the early stage and inhibited at the later stage. A western blot analysis showed that the lipopeptides induced apoptosis in Caco-2 cells via a mitochondrial-dependent pathway, as indicated by upregulated expression of the apoptotic genes bax and bad and downregulated expression of the antiapoptotic gene bcl-2. The induction of paraptosis in Caco-2 cells was indicated by the occurrence of many cytoplasmic vacuoles accompanied by endoplasmic reticulum (ER) dilatation and mitochondrial swelling and dysfunction. ER stress also occurred with significant increases in reactive oxygen species and Ca2+ levels in cells. Autophagy was detected by a transmission electron microscopy analysis and by upregulated expression of LC3-II and downregulated expression of LC3-I. The inhibition of autophagy at the later stage was shown by upregulated expression of p62. This study revealed the capability of iturin A-like B. subtilis lipopeptides to simultaneously execute antitumor potential via multiple pathways.	[Zhao, Haobin; Xu, Xiaoguang; Lei, Shuzhen; Shao, Dongyan; Jiang, Chunmei; Shi, Junling; Zhang, Yawen; Liu, Li; Lei, Shuzhen; Sun, Hui; Huang, Qingsheng] Northwestern Polytech Univ, Sch Life Sci, Key Lab Space Biosci & Biotechnol, 127 Youyi West Rd, Xian 710072, Shaanxi, Peoples R China; [Sun, Hui] Guilin Tourism Univ, Sch Hospitality Management, Guilin, Peoples R China		Shi, JL (corresponding author), Northwestern Polytech Univ, Sch Life Sci, Key Lab Space Biosci & Biotechnol, 127 Youyi West Rd, Xian 710072, Shaanxi, Peoples R China.	sjlshi2004@nwpu.edu.cn		Shi, Junling/0000-0002-4643-1792; Xu, Xiaoguang/0000-0001-9754-9857	Shaanxi Postdoctoral Science Foundation; Seed Foundation of Innovation and Creation for Graduate Students in Northwestern Polytechnical University [zz2017242]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [1701722, 31471718]; Key research and development plan of Shaanxi Province [2017ZDXL-NY-0304]; Modern Agricultural Industry Technology System [CARS-30]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2017M613211]	Shaanxi Postdoctoral Science Foundation, Seed Foundation of Innovation and Creation for Graduate Students in Northwestern Polytechnical University, Grant/Award Number: zz2017242; National Natural Science Foundation of China, Grant/Award Numbers: 1701722, 31471718; Key research and development plan of Shaanxi Province, Grant/Award Number: 2017ZDXL-NY-0304; Modern Agricultural Industry Technology System, Grant/Award Number: CARS-30; China Postdoctoral Science Foundation, Grant/Award Number: 2017M613211	Almutary A, 2016, INT J TOXICOL, V35, P454, DOI 10.1177/1091581816648906; Bardo S, 2006, TRENDS PHARMACOL SCI, V27, P78, DOI 10.1016/j.tips.2005.12.008; Borutaite V, 2007, J BIOL CHEM, V282, P31124, DOI 10.1074/jbc.M700322200; Cao XH, 2010, CHEM-BIOL INTERACT, V183, P357, DOI 10.1016/j.cbi.2009.11.027; Coutte F, 2015, BIOTECHNOL J, V10, P1216, DOI 10.1002/biot.201400541; Crowley Lisa C, 2016, Cold Spring Harb Protoc, V2016, DOI 10.1101/pdb.prot087221; 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Cell. Physiol.	MAY	2019	234	5					6414	6427		10.1002/jcp.27377			14	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	HK7AQ	WOS:000458138600092	30238995				2022-04-25	
J	Payen, VL; Zampieri, LX; Porporato, PE; Sonveaux, P				Payen, Valery L.; Zampieri, Luca X.; Porporato, Paolo E.; Sonveaux, Pierre			Pro- and antitumor effects of mitochondrial reactive oxygen species	CANCER AND METASTASIS REVIEWS			English	Review						Cancer; Mitochondria; Mitochondrial reactive oxygen species (mtROS); Antioxidants; Pro-oxidants; mitoQ	DNA G10398A POLYMORPHISM; COLORECTAL-CANCER CELLS; PYRUVATE-KINASE M2; OXIDATIVE STRESS; BREAST-CANCER; COMPLEX-III; PROSTATE-CANCER; SUPEROXIDE/HYDROGEN PEROXIDE; ALLOSTERIC REGULATION; ANTIOXIDANT VITAMINS	In cancer, mitochondrial functions are commonly altered. Directly involved in metabolic reprogramming, mitochondrial plasticity confers to cancer cells a high degree of adaptability to a wide range of stresses and to the harsh tumor microenvironment. Lack of nutrients or oxygen caused by altered perfusion, metabolic needs of proliferating cells, co-option of the microenvironment, control of the immune system, cell migration and metastasis, and evasion of exogenous stress (e.g., chemotherapy) are all, at least in part, influenced by mitochondria. Mitochondria are undoubtedly one of the key contributors to cancer development and progression. Understanding their protumoral (dys)functions may pave the way to therapeutic strategies capable of turning them into innocent entities. Here, we will focus on the production and detoxification of mitochondrial reactive oxygen species (mtROS), on their impact on tumorigenesis (genetic, prosurvival, and microenvironmental effects and their involvement in autophagy), and on tumor metastasis. We will also summarize the latest therapeutic approaches involving mtROS.	[Payen, Valery L.; Zampieri, Luca X.; Sonveaux, Pierre] Univ Catholique Louvain UCLouvain, IREC, Pole Pharmacol, Ave Hippocrate 57,Box B1-57-04, B-1200 Brussels, Belgium; [Payen, Valery L.] UCLouvain, Pole Pediat, IREC, Brussels, Belgium; [Payen, Valery L.] UCLouvain, Louvain Drug Res Inst, Brussels, Belgium; [Porporato, Paolo E.] Univ Torino, Dept Mol Biotechnol & Hlth Sci, Mol Biotechnol Ctr, Turin, Italy		Sonveaux, P (corresponding author), Univ Catholique Louvain UCLouvain, IREC, Pole Pharmacol, Ave Hippocrate 57,Box B1-57-04, B-1200 Brussels, Belgium.	pierre.sonveaux@uclouvain.be			European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant [642623 RADIATE, 722605 TRANSMIT]; Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS)Fonds de la Recherche Scientifique - FNRS; Belgian Televie; Fondation Louvain; Italian Ministry for University and Research (MIUR, Rita Levi-Montalcini program for young researchers 2014)Ministry of Education, Universities and Research (MIUR); Marie Skodowska-Curie grant [722605 TRANSMIT]	Works at authors' labs are supported by European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant agreement No. 642623 RADIATE and No. 722605 TRANSMIT, the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS), the Belgian Televie and the Fondation Louvain (all to PS), and the Italian Ministry for University and Research (MIUR, Rita Levi-Montalcini program for young researchers 2014) to PEP. PS is a F.R.S.-FNRS Senior Research Associate. LXZ is a PhD Fellow of Marie Skodowska-Curie grant No. 722605 TRANSMIT.	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JUN	2019	38	1-2					189	203		10.1007/s10555-019-09789-2			15	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IJ1TK	WOS:000475681100018	30820778				2022-04-25	
J	Fumet, JD; Limagne, E; Thibaudin, M; Ghiringhelli, F				Fumet, Jean-David; Limagne, Emeric; Thibaudin, Marion; Ghiringhelli, Francois			Immunogenic Cell Death and Elimination of Immunosuppressive Cells: A Double-Edged Sword of Chemotherapy	CANCERS			English	Review						cancer; chemotherapy; immunotherapy; immunogenic cell death; immunosuppression	REGULATORY T-CELLS; TUMOR-ASSOCIATED MACROPHAGES; SUPPRESSOR-CELLS; COLORECTAL-CANCER; APOPTOTIC CELLS; CYCLOPHOSPHAMIDE; CALRETICULIN; AUTOPHAGY; EFFICACY; TARGETS	Simple Summary The aim of this review is to detailed immunological effects of chemotherapies focusing on 2 main effects: immunogenic cell death and depletion of suppressive cells. It provides a strong rational for combination of chemotherapy and immunotherapy. Chemotherapy is initially used to kill proliferative cells. In the current area of emerging immunotherapy, chemotherapies have shown their ability to modulate the tumor micro environment and immune response. We focus here on two main effects: first, immunogenic cell death, defined as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response in immunocompetent hosts; and second, the depletion of suppressive cells, known to play a major role in immune escape and resistance to immunotherapy. In this review, we present a review of different classically used chemotherapies focusing on this double effect on immunity. These immunological effects of chemotherapy could be exploited to promote efficacy of immunotherapy. Broadening our understanding will make it possible to provide rationales for the combination of chemoimmunotherapy in early clinical trials.	[Fumet, Jean-David; Ghiringhelli, Francois] Ctr GF Leclerc, Dept Med Oncol, F-21000 Dijon, France; [Fumet, Jean-David; Limagne, Emeric; Thibaudin, Marion; Ghiringhelli, Francois] Ctr GF Leclerc, Platform Transfer Canc Biol, F-21000 Dijon, France; [Fumet, Jean-David; Limagne, Emeric; Thibaudin, Marion; Ghiringhelli, Francois] Univ Burgundy Franche Compte, F-21000 Dijon, France; [Fumet, Jean-David; Limagne, Emeric; Thibaudin, Marion; Ghiringhelli, Francois] UMR INSERM 1231 Lipides Nutr Canc, F-21000 Dijon, France		Fumet, JD (corresponding author), Ctr GF Leclerc, Dept Med Oncol, F-21000 Dijon, France.; Fumet, JD (corresponding author), Ctr GF Leclerc, Platform Transfer Canc Biol, F-21000 Dijon, France.; Fumet, JD (corresponding author), Univ Burgundy Franche Compte, F-21000 Dijon, France.; Fumet, JD (corresponding author), UMR INSERM 1231 Lipides Nutr Canc, F-21000 Dijon, France.	jd.fumet@gmail.com; elimagne@cgfl.fr; mthibaudin@cgfl.fr; fghiringhelli@cgfl.fr		Thibaudin, Marion/0000-0002-1046-5982; 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J	Tejeda-Munoz, N; Albrecht, LV; Bui, MH; De Robertis, EM				Tejeda-Munoz, Nydia; Albrecht, Lauren V.; Bui, Maggie H.; De Robertis, Edward M.			Wnt canonical pathway activates macropinocytosis and lysosomal degradation of extracellular proteins	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA			English	Article						macropinocytosis; arginine methylation; ESCRT; adenomatous polyposis coli; Wnt-STOP	COLI APC PROTEIN; ARGININE METHYLATION; LRP6; MECHANISMS; CANCER; SEQUESTRATION; PINOCYTOSIS; ENDOCYTOSIS; LOCALIZES; CELLS	6 Canonical Wnt signaling is emerging as a major regulator of endocytosis. Wnt treatment markedly increased the endocytosis and degradation in lysosomes of BSA. In this study, we report that in addition to receptor-mediated endocytosis, Wnt also triggers the intake of large amounts of extracellular fluid by macropinocytosis, a nonreceptor-mediated actin-driven process. Macropinocytosis induction is rapid and independent of protein synthesis. In the presence of Wnt, large amounts of nutrient-rich packages such as proteins and glycoproteins were channeled into lysosomes after fusing with smaller receptor-mediated vesicles containing glycogen synthase kinase 3 (GSK3) and protein arginine ethyltransferase 1 (PRMT1), an enzyme required for canonical Wnt signaling. Addition of Wnt3a, as well as overexpression of Disheveled (Dvl), Frizzled (Fz8), or dominant-negative Axin induced endocytosis. Depletion of the tumor suppressors adenomatous polyposis coli (APC) or Axin dramatically increased macropinocytosis, defined by incorporation of the high molecular weight marker tetramethylrhodamine (TMR)-dextran and its blockage by the Na+/H+ exchanger ethylisopropyl amiloride (EIPA). Macropinocytosis was blocked by dominant-negative vacuolar protein sorting 4 (Vps4), indicating that the Wnt pathway is dependent on multivesicular body formation, a process called microautophagy. SW480 colorectal cancer cells displayed constitutive macropinocytosis and increased extracellular protein degradation in lysosomes, which were suppressed by restoring full-length APC. Accumulation of the transcriptional activator beta-catenin in the nucleus of SW480 cells was inhibited by methyltransferase inhibition, EIPA, or the diuretic amiloride. The results indicate that Wnt signaling switches metabolism toward nutrient acquisition by engulfment of extracellular fluids and suggest possible treatments for Wnt-driven cancer progression.	[Tejeda-Munoz, Nydia; Albrecht, Lauren V.; Bui, Maggie H.; De Robertis, Edward M.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA; [Tejeda-Munoz, Nydia; Albrecht, Lauren V.; Bui, Maggie H.; De Robertis, Edward M.] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA		De Robertis, EM (corresponding author), Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.; De Robertis, EM (corresponding author), Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA.	ederobertis@mednet.ucla.edu	Munoz, Nydia Tejeda/ABF-3038-2020	Munoz, Nydia Tejeda/0000-0001-8314-412X; Albrecht, Lauren/0000-0002-3147-8010; De Robertis, Edward/0000-0002-7843-1869	University of California Institute for Mexico; University of California Institute for United States (UC MEXUS); Consejo Nacional de Ciencia y Tecnologia (CONACYT)Consejo Nacional de Ciencia y Tecnologia (CONACyT) [FE-17-65]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIH F32 GM123622]; UCLA Clinical and Translational Institute undergraduate fellowship [CTSI UL1TR000124]; Norman Sprague Endowment for Molecular Oncology; Howard Hughes Medical InstituteHoward Hughes Medical Institute; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [F32GM123622] Funding Source: NIH RePORTER	We thank Dr. M. Faux and the Ludwig Institute for SW480APC cells; Drs. S. Sokol, M. Bienz, R. Moon, and F. Costantini for plasmid constructs; Drs. K. Saito-Diaz and E. Lee for advice on APC siRNA; and Y. Moriyama, Y. Ding, S. Rundle, A. Dsouza, and G. Colozza for comments on the manuscript. N.T.-M. was supported by a joint University of California Institute for Mexico and the United States (UC MEXUS) and Consejo Nacional de Ciencia y Tecnologia (CONACYT) postdoctoral fellowship (FE-17-65); L.V.A. was supported by an NIH postdoctoral fellowship (NIH F32 GM123622); and M.H.B. was supported by a UCLA Clinical and Translational Institute undergraduate fellowship (CTSI UL1TR000124). This work was supported by the Norman Sprague Endowment for Molecular Oncology and the Howard Hughes Medical Institute, of which E.M.D.R. is an investigator.	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Natl. Acad. Sci. U. S. A.	MAY 21	2019	116	21					10402	10411		10.1073/pnas.1903506116			10	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	HY8PY	WOS:000468403400039	31061124	Green Published, hybrid			2022-04-25	
J	Bigelsen, S				Bigelsen, Stephen			Evidence-based complementary treatment of pancreatic cancer: a review of adjunct therapies including paricalcitol, hydroxychloroquine, intravenous vitamin C, statins, metformin, curcumin, and aspirin	CANCER MANAGEMENT AND RESEARCH			English	Review						vitamin D; autophagy; stroma; T cells; integrative medicine; supplements; stellate cell	NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NF-KAPPA-B; PHASE-II TRIAL; ASCORBIC-ACID; PHARMACOLOGICAL ASCORBATE; COLORECTAL-CANCER; DOWN-REGULATION; BREAST-CANCER; DOUBLE-BLIND; THERAPEUTIC APPLICATIONS	Despite new and exciting research and renewed optimism about future therapy, current statistics of survival from pancreatic cancer remains dismal. Patients seeking alternative or complementary treatments should be warned to avoid the hype and instead look to real science. A variety of relatively safe and inexpensive treatment options that have shown success in preclinical models and/or retrospective studies are currently available. Patients require their physicians to provide therapeutic guidance and assistance in obtaining and administrating these various therapies. Paricalcitol, an analog of vitamin D, has been shown by researchers at the Salk Institute for Biological Studies to break though the protective stroma surrounding tumor cells. Hydroxychloroquine has been shown to inhibit autophagy, a process by which dying cells recycle injured organelles and internal toxins to generate needed energy for survival and reproduction. Intravenous vitamin C creates a toxic accumulation of hydrogen peroxide within cancer cells, hastening their death. Metformin inhibits mitochondrial oxidative metabolism utilized by cancer stem cells. Statins inhibit not only cholesterol but also other factors in the same pathway that affect cancer cell growth, protein synthesis, and cell cycle progression. A novel formulation of curcumin may prevent resistance to chemotherapy and inhibit pancreatic cancer cell proliferation. Aspirin therapy has been shown to prevent pancreatic cancer and may be useful to prevent recurrence. These therapies are all currently available and are reviewed in this paper with emphasis on the most recent laboratory research and clinical studies.	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J	Sutradhar, M; Alegria, ECBA; Ferretti, F; Raposo, LR; da Silva, MFCG; Baptista, PV; Fernandes, AR; Pombeiro, AJL				Sutradhar, Manas; Alegria, Elisabete C. B. A.; Ferretti, Francesco; Raposo, Luis R.; Guedes da Silva, M. Fatima C.; Baptista, Pedro, V; Fernandes, Alexandra R.; Pombeiro, Armando J. L.			Antiproliferative activity of heterometallic sodium and potassium-dioxidovanadium(V) polymers	JOURNAL OF INORGANIC BIOCHEMISTRY			English	Article						Dioxidovanadium(V); Aroylhydrazone; X-ray structure; Antiproliferative agent	X-RAY-STRUCTURE; COPPER(II) COMPLEXES; IN-VIVO; COORDINATION CHEMISTRY; CATALYST PRECURSORS; VANADIUM COMPOUNDS; CRYSTAL-STRUCTURE; CU(II) COMPLEXES; DNA-BINDING; CANCER	The syntheses of the heterometallic sodium and potassium-dioxidovanadium 2D polymers, [NaVO2(1 kappa NOO';2 kappa O ''-L)(H2O)](n), (1) and [KVO2(1 kappa NOO';2 kappa O';3 kappa O ''-L)(EtOH)](n) (2) (where the kappa notation indicates the coordinating atoms of the polydentate ligand L) derived from (3,5-di-tert-butyl-2-hydroxybenzylidene)-2-hydroxybenzohydrazide (H2L) are reported. The polymers were characterized by IR, NMR, elemental analysis and single crystal X-ray diffraction analysis. The antiproliferative potential of 1 and 2 was examined towards four human cancer cell lines (ovarian carcinoma, A2780, colorectal carcinoma, HCT116, prostate carcinoma, PC3 and breast adenocarcinoma, MCF-7cell lines) and normal human fibroblasts. Complex 1 and 2 showed the highest cytotoxic activity against A2780 cell line (IC50 8.2 and 11.3 mu M, respectively) with 1 > 2 and an IC50 in the same range as cisplatin (IC50 3.4 mu M; obtained in the same experimental conditions) but, interestingly, with no cytotoxicity to healthy human fibroblasts for concentrations up to 75 mu M. This high cytotoxicity of 1 in ovarian cancer cells and its low cytotoxicity in healthy cells demonstrates its potential for further biological studies. Our results suggest that both complexes induce ovarian carcinoma cell death via apoptosis and autophagy, but autophagy is the main biological cause of the reduction of viability observed and that ROS (reactive oxygen species) may play an important role in triggering cell death.	[Sutradhar, Manas; Alegria, Elisabete C. B. A.; Ferretti, Francesco; Guedes da Silva, M. Fatima C.; Fernandes, Alexandra R.; Pombeiro, Armando J. L.] Univ Lisbon, Ctr Quim Estrutural, Inst Super Tecn, Av Rovisco Pais, P-1049001 Lisbon, Portugal; [Alegria, Elisabete C. B. A.] Inst Politecn Lisboa, Inst Super Engn Lisboa, Chem Engn Dept, R Conselheiro Emidio Navarro 1, P-1959007 Lisbon, Portugal; [Raposo, Luis R.; Baptista, Pedro, V; Fernandes, Alexandra R.] Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO, Campus Caparica, P-2829516 Caparica, Portugal		Sutradhar, M; Fernandes, AR (corresponding author), Univ Lisbon, Ctr Quim Estrutural, Inst Super Tecn, Av Rovisco Pais, P-1049001 Lisbon, Portugal.; Fernandes, AR (corresponding author), Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Ciencias Vida, UCIBIO, Campus Caparica, P-2829516 Caparica, Portugal.	manas@tecnico.ulisboa.pt; ma.fernandes@fct.unl.pt	da Silva, M. Fátima C Guedes/H-8274-2012; Pombeiro, Armando JL/I-5945-2012; Raposo, Luís/AAX-1610-2021; Alegria, Elisabete/E-9945-2012; Fernandes, Alexandra R/C-7465-2011; Raposo, Luís R/T-3754-2017; da Silva, Maria de Fatima Guedes/P-3458-2019; Sutradhar, Manas/M-4089-2013; Baptista, Pedro/A-1237-2009	da Silva, M. Fátima C Guedes/0000-0003-4836-2409; Pombeiro, Armando JL/0000-0001-8323-888X; Raposo, Luís/0000-0002-8637-346X; Alegria, Elisabete/0000-0003-4060-1057; Fernandes, Alexandra R/0000-0003-2054-4438; Raposo, Luís R/0000-0002-8637-346X; da Silva, Maria de Fatima Guedes/0000-0003-4836-2409; Sutradhar, Manas/0000-0003-3349-9154; Baptista, Pedro/0000-0001-5255-7095	Fundacao para a Ciencia e a Tecnologia (FCT), PortugalPortuguese Foundation for Science and Technology [PTDC/QEQ-ERQ/1648/2014, UID/QUI/00100/2019]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [DL/57/2017, IST-ID/102/2018]; IST [DL/57/2017, IST-ID/102/2018]; Applied Molecular Biosciences Unit - UCIBIO - national funds from FCT/MCTES [UID/Multi/04378/2019]	The authors gratefully acknowledge the Fundacao para a Ciencia e a Tecnologia (FCT), Portugal, and its projects PTDC/QEQ-ERQ/1648/2014 and UID/QUI/00100/2019. M.S. acknowledges the FCT and IST for a working contract "DL/57/2017" (Contract no. IST-ID/102/2018). This work was also supported by the Applied Molecular Biosciences Unit - UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019). Authors are thankful to the Portuguese NMR Network (IST-UL Centre) for access to the NMR facility and the IST Node of the Portuguese Network of mass -spectrometry for the ESI-MS measurements.	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Inorg. Biochem.	NOV	2019	200								110811	10.1016/j.jinorgbio.2019.110811			7	Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	JA8YB	WOS:000488136100006	31493756				2022-04-25	
J	Aftab, O; Fryknas, M; Zhang, XN; De Milito, A; Hammerling, U; Linder, S; Larsson, R; Gustafsson, MG				Aftab, Obaid; Fryknas, Marten; Zhang, Xiaonan; De Milito, Angelo; Hammerling, Ulf; Linder, Stig; Larsson, Rolf; Gustafsson, Mats G.			Label-free detection and dynamic monitoring of drug-induced intracellular vesicle formation enabled using a 2-dimensional matched filter	AUTOPHAGY			English	Article						phase-contrast microscopy; automated microscopy; vesicle detection; autophagy; image processing	LINEAGE CONSTRUCTION; CHEMICAL MODULATORS; AUTOPHAGY; ASSAY; INHIBITORS; PATHWAY; CELLS; LC3	Analysis of vesicle formation and degradation is a central issue in autophagy research and microscopy imaging is revolutionizing the study of such dynamic events inside living cells. A limiting factor is the need for labeling techniques that are labor intensive, expensive, and not always completely reliable. To enable label-free analyses we introduced a generic computational algorithm, the label-free vesicle detector (LFVD), which relies on a matched filter designed to identify circular vesicles within cells using only phase-contrast microscopy images. First, the usefulness of the LFVD is illustrated by presenting successful detections of autophagy modulating drugs found by analyzing the human colorectal carcinoma cell line HCT116 exposed to each substance among 1266 pharmacologically active compounds. Some top hits were characterized with respect to their activity as autophagy modulators using independent in vitro labeling of acidic organelles, detection of LC3-II protein, and analysis of the autophagic flux. Selected detection results for 2 additional cell lines (DLD1 and RKO) demonstrate the generality of the method. In a second experiment, label-free monitoring of dose-dependent vesicle formation kinetics is demonstrated by recorded detection of vesicles over time at different drug concentrations. In conclusion, label-free detection and dynamic monitoring of vesicle formation during autophagy is enabled using the LFVD approach introduced.	[Aftab, Obaid; Fryknas, Marten; Hammerling, Ulf; Larsson, Rolf; Gustafsson, Mats G.] Uppsala Univ, Dept Med Sci, Univ Hosp, Uppsala, Sweden; [Zhang, Xiaonan; De Milito, Angelo; Linder, Stig] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden		Gustafsson, MG (corresponding author), Uppsala Univ, Dept Med Sci, Univ Hosp, Uppsala, Sweden.	Mats.Gustafsson@medsci.uu.se		De Milito, Angelo/0000-0003-2591-2914	Higher Education Commission of PakistanHigher Education Commission of Pakistan; SSF framework project "Tools for diagnosis and drug discovery in cancer"; Association for International Cancer Research; Worldwide Cancer Research [11-0522] Funding Source: researchfish	This work was supported by the Higher Education Commission of Pakistan (OA), by the SSF framework project "Tools for diagnosis and drug discovery in cancer" (MF). ADM is supported by a grant from the Association for International Cancer Research. We thank the anonymous reviewers for their valuable suggestions for improvements to the paper.	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J	Han, ST; Zhu, LY; Zhu, YR; Meng, Y; Li, JQ; Song, P; Yousafzai, NA; Feng, LF; Chen, MQ; Wang, YM; Jin, HCA; Wang, X				Han, Shuting; Zhu, Liyuan; Zhu, Yiran; Meng, Yuan; Li, Jiaqiu; Song, Ping; Yousafzai, Neelum Aziz; Feng, Lifeng; Chen, Miaoqin; Wang, Yanmei; Jin, Hongchuan; Wang, Xian			Targeting ATF4-dependent pro-survival autophagy to synergize glutaminolysis inhibition	THERANOSTICS			English	Article						Glutaminolysis inhibition; ATF4; DDIT4; N-6-methyladenosine; metabolic synthetic lethality	AMINO-ACID; METABOLISM; GLUTAMINASE; STRESS; CANCER; ASPARAGINE; PATHWAY; GROWTH; MTOR; PROLIFERATION	As glutamine plays a central role in cancer metabolism, inhibition of glutaminolysis has become an ideal anticancer therapeutic target. However, glutaminolysis inhibition leads to activation of autophagy, which compromises its antitumor effect. Hence, we investigated the mechanism underlying glutaminolysis inhibition-induced pro-survival autophagy. Methods: High-throughput sequencing was performed on colorectal cancer (CRC) cells before and after glutaminolysis inhibition to identify differentially expressed genes. Activating transcription factor 4 (ATF4) pathway enrichment in glutaminolysis inhibited cells was identified through gene set enrichment analysis. ATF4 expression was assessed by quantitative real-time PCR (qRT-PCR) and western blotting. The function of ATF4 on mechanistic target of rapamycin (mTOR) regulation was assessed by western blotting. Luciferase reporter assays and chromatin immunoprecipitation were used to confirm the regulation of DNA damage inducible transcript 4 (DDIT4) by ATF4. mRNA half-life assays, RNA immunoprecipitation, qRT-PCR and western blotting were performed to determine the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N-6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 regulation of pro-survival autophagy was measured by tandem monomeric red fluorescent protein-green fluorescent protein fluorescence microscopy. Finally, the synergistic effect of autophagy and glutaminolysis inhibition was analyzed in an azoxymethane/dextran sodium sulfate mouse model. Results: The ATF4 pathway was activated in CRC cells upon glutaminolysis inhibition. Functionally, ATF4 transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition. Interestingly, glutaminolysis inhibition promoted ATF4 mRNA expression by abrogating N-6-methyladenosine (m(6)A) modification and YTHDF2-mediated RNA decay. Finally, inhibition of ATF4-induced autophagy enhanced the antitumor efficacy of glutaminolysis inhibition. Conclusion: Glutaminolysis inhibition upregulated ATF4 expression in an m(6)A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Targeting ATF4-induced autophagy is a new strategy to synergize glutaminolysis-targeting therapies for cancer treatment.	[Han, Shuting; Li, Jiaqiu; Song, Ping; Wang, Yanmei; Wang, Xian] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Med Oncol, Med Sch, Hangzhou, Peoples R China; [Zhu, Liyuan; Zhu, Yiran; Meng, Yuan; Feng, Lifeng; Chen, Miaoqin; Jin, Hongchuan] Zhejiang Univ, Med Sch, Sir Run Run Shaw Hosp, Lab Canc Biol,Canc Ctr,Key Lab Biotherapy, Hangzhou, Peoples R China; [Yousafzai, Neelum Aziz] Univ Poonch Rawalakot, Dept Allied Hlth Sci, Rawalakot, Ajk, Pakistan		Jin, HCA (corresponding author), Zhejiang Univ, Lab Canc Biol, Canc Ctr, Hangzhou 310016, Peoples R China.; Wang, X (corresponding author), Sir Run Run Shaw Hosp, Dept Med Oncol, Hangzhou 310016, Peoples R China.	jinhc@zju.edu.cn; wangx118@zju.edu.cn			national natural science foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC: 32070650, 82073035, 81772944]; Natural science foundation of ZhejiangNatural Science Foundation of Zhejiang Province [ZJNSF: LZ18H160001]	This work was supported by grants from national natural science foundation of China (NSFC: 32070650; 82073035 and 81772944 to WX and JH) and Natural science foundation of Zhejiang (ZJNSF: LZ18H160001 to FL) . We thank members of our laboratories for their suggestions.	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J	Wu, JY; Qin, J; Li, L; Zhang, KD; Chen, YS; Li, Y; Jin, T; Xu, JM				Wu, Jun-yi; Qin, Jun; Li, Lei; Zhang, Kun-dong; Chen, Yi-sheng; Li, Yang; Jin, Tao; Xu, Jun-ming			Roles of the Immune/Methylation/Autophagy Landscape on Single-Cell Genotypes and Stroke Risk in Breast Cancer Microenvironment	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY			English	Article							LONG-TERM SURVIVAL; CONDITIONAL SURVIVAL; MULTIINSTITUTIONAL ANALYSIS; TUMOR MICROENVIRONMENT; COLORECTAL-CANCER; GENE-EXPRESSION; IMMUNE CELLS; RESECTION; PROGNOSIS; MORTALITY	This study sought to perform integrative analysis of the immune/methylation/autophagy landscape on breast cancer prognosis and single-cell genotypes. Breast Cancer Recurrence Risk Score (BCRRS) and Breast Cancer Prognostic Risk Score (BCPRS) were determined based on 6 prognostic IMAAGs obtained from the TCGA-BRCA cohort. BCRRS and BCPRS, respectively, were used to construct a risk prediction model of overall survival and progression-free survival. Predictive capacity of the model was evaluated using clinical data. Analysis showed that BCRRS is associated with a high risk of stroke. In addition, PPI and drug-ceRNA networks based on differences in BCPRS were constructed. Single cells were genotyped through integrated scRNA-seq of the TNBC samples based on clustering results of BCPRS-related genes. The findings of this study show the potential regulatory effects of IMAAGs on breast cancer tumor microenvironment. High AUCs of 0.856 and 0.842 were obtained for the OS and PFS prognostic models, respectively. scRNA-seq analysis showed high expression levels of adipocytes and adipose tissue macrophages (ATMs) in high BCPRS clusters. Moreover, analysis of ligand-receptor interactions and potential regulatory mechanisms were performed. The LINC00276&MALAT1/miR-206/FZD4-Wnt7b pathway was also identified which may be useful in future research on targets against breast cancer metastasis and recurrence. Neural network-based deep learning models using BCPRS-related genes showed that these genes can be used to map the tumor microenvironment. In summary, analysis of IMAAGs, BCPRS, and BCRRS provides information on the breast cancer microenvironment at both the macro- and microlevels and provides a basis for development of personalized treatment therapy.	[Wu, Jun-yi; Qin, Jun; Li, Lei; Zhang, Kun-dong; Chen, Yi-sheng; Li, Yang; Jin, Tao; Xu, Jun-ming] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Gen Surg, Sch Med, Shanghai 200080, Peoples R China		Jin, T; Xu, JM (corresponding author), Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Gen Surg, Sch Med, Shanghai 200080, Peoples R China.	empiric_taojin@163.com; 1640423@tongji.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [8197032698]	We appreciate the valuable bioinformatics analysis support received from Dr. Xueran Kang (Contact Email: otokang@sjtu.edu.cn;1131303222@qq.com) over the years. This work was supported by grants from the National Natural Science Foundation of China (8197032698).	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Cell. Longev.	AUG 20	2021	2021								5633514	10.1155/2021/5633514			32	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	UJ2SM	WOS:000691141700002	34457116	Green Published, gold			2022-04-25	
J	Lee, JH; Yoon, YM; Han, YS; Yun, CW; Lee, SH				Lee, Jun Hee; Yoon, Yeo Min; Han, Yong-Seok; Yun, Chul Won; Lee, Sang Hun			Melatonin Promotes Apoptosis of Oxaliplatin-resistant Colorectal Cancer Cells Through Inhibition of Cellular Prion Protein	ANTICANCER RESEARCH			English	Article						Colorectal cancer cells; cellular prion protein; melatonin; oxaliplatin; drug resistance	OXIDATIVE STRESS; ANTIOXIDANT; PROGRESSION; AUTOPHAGY; AXIS	Background/Aim: Drug resistance restricts the efficacy of chemotherapy in colorectal cancer. However, the detailed molecular mechanism of drug resistance in colorectal cancer cells remains unclear. Materials and Methods: The level of cellular prion protein (PrPC) in oxaliplatin-resistant colorectal cancer (SNU-C5/Oxal-R) cells was assessed. Results: PrPC level in SNU-C5/Oxal-R cells was significantly increased compared to that in wildtype (SNU-C5) cells. Superoxide dismutase and catalase activities were higher in SNU-C5/Oxal-R cells than in SNU-C5 cells. Treatment of SNU-C5/Oxal-R cells with oxaliplatin and melatonin reduced PrPC expression, while suppressing antioxidant enzyme activity and increasing superoxide anion generation. In SNU-C5/Oxal-R cells, endoplasmic reticulum stress and apoptosis were significantly increased following co-treatment with oxaliplatin and melatonin compared to treatment with oxaliplatin alone. Conclusion: Co-treatment with oxaliplatin and melatonin increased endoplasmic reticulum stress in and apoptosis of SNU-C5/Oxal-R cells through inhibition of PrPC, suggesting that PrPC could be a key molecule in oxaliplatin resistance of colorectal cancer cells.	[Lee, Jun Hee] Univ Alabama Birmingham, Sch Med, Dept Pharmacol & Toxicol, Birmingham, AL USA; [Yoon, Yeo Min; Han, Yong-Seok; Yun, Chul Won; Lee, Sang Hun] Soonchunhyang Univ, Seoul Hosp, Med Sci Res Inst, Seoul, South Korea; [Lee, Sang Hun] Soonchunhyang Univ, Dept Med Biosci, Asan, South Korea		Lee, SH (corresponding author), Soonchunhyang Univ, Seoul Hosp, Soonchunhyang Med Sci Res Inst, 59 Daesagwan Ro 657 Hannam Dong, Seoul 140887, South Korea.	jhlee0407@sch.ac.kr	lee, sang hun/Q-4650-2019	lee, sang hun/0000-0002-9005-5966	National Research Foundation grant - Korean governmentNational Research Foundation of Korea [NRF-2016R1D1A3B01007727, NRF-2017M3A9B4032528]	This work was supported by the National Research Foundation grant funded by the Korean government (grant number NRF-2016R1D1A3B01007727, NRF-2017M3A9B4032528). The funding agencies had no role in formulating the study design, data collection or analysis, the decision to publish, or preparation of the manuscript.	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J	Chen, L; Liao, FY; Jiang, ZY; Zhang, C; Wang, ZW; Luo, P; Jiang, QZ; Wu, J; Wang, Q; Luo, M; Li, XR; Leng, Y; Ma, L; Shen, GF; Chen, ZL; Wang, Y; Tan, X; Gan, YB; Liu, DQ; Liu, YS; Shi, CM				Chen, Long; Liao, Fengying; Jiang, Zhongyong; Zhang, Chi; Wang, Ziwen; Luo, Peng; Jiang, Qingzhi; Wu, Jie; Wang, Qing; Luo, Min; Li, Xueru; Leng, Yu; Ma, Le; Shen, Gufang; Chen, Zelin; Wang, Yu; Tan, Xu; Gan, Yibo; Liu, Dengqun; Liu, Yunsheng; Shi, Chunmeng			Metformin mitigates gastrointestinal radiotoxicity and radiosensitises P53 mutation colorectal tumours via optimising autophagy	BRITISH JOURNAL OF PHARMACOLOGY			English	Article							IONIZING-RADIATION; DNA METHYLATION; OXIDATIVE STRESS; BOWEL TOXICITY; CANCER; IRRADIATION; APOPTOSIS; KINASE; INJURY; RADIOTHERAPY	Background and Purpose There is an urgent but unmet need for mitigating radiation-induced intestinal toxicity while radio sensitising tumours for abdominal radiotherapy. We aimed to investigate the effects of metformin on radiation-induced intestinal toxicity and radiosensitivity of colorectal tumours. Experimental Approach Acute and chronic histological injuries of the intestine from mice were used to assess radioprotection and IEC-6 cell line was used to investigate the mechanisms in vitro. The fractionated abdominal radiation model of HCT116 and HT29 tumour grafts was used to determine the effects on colorectal cancer. Key Results Metformin alleviated radiation-induced acute and chronic intestinal toxicity by optimising mitophagy which was AMPK-dependent. In addition, our data indicated that metformin increased the radiosensitivity of colorectal tumours with P53 mutation both in vitro and in vivo. Conclusion and Implications Metformin may be a radiotherapy adjuvant agent for colorectal cancers especially those carrying P53 mutation. Our findings provide a new strategy for further precise clinical trials for metformin on radiotherapy.	[Chen, Long; Liao, Fengying; Jiang, Zhongyong; Zhang, Chi; Wang, Ziwen; Luo, Peng; Jiang, Qingzhi; Wu, Jie; Wang, Qing; Luo, Min; Ma, Le; Shen, Gufang; Chen, Zelin; Wang, Yu; Tan, Xu; Gan, Yibo; Liu, Dengqun; Liu, Yunsheng; Shi, Chunmeng] Third Mil Med Univ, Army Med Univ, Inst Rocket Force Med, State Key Lab Trauma Burns & Combined Injury, Chongqing, Peoples R China; [Jiang, Qingzhi; Wang, Qing] Southwest Med Univ, Inst Clin Med, Luzhou, Peoples R China; [Luo, Min] Guizhou Med Univ, Minist Educ, Key Lab Environm Pollut Monitoring & Dis Control, Dept Toxicol, Guiyang, Peoples R China; [Li, Xueru; Leng, Yu] Chongqing Med Univ, Gener Hosp, Dept Ophthalmol, Chongqing, Peoples R China		Shi, CM (corresponding author), Third Mil Med Univ, State Key Lab Trauma Burns & Combined Injury, Inst Rocket Force Med, Chongqing 400038, Peoples R China.	shicm@tmmu.edu.cn	Wang, Ziwen/AAG-9607-2021	Shi, Chunmeng/0000-0002-8264-738X; chen, long/0000-0001-5907-6374	National Key Research and Development Program [2016YFC1000805]; University Innovation Team Building Program of Chongqing [CXTDG201602020];  [AWS17J007];  [2018-JCJQ-ZQ-001]	This work was supported by the National Key Research and Development Program (2016YFC1000805), University Innovation Team Building Program of Chongqing (CXTDG201602020) and Intramural Research Project Grants (AWS17J007 and 2018-JCJQ-ZQ-001).	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J. Pharmacol.	SEP	2020	177	17					3991	4006		10.1111/bph.15149		JUL 2020	16	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	NB5UP	WOS:000546356500001	32472692	Bronze, Green Published			2022-04-25	
J	Jung, HJ; Kang, JH; Choi, S; Son, YK; Lee, KR; Seong, JK; Kim, SY; Oh, SH				Jung, Hyun Jin; Kang, Ju-Hee; Choi, Seungho; Son, Youn Kyoung; Lee, Kang Ro; Seong, Je Kyung; Kim, Sun Yeou; Oh, Seung Hyun			Pharbitis Nil (PN) induces apoptosis and autophagy in lung cancer cells and autophagy inhibition enhances PN-induced apoptosis	JOURNAL OF ETHNOPHARMACOLOGY			English	Article						Pharbitis Nil; Apoptosis; Autophagy; STAT3; ERK1/2	PROKINETIC AGENT; OSTEOSARCOMA CELLS; COLORECTAL-CANCER; NATURAL-PRODUCTS; GENE-EXPRESSION; INDUCTION; STAT3; ACTIVATION; DA-9701; PATHWAY	Ethnopharmacological relevance: Pharbitis Nil (PN) is used as a main component of the existing drug, DA-9701, which was developed to treat functional dyspepsia (FD) in Korea. PN extracts isolated from its seeds have been reported to have anticancer effects. Aim of the study: The purpose of this study was to investigate the underlying mechanism of the chemotherapeutic effects of PN in lung cancer cells. Materials and methods: We performed MTT assays, colony formation assays, flow cytometry assays, Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence analysis, and cell counting assays to study the molecular mechanism of chemotherapeutic effects of PN in lung cancer cells. Results: Our results indicate that PN induced autophagy as well as apoptosis. PN inhibited cell proliferation and survival by inducing apoptosis in several lung cancer cell lines. PN-treated cells also exhibited induction of autophagy, as evidenced by increased protein expression levels and punctuate patterns of LC3 II. Moreover, activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), which plays an important role in autophagy activation, was shown to be related with PN-induced autophagy. Interestingly, pharmacological blockade of autophagy activation with wortmannin and inhibition of ERK1/2 phosphorylation by U0126 markedly enhanced PN-induced apoptosis and reduced cell viability, suggesting that autophagy induced by PN may have a cytoprotective effect by suppressing apoptosis. PN- induced apoptosis was regulated by signal transducer and activator of transcription 3 (STAT3) deactivation. Moreover, decrease of STAT3 activation in PN-treated cells was associated with reduced survivin expression, further demonstrating that PN-induced apoptosis was regulated by STAT3 deactivation. Conclusion: We believe that PN, which is already proven to treat human patients with FD, might be a potential anticancer drug for human lung cancer. In addition, our data suggest that the combination of PN treatment with an autophagy inhibitor or traditional anticancer agents may be an effective anticancer therapy.	[Jung, Hyun Jin; Seong, Je Kyung] Seoul Natl Univ, Coll Vet Med, Korea Mouse Phenotyping Ctr, Seoul 08826, South Korea; [Kang, Ju-Hee; Kim, Sun Yeou; Oh, Seung Hyun] Gachon Univ, Coll Pharm, 191 Hambangmoe Ro, Incheon 21936, South Korea; [Choi, Seungho] Seoul Natl Univ, Coll Vet Med, Seoul 08826, South Korea; [Son, Youn Kyoung] Natl Inst Biol Resources, Biol & Genet Resources Assessment Div, Incheon 22689, South Korea; [Lee, Kang Ro] Sungkyunkwan Univ, Sch Pharm, Nat Prod Lab, Suwon 1641916, South Korea		Oh, SH (corresponding author), Gachon Univ, Coll Pharm, 191 Hambangmoe Ro, Incheon 21936, South Korea.	eyeball@hanmail.net	Oh, Seung/AAN-6744-2021	Seong, Je Kyung/0000-0003-1177-6958	National Institute of Biological Resources (NIBR) - Ministry of Environment (MOE) of the Republic of Korea [NIBR201725201]; National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2012M3A9D1054622]	This work was supported by a grant from the National Institute of Biological Resources (NIBR), funded by the Ministry of Environment (MOE) of the Republic of Korea (NIBR201725201).; This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 2012M3A9D1054622)	Boulares AH, 1999, J BIOL CHEM, V274, P22932, DOI 10.1074/jbc.274.33.22932; Choi CH, 2010, MOL PHARMACOL, V78, P114, DOI 10.1124/mol.110.063495; Choi S, 2009, MOL CELLS, V27, P307, DOI 10.1007/s10059-009-0039-6; Corcelle E, 2007, AUTOPHAGY, V3, P57, DOI 10.4161/auto.3424; Ellington AA, 2006, CARCINOGENESIS, V27, P298, DOI 10.1093/carcin/bgi214; Gritsko T, 2006, CLIN CANCER RES, V12, P11, DOI 10.1158/1078-0432.CCR-04-1752; Guo SH, 2016, J DRUG TARGET, V24, P934, DOI 10.3109/1061186X.2016.1157882; Itakura E, 2011, J CELL BIOL, V192, P17, DOI 10.1083/jcb.201009067; Ju JH, 2011, J ETHNOPHARMACOL, V133, P126, DOI 10.1016/j.jep.2010.09.021; Kang JH, 2015, J ETHNOPHARMACOL, V173, P303, DOI 10.1016/j.jep.2015.07.030; Kang TS, 2017, CANCER LETT, V396, P76, DOI 10.1016/j.canlet.2017.03.016; Kim HJ, 2013, INT J ONCOL, V42, P1985, DOI 10.3892/ijo.2013.1884; Kim KH, 2014, J AGR FOOD CHEM, V62, P7746, DOI 10.1021/jf501470k; Klabunde CN, 2007, ANN EPIDEMIOL, V17, P584, DOI 10.1016/j.annepidem.2007.03.011; Ko SG, 2004, BIOL PHARM BULL, V27, P1604, DOI 10.1248/bpb.27.1604; Komatsu M, 2005, J CELL BIOL, V169, P425, DOI 10.1083/jcb.200412022; Kondo Y, 2005, NAT REV CANCER, V5, P726, DOI 10.1038/nrc1692; Lang FF, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0129196; Lee J.I., 2013, 2013 IEEE INT C IEEE, P1, DOI [10.1109/tencon.2013.6718487, DOI 10.1109/TENCON.2013.6718487, DOI 10.1007/S12282-013-0442-X#]; Lee SP, 2017, J NEUROGASTROENTEROL, V23, P109, DOI 10.5056/jnm16003; Lee TH, 2008, PHYTOMEDICINE, V15, P836, DOI 10.1016/j.phymed.2008.02.019; Levine B, 2007, NATURE, V446, P745, DOI 10.1038/446745a; Li X, 2011, TOXICOL APPL PHARM, V251, P146, DOI 10.1016/j.taap.2010.12.007; Mann J, 2002, NAT REV CANCER, V2, P143, DOI 10.1038/nrc723; Martinez-Lopez N, 2013, NAT COMMUN, V4, DOI 10.1038/ncomms3799; Mizushima N, 2010, CELL, V140, P313, DOI 10.1016/j.cell.2010.01.028; Paez JG, 2004, SCIENCE, V304, P1497, DOI 10.1126/science.1099314; Pao W, 2004, P NATL ACAD SCI USA, V101, P13306, DOI 10.1073/pnas.0405220101; Peng X, 2014, CELL DEATH DIS, V5, DOI 10.1038/cddis.2014.297; Prick T, 2006, BIOCHEM J, V394, P153, DOI 10.1042/BJ20051243; Qin BB, 2015, SCI REP-UK, V5, DOI 10.1038/srep15701; Reddy L, 2003, PHARMACOL THERAPEUT, V99, P1, DOI 10.1016/S0163-7258(03)00042-1; Shen SS, 2012, MOL CELL, V48, P667, DOI 10.1016/j.molcel.2012.09.013; Song JR, 2009, AUTOPHAGY, V5, P1131, DOI 10.4161/auto.5.8.9996; Sridharan Savitha, 2011, Cancers (Basel), V3, P2630, DOI 10.3390/cancers3022630; Wang YY, 2013, TOXICOL IN VITRO, V27, P1928, DOI 10.1016/j.tiv.2013.06.001; Xiong H, 2008, NEOPLASIA, V10, P287, DOI 10.1593/neo.07971; You LK, 2015, ONCOTARGET, V6, P40268, DOI 10.18632/oncotarget.5592; You LK, 2015, AUTOPHAGY, V11, P729, DOI 10.1080/15548627.2015.1017192; Yuan G, 2014, J BIOL CHEM, V289, P10607, DOI 10.1074/jbc.M113.528760; Zeng YJ, 2012, PLOS ONE, V7, DOI [10.1371/journal.pone.0030312, 10.1371/journal.pone.0043478]; Zhang J, 2013, ONCOL LETT, V5, P756, DOI 10.3892/ol.2013.1132; Zhou J, 2013, CELL RES, V23, P508, DOI 10.1038/cr.2013.11	43	14	14	0	6	ELSEVIER IRELAND LTD	CLARE	ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND	0378-8741			J ETHNOPHARMACOL	J. Ethnopharmacol.	SEP 17	2017	208						253	263		10.1016/j.jep.2017.07.020			11	Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine	FI8MC	WOS:000412255700026	28729229				2022-04-25	
J	Kobayashi, T; Ishida, M; Miki, H; Matsumi, Y; Fukui, T; Hamada, M; Tsuta, K; Sekimoto, M				Kobayashi, Toshinori; Ishida, Mitsuaki; Miki, Hisanori; Matsumi, Yuki; Fukui, Toshiro; Hamada, Madoka; Tsuta, Koji; Sekimoto, Mitsugu			p62 is a useful predictive marker for tumour regression after chemoradiation therapy in patients with advanced rectal cancer: an immunohistochemical study	COLORECTAL DISEASE			English	Article						advanced rectal cancer; autophagy; chemoradiation therapy; p62; tumour regression grade	PROGNOSTIC-SIGNIFICANCE; EXPRESSION; RADIOTHERAPY; PROTEIN; WATCH	Aim: This study aimed to evaluate the relationship between p62 expression status and tumour regression grade in advanced rectal cancer. Methods: We enrolled 47 consecutive patients with advanced rectal cancer who underwent chemoradiation therapy (CRT) before surgery. p62 expression in the biopsy specimens was immunohistochemically evaluated, and p62 expression score (staining intensity x positive tumour cells, %) was calculated (range 0-300). The relationship between p62 expression score and CRT effect was analysed. Results: The staining intensity was +2 and +3 in 29 and 18 patients, respectively. The median proportion of positive neoplastic cells was 87.8%, and that of the p62 expression score was 200. Stronger staining intensity and a higher proportion of p62-positive neoplastic cells were significantly associated with CRT non-effectiveness (P = 0.0002 and P = 0.0116, respectively), and a higher p62 expression score was significantly associated with CRT non-effectiveness (P < 0.0001). The optimal cut-off value for predicting the CRT effect was 240. Conclusions: A higher p62 expression score was significantly associated with less CRT effectiveness in patients with advanced rectal cancer. Analysis of p62 expression score using biopsy specimens is a useful and easily assessable prediction marker for CRT effect and might help select patients who can undergo a 'watch-and-wait' strategy after CRT.	[Kobayashi, Toshinori; Miki, Hisanori; Matsumi, Yuki; Hamada, Madoka; Sekimoto, Mitsugu] Kansai Med Univ, Dept Surg, Osaka, Japan; [Ishida, Mitsuaki; Tsuta, Koji] Kansai Med Univ, Dept Pathol, Osaka, Japan; [Ishida, Mitsuaki; Tsuta, Koji] Kansai Med Univ, Clin Lab, Osaka, Japan; [Fukui, Toshiro] Kansai Med Univ, Div Gastroenterol & Hepatol, Dept Internal Med 3, Osaka, Japan		Ishida, M (corresponding author), Kansai Med Univ, Dept Pathol, 2-5-1,Shinmachi, Hirakata, Osaka 5731010, Japan.	ishidamt@hirakata.kmu.ac.jp	Hamada, Madoka/AFG-8058-2022	Fukui, Toshiro/0000-0003-1131-4067; Kobayashi, Toshinori/0000-0001-8042-5073	Kansai Medical University	This study was partially supported by the research grant D2 from the Kansai Medical University (to TK). The paper has not been in a podium or poster meeting presentation.	Arai A, 2017, AM J CANCER RES, V7, P881; Dayde D, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18030573; Dreyer SB, 2017, ANN SURG ONCOL, V24, P1295, DOI 10.1245/s10434-016-5684-3; Dworak O, 1997, INT J COLORECTAL DIS, V12, P19, DOI 10.1007/s003840050072; Fluss R, 2005, BIOMETRICAL J, V47, P458, DOI 10.1002/bimj.200410135; Galluzzi L, 2017, NAT REV CLIN ONCOL, V14, P247, DOI 10.1038/nrclinonc.2016.183; Habr-Gama A, 2004, ANN SURG, V240, P711, DOI 10.1097/01.sla.0000141194.27992.32; Hupkens BJP, 2017, DIS COLON RECTUM, V60, P1032, DOI 10.1097/DCR.0000000000000862; Hur H, 2016, DIS COLON RECTUM, V59, P1174, DOI 10.1097/DCR.0000000000000711; Inomata M, 2016, MOL CLIN ONCOL, V4, P510, DOI 10.3892/mco.2016.767; Iwadate R, 2015, AM J PATHOL, V185, P2523, DOI 10.1016/j.ajpath.2015.05.008; Kosumi K, 2017, ONCOIMMUNOLOGY, V6, DOI 10.1080/2162402X.2017.1284720; Lei C, 2020, MEDICINE, V99, DOI 10.1097/MD.0000000000018791; Li XF, 2016, WORLD J GASTROENTERO, V22, P8576, DOI 10.3748/wjg.v22.i38.8576; Liu JL, 2014, BRIT J CANCER, V111, P944, DOI 10.1038/bjc.2014.355; Nakayama S, 2017, CANCER MED-US, V6, P1264, DOI 10.1002/cam4.1093; Pankiv S, 2007, J BIOL CHEM, V282, P24131, DOI 10.1074/jbc.M702824200; Rodel C, 2005, J CLIN ONCOL, V23, P8688, DOI 10.1200/JCO.2005.02.1329; Rogov V, 2014, MOL CELL, V53, P167, DOI 10.1016/j.molcel.2013.12.014; Saito T, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms12030; Su YX, 2005, CLIN IMMUNOL, V116, P118, DOI 10.1016/j.clim.2005.04.004; van der Sande ME, 2021, ANN SURG, V274, pE541, DOI 10.1097/SLA.0000000000003718; van der Valk MJM, 2018, LANCET, V391, P2537, DOI 10.1016/S0140-6736(18)31078-X; Wang Z, 2020, THORAC CANCER, V11, P130, DOI 10.1111/1759-7714.13252; Zhao MF, 2015, HUM PATHOL, V46, P843, DOI 10.1016/j.humpath.2015.02.009	25	0	0	0	1	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1462-8910	1463-1318		COLORECTAL DIS	Colorectal Dis.	MAY	2021	23	5					1083	1090		10.1111/codi.15486		JAN 2021	8	Gastroenterology & Hepatology; Surgery	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology; Surgery	RZ5NR	WOS:000606007100001	33316131				2022-04-25	
J	Sun, B; Xu, Y; Liu, ZY; Meng, WX; Yang, H				Sun, B.; Xu, Y.; Liu, Z-Y; Meng, W-X; Yang, H.			Autophagy assuages myocardial infarction through Nrf2 signaling activation-mediated reactive oxygen species clear	EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES			English	Article						Autophagy; Nrf2; Apoptosis; CytC; ROS; Myocardial infarction	OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; REPERFUSION INJURY; PRIMARY PREVENTION; COLORECTAL-CANCER; ASPIRIN; RATS; PROTECTS	OBJECTIVE: The activation of autophagy was shown to shrink infarct size and mitigate cardiac dysfunction caused by myocardial infarction (MI). However, the underlying mechanisms remain largely unknown. As excessive generation of reactive oxygen species (ROS) deteriorates MI process and Nrf2 signaling exerts an antioxidant role, we explored whether autophagy assuaged MI through Nrf2 signaling activation-mediated ROS clear. MATERIALS AND METHODS: MI models were induced by ligation of the left descending coronary artery (LAD) in C57BL/6J mice or Nrf2 knockout mice (Nrf2-KO). Rapamycin and 3-methyladenine (3-MA) were used to activate and repress autophagy in MI mice, respectively. Aspirin, a cardioprotective drug was given to MI mice to evaluate its effects on autophagy. RESULTS: Compared with the MI group, rapamycin treatment remarkably decreased the infarct size, cell apoptosis and blood troponin I level, accompanied by the reduced redox potential (Eh), ROS, malondialdehyde (MDA) and cytochrome C levels, and the increased reduced glutathione (GSH) level. Also, rapamycin treatment increased the expressions of bcl-2, bcl-xL, HSP70, and HSP90. In addition, rapamycin treatment promoted the nuclear accumulation of Nrf2 protein. However, Nrf2 downregulation significantly impaired the effects of rapamycin on the reductions of infarct size, cell apoptosis, troponin I and ROS levels. Similarly, to rapamycin roles, aspirin treatment also remarkably reduced infarct size, cell apoptosis and troponin I in mice with MI surgery, as well as increased the expression level of LC3II/LC3I. CONCLUSIONS: This study demonstrated that autophagy enhancement contributed to the improvement of MI through Nrf2 signaling activation-mediated ROS clear.	[Sun, B.; Meng, W-X; Yang, H.] Harbin Med Univ, Dept Cardiovasc Surg, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China; [Xu, Y.] Harbin Med Univ, Editorial Board Journal, Harbin, Heilongjiang, Peoples R China; [Liu, Z-Y] Harbin Med Univ, Affiliated Hosp 1, Cent Lab Hematol & Oncol, Harbin, Heilongjiang, Peoples R China		Yang, H (corresponding author), Harbin Med Univ, Dept Cardiovasc Surg, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China.	redrosefive@163.com					Aisa Z, 2017, EUR REV MED PHARMACO, V21, P3705; [Anonymous], 2002, Methods Enzymol, V355, P1; Bibbins-Domingo K, 2016, ANN INTERN MED, V164, P836, DOI 10.7326/M16-0577; Cho JS, 2015, J KOREAN MED SCI, V30, P903, DOI 10.3346/jkms.2015.30.7.903; Dehmer SP, 2016, ANN INTERN MED, V164, P777, DOI 10.7326/M15-2129; Filomeni G, 2015, CELL DEATH DIFFER, V22, P377, DOI 10.1038/cdd.2014.150; Fisher CD, 2007, DRUG METAB DISPOS, V35, P995, DOI 10.1124/dmd.106.014340; Florczyk Urszula, 2010, Postepy Biochem, V56, P147; Gonzalez-Montero J, 2018, WORLD J CARDIOL, V10, P74, DOI 10.4330/wjc.v10.i9.74; Grunwell JR, 2015, FRONT PEDIATR, V3, DOI 10.3389/fped.2015.00046; Harris Craig, 2012, Methods Mol Biol, V889, P325, DOI 10.1007/978-1-61779-867-2_21; Hausenloy DJ, 2013, J CLIN INVEST, V123, P92, DOI 10.1172/JCI62874; Hori M, 2009, CARDIOVASC RES, V81, P457, DOI 10.1093/cvr/cvn335; Huang ZJ, 2018, EUR J PHARMACOL, V823, P58, DOI 10.1016/j.ejphar.2018.01.031; Kirchberger I, 2015, BMC PUBLIC HEALTH, V15, DOI 10.1186/s12889-015-2124-4; Levine B, 2004, DEV CELL, V6, P463, DOI 10.1016/S1534-5807(04)00099-1; Lin C, 2016, J PHARM PHARMACOL, V68, P941, DOI 10.1111/jphp.12567; Liu ZH, 2017, AM J PHYSIOL-HEART C, V312, pH422, DOI 10.1152/ajpheart.00249.2016; McCormick J, 2012, J CELL MOL MED, V16, P386, DOI 10.1111/j.1582-4934.2011.01323.x; McDonald H, 2018, PHYSIOL REP, V6, DOI 10.14814/phy2.13699; Sable A, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-21866-0; Sciarretta S, 2018, ANNU REV PHYSIOL, V80, P1, DOI 10.1146/annurev-physiol-021317-121427; Shi XM, 2014, INT J CLIN EXP MED, V7, P5310; Sun LJ, 2012, EXP THER MED, V4, P811, DOI 10.3892/etm.2012.674; von Knethen A, 1999, J IMMUNOL, V163, P2858; Wang S, 2018, EUR REV MED PHARMACO, V22, P8990, DOI 10.26355/eurrev_201812_16670; Wang Y, 2018, BIOCHEM BIOPH RES CO, V503, P3219, DOI 10.1016/j.bbrc.2018.08.129; Waypa GB, 2002, CIRC RES, V91, P719, DOI 10.1161/01.RES.0000036751.04896.F1; Wei P, 2015, INT J CLIN EXP PATHO, V8, P9836; Wu XQ, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0112891; Xiao JH, 2018, J CELL BIOCHEM, V119, DOI 10.1002/jcb.26878; Yang ZF, 2010, NAT CELL BIOL, V12, P814, DOI 10.1038/ncb0910-814; Zhang JL, 2009, CHINESE MED J-PEKING, V122, P2372, DOI 10.3760/cma.j.issn.0366-6999.2009.19.033; Zhao QX, 2018, INT J MOL MED, V41, P3243, DOI 10.3892/ijmm.2018.3552; Zhao ZS, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms7212; Zhu HH, 2018, CELL PHYSIOL BIOCHEM, V49, P2138, DOI 10.1159/000493817	36	2	2	0	3	VERDUCI PUBLISHER	ROME	VIA GREGORIO VII, ROME, 186-00165, ITALY	1128-3602			EUR REV MED PHARMACO	Eur. Rev. Med. Pharmacol. Sci.		2020	24	13					7381	7390		10.26355/eurrev_202007_21906			10	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	MN9OX	WOS:000551170100021	32706077				2022-04-25	
J	Liu, Q; Zhu, DC; Hao, BZ; Zhang, ZW; Tian, YJ				Liu, Qing; Zhu, Dongchuan; Hao, Baozhen; Zhang, Zhiwei; Tian, Yongjie			Luteolin promotes the sensitivity of cisplatin in ovarian cancer by decreasing PRPA1-medicated autophagy	CELLULAR AND MOLECULAR BIOLOGY			English	Article						Ovarian cancer; Luteolin; Cisplatin; Autophagy; Chemosensitivity	PARP1 INHIBITORS; CELLS; APOPTOSIS; STRESS; ROLES	Luteolin (LUT) is a flavone universally presented in plants. It shows an anti-carcinogenic effect in different cancers and could increase the sensitivity of cisplatin in colorectal cancer cell lines through Nrf2 pathway. However, the effect of luteolin on the sensitivity to ovarian cancer cells has not been studied. In this study, luteolin was found to suppress autophagy with reduced expression of LC3-II, but enhanced the inhibition of cell vitality and promoted apoptosis induced by cisplatin, leading to restoration of the sensitivity to cisplatin in ovarian cancer cells through CCK-8, flow cytometry and immunofluorescent assays. Although cisplatin elevated the PARP1 for cell survival, the cisplatin-induced expression of PARP1 was inhibited by luteolin a dose- and time-dependent manner through Q-PCR and WB assays. Further, PARP1 siRNA could further improve the LUT-induced inhibition of cell vitality and restore the sensitivity to cisplatin with reduced LC3-II levels. Our present work demonstrate that LUT can suppresses autophagy but enhance apoptosis induced by cisplatin and promote the sensitivity to cisplatin through suppressing the expression of RARP1 in ovarian cancer.	[Liu, Qing; Tian, Yongjie] Shandong Univ, Shandong Prov Hosp, Dept Obstet & Gynecol, Jinan, Shandong, Peoples R China; [Liu, Qing; Zhang, Zhiwei] Shandong Univ, Shandong Prov Qianfoshan Hosp, Dept Obstet & Gynecol, Jinan, Shandong, Peoples R China; [Zhu, Dongchuan] First Peoples Hosp Jinan, Dept Urol, Jinan, Shandong, Peoples R China; [Hao, Baozhen] Shandong Matern & Child Hlth Care Hosp, Dept Gynecol, Jinan, Shandong, Peoples R China		Tian, YJ (corresponding author), Shandong Univ, Shandong Prov Hosp, Dept Obstet & Gynecol, Jinan, Shandong, Peoples R China.	tianyongjie@sdu.edu.cn			Key Research and Development Program of Shandong Province [2015GSF118140]; Natural Science Foundation of Shandong ProvinceNatural Science Foundation of Shandong Province [ZR2014HM108]	This work was supported by Key Research and Development Program of Shandong Province (2015GSF118140) and Natural Science Foundation of Shandong Province (ZR2014HM108).	Beck C, 2014, EXP CELL RES, V329, P18, DOI 10.1016/j.yexcr.2014.07.003; Booth LA, 2014, CELL SIGNAL, V26, P549, DOI 10.1016/j.cellsig.2013.11.028; Bravo-San Pedro JM, 2017, CIRC RES, V120, P1812, DOI 10.1161/CIRCRESAHA.117.311082; Chakrabarti M, 2016, APOPTOSIS, V21, P312, DOI 10.1007/s10495-015-1198-x; Deng L, 2017, ONCOL LETT, V13, P1370, DOI 10.3892/ol.2017.5597; Dia VP, 2017, J CELL PHYSIOL, V232, P391, DOI 10.1002/jcp.25436; Guo YF, 2017, ONCOTARGET, V8, P28481, DOI 10.18632/oncotarget.16092; Hou XY, 2015, MOL CELLS, V38, P396, DOI 10.14348/molcells.2015.2183; Ji YBA, 2010, CURR OPIN GENET DEV, V20, P512, DOI 10.1016/j.gde.2010.06.001; Kwon Do Youn, 2017, Obstet Gynecol Sci, V60, P115, DOI 10.5468/ogs.2017.60.1.115; Lluesma SM, 2016, BIOMEDICINES, V4, DOI 10.3390/biomedicines4020010; Lu DF, 2012, J AGR FOOD CHEM, V60, P8411, DOI 10.1021/jf3022817; Malyuchenko NV, 2015, ACTA NATURAE, V7, P27, DOI 10.32607/20758251-2015-7-3-27-37; Mangerich A, 2012, OXID MED CELL LONGEV, V2012, DOI 10.1155/2012/321653; Muller S., 2017, AUTOIMMUN REV, V29, P30139; Park SH, 2013, FOOD CHEM TOXICOL, V56, P100, DOI 10.1016/j.fct.2013.02.022; Peng MH, 2017, ANTIVIR RES, V143, P176, DOI 10.1016/j.antiviral.2017.03.026; Rouleau M, 2010, NAT REV CANCER, V10, P293, DOI 10.1038/nrc2812; Samuel P, 2016, EXPERT REV ANTICANC, V16, P57, DOI 10.1586/14737140.2016.1121107; Schiewer MJ, 2014, MOL CANCER RES, V12, P1069, DOI 10.1158/1541-7786.MCR-13-0672; Singh SS, 2014, CURR TOP MED CHEM, V14, P2020, DOI 10.2174/1568026614666140929152123; Sui XB, 2014, CANCER LETT, V344, P174, DOI 10.1016/j.canlet.2013.11.019; Tomao F, 2017, EXPERT OPIN PHARMACO, V18, P1443, DOI 10.1080/14656566.2017.1328055; Verdoodt F, 2017, MATURITAS, V100, P1, DOI 10.1016/j.maturitas.2017.03.001; Wang Q, 2017, CANCER CHEMOTH PHARM, V79, P1031, DOI 10.1007/s00280-017-3299-4; Yan MM, 2016, MOL MED REP, V14, P1986, DOI 10.3892/mmr.2016.5517	26	17	18	6	15	C M B  ASSOC	POITIERS	34 BOULEVARD SOLFERINO, 86000 POITIERS, FRANCE	0145-5680	1165-158X		CELL MOL BIOL	Cell. Mol. Biol.		2018	64	6					17	22		10.14715/cmb/2018.64.6.4			6	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	HD3SN	WOS:000452439600001	29808795	Bronze			2022-04-25	
J	Hu, M; Yu, ZM; Mei, PY; Li, JX; Luo, D; Zhang, HM; Zhou, MF; Liang, FX; Chen, R				Hu, Man; Yu, Zhaomin; Mei, Peiyuan; Li, Jinxiao; Luo, Dan; Zhang, Haiming; Zhou, Minfeng; Liang, Fengxia; Chen, Rui			Lycorine Induces autophagy-associated apoptosis by targeting MEK2 and enhances vemurafenib activity in colorectal cancer	AGING-US			English	Article						apoptosis; colorectal cancer; lycorine; vemurafenib	MAP KINASE; BRAF; MELANOMA; SURVIVAL; CELLS; COBIMETINIB; EVOLUTION; PROMOTES; PATHWAY; BCL-2	Lycorine is a powerful anti-cancer agent against various cancer cell lines with minor side effects. However, the detailed mechanisms of its effects in colorectal cancer (CRC) remain unclear. In this study, we investigated the function and mechanism of lycorine against CRC both in vitro and in vivo. Molecular docking modeling was used to identify potential inhibitory targets of lycorine in CRC. Cell viability was measured using the Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometry. Autophagosomes were examined using transmission electron microscopy and confocal microscopy. HCT116-derived xenografts were constructed to analyze the effect of lycorine in CRC in vivo. Using the CDOCKER algorithm, we determined that lycorine has four interactions with the conserved domain of mitogen-activated protein kinase kinase 2 (MEK2). This prediction was further confirmed by the degradation of phosphorylated MEK2 and its downstream targets after lycorine treatment, and MEK2 overexpression abolished lycorine-induced autophagy-associated apoptosis. Additionally, we revealed that the combination of vemurafenib and lycorine had better effects in CRC models in vitro and in vivo than monotherapy. Our findings identified lycorine as an effective MEK2 inhibitor and suggested that the combination of lycorine and vemurafenib could be used to treat CRC.	[Hu, Man; Yu, Zhaomin; Li, Jinxiao; Chen, Rui] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Integrated Tradit Chinese & Western Med, Wuhan, Peoples R China; [Mei, Peiyuan] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Thorac Surg, Wuhan, Peoples R China; [Luo, Dan] Wuhan First Hosp, Dept Resp Med, Wuhan, Peoples R China; [Zhang, Haiming] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Oncol,Integrated Tradit Chinese & Western Me, Wuhan, Peoples R China; [Zhou, Minfeng; Liang, Fengxia] Hubei Prov Hosp Tradit Chinese Med, Dept Acupuncture, Wuhan, Peoples R China		Chen, R (corresponding author), Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Integrated Tradit Chinese & Western Med, Wuhan, Peoples R China.	unioncr@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81774401, 81574065]	This work was supported by grants from the National Natural Science Foundation of China (81774401, 81574065).	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J	Maranhao, SS; Moura, AF; Oliveira, ACA; Lima, DJB; Barros-Nepomuceno, FWA; Paier, CRK; Pinheiro, AC; Nogueira, TCM; de Souza, MVN; Pessoa, C				Maranhao, Sarah Sant'Anna; Moura, Andrea Felinto; Aragao Oliveira, Augusto Cesar; Barbosa Lima, Daisy Jereissati; Araujo Barros-Nepomuceno, Francisco Washington; Koscky Paier, Carlos Roberto; Pinheiro, Alessandra Campbell; Mendonca Nogueira, Thais Cristina; Nora de Souza, Marcus Vinicius; Pessoa, Claudia			Synthesis of PJOV56, a new quinoxalinyl-hydrazone derivative able to induce autophagy and apoptosis in colorectal cancer cells, and related compounds	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS			English	Article						Quinoxalines; Cytotoxicity; HCT-116 cells; Cell cycle arrest	BIOLOGICAL EVALUATION; IN-VITRO; ANTIPROLIFERATIVE ACTIVITY; PHASE-I; INHIBITION; POTENT	Quinoxaline derivatives are reported as antineoplastic agents against a variety of human cancer cell lines, with some compounds being submitted to clinical trials. In this work, we report the synthesis, characterization and cytotoxicity potential of a new series of quinoxalinyl-hydrazones. The most cytotoxic compound was (E)-2-[2-(2-pyridin-2-ylmethylene)hydrazinyl] quinoxaline (PJOV56) that presented a time-dependent effect against HCT116 cells. After 48 h of incubation, PJOV56 was able to induce autophagy and apoptosis of HCT-116 cells, mediated by upregulation of Beclin 1, upregulation of LC3A/B II and activation of caspase 7. Apoptosis was induced along with G0/G1 cell cycle arrest at the highest concentration of PJOV56 (6.0 mu M). Thus, PJOV56 showed a dose-dependent mode of action related to induction of autophagy and apoptosis in HCT-116 cells.	[Maranhao, Sarah Sant'Anna; Moura, Andrea Felinto; Aragao Oliveira, Augusto Cesar; Barbosa Lima, Daisy Jereissati; Araujo Barros-Nepomuceno, Francisco Washington; Koscky Paier, Carlos Roberto; Pessoa, Claudia] Univ Fed Ceara, Ctr Res & Drug Dev, Lab Expt Oncol, Rua Coronel Nunes Melo 1000, BR-60430275 Fortaleza, Ceara, Brazil; [Araujo Barros-Nepomuceno, Francisco Washington] Univ Int Integrat Afro Brazilian Lusophony, Inst Hlth Sci, CE 060,Km 51, BR-62785000 Acarape, Ceara, Brazil; [Pinheiro, Alessandra Campbell; Mendonca Nogueira, Thais Cristina; Nora de Souza, Marcus Vinicius] Fundacao Oswaldo Cruz, Inst Technol Drugs Farmanguinhos, BR-21041250 Rio De Janeiro, RJ, Brazil; [Nora de Souza, Marcus Vinicius] Univ Fed Rio de Janeiro, Inst Chem, Dept Organ Chem, CP 68563, BR-21945970 Rio De Janeiro, RJ, Brazil		Pessoa, C (corresponding author), Univ Fed Ceara, Ctr Res & Drug Dev, Lab Expt Oncol, Rua Coronel Nunes Melo 1000, BR-60430275 Fortaleza, Ceara, Brazil.	cpessoa@ufc.br	pinheiro, alessandra/AAA-3523-2022; de Souza, Marcus/W-5002-2019; Barros-Nepomuceno, Francisco Washington Araujo/B-3111-2018; Koscky Paier, Carlos Roberto/M-9072-2017	Barros-Nepomuceno, Francisco Washington Araujo/0000-0001-9932-028X; Koscky Paier, Carlos Roberto/0000-0001-5255-4644; Pessoa, Claudia/0000-0002-4344-4336	CAPESCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); CNPqConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ); FAPERJFundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio De Janeiro (FAPERJ); FUNCAPFundacao Cearense de Apoio ao Desenvolvimento Cientifico e Tecnologico (FUNCAP); Fiocruz	We thank federal and state Brazilian research agencies CAPES, CNPq, FAPERJ and FUNCAP for funding. We also thank Fiocruz for funding and provisioning the necessary equipment and infrastructure for chemical synthesis and structural characterization of quinoxalinylhydrazones. The authors also thank the National Cancer Institute (Bethesda, MD, USA) for the donation of the tumor cell lines used in this study.	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Med. Chem. Lett.	JAN 15	2020	30	2							126851	10.1016/j.bmcl.2019.126851			8	Chemistry, Medicinal; Chemistry, Organic	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Pharmacology & Pharmacy; Chemistry	JZ1OE	WOS:000504873300051	31836446				2022-04-25	
J	Zhu, YY; Liu, WW; Chen, SG; Xu, FX; Zhang, LX; Hayashi, T; Mizuno, K; Hattori, S; Fujisaki, H; Ikejima, T				Zhu, Yingying; Liu, Weiwei; Chen, Shuaigao; Xu, Fanxing; Zhang, Luxin; Hayashi, Toshihiko; Mizuno, Kazunori; Hattori, Shunji; Fujisaki, Hitomi; Ikejima, Takashi			Collagen type 1 enhances cell growth and insulin biosynthesis in rat pancreatic cells	JOURNAL OF MOLECULAR ENDOCRINOLOGY			English	Article						type 1 diabetes mellitus; collagen I; IGF-1R; autophagy; beta-catenin	FACTOR-I; COLORECTAL-CANCER; AUTOPHAGY; MATRIX; PROLIFERATION; SECRETION; PATHWAY; SYSTEM; ISLETS	Type I collagen (collagen I) is the most abundant component of the extracellular matrix (ECM) in the pancreas. We previously reported that collagen I-coated culture dishes enhanced proliferation of rat pancreatic beta cell line, INS-1 cells, via up-regulation of beta-catenin nuclear translocation. In this study, we further investigated the effects of collagen I on insulin production of INS-1 cells. The results indicate that insulin synthesis as well as cell proliferation is increased in the INS-1 cells cultured on the dishes coated with collagen I. Up-regulation of insulin-like growth factor 1 receptor (IGF-1 R) on the INS-1 cells cultured on the collagen-coated dishes is involved in up-regulation of cell proliferation and increase of insulin biosynthesis; however, up-regulation of insulin secretion in the INS-1 cells on collagen I-coated dishes was further enhanced by inhibition of IGF-1R. Autophagy of INS-1 cells on collagen I-coated dishes was repressed via IGF-1R upregulation, and inhibition of a utophagy with 3MA further enhanced cell proliferation and insulin biosynthesis but did not affect insulin secretion. E-cadherin/beta-catenin adherent junction complexes are stabilized by autophagy. That is, autophagy negatively regulates the nuclear translocation of beta-catenin that leads to insulin biosynthesis and cell proliferation. In conclusion, IGF-1R/downregulation of autophagy/nuclear translocation of beta-catenin is involved in collagen I-induced INS-1 cell proliferation and insulin synthesis.	[Zhu, Yingying; Liu, Weiwei; Chen, Shuaigao; Xu, Fanxing; Zhang, Luxin; Hayashi, Toshihiko; Ikejima, Takashi] Shenyang Pharmaceut Univ, Wuya Coll Innovat, Shenyang, Liaoning, Peoples R China; [Hayashi, Toshihiko] Kogakuin Univ, Sch Adv Engn, Dept Chem & Life Sci, Tokyo, Japan; [Hayashi, Toshihiko; Mizuno, Kazunori; Hattori, Shunji; Fujisaki, Hitomi] Nippi Res Inst Biomatrix, Toride, Ibaraki, Japan; [Ikejima, Takashi] Key Lab Computat Chem Based Nat Antitumor Drug Re, Shenyang, Liaoning, Peoples R China		Ikejima, T (corresponding author), Shenyang Pharmaceut Univ, Wuya Coll Innovat, Shenyang, Liaoning, Peoples R China.; Ikejima, T (corresponding author), Key Lab Computat Chem Based Nat Antitumor Drug Re, Shenyang, Liaoning, Peoples R China.	ikejimat@vip.sina.com		Mizuno, Kazunori/0000-0003-3354-6264			Llacua LA, 2018, DIABETOLOGIA, V61, P1261, DOI 10.1007/s00125-017-4524-8; Aragona M, 2013, CELL, V154, P1047, DOI 10.1016/j.cell.2013.07.042; Baarsma HA, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0025450; 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Mol. Endocrinol.	OCT	2021	67	3					135	148		10.1530/JME-21-0032			14	Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Endocrinology & Metabolism	UN1DE	WOS:000693761100007	34370695				2022-04-25	
J	Zhu, ZL; Du, SS; Ding, FX; Guo, SS; Ying, GG; Yan, Z				Zhu, Zhongling; Du, Shuangshuang; Ding, Fengxia; Guo, Shanshan; Ying, Guoguang; Yan, Zhao			Ursolic acid attenuates temozolomide resistance in glioblastoma cells by downregulating O-6-methylguanine-DNA methyltransferase (MGMT) expression	AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH			English	Article						Ursolic acid; temozolomide; glioblastoma; O-6-methylguanine-DNA methyltransferase; senescence	COLORECTAL-CANCER CELLS; HIGH-GRADE GLIOMAS; MALIGNANT GLIOMA; OLEANOLIC ACID; PHASE-II; IN-VITRO; APOPTOSIS; AUTOPHAGY; PATHWAY; PROLIFERATION	The DNA-alkylating agent temozolomide (TMZ) is an effective chemotherapeutic agent against malignant glioma, including glioblastoma multiforme (GBM). However, the clinical efficacy of TMZ is limited in many patients because of O-6-methylguanine-DNA methyltransferase (MGMT)-driven resistance. Thus, new strategies to overcome TMZ resistance are urgently needed. Ursolic acid (UA) is a naturally derived pentacyclic triterpene acid that exerts broad anticancer effects, and shows capability to cross the blood-brain barrier. In this study, we evaluated the possible synergistic effect of TMZ and UA in resistant GBM cell lines. The results showed that UA prevented the proliferation of resistant GBM cells in a concentration-dependent manner. Compared with TMZ or UA treatment alone, the combination treatment of TMZ and UA synergistically enhanced cytotoxicity and senescence in TMZ-resistant GBM cells. This effect was correlated with the downregulation of MGMT. Moreover, experimental results with an in vivo mouse xenograft model showed that the combination treatment of UA and TMZ reduced tumor volumes by depleting MGMT. Therefore, UA as both a monotherapy and a resensitizer, might be a candidate agent for patients with refractory malignant gliomas.	[Zhu, Zhongling; Du, Shuangshuang; Ding, Fengxia; Guo, Shanshan; Yan, Zhao] Tianjin Med Univ Canc Inst & Hosp, Dept Clin Pharmacol, Tianjin 300060, Peoples R China; [Zhu, Zhongling; Du, Shuangshuang; Ding, Fengxia; Guo, Shanshan; Ying, Guoguang; Yan, Zhao] Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China; [Ying, Guoguang] Tianjin Med Univ Canc Inst & Hosp, Dept Tumor Cell Biol, Tianjin 300060, Peoples R China		Ying, GG; Yan, Z (corresponding author), Tianjin Med Univ Canc Inst & Hosp, Key Lab Canc Prevent & Therapy, Natl Clin Res Ctr Canc, Huan Hu Xi Rd, Tianjin 300060, Peoples R China.	yingguoguang163@163.com; yanzhaopaper@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81402481]; Tianjin Municipal Health Bureau fund [2014KZ085]; Doctoral Foundation of Tianjin Medical University Cancer Institute and Hospital [B1312]	This work was supported by grants from the National Natural Science Foundation of China (No. 81402481), Tianjin Municipal Health Bureau fund (No. 2014KZ085) and Doctoral Foundation of Tianjin Medical University Cancer Institute and Hospital (No. B1312).	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J. Transl. Res.		2016	8	7					3299	3308					10	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	DT7DM	WOS:000381647300044	27508051				2022-04-25	
J	El-Far, AH; Sroga, G; Al Jaouni, SK; Mousa, SA				El-Far, Ali H.; Sroga, Grazyna; Al Jaouni, Soad K.; Mousa, Shaker A.			Role and Mechanisms of RAGE-Ligand Complexes and RAGE-Inhibitors in Cancer Progression	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						RAGE-ligands; AGEs; HMGB1; S100s; RAGE-inhibitors; carcinogenesis	GLYCATION END-PRODUCTS; GROUP BOX 1; HUMAN NASOPHARYNGEAL CARCINOMA; PROMOTES CELL-PROLIFERATION; COLORECTAL-CANCER; EXTRACELLULAR S100A4; HEPATOCELLULAR-CARCINOMA; REGULATES AUTOPHAGY; MALIGNANT PHENOTYPE; CYTOPLASMIC DOMAIN	Interactions of the receptor for advanced glycation end product (RAGE) and its ligands in the context of their role in diabetes mellitus, inflammation, and carcinogenesis have been extensively investigated. This review focuses on the role of RAGE-ligands and anti-RAGE drugs capable of controlling cancer progression. Different studies have demonstrated interaction of RAGE with a diverse range of acidic (negatively charged) ligands such as advanced glycation end products (AGEs), high-mobility group box1 (HMGB1), and S100s, and their importance to cancer progression. Some RAGE-ligands displayed effects on anti- and pro-apoptotic proteins through upregulation of the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-kappa B) pathways, while downregulating p53 in cancer progression. In addition, RAGE may undergo ligand-driven multimodal dimerization or oligomerization mediated through self-association of some of its subunits. We conclude our review by proposing possible future lines of study that could result in control of cancer progression through RAGE inhibition.	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J. Mol. Sci.	MAY	2020	21	10								10.3390/ijms21103613			21	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	LW7GO	WOS:000539312100209	32443845	Green Published, gold			2022-04-25	
J	Lu, WC; Saha, A; Yan, WP; Garrison, K; Lamb, C; Pandey, R; Irani, S; Lodi, A; Lu, XY; Tiziani, S; Zhang, YJ; Georgiou, G; DiGiovanni, J; Stone, E				Lu, Wei-Cheng; Saha, Achinto; Yan, Wupeng; Garrison, Kendra; Lamb, Candice; Pandey, Renu; Irani, Seema; Lodi, Alessia; Lu, Xiyuan; Tiziani, Stefano; Zhang, Yan Jessie; Georgiou, George; DiGiovanni, John; Stone, Everett			Enzyme-mediated depletion of serum L-Met abrogates prostate cancer growth via multiple mechanisms without evidence of systemic toxicity	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA			English	Article						prostate cancer; L-methionine depletion; hMGL	DIETARY METHIONINE RESTRICTION; VIRUS 40-TRANSFORMED HUMAN; CYSTATHIONINE-GAMMA-LYASE; RECOMBINANT METHIONINASE; DNA METHYLTRANSFERASE; COLORECTAL-CANCER; CELL-CYCLE; IN-VITRO; INHIBITION; TUMORS	Extensive studies in prostate cancer and other malignancies have revealed that L-methionine (L-Met) and its metabolites play a critical role in tumorigenesis. Preclinical and clinical studies have demonstrated that systemic restriction of serum L-Met, either via partial dietary restriction or with bacterial L-Met-degrading enzymes exerts potent antitumor effects. However, administration of bacterial L-Met-degrading enzymes has not proven practical for human therapy because of problems with immunogenicity. As the human genome does not encode L-Met-degrading enzymes, we engineered the human cystathionine-gamma-lyase (hMGL-4.0) to catalyze the selective degradation of L-Met. At therapeutically relevant dosing, hMGL-4.0 reduces serum L-Met levels to >75% for >72 h and significantly inhibits the growth of multiple prostate cancer allografts/xenografts without weight loss or toxicity. We demonstrate that in vitro, hMGL-4.0 causes tumor cell death, associated with increased reactive oxygen species, S-adenosyl-methionine depletion, global hypomethylation, induction of autophagy, and robust poly(ADP-ribose) polymerase (PARP) cleavage indicative of DNA damage and apoptosis.	[Lu, Wei-Cheng; Garrison, Kendra; Lamb, Candice; Irani, Seema; Georgiou, George] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA; [Saha, Achinto; DiGiovanni, John] Univ Texas Austin, Div Pharmacol & Toxicol, Dell Pediat Res Inst, Austin, TX 78712 USA; [Yan, Wupeng; Zhang, Yan Jessie; Georgiou, George; Stone, Everett] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA; [Pandey, Renu; Lodi, Alessia; Lu, Xiyuan; Tiziani, Stefano] Univ Texas Austin, Dept Nutr Sci, Austin, TX 78712 USA; [Zhang, Yan Jessie; Georgiou, George] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA; [Georgiou, George; DiGiovanni, John; Stone, Everett] Univ Texas Dell Med Sch, Dept Oncol, LiveSTRONG Canc Inst, Austin, TX 78712 USA		Georgiou, G (corresponding author), Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.; DiGiovanni, J (corresponding author), Univ Texas Austin, Div Pharmacol & Toxicol, Dell Pediat Res Inst, Austin, TX 78712 USA.; Georgiou, G; Stone, E (corresponding author), Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA.; Georgiou, G (corresponding author), Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA.; Georgiou, G; DiGiovanni, J; Stone, E (corresponding author), Univ Texas Dell Med Sch, Dept Oncol, LiveSTRONG Canc Inst, Austin, TX 78712 USA.	gg@che.utexas.edu; john.digiovanni@austin.utexas.edu; stonesci@utexas.edu		Pandey, Renu/0000-0003-1892-2495	College of Natural Sciences at The University of Texas at Austin; Office of the Executive Vice President and Provost at The University of Texas at Austin; Institute for Cellular and Molecular Biology at The University of Texas at Austin; US Department of EnergyUnited States Department of Energy (DOE) [DE-AC02-06CH11357]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 GM104896, GM125882, CA154754, CA189623]; Cancer Prevention and Research Institute of Texas [RP180590]; Welch FoundationThe Welch Foundation [F-1778]	Instrumentation and technical assistance for this work were provided by the Macromolecular Crystallography Facility, with financial support from the College of Natural Sciences, the Office of the Executive Vice President and Provost, and the Institute for Cellular and Molecular Biology at The University of Texas at Austin. We acknowledge the support of the Advanced Light Source and the Advanced Photon Source (operated for the US Department of Energy Office of Science by Argonne National Laboratory and supported by the US Department of Energy under Contract DE-AC02-06CH11357) for X-ray crystallographic data collection. This work was supported by grants funded by the National Institutes of Health R01 GM104896 and GM125882 (to Y.J.Z.), CA154754 (to G.G. and E.S.), and CA189623 (to J.D., G.G., and E.S.); the Cancer Prevention and Research Institute of Texas RP180590 (to E.S. and J.D.); and the Welch Foundation F-1778 (to Y.J.Z.).	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Natl. Acad. Sci. U. S. A.	JUN 9	2020	117	23					13000	13011		10.1073/pnas.1917362117			12	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	MG3PN	WOS:000545946100009	32434918	hybrid, Green Submitted, Green Published			2022-04-25	
J	Pileczki, V; Pop, L; Braicu, C; Budisan, L; Morar, GB; Monroig-Bosque, PD; Sandulescu, RV; Berindan-Neagoe, I				Pileczki, Valentina; Pop, Laura; Braicu, Cornelia; Budisan, Livia; Morar, Gabriela Bolba; Monroig-Bosque, Paloma del C.; Sandulescu, Robert V.; Berindan-Neagoe, Ioana			Double gene siRNA knockdown of mutant p53 and TNF induces apoptosis in triple-negative breast cancer cells	ONCOTARGETS AND THERAPY			English	Article						apoptosis; double gene silencing; mut-p53; TNF; TNBC	NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; COLORECTAL-CANCER; TRAIL; THERAPY; INFLAMMATION; COMBINATION; ACTIVATION; EXPRESSION; RECEPTOR	Apoptosis is the major downregulated pathway in cancer. Simultaneous inhibition using specific small interfering RNA (siRNA) of two key player genes, p53 and TNF, is an interesting and feasible strategy when it comes to investigating various molecular pathways and biological processes in triple-negative breast cancer (TNBC), which is one of the most aggressive and therapeutically unresponsive forms of breast cancers. Our present research focuses on evaluating the impact of double p53-siRNA and TNF-siRNA knockdown at a cellular level, and also evaluating cell proliferation, apoptosis, induction of autophagy, and gene expression by using reverse transcription polymerase chain reaction array approaches. Simultaneous inhibition of p53 and TNF in Hs578T TNBC human cell line revealed a panel of up-and downregulated genes involved in apoptosis. Furthermore, the effects of double gene knockdown were validated in a second TNBC cell line, MDA-MB-231, by using reverse transcription polymerase chain reaction TaqMan assay. All our findings help in understanding the functional mechanisms of extrinsic apoptosis, cell signaling pathways, and the mechanisms involved in tumor cell survival, growth, and death in TNBC.	[Pileczki, Valentina; Pop, Laura; Braicu, Cornelia; Budisan, Livia; Berindan-Neagoe, Ioana] Iuliu Hatieganu Univ Med & Pharm, Res Ctr Funct Genom Biomed & Translat Med, 23 Gh Marinescu St, Cluj Napoca 400337, Romania; [Pileczki, Valentina; Sandulescu, Robert V.] Iuliu Hatieganu Univ Med & Pharm, Dept Analyt Chem, Fac Pharm, Cluj Napoca, Romania; [Morar, Gabriela Bolba] Oncol Inst Prof Dr Ion Chiricuta, Dept Senol, Cluj Napoca, Romania; [Monroig-Bosque, Paloma del C.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA; [Berindan-Neagoe, Ioana] Iuliu Hatieganu Univ Med & Pharm, MedFuture Res Ctr Adv Med, Cluj Napoca, Romania; [Berindan-Neagoe, Ioana] Oncol Inst Prof Dr Ion Chiricuta, Dept Funct Genom & Expt Pathol, Cluj Napoca, Romania		Berindan-Neagoe, I (corresponding author), Iuliu Hatieganu Univ Med & Pharm, Res Ctr Funct Genom Biomed & Translat Med, 23 Gh Marinescu St, Cluj Napoca 400337, Romania.	ioananeagoe29@gmail.com	Săndulescu, Robert/C-4953-2011; Berindan-Neagoe, Ioana/AAH-9854-2019; Pop, Laura/AAY-8349-2020; Pileczki, Valentina/ABB-6273-2020	Pop, Laura/0000-0002-5806-0220; 	"Iuliu Hatieganu" University of Medicine and Pharmacy, The Research Center for Functional Genomics, Biomedicine and Translational Medicine, Cluj-Napoca, Romania [1492/4/28.01.2014]; POSCCE [709/2010]	Valentina Pileczki's work was partially financed by "Iuliu Hatieganu" University of Medicine and Pharmacy, The Research Center for Functional Genomics, Biomedicine and Translational Medicine, Cluj-Napoca, Romania, internal grant no: 1492/4/28.01.2014.; This work was financed by the POSCCE 709/2010 grant with the title, "Clinical and economical impact of proteom and transcriptom molecular profiling in neoadjuvant therapy of triple negative breast cancer (BREASTIMPACT)".	Al-Lazikani B, 2012, NAT BIOTECHNOL, V30, P679, DOI 10.1038/nbt.2284; Alkim C, 2009, DIGEST DIS SCI, V54, P1979, DOI 10.1007/s10620-008-0554-x; Anders C, 2008, ONCOLOGY-NY, V22, P1233; Arnedos M, 2012, THER ADV MED ONCOL, V4, P195, DOI 10.1177/1758834012444711; Braicu C, 2013, MOL CELL BIOCHEM, V381, P61, DOI 10.1007/s11010-013-1688-5; Buchsbaum DJ, 2003, CLIN CANCER RES, V9, P3731; Cai W, 2008, BIOCHEM INSIGHTS, V1, P5; Choi J, 2007, J KOREAN MED SCI, V22, pS17, DOI 10.3346/jkms.2007.22.S.S17; Cooks T, 2014, MOL CELL, V56, P611, DOI 10.1016/j.molcel.2014.11.018; Cooks T, 2013, CANCER CELL, V23, P634, DOI 10.1016/j.ccr.2013.03.022; Di Minin G, 2014, MOL CELL, V56, P617, DOI 10.1016/j.molcel.2014.10.013; Fakhr E, 2016, CANCER GENE THER, V23, P73, DOI 10.1038/cgt.2016.4; Fox JL, 2015, CANCER RES, V75, P1345, DOI 10.1158/0008-5472.CAN-14-1340; Fu QS, 2016, MOL CELL, V61, P602, DOI 10.1016/j.molcel.2016.01.009; Garimella SV, 2014, BREAST CANCER RES, V16, DOI 10.1186/bcr3645; Green DR, 2015, CSH PERSPECT BIOL, V7, DOI 10.1101/cshperspect.a006080; Hellwig CT, 2012, MOL CANCER THER, V11, P3, DOI 10.1158/1535-7163.MCT-11-0434; Keane MM, 2000, BREAST CANCER RES TR, V64, P211, DOI 10.1023/A:1006458407515; Lacroix M, 2006, ENDOCR-RELAT CANCER, V13, P293, DOI 10.1677/erc.1.01172; Lamy L, 2013, CANCER CELL, V23, P435, DOI 10.1016/j.ccr.2013.02.017; Li HH, 2015, SCI REP-UK, V5, DOI 10.1038/srep10244; Mitsuhashi J, 2005, PATHOL INT, V55, P113, DOI 10.1111/j.1440-1827.2005.01802.x; Ozbayer C, 2015, INFLAMM RES, V64, P775, DOI 10.1007/s00011-015-0859-0; Pal SK, 2011, BREAST CANCER RES TR, V125, P627, DOI 10.1007/s10549-010-1293-1; Pastor DM, 2010, DIS COLON RECTUM, V53, P257, DOI 10.1007/DCR.0b013e3181c522c7; Peddi PF, 2012, INT J BREAST CANCER, V2012, DOI 10.1155/2012/217185; Pileczki V, 2013, INT J MOL SCI, V14, P411, DOI 10.3390/ijms14010411; Rahman M, 2009, ADV CANCER RES, V103, P43, DOI 10.1016/S0065-230X(09)03003-6; Rahman M, 2009, BREAST CANCER RES TR, V113, P217, DOI 10.1007/s10549-008-9924-5; Ramachandran PV, 2012, ASIAN PAC J CANCER P, V13, P2445, DOI 10.7314/APJCP.2012.13.6.2445; Schneider G, 2010, ONCOGENE, V29, P2795, DOI 10.1038/onc.2010.46; Tatsumi Y, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2014.568; Varfolomeev E, 2016, CYTOKINE; Walczak H, 1999, NAT MED, V5, P157, DOI 10.1038/5517; Wang YD, 2016, ONCOL LETT, V11, P984, DOI 10.3892/ol.2015.4003; Weisz L, 2007, CANCER RES, V67, P2396, DOI 10.1158/0008-5472.CAN-06-2425; Yerbes R, 2011, CLIN TRANSL ONCOL, V13, P839, DOI 10.1007/s12094-011-0744-4; Yu MX, 2013, CANCER RES, V73, P4061, DOI 10.1158/0008-5472.CAN-12-3946; Yu ZR, 2012, J MAMMARY GLAND BIOL, V17, P59, DOI 10.1007/s10911-012-9246-4	39	7	7	0	9	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2016	9						6921	6933		10.2147/OTT.S110719			13	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	EB7ZJ	WOS:000387610000001	27956838	gold, Green Published, Green Submitted			2022-04-25	
J	Yang, ZL; Ghoorun, RA; Fan, XJ; Wu, PH; Bai, Y; Li, JZ; Chen, H; Wang, L; Wang, JP				Yang, Zuli; Ghoorun, Roshan Ara; Fan, Xinjuan; Wu, Peihuang; Bai, Yang; Li, Jizheng; Chen, Hao; Wang, Lei; Wang, Jianping			High expression of Beclin-1 predicts favorable prognosis for patients with colorectal cancer	CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY			English	Article							AUTOPHAGY; PANITUMUMAB; EFFICACY; PROTEIN; GROWTH; GENE; KRAS	Purpose: Beclin-1 is an autophagy gene. It promotes the formation of the autophagic vesicle as well as plays an essential role in guarding the cells against chromosomal instability. Overexpression of Beclin-1 has been reported to predict a favorable survival in various cancers. However, little is known about its prognostic significance in colorectal cancer. Methods and materials: A total of three hundred and sixty-three (363) colorectal tissues from colorectal cancer (CRC) patients were collected. Tissue micro-arrays and immunohistochemistry were used to investigate the expression and prognostic significance of Beclin-1 in CRC. The associations among Beclin-1 expression, clinicopathological parameters and prognosis were evaluated. Results: Bectin-1 had a higher expression in CRC tissues than in normal tissues. A high expression of Beclin-1 was positively correlated with gender (P=0.027), histological grade (P=0.003), pM status (P=0.003) and clinical stage (P=0.024). Patients with a high Beclin-1 expression, when compared to those with a lower expression had both a better overall survival (OS, P=0.006) and disease-free survival (DFS. P=0.008). In the pT3 subgroup, Beclin-1 was also found to be a good prognostic indicator (P < 0.05). Multivariate analysis showed a high expression of Bectin-1 was indeed a positive independent prognostic factor of OS and DES for CRC patients (P < 0.05). Conclusion: Our results demonstrated that a high expression of Beaclin-1 correlated with a better overall survival and disease-free survival, thus serving as a favorable independent prognostic marker in CRC. (C) 2014 Elsevier Masson SAS. All rights reserved.	[Yang, Zuli; Ghoorun, Roshan Ara; Bai, Yang; Li, Jizheng; Chen, Hao] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Gastrointestinal Surg, Guangdong Gastrointestinal & Anal Hosp, Guangzhou 510655, Guangdong, Peoples R China; [Fan, Xinjuan; Wu, Peihuang] Sun Yat Sen Univ, Gastrointestinal Inst, Guangzhou 510655, Guangdong, Peoples R China; [Wang, Lei; Wang, Jianping] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colon & Rectum Surg, Guangdong Gastrointestinal & Anal Hosp, Guangzhou 510655, Guangdong, Peoples R China		Wang, JP (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colon & Rectum Surg, Guangdong Gastrointestinal & Anal Hosp, 26 Yuancun Erheng Rd, Guangzhou 510655, Guangdong, Peoples R China.	wangjply01@sohu.com			Natural Science Fund Committee of Guangdong Province, China [10251008901000008]	This study was supported by the grant from Natural Science Fund Committee of Guangdong Province, China (No. 10251008901000008).	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Res. Hepatol. Gastroenterol.	FEB	2015	39	1					98	106		10.1016/j.clinre.2014.06.014			9	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	CB3SV	WOS:000349549800014	25130795				2022-04-25	
J	Li, LD; Sun, HF; Liu, XX; Gao, SP; Jiang, HL; Hu, X; Jin, W				Li, Liang-Dong; Sun, He-Fen; Liu, Xue-Xiao; Gao, Shui-Ping; Jiang, Hong-Lin; Hu, Xin; Jin, Wei			Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism	PLOS ONE			English	Article							EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL-CANCER; COMPLEX-I; TARGET; GENES; TUMORIGENESIS; ACTIVATION; AUTOPHAGY; MOTILITY; PATHWAY	Despite advances in basic and clinical research, metastasis remains the leading cause of death in breast cancer patients. Genetic abnormalities in mitochondria, including mutations affecting complex I and oxidative phosphorylation, are found in breast cancers and might facilitate metastasis. Genes encoding complex I components have significant breast cancer prognostic value. In this study, we used quantitative proteomic analyses to compare a highly metastatic cancer cell line and a parental breast cancer cell line; and observed that NDUFB9, an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I), was down-regulated in highly metastatic breast cancer cells. Furthermore, we demonstrated that loss of NDUFB9 promotes MDA-MB-231 cells proliferation, migration, and invasion because of elevated levels of mtROS, disturbance of the NAD(+)/NADH balance, and depletion of mtDNA. We also showed that, the Akt/mTOR/p70S6K signaling pathway and EMT might be involved in this mechanism. Thus, our findings contribute novel data to support the hypothesis that misregulation of mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, suggesting that complex I deficiency is a potential and important biomarker for further basic research or clinical application.	[Li, Liang-Dong; Sun, He-Fen; Gao, Shui-Ping; Jiang, Hong-Lin; Hu, Xin; Jin, Wei] Fudan Univ, Shanghai Canc Ctr, Dept Breast Surg, Key Lab Breast Canc Shanghai, Shanghai 200030, Peoples R China; [Li, Liang-Dong; Sun, He-Fen; Gao, Shui-Ping; Jiang, Hong-Lin; Jin, Wei] Fudan Univ, Dept Oncol, Shanghai Med Coll, Shanghai 200030, Peoples R China; [Liu, Xue-Xiao] Lishui Cent Hosp, Dept Radiotherapy, Lishui 323000, Zhejiang, Peoples R China		Jin, W (corresponding author), Fudan Univ, Shanghai Canc Ctr, Dept Breast Surg, Key Lab Breast Canc Shanghai, Shanghai 200030, Peoples R China.	weijin7207@126.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272923]; Program for New Century Excellent Talents in UniversityProgram for New Century Excellent Talents in University (NCET) [NCET-12-0127]	This work was supported by National Natural Science Foundation of China (81272923), Program for New Century Excellent Talents in University (NCET-12-0127) http://www.nsfc.gov.cn/publish/portal1/. 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	Zhou, Y; Sha, ZH; Yang, Y; Wu, SM; Chen, H				Zhou, Yun; Sha, Zhenghong; Yang, Yong; Wu, Shuimei; Chen, Hong			lncRNA NEAT1 regulates gastric carcinoma cell proliferation, invasion and apoptosis via the miR-500a-3p/XBP-1 axis	MOLECULAR MEDICINE REPORTS			English	Article						long non-coding RNA nuclear paraspeckle assembly transcript 1; microRNA-500A; X-box binding protein-1; proliferation; invasion; apoptosis	ENDOPLASMIC-RETICULUM STRESS; CANCER STATISTICS; EXPRESSION; IRE1-ALPHA/XBP-1; CLASSIFICATION; ACTIVATION; PROGNOSIS; XBP-1	Gastric cancer is a serious malignant tumor. Despite progression in gastric cancer research in recent years, the specific molecular mechanism underlying the pathogenesis of the disease is not completely understood. Long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) affects the proliferation and metastasis of multiple types of tumor cells in colorectal cancer and breast cancer but its specific role in gastric cancer requires further investigation. The aim of the present study was to analyze the role of NEAT1 in gastric cancer. The expression of endoplasmic reticulum stress marker proteins and apoptosis-related proteins in gastric cancer tissue and cell lines was analyzed using western blotting. The targeting relationship of NEAT1 and miR-500a-3p was analyzed using dual-luciferase reporter assay. Cell proliferation was analyzed using CCK8 assay and colony formation assay while cell invasion was detected using Transwell assay. Cell apoptosis was analyzed using TUNEL staining and LC3 expression through immunofluorescent staining (IF). The results showed that lncRNA NEAT1-overexpression gastric cancer cells were established to determine its effects on cell proliferation, invasion, apoptosis, autophagy and endoplasmic reticulum stress. Subsequently, microRNA (miR)-500a was overexpressed in lncRNA NEAT1-overexpression cells. Compared with the vector group, lncRNA NEAT1 overexpression significantly inhibited gastric cancer cell proliferation and invasion, but significantly promoted cell apoptosis. Furthermore, the results indicated that lncRNA NEAT1 targeted and downregulated the expression of miR-500a-3p, and miR-500a-3p targeted X-box binding protein-1 (XBP-1) mRNA. lncRNA NEAT1 overexpression-mediated inhibition of gastric cancer cell proliferation and invasion was significantly reversed by miR-500a-3p overexpression. Furthermore, compared with the vector group, the expression levels of endoplasmic reticulum stress-related proteins (XBP-1S/XBP-1U ratio and 78-kDa glucose-regulated protein) and apoptosis-related proteins (Bax and cleaved-caspase-3) were significantly upregulated by lncRNA NEAT1 overexpression; however, miR-500a-3p overexpression reversed lncRNA NEAT1 overexpression-mediated effects on protein expression. The present study demonstrated that lncRNA NEAT1 inhibited gastric cancer cell proliferation and invasion, and promoted apoptosis by regulating the miR-500a-3p/XBP-1 axis.	[Zhou, Yun; Chen, Hong] Southeast Univ, Med Coll, Zhongda Hosp, Dept Gastroenterol, 87 Dingjiaqiao Rd, Nanjing 210000, Jiangsu, Peoples R China; [Sha, Zhenghong] Wuhu 1 Peoples Hosp, Dept Gen Surg, Wuhu 241000, Anhui, Peoples R China; [Yang, Yong; Wu, Shuimei] Wuhu 1 Peoples Hosp, Dept Gastroenterol, Wuhu 241000, Anhui, Peoples R China		Chen, H (corresponding author), Southeast Univ, Med Coll, Zhongda Hosp, Dept Gastroenterol, 87 Dingjiaqiao Rd, Nanjing 210000, Jiangsu, Peoples R China.	zkw201912@126.com					Bao LL, 2018, CELL PHYSIOL BIOCHEM, V47, P2046, DOI 10.1159/000491472; Barez SR, 2020, J CELL COMMUN SIGNAL, V14, P403, DOI 10.1007/s12079-020-00562-7; Bertuccio P, 2009, INT J CANCER, V125, P666, DOI 10.1002/ijc.24290; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Chern YJ, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-1687-x; Cubillos-Ruiz JR, 2017, CELL, V168, P692, DOI 10.1016/j.cell.2016.12.004; Davies MPA, 2008, INT J CANCER, V123, P85, DOI 10.1002/ijc.23479; Ding Li-Hua, 2004, Acta Genetica Sinica, V31, P380; Duplan E, 2013, J CELL SCI, V126, P2124, DOI 10.1242/jcs.127340; Guo YT, 2017, BIOMED PHARMACOTHER, V91, P13, DOI 10.1016/j.biopha.2017.04.018; Hsu HT, 2018, CLIN CHIM ACTA, V479, P66, DOI 10.1016/j.cca.2018.01.001; Hsu SK, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20102518; Hu H, 2019, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.03083; Kopp F, 2018, CELL, V172, P393, DOI 10.1016/j.cell.2018.01.011; Larsen AC, 2016, ACTA OPHTHALMOL, V94, P1, DOI 10.1111/aos.13100; Li JH, 2014, NUCLEIC ACIDS RES, V42, pD92, DOI 10.1093/nar/gkt1248; Li RT, 2017, CANCER LETT, V386, P123, DOI 10.1016/j.canlet.2016.10.032; Liao XH, 2018, NEOPLASMA, V65, P673, DOI 10.4149/neo_2018_170516N355; Liu ZY, 2018, MOL MED REP, V18, P2689, DOI 10.3892/mmr.2018.9259; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Lopez J, 2015, BRIT J CANCER, V112, P957, DOI 10.1038/bjc.2015.85; Mohamed E, 2017, CANCER IMMUNOL IMMUN, V66, P1069, DOI 10.1007/s00262-017-2019-6; Mowers EE, 2018, FEBS J, V285, P1751, DOI 10.1111/febs.14388; Oakes SA, 2015, ANNU REV PATHOL-MECH, V10, P173, DOI 10.1146/annurev-pathol-012513-104649; Rona KA, 2017, J SURG ONCOL, V115, P371, DOI 10.1002/jso.24533; Saito Y, 2019, NATURE, V569, P275, DOI 10.1038/s41586-019-1126-2; Sepulveda D, 2018, RHEUMATOLOGY, V57, P1021, DOI 10.1093/rheumatology/key021; Siegel R, 2013, CA-CANCER J CLIN, V63, P11, DOI 10.3322/caac.21166; Torre LA, 2015, CA-CANCER J CLIN, V65, P87, DOI 10.3322/caac.21262; Travis WD, 2013, J CLIN ONCOL, V31, P992, DOI 10.1200/JCO.2012.46.9270; Urra H, 2016, TRENDS CANCER, V2, P252, DOI 10.1016/j.trecan.2016.03.007; Wang M, 2013, EUR J CANCER, V49, P2010, DOI 10.1016/j.ejca.2012.12.017; Yu HG, 2008, INT J CANCER, V122, P433, DOI 10.1002/ijc.23049; Zhang L, 2015, ONCOTARGET, V6, P2483, DOI 10.18632/oncotarget.2800; Zhang M, 2018, J HEMATOL ONCOL, V11, DOI 10.1186/s13045-018-0656-7; Zhao YF, 2017, BIOSCIENCE REP, V37, DOI 10.1042/BSR20170837; Zhu XM, 2012, INT J BIOCHEM CELL B, V44, P1097, DOI 10.1016/j.biocel.2012.03.018	37	1	1	3	5	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1791-2997	1791-3004		MOL MED REP	Mol. Med. Rep.	JUL	2021	24	1							503	10.3892/mmr.2021.12142			10	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	SF2DS	WOS:000652572300001	33982777	hybrid, Green Published			2022-04-25	
J	Quintana, M; Bilbao, A; Comas-Barcelo, J; Bujons, J; Triola, G				Quintana, Mireia; Bilbao, Ana; Comas-Barcelo, Julia; Bujons, Jordi; Triola, Gemma			Identification of benzo[cd]indol-2(1H)-ones as novel Atg4B inhibitors via a structure-based virtual screening and a novel AlphaScreen assay	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						Atg4B; LC3; Autophagy; AlphaScreen	CYSTEINE PROTEASE ENZYME; PARTICLE MESH EWALD; CRYSTAL-STRUCTURE; ACCURATE DOCKING; SMALL MOLECULES; CANCER-CELLS; AUTOPHAGY; DISCOVERY; DESIGN; GLIDE	Targeting autophagy is a promising therapeutic strategy for cancer treatment. As a result, the identification of novel autophagy inhibitors is an emerging field of research. Herein, we report the development of a novel AlphaScreen HTS assay that combined with a MS-based assay and a structure-based high-throughput virtual screening have enabled the identification of benzo[cd]indol-2(1H)-one as a novel scaffold that targets Atg4B. Thus, an initial screening campaign led to the identification of NSC126353 and NSC611216 bearing a chlorohydrin moiety. Structural-activity relationship analysis of the initial hits provided an optimized lead, compound 33, bearing a 7-aminobenzo[cd]indol-2-[1H]-one scaffold and a propyl group replacing the chlorine. Inhibition of autophagy was also investigated in cells by measuring LC3-II and p62 protein levels. Moreover, the synergistic effect of 33 combined with oxaliplatin resulted in an enhanced cell death in the human colorectal adenocarcinoma cell line HT-29. We are convinced that the developed AlphaScreen and MS-based assays can be key tools enabling the high-throughput identification of novel Atg4B inhibitors. Moreover, the aminobenzo[cd]indol-2-[1H]-one scaffold represents a novel chemotype for the further development of small molecule inhibitors of Atg4B. (C) 2019 Elsevier Masson SAS. All rights reserved.	[Quintana, Mireia; Bilbao, Ana; Comas-Barcelo, Julia; Bujons, Jordi; Triola, Gemma] IQAC CSIC, Dept Biol Chem, Inst Adv Chem Catalonia, Barcelona, Spain		Triola, G (corresponding author), IQAC CSIC, Dept Biol Chem, Inst Adv Chem Catalonia, Barcelona, Spain.	gemma.triola@iqac.csic.es	Triola, Gemma/E-2235-2017; Quintana, Mireia/AAD-6864-2020; Bujons, Jordi/AAA-9283-2020	Triola, Gemma/0000-0003-4177-8989; Bujons, Jordi/0000-0003-2944-2905	Ministerio de Economia and CompetitividadSpanish Government [CTQ2013-44334-P]; FPI fellowshipSpanish Government [BES-2014-070026]	We would like to thank Karel Hernandez and Roman Bonet for his support in the expression and purification of recombinant proteins and Kristina Lang for her help in the preparation of N-(His)<INF>6</INF>-LC3B-L123C. We are grateful to the Ministerio de Economia and Competitividad for supporting this work with a research grant CTQ2013-44334-P) and FPI fellowship to A.B.G (BES-2014-070026).	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J	He, LW; Han, JJ; Li, BW; Huang, L; Ma, K; Chen, Q; Liu, XZ; Bao, L; Liu, HW				He, Luwei; Han, Junjie; Li, Baowei; Huang, Li; Ma, Ke; Chen, Quan; Liu, Xinzhong; Bao, Li; Liu, Hongwei			Identification of a new cyathane diterpene that induces mitochondrial and autophagy-dependent apoptosis and shows a potent in vivo anti-colorectal cancer activity	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						Fungal diterpene; Cyathin Q; Apoptosis; Autophagy; ATG5 cleavage; ROS	BAX-INDEPENDENT APOPTOSIS; DRUG-RESISTANCE; CELL-DEATH; BCL-2; FAMILY; ATG5; P53; INHIBITION; ALCOHOLS	Diterpenes has been reported to possess multiple bioactivities consisting of anti-microbial and anti-inflammatory properties. This study reveals a new cyathane-type diterpene (cyathin Q) from the culture of the fungus Cyathus africanus by bioactivity-guided separation. The structure of cyathin Q was determined based on spectroscopic measurements (NMR and MS). The bioactivity evaluation shows that cyathin Q has a strong anticancer activity against HCT116 cells and Bax-deficient HCT116 in vitro and in vivo. This compound induced hallmarks of apoptotic events in HCT116 cells, including caspase activation, cytochrome c release, poly (ADP-ribose) polymerase (PARP) cleavage, and depolarization of the mitochondrial inner transmembrane potential. This process is accompanied with the increased mitochondrial ROS, down-regulation of Bcl-2 protein, and up-regulation of Bim protein. We also observed the cleavage of autophagy-related protein ATG5 in cyathin Q-induced apoptosis. Taken together, our study identified a new fungal diterpene that exhibited anticancer activity via induction of mitochondria and autophagy-dependent apoptosis in HCT116 cells. (C) 2016 Elsevier Masson SAS. All rights reserved.	[He, Luwei; Han, Junjie; Ma, Ke; Liu, Xinzhong; Bao, Li; Liu, Hongwei] Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China; [Li, Baowei; Huang, Li; Chen, Quan] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China		Liu, HW (corresponding author), Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China.	liuhw@im.ac.cn	Liu, Xingzhong/B-6280-2015	Liu, Xingzhong/0000-0002-3224-8604; Ma, Ke/0000-0002-9716-6968	National Nature Science FoundationNational Natural Science Foundation of China (NSFC) [21472233]; Ministry of Science and Technology of ChinaMinistry of Science and Technology, China [2014CB138304]	Financial supports of the National Nature Science Foundation (21472233) and the Ministry of Science and Technology of China (2014CB138304) are acknowledged. Dr. Jinwei Ren (State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences) is appreciated for their help in measuring the NMR data. We also thank Mrs. Jing Wang (State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences) for operating the flow cytometer.	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J. Med. Chem.	MAR 23	2016	111						183	192		10.1016/j.ejmech.2016.01.056			10	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED); Index Chemicus (IC)	Pharmacology & Pharmacy	DG1PY	WOS:000371841200015	26871659				2022-04-25	
J	Cao, HX; Miao, CF; Sang, LN; Huang, YM; Zhang, R; Sun, L; Jiang, ZX				Cao, Hai-xia; Miao, Chao-feng; Sang, Li-na; Huang, Yu-min; Zhang, Ran; Sun, Ling; Jiang, Zhong-xing			Circ_0009910 promotes imatinib resistance through ULK1-induced autophagy by sponging miR-34a-5p in chronic myeloid leukemia	LIFE SCIENCES			English	Article						CML; Circ_0009910; MiR-34a-5p; Autophagy; ULK1	BREAST-CANCER CELLS; COLORECTAL-CANCER; PROLIFERATION; METASTASIS; SENSITIVITY; ACTIVATION; APOPTOSIS; THERAPY; TARGET; GROWTH	Background: The occurrence in drug resistance of chronic myeloid leukemia (CML) was accompanied by autophagy activation. Abnormal circular RNAs (circRNAs) participated in this progression. This study attempted to investigate the potential role of circ_0009910 in imatinib resistance of CML cells. Methods: The expression of circ_0009910 and miR-34a-5p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The characterization of circ_0009910 was investigated using oligo (dT)18 primers, Actinomycin D and RNase R. Cell viability (IC50 value) and apoptosis were assessed by Cell Counting Kit-8 (CCK8) assay and flow cytometry assay, respectively. The relative protein expression was quantified by western blot. The relationship among miR-34a-5p, circ_0009910 and ULK1 was predicted by online bioinformatics tool, and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Results: The expression of circ_0009910 was up-regulated in the serum of imatinib-resistance CML patients and K562/R cells, and associated with unfavorable clinicopathologic features. Circ_0009910 in K562 and K562/R cells was mainly localized in the cytoplasm. Circ_0009910 knockdown inhibited cell proliferation and autophagy, but induced apoptosis in K562/R cells. Circ_0009910 targeted miR-34a-5p to regulate ULK1. MiR-34a-5p depression rescued the effects of circ_0009910 knockdown on apoptosis and autophagy in K562/R cells. Conclusion: Circ_0009910 accelerated imatinib-resistance in CML cells by modulating ULK1-induced autophagy via targeting miR-34a-5p, providing a potential target in imatinib resistance of CML.	[Cao, Hai-xia; Sang, Li-na; Huang, Yu-min; Zhang, Ran; Sun, Ling; Jiang, Zhong-xing] Zhengzhou Univ, Dept Hematol, Affiliated Hosp 1, 1 Jianshedong Rd, Zhengzhou 450052, Henan, Peoples R China; [Miao, Chao-feng] Zhengzhou Univ, Dept Vasc Surg, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China		Jiang, ZX (corresponding author), Zhengzhou Univ, Dept Hematol, Affiliated Hosp 1, 1 Jianshedong Rd, Zhengzhou 450052, Henan, Peoples R China.	liangwei16037@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81800104]	This work was approved by National Natural Science Foundation of China (81800104).	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FEB 15	2020	243								117255	10.1016/j.lfs.2020.117255			9	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	KK8OR	WOS:000512996200014	31923418				2022-04-25	
J	Li, GW; Chen, T; Zhu, YX; Xiao, XY; Bu, JY; Huang, ZW				Li, Guowei; Chen, Tao; Zhu, Yingxian; Xiao, Xiaoyu; Bu, Juyuan; Huang, Zongwen			MiR-103 alleviates autophagy and apoptosis by regulating SOX2 in LPS-injured PC12 cells and SCI rats	IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES			English	Article						Apoptosis; Autophagy; MAPK/ERK and JAK/STAT -pathway; MiR-103; SOX2; Spinal cord injury	SPINAL-CORD-INJURY; NEURAL STEM-CELLS; SIGNALING PATHWAYS; COLORECTAL-CANCER; PANCREATIC-CANCER; MICRORNAS; EXPRESSION; KINASE; ROLES; STAT3	Objective(s): Recent studies revealed that microRNAs (miRNAs) may play crucial roles in the responses and pathologic processes of spinal cord injury (SCI). This study aimed to investigate the effect and the molecular basis of miR-103 on LPS-induced injuries in PC12 cells in vitro and SCI rats in vivo. Materials and Methods: PC12 cells were exposed to LPS to induce cell injuries to mimic the in vitro model of SCI. The expression of miR-103 and SOX2 in PC12 cells were altered by transient transfections. Cell viability and apoptotic cell rate were measured by CCK-8 assay and flow cytometry assay. Furthermore, Western blot analysis was performed to detect the expression levels of apoptosis-and autophagy-related proteins, MAPK/ERK pathway- and JAK/STAT pathway-related proteins. In addition, we also assessed the effect of miR-103 agomir on SCI rats. Results: LPS exposure induced cell injuries in PC12 cells. miR-103 overexpression significantly increased cell viability, reduced cell apoptosis and autophagy, and opposite results were observed in miR-103 inhibition. miR-103 attenuated LPS-induced injuries by indirect upregulation of SOX2. SOX2 overexpression protected PC12 cells against LPS-induced injuries, while SOX2 inhibition expedited LPS-induced cell injuries. Furthermore, miR-103 overexpression inhibited MAPK/ERK pathway and JAK/STAT pathway through upregulation of SOX2. We also found that miR-103 agomir inhibited cell apoptosis and autophagy in SCI rats. Conclusion: This study demonstrates that miR-103 may represent a protective effect against cell apoptosis and autophagy in LPS-injured PC12 cells and SCI rats by upregulation of SOX2 expression.	[Li, Guowei; Chen, Tao; Huang, Zongwen] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Spine Surg, Zhuhai 519000, Guangdong, Peoples R China; [Zhu, Yingxian; Xiao, Xiaoyu] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Anaesthesiol, Zhuhai 519000, Guangdong, Peoples R China; [Bu, Juyuan] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Gastroenterol Surg, Zhuhai 519000, Guangdong, Peoples R China		Huang, ZW (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 5, Dept Spine Surg, Zhuhai 519000, Guangdong, Peoples R China.	zwhuang0031@126.com			Zhuhai Science and Technology Program [20161027E030050, 20171009E030027]	This work was supported by Zhuhai Science and Technology Program (No. 20161027E030050 and 20171009E030027).	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J	Menconi, A; Marzo, T; Massai, L; Pratesi, A; Severi, M; Petroni, G; Antonuzzo, L; Messori, L; Pillozzi, S; Cirri, D				Menconi, Alessio; Marzo, Tiziano; Massai, Lara; Pratesi, Alessandro; Severi, Mirko; Petroni, Giulia; Antonuzzo, Lorenzo; Messori, Luigi; Pillozzi, Serena; Cirri, Damiano			Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA-PEG nanoparticles	BIOMETALS			English	Article						PLGA&#8211; PEG nanoparticles; Auranofin; Anticancer complexes; Colorectal cancer		Chloro(triethylphosphine)gold(I), (Et3PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et3PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et3PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et3PAuCl was encapsulated in biocompatible PLGA-PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et3PAuCl (nano-Et3PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et3PAuCl, was clearly documented. The implications of these findings are discussed.	[Menconi, Alessio; Petroni, Giulia; Pillozzi, Serena] Univ Florence, Dept Expt & Clin Med, Viale GB Morgagni 50, I-50134 Florence, Italy; [Marzo, Tiziano] Univ Pisa, Dept Pharm, Via Bonanno Pisano 6, I-56126 Pisa, Italy; [Massai, Lara; Severi, Mirko; Messori, Luigi] Univ Florence, Dept Chem Schiff, Lab Met Med MetMed, Via Lastruccia 3, I-50019 Sesto Fiorentino, Italy; [Pratesi, Alessandro; Cirri, Damiano] Univ Pisa, Dept Chem & Ind Chem DCCI, Via G Moruzzi 13, I-56124 Pisa, Italy; [Antonuzzo, Lorenzo] Azienda Osped Univ Careggi, SC Oncol Med 1, Florence, Italy; [Pillozzi, Serena] DIVAL Toscana SRL, Via Madonna del Piano 6, I-50019 Sesto Fiorentino, Italy		Pillozzi, S (corresponding author), Univ Florence, Dept Expt & Clin Med, Viale GB Morgagni 50, I-50134 Florence, Italy.; Marzo, T (corresponding author), Univ Pisa, Dept Pharm, Via Bonanno Pisano 6, I-56126 Pisa, Italy.; Cirri, D (corresponding author), Univ Pisa, Dept Chem & Ind Chem DCCI, Via G Moruzzi 13, I-56124 Pisa, Italy.	tiziano.marzo@unipi.it; serena.pillozzi@unifi.it; damiano.cirri@dcci.unipi.it	Pratesi, Alessandro/AAB-4169-2019; Severi, Mirko/J-2508-2012	Pratesi, Alessandro/0000-0002-9553-9943; Severi, Mirko/0000-0003-1511-6762; MARZO, TIZIANO/0000-0002-2567-3637; messori, luigi/0000-0002-9490-8014; Antonuzzo, Lorenzo/0000-0003-3349-5604; MASSAI, LARA/0000-0003-0765-1802	AIRC (Associazione Italiana per la Ricerca sul Cancro)Fondazione AIRC per la ricerca sul cancro [22294, 23852]; AIRC (Associazione Italiana per la Ricerca sul Cancro)Fondazione AIRC per la ricerca sul cancro; ECRF (Ente Cassa di Risparmio di Firenze) [AIRCECRF19650]; Beneficentia Stiftung (Vaduz) [BEN2019/48, BEN2020/34]; University of Pisa under the ``PRA-Progetti di Ricerca di Ateneo'' Institutional Research Grants [PRA_2020_58]	D.C. gratefully acknowledges AIRC (Associazione Italiana per la Ricerca sul Cancro) for the financial support (one-year Fellowship for Italy-Project Code: 22294 and 2-year fellowship for Italy-Project Code: 23852). L.M. and A.P. gratefully acknowledge AIRC (Associazione Italiana per la Ricerca sul Cancro) and ECRF (Ente Cassa di Risparmio di Firenze) for the financial support (AIRCECRF19650). Authors thank CSGI (Department of Chemistry, University of Florence) for DLS experiments. T.M. and A.P. thank University of Pisa (Rating Ateneo 2019 and 2020). T.M. and A.P. thank Beneficentia Stiftung (Vaduz) for supporting projects BEN2019/48 and BEN2020/34, respectively. This work is also supported by the University of Pisa under the ``PRA-Progetti di Ricerca di Ateneo'' Institutional Research Grants-Project no. PRA_2020_58 ``Agenti innovative e nanosistemi per target molecolari nell'ambito dell'oncologia di precisione'' to TM.	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J	Zhang, XQ; Zhao, H				Zhang, Xueqin; Zhao, Hu			Deoxyelephantopin Suppresses Invasion and Migration of Colorectal Cancer Cells Through Matrix Metalloproteinase-13	INTERNATIONAL JOURNAL OF PHARMACOLOGY			English	Article						Deoxyelephantopin; colorectal cancer cells; proliferation; metastasis; matrix metalloproteinase-13	ELEPHANTOPUS-SCABER; OSTEOSARCOMA CELLS; IN-VITRO; METASTASIS; APOPTOSIS; EXPRESSION; GROWTH; MMP13; AUTOPHAGY; PATHWAYS	Background and Objective: Deoxyelephantopin (DET), the major constituent of Elephantopus scaber, has been shown to have anti-inflammatory effect in vitro. However, there is no direct evidence that DET can inhibit colorectal cancer cells migration and invasion. The anticancer activity of DET was evaluated by a MTT assay. Materials and Methods: Cell apoptosis were detected by Annexin V/PI staining. Cell invasion and transwell migration assays were used to observe the effect of DET on cells invasion and migration. Results: In the present study, data showed that DET treatment reduced colorectal cancer (CRC) cells migration and invasion and DET treatment decreased the protein levels of matrix metalloproteinase-13 (MMP-13). This is the first paper suggested DET-reduced MMP-13 expression can inhibit CRC invasion and migration. Conclusion: Therefore, the present study provides evidence that the DET reduced MMP-13 expression, leading to decrease the migration and invasion of CRC cells. This study provides a mechanistic insight into the inhibiting CRC functions of DET.	[Zhang, Xueqin; Zhao, Hu] First Peoples Hosp Qujing, Dept Gastroenterol, Qujing, Yunnan, Peoples R China		Zhang, XQ (corresponding author), First Peoples Hosp Qujing, Dept Gastroenterol, Qujing, Yunnan, Peoples R China.						Al Bandar MH, 2017, ONCOL REP, V37, P2553, DOI 10.3892/or.2017.5531; Bersini S, 2014, DRUG DISCOV TODAY, V19, P735, DOI 10.1016/j.drudis.2013.12.006; Chan CK, 2016, MOLECULES, V21, DOI 10.3390/molecules21030385; Chen N, 2017, ONCOTARGET, V8, P32356, DOI 10.18632/oncotarget.16020; Chen RX, 2014, INT J CLIN EXP PATHO, V7, P2527; Deng BY, 2015, CELL PHYSIOL BIOCHEM, V37, P2434, DOI 10.1159/000438596; Fan L, 2015, MOL MED REP, V11, P705, DOI 10.3892/mmr.2014.2728; Farha AK, 2015, NAT PROD RES, V29, P2341, DOI 10.1080/14786419.2015.1012165; Farha AK, 2014, CELL BIOL TOXICOL, V30, P331, DOI 10.1007/s10565-014-9288-z; Huang CC, 2010, BRIT J PHARMACOL, V159, P856, DOI 10.1111/j.1476-5381.2009.00581.x; Huang RH, 2017, CELL PHYSIOL BIOCHEM, V41, P1851, DOI 10.1159/000471933; Jin D, 2015, ONCOTARGET, V6, P33523, DOI 10.18632/oncotarget.5590; Leake Isobel, 2013, Nat Rev Gastroenterol Hepatol, V10, P260, DOI 10.1038/nrgastro.2013.58; Li Y, 2013, GASTROENTEROLOGY, V144, P179, DOI 10.1053/j.gastro.2012.09.042; Liu WJ, 2016, MOL MED REP, V13, P4221, DOI 10.3892/mmr.2016.5086; Mehmood T, 2017, MOLECULES, V22, DOI 10.3390/molecules22061013; Moss LAS, 2012, AM J PATHOL, V181, P1895, DOI 10.1016/j.ajpath.2012.08.044; Nian JY, 2017, CLIN TRANSL GASTROEN, V8, DOI 10.1038/ctg.2016.66; Ou BC, 2016, ONCOTARGET, V7, P47637, DOI 10.18632/oncotarget.10256; Shiau JY, 2017, ONCOTARGET, V8, P56942, DOI 10.18632/oncotarget.18183; Su MX, 2011, BIOCHEM BIOPH RES CO, V411, P342, DOI 10.1016/j.bbrc.2011.06.144; Tan MY, 2013, CELL PHYSIOL BIOCHEM, V32, P542, DOI 10.1159/000354458; Vermeer NCA, 2017, CANCER TREAT REV, V54, P87, DOI 10.1016/j.ctrv.2017.02.002; Wei W, 2016, CELL PHYSIOL BIOCHEM, V39, P1165, DOI 10.1159/000447823; Wu MH, 2012, J CELL PHYSIOL, V227, P3016, DOI 10.1002/jcp.23043; Xu LY, 2015, CELL PHYSIOL BIOCHEM, V36, P509, DOI 10.1159/000430116; Yang B, 2012, SCAND J CLIN LAB INV, V72, P501, DOI 10.3109/00365513.2012.699638; Zhang NN, 2016, CELL PHYSIOL BIOCHEM, V40, P1559, DOI 10.1159/000453206; Zhu GW, 2016, CELL PHYSIOL BIOCHEM, V39, P1665, DOI 10.1159/000447868; Zou JL, 2017, CELL PHYSIOL BIOCHEM, V42, P1812, DOI 10.1159/000479537	30	1	1	0	1	ASIAN NETWORK SCIENTIFIC INFORMATION-ANSINET	FAISALABAD	308-LASANI TOWN, SARGODHA RD, FAISALABAD, 38090, PAKISTAN	1811-7775	1812-5700		INT J PHARMACOL	Int. J. Pharmacol.		2018	14	6					751	757		10.3923/ijp.2018.751.757			7	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	GN3LW	WOS:000438908200001					2022-04-25	
J	Han, YD; Tan, Y; Zhao, YY; Zhang, YC; He, XJ; Yu, L; Jiang, HP; Lu, HJ; Tian, HY				Han, Yudong; Tan, Ye; Zhao, Yuanyuan; Zhang, Yongchun; He, Xinjia; Yu, Li; Jiang, Haiping; Lu, Haijun; Tian, Haiying			TRIM23 overexpression is a poor prognostic factor and contributes to carcinogenesis in colorectal cancer	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						cell cycle; colorectal cancer; P53; proliferation; TRIM23	PROTEINS; P53; AUTOPHAGY	The tripartite motif (TRIM) family proteins play a great role in carcinogenesis. However, the expression pattern, prognostic value and biological functions of tripartite motif containing 23 (TRIM23) in colorectal cancer (CRC) are poorly understood. Here, we found that TRIM23 is up-regulated and associated with tumour size, lymph node metastasis, American Joint Committee on Cancer (AJCC) stage and poor prognosis in CRC. Multivariate Cox regression analyses revealed that TRIM23 overexpression could be identified as an independent prognostic factor for CRC. TRIM23 could promote the proliferation of CRC cell in vitro and in vivo; additionally, TRIM23 depletion induced G1-phase arrest. Gene set enrichment analysis (GSEA) revealed that P53 and cell cycle signalling pathway-related genes were enriched in patients with high TRIM23 expression levels. We show in this study that TRIM23 physically binds to P53 and enhances the ubiquitination of P53, thereby promoting tumour proliferation. Thus, our data indicated that TRIM23 acts as an oncogene in colorectal carcinogenesis and may provide a novel therapeutic target for CRC management.	[Han, Yudong] Qingdao Univ, Dept Thorac Surg, Affiliated Hosp, Qingdao, Peoples R China; [Tan, Ye; Zhao, Yuanyuan; Zhang, Yongchun; He, Xinjia; Yu, Li; Jiang, Haiping; Lu, Haijun; Tian, Haiying] Qingdao Univ, Dept Radiat Oncol, Affiliated Hosp, 16 Jiangsu Rd, Qingdao 266000, Peoples R China		Lu, HJ; Tian, HY (corresponding author), Qingdao Univ, Dept Radiat Oncol, Affiliated Hosp, 16 Jiangsu Rd, Qingdao 266000, Peoples R China.	lhj82920608@163.com; tianhaiying123@126.com					Allton K, 2009, P NATL ACAD SCI USA, V106, P11612, DOI 10.1073/pnas.0813177106; Arnold M, 2017, GUT, V66, P683, DOI 10.1136/gutjnl-2015-310912; Bao CY, 2015, SCI SIGNAL, V8, DOI 10.1126/scisignal.aaa8441; Bhatnagar S, 2014, NATURE, V516, P116, DOI 10.1038/nature13955; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Brenner H, 2014, LANCET, V383, P1490, DOI 10.1016/S0140-6736(13)61649-9; Cambiaghi V, 2012, ADV EXP MED BIOL, V770, P77; Crawford LJ, 2018, J CELL COMMUN SIGNAL, V12, P21, DOI 10.1007/s12079-017-0423-5; Eymin B, 2010, CELL ADHES MIGR, V4, P114, DOI 10.4161/cam.4.1.10977; Gushchina LV, 2018, PHARMACOL THERAPEUT, V185, P12, DOI 10.1016/j.pharmthera.2017.10.020; Han YD, 2017, ONCOTARGET, V8, P22730, DOI 10.18632/oncotarget.15188; Hatakeyama S, 2017, TRENDS BIOCHEM SCI, V42, P297, DOI 10.1016/j.tibs.2017.01.002; Hatakeyama S, 2011, NAT REV CANCER, V11, P792, DOI 10.1038/nrc3139; Liang Q, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1143-x; Micale L, 2012, ADV EXP MED BIOL, V770, P11; Reymond A, 2001, EMBO J, V20, P2140, DOI 10.1093/emboj/20.9.2140; Seton-Rogers S, 2015, NAT REV CANCER, V15, P318, DOI 10.1038/nrc3962; Siegel RL, 2017, CA-CANCER J CLIN, V67, P177, DOI 10.3322/caac.21395; Sparrer KMJ, 2017, NAT MICROBIOL, V2, P1543, DOI 10.1038/s41564-017-0017-2; Subramanian A, 2005, P NATL ACAD SCI USA, V102, P15545, DOI 10.1073/pnas.0506580102; Takayama K, 2018, ONCOGENE, V37, P2165, DOI 10.1038/s41388-017-0095-x; Valletti A, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20071776; Venuto S, 2019, CELLS-BASEL, V8, DOI 10.3390/cells8050510; Vieler M, 2018, CANCERS, V10, DOI 10.3390/cancers10090288; Vunjak M, 2019, CURR BIOL, V29, pR42, DOI 10.1016/j.cub.2018.11.026; Watanabe M, 2017, J BIOCHEM, V161, P135, DOI 10.1093/jb/mvw087; Watanabe M, 2015, ELIFE, V4, DOI 10.7554/eLife.05615; Wei WS, 2018, CANCER LETT, V435, P10, DOI 10.1016/j.canlet.2018.07.036; Yao YY, 2018, PATHOL RES PRACT, V214, P2062, DOI 10.1016/j.prp.2018.10.010; Yuan ZG, 2010, MOL CELL BIOL, V30, P3004, DOI 10.1128/MCB.01023-09; Zhang P, 2015, ONCOGENE, V34, P5729, DOI 10.1038/onc.2015.21; Zhang XQ, 2016, EUR J GYNAECOL ONCOL, V37, P30; Zhang Y, 2018, INT J ONCOL, V53, P620, DOI 10.3892/ijo.2018.4408; Zhou ZC, 2014, GASTROENTEROLOGY, V147, P1043, DOI 10.1053/j.gastro.2014.07.021	34	13	13	2	6	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	1582-1838	1582-4934		J CELL MOL MED	J. Cell. Mol. Med.	MAY	2020	24	10					5491	5500		10.1111/jcmm.15203		MAR 2020	10	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	LL3FK	WOS:000522311200001	32227572	gold, Green Published			2022-04-25	
J	Maniam, S; Maniam, S				Maniam, Subashani; Maniam, Sandra			Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						programmed cell death; apoptosis; autophagy; breast cancer; small molecule	TYROSINE KINASE INHIBITOR; LEUCINE-ZIPPER KINASE; 2 HUMAN HOMOLOGS; DNA-REPAIR; IN-VITRO; SURVIVIN SUPPRESSANT; GOLD NANOPARTICLES; OXIDATIVE STRESS; WILD-TYPE; AUTOPHAGY	Targeted chemotherapy has become the forefront for cancer treatment in recent years. The selective and specific features allow more effective treatment with reduced side effects. Most targeted therapies, which include small molecules, act on specific molecular targets that are altered in tumour cells, mainly in cancers such as breast, lung, colorectal, lymphoma and leukaemia. With the recent exponential progress in drug development, programmed cell death, which includes apoptosis and autophagy, has become a promising therapeutic target. The research in identifying effective small molecules that target compensatory mechanisms in tumour cells alleviates the emergence of drug resistance. Due to the heterogenous nature of breast cancer, various attempts were made to overcome chemoresistance. Amongst breast cancers, triple negative breast cancer (TNBC) is of particular interest due to its heterogeneous nature in response to chemotherapy. TNBC represents approximately 15% of all breast tumours, however, and still has a poor prognosis. Unlike other breast tumours, signature targets lack for TNBCs, causing high morbidity and mortality. This review highlights several small molecules with promising preclinical data that target autophagy and apoptosis to induce cell death in TNBC cells.	[Maniam, Subashani] RMIT Univ, Sch Sci, STEM Coll, Melbourne, Vic 3001, Australia; [Maniam, Sandra] Univ Putra Malaysia, Dept Human Anat, Fac Med & Hlth Sci, Serdang 43400, Malaysia		Maniam, S (corresponding author), RMIT Univ, Sch Sci, STEM Coll, Melbourne, Vic 3001, Australia.; Maniam, S (corresponding author), Univ Putra Malaysia, Dept Human Anat, Fac Med & Hlth Sci, Serdang 43400, Malaysia.	subashani.maniam@rmit.edu.au; sandra@upm.edu.my	Maniam, Subashani/AAB-4651-2020	Maniam, Subashani/0000-0002-0272-864X; Maniam, Sandra/0000-0001-5335-6666	Universiti Putra Malaysia [GP/2018/9616500]; RMIT ECDF scheme	This research was funded by RMIT ECDF scheme and Universiti Putra Malaysia, grant number GP/2018/9616500.	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J. Mol. Sci.	SEP	2021	22	18							9722	10.3390/ijms22189722			34	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	UV9ZP	WOS:000699827900001	34575883	Green Published, gold			2022-04-25	
J	Zhong, Y; Long, T; Gu, CS; Tang, JY; Gao, LF; Zhu, JX; Hu, ZY; Wang, X; Ma, YD; Ding, YQ; Li, ZG; Wang, XY				Zhong, Yan; Long, Ting; Gu, Chuan-Sha; Tang, Jing-Yi; Gao, Ling-Fang; Zhu, Jia-Xian; Hu, Zhi-Yan; Wang, Xia; Ma, Yi-Dan; Ding, Yan-Qing; Li, Zu-Guo; Wang, Xiao-Yan			MYH9-dependent polarization of ATG9B promotes colorectal cancer metastasis by accelerating focal adhesion assembly	CELL DEATH AND DIFFERENTIATION			English	Article							AUTOPHAGY; MEMBRANE	Tumour metastasis is a major reason accounting for the poor prognosis of colorectal cancer (CRC), and the discovery of targets in the primary tumours that can predict the risk of CRC metastasis is now urgently needed. In this study, we identified autophagy-related protein 9B (ATG9B) as a key potential target gene for CRC metastasis. High expression of ATG9B in tumour significantly increased the risk of metastasis and poor prognosis of CRC. Mechanistically, we further find that ATG9B promoted CRC invasion mainly through autophagy-independent manner. MYH9 is the pivotal interacting protein for ATG9B functioning, which directly binds to cytoplasmic peptide segments aa368-411 of ATG9B by its head domain. Furthermore, the combination of ATG9B and MYH9 enhance the stability of each other by decreasing their binding to E3 ubiquitin ligase STUB1, therefore preventing them from ubiquitin-mediated degradation, which further amplified the effect of ATG9B and MYH9 in CRC cells. During CRC cell invasion, ATG9B is transported to the cell edge with the assistance of MYH9 and accelerates focal adhesion (FA) assembly through mediating the interaction of endocytosed integrin beta 1 and Talin-1, which facilitated to integrin beta 1 activation. Clinically, upregulated expression of ATG9B in human CRC tissue is always accompanied with highly elevated expression of MYH9 and associated with advanced CRC stage and poor prognosis. Taken together, this study highlighted the important role of ATG9B in CRC metastasis by promoting focal adhesion assembly, and ATG9B together with MYH9 can provide a pair of potential therapeutic targets for preventing CRC progression.	[Zhong, Yan; Long, Ting; Gao, Ling-Fang; Zhu, Jia-Xian; Li, Zu-Guo] Southern Med Univ, Shenzhen Hosp, Dept Pathol, Shenzhen, Guangdong, Peoples R China; [Zhong, Yan; Gu, Chuan-Sha; Tang, Jing-Yi; Gao, Ling-Fang; Zhu, Jia-Xian; Hu, Zhi-Yan; Wang, Xia; Ma, Yi-Dan; Ding, Yan-Qing; Wang, Xiao-Yan] Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou, Guangdong, Peoples R China; [Gu, Chuan-Sha; Tang, Jing-Yi; Hu, Zhi-Yan; Wang, Xia; Ma, Yi-Dan; Ding, Yan-Qing; Li, Zu-Guo; Wang, Xiao-Yan] Key Lab Mol Tumour Pathol Guangdong Prov, Guangzhou, Guangdong, Peoples R China; [Hu, Zhi-Yan; Ding, Yan-Qing; Wang, Xiao-Yan] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou, Guangdong, Peoples R China		Li, ZG; Wang, XY (corresponding author), Southern Med Univ, Shenzhen Hosp, Dept Pathol, Shenzhen, Guangdong, Peoples R China.; Ding, YQ; Wang, XY (corresponding author), Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou, Guangdong, Peoples R China.; Ding, YQ; Li, ZG; Wang, XY (corresponding author), Key Lab Mol Tumour Pathol Guangdong Prov, Guangzhou, Guangdong, Peoples R China.; Ding, YQ; Wang, XY (corresponding author), Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou, Guangdong, Peoples R China.	dyqgz@126.com; lizg@smu.edu.cn; wangxiaoyan639@163.com		Li, Zuguo/0000-0001-9229-1973	National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81201664, 81672437, 81974441]	This research was partly supported by grants from the National Natural Science Foundation of China (NSFC) (Nos. 81201664, 81672437, 81974441).	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DEC	2021	28	12					3251	3269		10.1038/s41418-021-00813-z		JUN 2021	19	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	XE9TM	WOS:000661843600002	34131310	Green Published, hybrid			2022-04-25	
J	Lin, XT; Zheng, XB; Fan, DJ; Yao, QQ; Hu, JC; Lian, L; Wu, XJ; Lan, P; He, XS				Lin, Xu-tao; Zheng, Xiao-bin; Fan, De-jun; Yao, Qiu-qiong; Hu, Jian-cong; Lian, Lei; Wu, Xiao-jian; Lan, Ping; He, Xiao-sheng			MicroRNA-143 Targets ATG2B to Inhibit Autophagy and Increase Inflammatory Responses in Crohn's Disease	INFLAMMATORY BOWEL DISEASES			English	Article						autophagy; ATG2B; miR-143; Crohn's disease; inflammatory responses	GENOME-WIDE ASSOCIATION; TANDEM 3' UTRS; FACTOR-KAPPA-B; ALTERNATIVE POLYADENYLATION; SUSCEPTIBILITY LOCI; COLORECTAL-CANCER; ESCHERICHIA-COLI; EPITHELIAL-CELLS; DENDRITIC CELLS; BOWEL-DISEASE	Background: Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including Crohn's disease (CD). Genetic analyses have found that microRNA (miRNA) levels are altered in the intestinal tissues of CD patients. Methods: The Sequencing Alternative Poly-Adenylation Sites (SAPAS) method was used to compare the 3' end of the total mRNA sequence of 3 surgical specimens of CD patients (including inflamed tissues and corresponding noninflamed tissues in each case). The levels of autophagy-related 2B (ATG2B), LC3, and miR-143 were compared between inflamed tissues and noninflamed tissues using immunoblot and quantitative reverse transcription polymerase chain reaction. Luciferase assays were used to verify the interactions between miR-143 and ATG2B. Autophagy was measured by immunoblot analyses of LC3 and transmission electron microscopy. Inflammatory cytokines and I kappa B alpha were analyzed to evaluate the effect of miR-143 on inflammatory response. Results: The tandem repeat 3'-UTR of ATG2B was longer in inflamed tissues than in corresponding noninflamed tissues and contained an miR-143 target site. miR-143 expression was elevated, whereas ATG2B and LC3-II were downregulated in inflamed tissues. The direct interaction between miR-143 and ATG2B was verified by a 3'-UTR dual-luciferase reporter assay. Constitutive expression of miR-143 or depletion of ATG2B in cultured intestinal epithelial cells inhibited autophagy, reduced I kappa B alpha levels, and increased inflammatory responses. Conclusions: miR-143 may induce bowel inflammation by regulating ATG2B and autophagy, suggesting that miR-143 might play a critical role in the development of CD. Therefore, miR-143 could be a promising novel target for gene therapy in CD patients.	[Lin, Xu-tao; Fan, De-jun] Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Inst Gastroenterol, Dept Gastrointestinal Endoscopy, Guangzhou, Guangdong, Peoples R China; [Lin, Xu-tao; Zheng, Xiao-bin; Fan, De-jun; Yao, Qiu-qiong; Hu, Jian-cong; Lian, Lei; Wu, Xiao-jian; Lan, Ping; He, Xiao-sheng] Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Inst Gastroenterol, Dept Colorectal Surg, Guangzhou, Guangdong, Peoples R China; [Lin, Xu-tao; Zheng, Xiao-bin; Fan, De-jun; Yao, Qiu-qiong; Hu, Jian-cong; Lian, Lei; Wu, Xiao-jian; Lan, Ping; He, Xiao-sheng] Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Inst Gastroenterol, Guangdong Prov Key Lab Colorectal & Pelv Floor Di, Guangzhou, Guangdong, Peoples R China		Wu, XJ; Lan, P; He, XS (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 6, 26 Yuancun Erheng Rd, Guangzhou 510655, Guangdong, Peoples R China.	sumswxj@126.com; sumslp@163.com; hexsheng@mail.sysu.edu.cn					Arroyo DS, 2014, INT IMMUNOPHARMACOL, V18, P55, DOI 10.1016/j.intimp.2013.11.001; Awan MUF, 2014, APPL MICROBIOL BIOT, V98, P5319, DOI 10.1007/s00253-014-5721-8; Barrett JC, 2008, NAT GENET, V40, P955, DOI 10.1038/ng.175; Brain O, 2013, IMMUNITY, V39, P521, DOI 10.1016/j.immuni.2013.08.035; Brest P, 2011, NAT GENET, V43, P242, DOI 10.1038/ng.762; Cadwell K, 2010, GASTROENTEROLOGY, V139, P1448, DOI 10.1053/j.gastro.2010.09.023; Chen Y, 2013, BIOCHEM BIOPH RES CO, V438, P133, DOI 10.1016/j.bbrc.2013.07.040; Cooney R, 2010, NAT MED, V16, P90, DOI 10.1038/nm.2069; Denton D, 2015, IMMUNOL CELL BIOL, V93, P35, DOI 10.1038/icb.2014.85; Di Giammartino DC, 2011, MOL CELL, V43, P853, DOI 10.1016/j.molcel.2011.08.017; El-Khider F, 2016, DIGEST DIS, V34, P27, DOI 10.1159/000442921; Elliott TR, 2015, J GASTROEN HEPATOL, V30, P1265, DOI 10.1111/jgh.12955; Fasseu M, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0013160; Fu YG, 2011, GENOME RES, V21, P741, DOI 10.1101/gr.115295.110; Fujishima Y, 2011, ARCH BIOCHEM BIOPHYS, V506, P223, DOI 10.1016/j.abb.2010.12.009; Ghorpade DS, 2013, J BIOL CHEM, V288, P33037, DOI 10.1074/jbc.M113.492496; Ghosh S, 2002, CELL, V109, pS81, DOI 10.1016/S0092-8674(02)00703-1; Hale AN, 2013, AUTOPHAGY, V9, P951, DOI 10.4161/auto.24273; Hampe J, 2007, NAT GENET, V39, P207, DOI 10.1038/ng1954; Nguyen HTT, 2014, GASTROENTEROLOGY, V146, P508, DOI 10.1053/j.gastro.2013.10.021; He L, 2005, NATURE, V435, P828, DOI 10.1038/nature03552; Hollenbach E, 2005, J BIOL CHEM, V280, P14981, DOI 10.1074/jbc.M500966200; Holtta V, 2008, INFLAMM BOWEL DIS, V14, P1175, DOI 10.1002/ibd.20475; Homer CR, 2010, GASTROENTEROLOGY, V139, P1630, DOI 10.1053/j.gastro.2010.07.006; Jiang PD, 2014, CELL RES, V24, P69, DOI 10.1038/cr.2013.161; Jones SA, 2013, IMMUNOL CELL BIOL, V91, P250, DOI 10.1038/icb.2012.82; Liu CD, 2015, INFLAMM BOWEL DIS, V21, P1918, DOI 10.1097/MIB.0000000000000439; Lu CM, 2014, GASTROENTEROLOGY, V146, P188, DOI 10.1053/j.gastro.2013.09.006; Massey DCO, 2007, AUTOPHAGY, V3, P649, DOI 10.4161/auto.5075; Mizushima N, 2010, CELL, V140, P313, DOI 10.1016/j.cell.2010.01.028; Mukhopadhyay S, 2014, APOPTOSIS, V19, P555, DOI 10.1007/s10495-014-0967-2; O'Donnell KA, 2005, NATURE, V435, P839, DOI 10.1038/nature03677; Plantinga TS, 2011, GUT, V60, P1229, DOI 10.1136/gut.2010.228908; Rioux JD, 2007, NAT GENET, V39, P596, DOI 10.1038/ng2032; Sadabad MS, 2015, GUT, V64, P1546, DOI 10.1136/gutjnl-2014-307289; Salem M, 2015, CLIN TRANSL GASTROEN, V6, DOI 10.1038/ctg.2015.47; Sato K, 2007, CANCER RES, V67, P9677, DOI 10.1158/0008-5472.CAN-07-1462; Strober W, 2011, MUCOSAL IMMUNOL, V4, P484, DOI 10.1038/mi.2011.29; Sun MZ, 2014, MOL MED REP, V9, P1597, DOI 10.3892/mmr.2014.2003; Sun Y, 2012, J MOL CELL BIOL, V4, P352, DOI 10.1093/jmcb/mjs041; Tian B, 2005, NUCLEIC ACIDS RES, V33, P201, DOI 10.1093/nar/gki158; Tian P, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0048997; Torres J, 2017, LANCET, V389, P1741, DOI 10.1016/S0140-6736(16)31711-1; Warner N, 2014, J BIOL CHEM, V289, P28213, DOI 10.1074/jbc.M114.574756; Xi C, 2016, INFLAMM RES, V65, P325, DOI 10.1007/s00011-016-0919-0; Yu C, 2011, FITOTERAPIA, V82, P709, DOI 10.1016/j.fitote.2011.02.011; Yuan RX, 2015, CLIN EXP METASTAS, V32, P169, DOI 10.1007/s10585-015-9700-y; Zhai ZL, 2014, AUTOPHAGY, V10, P468, DOI 10.4161/auto.27553	48	25	29	2	11	LIPPINCOTT WILLIAMS & WILKINS	PHILADELPHIA	TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA	1078-0998	1536-4844		INFLAMM BOWEL DIS	Inflamm. Bowel Dis.	APR	2018	24	4					781	791		10.1093/ibd/izx075			11	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	GA7VO	WOS:000428546400012	29562274	Bronze			2022-04-25	
J	Zhang, WJ; Peng, C; Shen, X; Yuan, YM; Zhang, W; Yang, CJ; Yao, MC				Zhang, Weijia; Peng, Chang; Shen, Xue; Yuan, Yuemei; Zhang, Wei; Yang, Chunjuan; Yao, Meicun			A Bioactive Compound from Sanguisorba officinalis L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells	MOLECULES			English	Article						colorectal cancer; AGE; apoptosis; autophagy; Wnt/beta-catenin signaling pathway	CHEMICAL-CONSTITUENTS; APOPTOSIS; CHEMOTHERAPY; TRANSITION; PATHWAY; PLANTS	Colorectal cancer (CRC) is one of the most common cancer in the world. The first line chemotherapeutic agent, 5-fluorouracil (5-FU), plays a predominant role in the clinical treatment of CRC. However, with the wide use of 5-FU, more and more CRC patients have been obtaining drug resistance to 5-FU, which leads to a large amount of treatment failures. One of the effective strategies to overcome this obstacle is to find bioactive natural products from traditional medicine. In our previous work, Sanguisorba officinalis L. was found to exert a strong anti-proliferative activity against 5-FU-senstive/resistant CRC cells. Therefore, several compounds were isolated from this herb and screened for their anti-CRC effects to find promising compounds. Among them, a triterpenoid compound named 3 beta-[(alpha-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid beta-d-glucopyranosyl ester (AGE), showed strong activity against both 5-FU-senstive and resistant CRC cells. In order to further study the mechanism of AGE on CRC cells, flow cytometer analysis, mitochondrial membrane potential (MMP) measurement, Western blotting, and RT-PCR assays were performed. Results demonstrated that AGE induced cell death by apoptosis pathway and autophagy, and inhibited cell proliferation via cell cycle arrest in G0-G1 phase mediated by Wnt signaling pathway. Therefore, AGE may be a potential bioactive compound for CRC treatment in clinic.	[Zhang, Weijia; Shen, Xue] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China; [Peng, Chang; Yao, Meicun] Sun Yat Sen Univ, Sch Pharmaceut Sci Shenzhen, Shenzhen 518107, Peoples R China; [Yuan, Yuemei] Sun Yat Sen Univ, Sch Ecol, 6 Ming Yuan, Guangzhou 510006, Peoples R China; [Zhang, Wei] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China; [Yang, Chunjuan] Harbin Med Univ, Coll Pharm, Dept Pharmaceut Anal & Analyt Chem, Harbin 150081, Peoples R China		Yao, MC (corresponding author), Sun Yat Sen Univ, Sch Pharmaceut Sci Shenzhen, Shenzhen 518107, Peoples R China.; Yang, CJ (corresponding author), Harbin Med Univ, Coll Pharm, Dept Pharmaceut Anal & Analyt Chem, Harbin 150081, Peoples R China.	zhangwj66@mail2.sysu.edu.cn; pengch56@mail2.sysu.edu.cn; shenx27@mail2.sysu.edu.cn; yuanym@mail.sysu.edu.cn; wzhang@must.edu.mo; chunjuanyang@hrbmu.edu.cn; lssymc@mail.sysu.edu.cn		Yao, Meicun/0000-0002-4372-6528; Peng, Chang/0000-0003-0462-0373	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81973552, 81573551]	This work was supported by National Natural Science Foundation of China (No. 81973552 and No. 81573551).	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J	Xu, CF; Liu, ZL; Xiao, JW				Xu, Chengfei; Liu, Ziling; Xiao, Jiangwei			Ferroptosis: A Double-Edged Sword in Gastrointestinal Disease	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						ferroptosis; ischemia/reperfusion injury; inflammatory bowel disease; gastric cancer; colorectal cancer	ERASTIN-INDUCED FERROPTOSIS; MUTANT COLORECTAL-CANCER; CELL-DEATH; GASTRIC-CANCER; INTESTINAL ISCHEMIA; LIPID-PEROXIDATION; OXIDATIVE STRESS; COENZYME Q(10); IN-VITRO; IRON	Ferroptosis is a novel form of regulated cell death (RCD) that is typically accompanied by iron accumulation and lipid peroxidation. In contrast to apoptosis, autophagy, and necroptosis, ferroptosis has unique biological processes and pathophysiological characteristics. Since it was first proposed in 2012, ferroptosis has attracted attention worldwide. Ferroptosis is involved in the progression of multiple diseases and could be a novel therapeutic target in the future. Recently, tremendous progress has been made regarding ferroptosis and gastrointestinal diseases, including intestinal ischemia/reperfusion (I/R) injury, inflammatory bowel disease (IBD), gastric cancer (GC), and colorectal cancer (CRC). In this review, we summarize the recent progress on ferroptosis and its interaction with gastrointestinal diseases. Understanding the role of ferroptosis in gastrointestinal disease pathogenesis could provide novel therapeutic targets for clinical treatment.	[Xu, Chengfei; Liu, Ziling; Xiao, Jiangwei] Chengdu Med Coll, Dept Gastrointestinal Surg, Chengdu 610500, Peoples R China		Xiao, JW (corresponding author), Chengdu Med Coll, Dept Gastrointestinal Surg, Chengdu 610500, Peoples R China.	cos119@163.com; nsmc2007@163.com; xiaojiangwei@126.com			National Natural Science Foundation of the P.R. of ChinaNational Natural Science Foundation of China (NSFC) [81070378, 81270561]; Sichuan Outstanding Youth Fund Project Grant [2015JQ0060]	This study was financially supported by the National Natural Science Foundation of the P.R. of China (No. 81070378 and No. 81270561); Sichuan Outstanding Youth Fund Project Grant (No. 2015JQ0060).	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J. Mol. Sci.	NOV	2021	22	22							12403	10.3390/ijms222212403			15	Biochemistry & Molecular Biology; Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	XE7WG	WOS:000723593100001	34830285	gold, Green Published			2022-04-25	
J	Ren, LQ; Li, Q; Zhang, Y				Ren, Li-Qun; Li, Qi; Zhang, Yang			Luteolin Suppresses the Proliferation of Gastric Cancer Cells and Acts in Synergy with Oxaliplatin	BIOMED RESEARCH INTERNATIONAL			English	Article							COLORECTAL-CANCER; IN-VITRO; CISPLATIN; APOPTOSIS; INHIBITION; EXPRESSION; AUTOPHAGY; MICE	Objective. Gastric cancer, one of the most common malignant tumors worldwide, arises from the gastric mucosal epithelium and severely affects patient health and quality of life. Luteolin (LUT) is a flavonoid found in vegetables and fruits with diverse functions. A large number of studies have confirmed that LUT has an antitumor effect. Therefore, this study is aimed at verifying whether LUT can exert antitumor effects in synergy with oxaliplatin (OXA). As such, we examined the effects of LUT, OXA, and their coadministration in a gastric adenocarcinoma cell line (SGC-7901). We used the MTT assay to quantify the proliferation of SGC-7901 cells, flow cytometry to detect the cell cycle and apoptosis, ELISA to detect the expression of cell-cycle-related proteins, and western blot to detect the expression of related apoptotic factors. The results of this study show that the combination of LUT and OXA inhibited SGC-7901 cell proliferation and induced apoptosis by altering cell-cycle proportions. In addition, the combination also activated Cyt c/caspase signaling in SGC-7901 cells. In summary, LUT synergy with OXA inhibited the proliferation of gastric cancer cells in vitro. The present study also elucidated the mechanism by which LUT potentiated the sensitivity of SGC-7901 cells to OXA through the Cyt c/caspase pathway.	[Ren, Li-Qun; Li, Qi; Zhang, Yang] Jilin Univ, Sch Pharmaceut Sci, Dept Expt Pharmacol & Toxicol, Changchun, Jilin, Peoples R China; [Li, Qi] Jinzhou Med Univ, Dept Pathol, Affiliated Hosp 3, Jinzhou, Liaoning, Peoples R China		Zhang, Y (corresponding author), Jilin Univ, Sch Pharmaceut Sci, Dept Expt Pharmacol & Toxicol, Changchun, Jilin, Peoples R China.	renlq630210@163.com; 1758365335@qq.com; 807525580@qq.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773934]	This work was supported by the National Natural Science Foundation of China (No. 81773934).	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Int.	FEB 22	2020	2020								9396512	10.1155/2020/9396512			9	Biotechnology & Applied Microbiology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Research & Experimental Medicine	KS9JB	WOS:000518623200002	32149146	Green Published, gold			2022-04-25	
J	Jabir, NR; Islam, MT; Tabrez, S; Shakil, S; Zaidi, SK; Khan, FR; Araujo, LD; de Meneses, AAPM; Santos, JVD; Melo-Cavalcante, AAD				Jabir, Nasimudeen R.; Islam, Muhammad Torequl; Tabrez, Shams; Shakil, Shazi; Zaidi, Syed Kashif; Khan, Fayaz Rahman; Araujo, Lidiane da Silva; Melo de Meneses, Ag-Anne Pereira; de Oliveira Santos, Jose Victor; de Carvalho Melo-Cavalcante, Ana Amelia			An insight towards anticancer potential of major coffee constituents	BIOFACTORS			English	Review						antioxidants; autophagy; cancer; coffee; genotoxicity	ACID PHENETHYL ESTER; POLYCYCLIC AROMATIC AGENTS; CANCER-CELLS; COMPONENTS KAHWEOL; COLORECTAL-CANCER; FERULIC ACID; QUINACRINE MUSTARD; SIGNALING PATHWAY; TUMOR INITIATION; DNA-DAMAGE	Cancer is a complex disease that transforms a normal cell into a malignant cell by disturbing different molecular mechanisms. Lately, plant-derived bioactive products have gained prominent attention to serve as anti-cancer agents. These natural anti-neoplastic agents are believed to act as alternatives for the synthetic drugs or could be used to enhance the prospect of other drugs in reducing their dose, thus limiting their possible toxic effects. They could also counterbalance the other anti-cancer drug-induced adverse effects. Among natural plant-derived products, coffee has been reported for its significant anti-carcinogenic effects in the scientific literature. This article aims to highlight the anti-cancer potential of different coffee components viz. caffeic acid, chlorogenic acids, caffeine (1,3,7-trimethylxanthine), cafestol, ferulic acid, and kahweol together in a single article. Based on our article, it is quite clear that these bioactive components have important therapeutic potentials against cancerous cells. However, the lack of clinical data negates their use in humans. Therefore, more research is recommended to achieve the desired pharmaceutical value. We also implore assessing their safety and possible adverse effects prior to their progress into clinical trials. (c) 2018 BioFactors, 44(4):315-326, 2018	[Jabir, Nasimudeen R.; Tabrez, Shams] King Abdulaziz Univ, King Fahd Med Res Ctr, POB 80216, Jeddah 21589, Saudi Arabia; [Islam, Muhammad Torequl] Ton Duc Thang Univ, Dept Management Sci & Technol Dev, Ho Chi Minh City 700000, Vietnam; [Islam, Muhammad Torequl] Ton Duc Thang Univ, Fac Pharm, Ho Chi Minh City 700000, Vietnam; [Shakil, Shazi] King Abdulaziz Univ, Ctr Innovat Personalized Med, Jeddah, Saudi Arabia; [Shakil, Shazi] King Abdulaziz Univ, Fac Appl Med Sci, Dept Med Lab Technol, Jeddah, Saudi Arabia; [Shakil, Shazi; Zaidi, Syed Kashif] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah, Saudi Arabia; [Khan, Fayaz Rahman] King Abdulaziz Univ, Fac Appl Med Sci, Dept Phys Therapy, Jeddah, Saudi Arabia; [Araujo, Lidiane da Silva; Melo de Meneses, Ag-Anne Pereira; de Oliveira Santos, Jose Victor; de Carvalho Melo-Cavalcante, Ana Amelia] Univ Fed Piaui, Postgrad Program Pharmaceut Sci, Teresina, Brazil		Tabrez, S (corresponding author), King Abdulaziz Univ, King Fahd Med Res Ctr, POB 80216, Jeddah 21589, Saudi Arabia.; Islam, MT (corresponding author), Ton Duc Thang Univ, Dept Management Sci & Technol Dev, Ho Chi Minh City 700000, Vietnam.; Islam, MT (corresponding author), Ton Duc Thang Univ, Fac Pharm, Ho Chi Minh City 700000, Vietnam.	muhammad.torequl.islam@tdt.edu.vn; shamstabrez1@gmail.com	Shakil, Shazi/K-4132-2015; Zaidi, Syed Kashif M/A-6160-2013; Shakil, Shazi/AAA-1449-2022; Tabrez, Shams/H-9476-2012; Khan, Fayaz R/O-1281-2015; Tabrez, Shams/H-7315-2019; Zaidi, Syed Kashif/AAA-3924-2022; Rehumathbeevi, Jabir Nasimudeen/H-9483-2012; Islam, Muhammad/Q-9563-2017	Shakil, Shazi/0000-0003-4075-9153; Zaidi, Syed Kashif M/0000-0003-2391-414X; Shakil, Shazi/0000-0003-4075-9153; Tabrez, Shams/0000-0003-4550-415X; Khan, Fayaz R/0000-0003-2512-4563; Tabrez, Shams/0000-0003-4550-415X; Zaidi, Syed Kashif/0000-0003-2391-414X; Rehumathbeevi, Jabir Nasimudeen/0000-0001-8548-7986; de Oliveira Santos, Jose Victor/0000-0002-9811-641X; Islam, Muhammad/0000-0003-0034-8202; Pereira Melo de Menezes, Ag-Anne/0000-0003-2830-990X			Aleksandrova K, 2015, AM J CLIN NUTR, V102, P1498, DOI 10.3945/ajcn.115.116095; Anbazhagan AN, 2016, AM J PHYSIOL-CELL PH, V310, pC612, DOI 10.1152/ajpcell.00123.2015; Anese M, 2003, J AGR FOOD CHEM, V51, P942, DOI 10.1021/jf025859+; Baig S, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2015.275; Boya P, 2005, MOL CELL BIOL, V25, P1025, DOI 10.1128/MCB.25.3.1025-1040.2005; Bravi F, 2009, AM J OBSTET GYNECOL, V200, P130, DOI 10.1016/j.ajog.2008.10.032; Bruning A, 2015, FRONT ONCOL, V5, DOI 10.3389/fonc.2015.00047; Bruunsgaard H, 2006, DAN MED BULL, V53, P285; Burdan F., 2015, COFFEE HLTH DIS PREV, P823; Camouse MM, 2005, EXPERT REV ANTICANC, V5, P1061, DOI 10.1586/14737140.5.6.1061; Cardenas C, 2014, BIOCHEM BIOPH RES CO, V447, P452, DOI 10.1016/j.bbrc.2014.04.026; Cardenas C, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0023407; Carrillo JA, 2000, THER DRUG MONIT, V22, P409, DOI 10.1097/00007691-200008000-00008; Cavaliere V, 2009, TRANSL ONCOL, V2, P46, DOI 10.1593/tlo.08202; Chae JI, 2014, PHYTOTHER RES, V28, P1879, DOI 10.1002/ptr.5217; Chauhan P.S., 2011, J APPL PHARM SCI, V1, P67; Chen JC, 2015, TZU CHI MED J, V27, P74, DOI 10.1016/j.tcmj.2015.03.002; Chiang EPI, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0099631; Choi DW, 2015, BIOMOL THER, V23, P128, DOI 10.4062/biomolther.2014.133; Choi MJ, 2011, CHEM-BIOL INTERACT, V190, P102, DOI 10.1016/j.cbi.2011.02.013; Coussens LM, 2002, NATURE, V420, P860, DOI 10.1038/nature01322; Cuesta-Gragera A, 2015, EUR J PHARM SCI, V73, P57, DOI 10.1016/j.ejps.2015.03.018; Dai JZ, 2017, CELL PHYSIOL BIOCHEM, V43, P247, DOI 10.1159/000480367; dos Santos MD, 2006, BIOL PHARM BULL, V29, P2236, DOI 10.1248/bpb.29.2236; de Mejia EG, 2014, TRENDS ENDOCRIN MET, V25, P489, DOI 10.1016/j.tem.2014.07.003; Ding WX, 2014, HEPATOLOGY, V59, P1235, DOI 10.1002/hep.26736; Dixit A, 2016, INDIAN J CLIN BIOCHE, V31, P125, DOI 10.1007/s12291-016-0561-1; Dodurga Y, 2016, TUMOR BIOL, V37, P1933, DOI 10.1007/s13277-015-3984-z; dos Santos JS, 2013, J BURN CARE RES, V34, P682, DOI 10.1097/BCR.0b013e3182839b1c; Eini H, 2015, BIOCHEM PHARMACOL, V98, P110, DOI 10.1016/j.bcp.2015.08.092; Eisenberg-Lerner A, 2009, CELL DEATH DIFFER, V16, P966, DOI 10.1038/cdd.2009.33; Carrasco-Legleu CE, 2006, WORLD J GASTROENTERO, V12, P6779, DOI 10.3748/wjg.v12.i42.6779; Fahrioglu U, 2016, GENE, V576, P476, DOI 10.1016/j.gene.2015.10.061; Feng D, 2013, EXP CELL RES, V319, P1697, DOI 10.1016/j.yexcr.2013.03.034; Ferk F, 2014, MOL NUTR FOOD RES, V58, P229, DOI 10.1002/mnfr.201300154; Firat U, 2015, EUR REV MED PHARMACO, V19, P1907; Fukuma Y, 2015, BIOFACTORS, V41, P222, DOI 10.1002/biof.1218; Galeone C, 2010, CANCER CAUSE CONTROL, V21, P1949, DOI 10.1007/s10552-010-9623-5; Gasscht F, 2015, GENES NUTR, V10, DOI 10.1007/s12263-015-0501-3; Genkinger J. 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Zhao Y, 2014, J ETHNOPHARMACOL, V156, P147, DOI 10.1016/j.jep.2014.08.043	141	6	6	0	27	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0951-6433	1872-8081		BIOFACTORS	Biofactors	JUL-AUG	2018	44	4					315	326		10.1002/biof.1437			12	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	GR0LF	WOS:000442207300001					2022-04-25	
J	Li, G; Yang, TQ; Chen, YL; Bao, JP; Wu, D; Hu, XH; Feng, CX; Xu, LX; Li, M; Li, G; Jin, MF; Xu, YY; Zhang, R; Qian, GH; Pan, J				Li, Gen; Yang, Tianquan; Chen, Yanling; Bao, Jianping; Wu, Di; Hu, Xiaohan; Feng, Chenxi; Xu, Lixiao; Li, Mei; Li, Gang; Jin, Meifang; Xu, Yunyun; Zhang, Rui; Qian, Guanghui; Pan, Jian			USP5 Sustains the Proliferation of Glioblastoma Through Stabilization of CyclinD1	FRONTIERS IN PHARMACOLOGY			English	Article						glioblastoma multiforme; USP5; CyclinD1; deubiquitination; cell cycle	CELL LUNG-CANCER; COLORECTAL-CANCER; UBIQUITIN; INHIBITION; DEGRADATION; PROGRESSION; PATHWAY; TUMORIGENESIS; RESISTANCE; INVASION	Glioblastoma multiforme (GBM) is one of the most malignant primary tumors in humans. Despite standard therapeutic strategy with tumor resection combined with radiochemotherapy, the prognosis remains disappointed. Recently, deubiquitinating enzymes (DUBs) has been reported as potential cancer therapy targets due to their multifunctions involved in the regulation of tumorigenesis, cell cycle, apoptosis, and autophagy. In this study, we found that knockdown of ubiquitin specific protease (USP5), a family member of DUB, could significantly suppress GBM cell line U251 and DBTRG-05MG proliferation and colony formation by inducing cell cycle G1/S arrest, which was correlated with downregulation of CyclinD1 protein level. CyclinD1 had been reported to play a critical role in the tumorigenesis and development of GBM via regulating cell cycle transition. Overexpression of USP5 could significantly extend the half-life of CyclinD1, while knockdown of USP5 decreased the protein level of CyclinD1, which could be restored by proteasome inhibitor MG-132. Indeed, USP5 was found to directly interact with CyclinD1, and decrease its K48-linked polyubiquitination level. Furthermore, knockdown of USP5 in U251 cells remarkably inhibited tumor growth in vivo. Taken together, these findings demonstrate that USP5 plays a critical role in tumorigenesis and progression of GBM by stabilizing CyclinD1 protein. Targeting USP5 could be a potential therapeutic strategy for GBM.	[Li, Gen; Wu, Di; Hu, Xiaohan; Feng, Chenxi; Xu, Lixiao; Li, Mei; Li, Gang; Jin, Meifang; Xu, Yunyun; Qian, Guanghui; Pan, Jian] Soochow Univ, Inst Pediat Res, Childrens Hosp, Suzhou, Peoples R China; [Li, Gen] Soochow Univ, Coll Pharmaceut Sci, Lab Mol Neuropathol, Suzhou, Peoples R China; [Yang, Tianquan] Soochow Univ, Dept Neurosurg, Childrens Hosp, Suzhou, Peoples R China; [Chen, Yanling] Soochow Univ, Sch Basic Med & Biol Sci, Suzhou, Peoples R China; [Bao, Jianping] Soochow Univ, Dept Neonatol, Childrens Hosp, Suzhou, Peoples R China; [Zhang, Rui] Soochow Univ, Clin Pediat Sch, Suzhou, Peoples R China		Qian, GH; Pan, J (corresponding author), Soochow Univ, Inst Pediat Res, Childrens Hosp, Suzhou, Peoples R China.	ghqian@suda.edu.cn; panjian2008@163.com			National Natural Science FoundationNational Natural Science Foundation of China (NSFC) [81702737, 81902972, 82072767, 81770145, 81971477, 81701596]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20191175]; Jiangsu Provincial Medical Young Talents [QNRC2016756]; Applied Foundational Research of Medical and Health Care of Suzhou City [SYS2019086]; Suzhou Health Talent Training Project [GSWS2020048]; project of Soochow Science and Technology Plan [SYS201761]	This work was supported by the grants from the National Natural Science Foundation (81702737, 81902972, 82072767, 81770145, 81971477, 81701596), Natural Science Foundation of Jiangsu Province BK20191175, Jiangsu Provincial Medical Young Talents (QNRC2016756), the Applied Foundational Research of Medical and Health Care of Suzhou City (SYS2019086), Suzhou Health Talent Training Project (YX, GSWS2020048), the project of Soochow Science and Technology Plan (XH, SYS201761).	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Pharmacol.	AUG 16	2021	12									10.3389/fphar.2021.720307			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	UM6UN	WOS:000693465700001	34483932	Green Published, gold			2022-04-25	
J	Santos, P; Almeida, F				Santos, Patrick; Almeida, Fausto			Role of Exosomal miRNAs and the Tumor Microenvironment in Drug Resistance	CELLS			English	Review						exosomal miRNAs; chemoresistance; therapy resistance; extracellular vesicles	EPITHELIAL-MESENCHYMAL TRANSITION; PANCREATIC-CANCER CELLS; STEM-CELLS; CISPLATIN RESISTANCE; COLORECTAL-CANCER; PROSTATE-CANCER; P-GLYCOPROTEIN; LIGAND 2; AUTOPHAGY; HETEROGENEITY	Tumor microenvironment (TME) is composed of different cellular populations, such as stromal, immune, endothelial, and cancer stem cells. TME represents a key factor for tumor heterogeneity maintenance, tumor progression, and drug resistance. The transport of molecules via extracellular vesicles emerged as a key messenger in intercellular communication in the TME. Exosomes are small double-layered lipid extracellular vesicles that can carry a variety of molecules, including proteins, lipids, and nucleic acids. Exosomal miRNA released by cancer cells can mediate phenotypical changes in the cells of TME to promote tumor growth and therapy resistance, for example, fibroblast- and macrophages-induced differentiation. Cancer stem cells can transfer and enhance drug resistance in neighboring sensitive cancer cells by releasing exosomal miRNAs that target antiapoptotic and immune-suppressive pathways. Exosomes induce drug resistance by carrying ABC transporters, which export chemotherapeutic agents out of the recipient cells, thereby reducing the drug concentration to suboptimal levels. Exosome biogenesis inhibitors represent a promising adjunct therapeutic approach in cancer therapy to avoid the acquisition of a resistant phenotype. In conclusion, exosomal miRNAs play a crucial role in the TME to confer drug resistance and survivability to tumor cells, and we also highlight the need for further investigations in this promising field.	[Santos, Patrick; Almeida, Fausto] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, 3900 Bandeirantes Ave, BR-14049900 Sao Paulo, SP, Brazil		Almeida, F (corresponding author), Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, 3900 Bandeirantes Ave, BR-14049900 Sao Paulo, SP, Brazil.	patricksantos@usp.br; fbralmeida@usp.br	dos Santos, Patrick Wellington da Silva/M-5709-2019; Almeida, Fausto/N-6540-2013	dos Santos, Patrick Wellington da Silva/0000-0001-5722-023X; Almeida, Fausto/0000-0002-3782-3698	Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/03322-7]; Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [420670/2018-1]; CAPES (Coordenacao de Aperfeicoamento de Nivel Superior)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)	This research was funded by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (2016/03322-7); Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - 420670/2018-1); and CAPES (Coordenacao de Aperfeicoamento de Nivel Superior).	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J	Galluzzi, L; Morselli, E; Kepp, O; Vitale, I; Pinti, M; Kroemer, G				Galluzzi, Lorenzo; Morselli, Eugenia; Kepp, Oliver; Vitale, Ilio; Pinti, Marcello; Kroemer, Guido			Mitochondrial Liaisons of p53	ANTIOXIDANTS & REDOX SIGNALING			English	Review							TUMOR-SUPPRESSOR P53; WILD-TYPE P53; ADENINE-NUCLEOTIDE TRANSLOCATOR; APOPTOSIS-INDUCING FACTOR; TRANSITION PORE COMPLEX; PROGRAMMED CELL-DEATH; DNA-BINDING DOMAIN; STRESS-INDUCED APOPTOSIS; COLORECTAL-CANCER CELLS; BCL-2 PROTEIN FAMILY	Mitochondria play a central role in cell survival and cell death. While producing the bulk of intracellular ATP, mitochondrial respiration represents the most prominent source of harmful reactive oxygen species. Mitochondria participate in many anabolic pathways, including cholesterol and nucleotide biosynthesis, yet also control multiple biochemical cascades that contribute to the programmed demise of cells. The tumor suppressor protein p53 is best known for its ability to orchestrate a transcriptional response to stress that can have multiple outcomes, including cell cycle arrest and cell death. p53-mediated tumor suppression, however, also involves transcription-independent mechanisms. Cytoplasmic p53 can physically interact with members of the BCL-2 protein family, thereby promoting mitochondrial membrane permeabilization. Moreover, extranuclear p53 can suppress autophagy, a major prosurvival mechanism that is activated in response to multiple stress conditions. Thirty years have passed since its discovery, and p53 has been ascribed with an ever-increasing number of functions. For instance, p53 has turned out to influence the cell's redox status, by transactivating either anti- or pro-oxidant factors, and to regulate the metabolic switch between glycolysis and aerobic respiration. In this review, we will analyze the mechanisms by which p53 affects the balance between the vital and lethal functions of mitochondria. Antioxid. Redox Signal. 15, 1691-1714.	[Galluzzi, Lorenzo; Morselli, Eugenia; Kepp, Oliver; Vitale, Ilio; Kroemer, Guido] Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, France; [Pinti, Marcello] Univ Modena & Reggio Emilia, Dipartimento Sci Biomed, Modena, Italy; [Kroemer, Guido] Ctr Rech Cordeliers, Paris, France; [Kroemer, Guido] Hop Europeen Georges Pompidou, Paris, France; [Kroemer, Guido] Univ Paris 05, Paris, France; [Galluzzi, Lorenzo; Morselli, Eugenia; Kepp, Oliver; Vitale, Ilio] Univ Paris 11, Villejuif, France		Kroemer, G (corresponding author), Inst Gustave Roussy, INSERM, U848, Pavillon Rech 1, F-94805 Paris, France.	kroemer@orange.fr	Kroemer, Guido/AAY-9859-2020; Pinti, Marcello/C-9351-2015; Kepp, Oliver/N-2763-2017; Galluzzi, Lorenzo/K-2709-2012; Galluzzi, Lorenzo/AAG-6294-2019; Galluzzi, Lorenzo/AAH-3286-2021; Galluzzi, Lorenzo/AAG-6432-2019; Vitale, Ilio/M-3960-2017; KROEMER, Guido/B-4263-2013	Pinti, Marcello/0000-0001-9118-1262; Kepp, Oliver/0000-0002-6081-9558; Galluzzi, Lorenzo/0000-0003-2257-8500; Vitale, Ilio/0000-0002-5918-1841; KROEMER, Guido/0000-0002-9334-4405	Ligue Nationale contre le Cancer (Equipe labellisee)Ligue nationale contre le cancer; Agence Nationale pour la RechercheFrench National Research Agency (ANR); European CommissionEuropean CommissionEuropean Commission Joint Research Centre; Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale; Institut National du CancerInstitut National du Cancer (INCA) France; Canceropole Ile-de-FranceRegion Ile-de-France; European UnionEuropean Commission; ApopTrain; INSERMInstitut National de la Sante et de la Recherche Medicale (Inserm)European Commission	G. K. is supported by the Ligue Nationale contre le Cancer (Equipe labellisee), Agence Nationale pour la Recherche, European Commission (Apo-Sys, ChemoRes, ApopTrain, Active p53), Fondation pour la Recherche Medicale, Institut National du Cancer, and Canceropole Ile-de-France. L.G. is supported by the Apo-Sys consortium of the European Union. E. M. is funded by a Ph.D. student grant from ApopTrain. O.K. receives a postdoctoral fellowship from INSERM.	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Redox Signal.	SEP	2011	15	6					1691	1714		10.1089/ars.2010.3504			24	Biochemistry & Molecular Biology; Endocrinology & Metabolism	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Endocrinology & Metabolism	803JA	WOS:000293576400014	20712408				2022-04-25	
J	Chen, TQ; Yang, PY; Jia, YJ				Chen, Tianqi; Yang, Peiying; Jia, Yingjie			Molecular mechanisms of astragaloside-IV in cancer therapy (Review)	INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE			English	Review						astragaloside IV; epithelial-mesenchymal transformation; cancer; molecular mechanisms; chemosensitivity	EPITHELIAL-MESENCHYMAL TRANSITION; ENHANCES CISPLATIN CHEMOSENSITIVITY; LUNG-CANCER; DOWN-REGULATION; COLORECTAL-CANCER; MULTIDRUG-RESISTANCE; INHIBITS PROGRESSION; CELL-PROLIFERATION; SIGNALING PATHWAYS; TUMOR-SUPPRESSOR	Radix Astragali (RA) is widely used in traditional Chinese medicine (TCM), and astragaloside IV (AS-IV) is the most critical component of RA. Previous studies have demonstrated that AS-IV exerts effects on the myocardium, nervous system and endocrine system, among others. In the present review article, data from studies conducted over the past 20 years were collated, which have evaluated the effects of AS-IV on tumors. The mechanisms of action of AS-IV on malignant cells both in vivo and in vitro were summarized and it was demonstrated that AS-IV plays a vital role, particularly in inhibiting tumor growth and metastasis, promoting the apoptosis of tumor cells, enhancing immune function and preventing drug resistance. Moreover, AS-IV controls several epithelial-mesenchymal transformation (EMT)-related and autophagy-related pathways, such as the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT), Wnt/beta-catenin, mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase (ERK) and transforming growth factor-beta (TGF-beta)/SMAD signaling pathways, which are commonly affected in the majority of tumors. The present review provides new perspectives on the functions of AS-IV and its role as an adjuvant treatment in cancer chemotherapy.	[Chen, Tianqi; Yang, Peiying; Jia, Yingjie] Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Dept Oncol, 88 Changling Rd, Tianjin 300380, Peoples R China		Jia, YJ (corresponding author), Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Dept Oncol, 88 Changling Rd, Tianjin 300380, Peoples R China.	bchen@casit.com.cn			Tianjin Science & Technology Plan Projects [17ZXMFSY00190]; Tianjin Traditional Chinese Medicine Research Project, Tianjin health and family planning commission [2017003]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81403220]	The present study was supported by Tianjin Science & Technology Plan Projects (no. 17ZXMFSY00190), the Tianjin Traditional Chinese Medicine Research Project, Tianjin health and family planning commission (no. 2017003) and the National Natural Science Foundation of China (no. 81403220).	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J. Mol. Med.	MAR	2021	47	3							13	10.3892/ijmm.2021.4846			13	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	PY4XK	WOS:000612048900001	33448320	hybrid, Green Published			2022-04-25	
J	Ham, J; Lee, S; Lee, H; Jeong, D; Park, S; Kim, SJ				Ham, Juyeon; Lee, Seungyeon; Lee, Hyunkyung; Jeong, Dawoon; Park, Sungbin; Kim, Sun Jung			Genome-Wide Methylation Analysis Identifies NOX4 and KDM5A as Key Regulators in Inhibiting Breast Cancer Cell Proliferation by Ginsenoside Rg3	AMERICAN JOURNAL OF CHINESE MEDICINE			English	Article						Breast Cancer; Ginsenoside Rg3; KDM5A; Methylation; NOX4	EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN HEPATOCARCINOMA CELLS; HUMAN COLORECTAL-CANCER; DNA METHYLATION; LUNG-CANCER; TUMOR PROGRESSION; SIGNALING PATHWAY; OVARIAN-CANCER; EXPRESSION; AUTOPHAGY	Ginsenoside Rg3 is a key metabolite of ginseng and is known to inhibit cancer cell growth. However, the epigenetics of CpG methylation and its regulatory mechanism have yet to be determined. Genome-wide methylation analysis of MCF-7 breast cancer cells treated with Rg3 was performed to identify epigenetically regulated genes and pathways. The effect of Rg3 on apoptosis and cell proliferation was examined by a colony formation assay and a dye-based cell proliferation assay. The association between methylation and gene expression was monitored by RT-PCR and Western blot analysis. Genome-wide methylation analysis identified the "cell morphology"-related pathway as the top network. Rg3 induced late stage apoptosis but inhibited cell proliferation up to 60%. Hypermethylated TRMT1L, PSMC6 and NOX4 were downregulated by Rg3, while hypomethylated ST3GAL4, RNLS and KDM5A were upregulated. In accordance, downregulation of NOX4 by siRNA abrogated the cell growth effect of Rg3, while the effect was opposite for KDM5A. Notably, breast cancer patients with a higher expression of NOX4 and KDM5A showed poor and good prognosis of survival, respectively. In conclusion, Rg3 deregulated tumor-related genes through alteration of the epigenetic methylation level leading to growth inhibition of cancer cells.	[Ham, Juyeon; Lee, Seungyeon; Lee, Hyunkyung; Jeong, Dawoon; Park, Sungbin; Kim, Sun Jung] Dongguk Univ Seoul, Dept Life Sci, Goyang, South Korea		Kim, SJ (corresponding author), Dongguk Univ, Dept Life Sci, 32 Dongguk Ro, Ilsan 10326, Goyang, South Korea.	sun-jungk@dongguk.edu	kim, sun jung/T-1013-2019		National Research Foundation of Korea (NRF) - Ministry of Education, Science, and TechnologyMinistry of Education, Science and Technology, Republic of KoreaNational Research Foundation of Korea [2016R1D 1A1B01009235]	This study was supported by the Basic Science Research Program (2016R1D 1A1B01009235) through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology.	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J. Chin. Med.		2018	46	6					1333	1355		10.1142/S0192415X18500702			23	Integrative & Complementary Medicine; Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine; General & Internal Medicine	GW2US	WOS:000446743100010	30149757				2022-04-25	
J	Iratni, R; Ayoub, MA				Iratni, Rabah; Ayoub, Mohammed Akli			Sildenafil in Combination Therapy against Cancer: A Literature Review	CURRENT MEDICINAL CHEMISTRY			English	Review						Sildenafil; drug repurposing; PDE-5 inhibitor; cancer; combination therapy; cancer therapy	PDE5 INHIBITORS; MULTIDRUG-RESISTANCE; ERECTILE DYSFUNCTION; COLORECTAL-CANCER; PROSTATE-CANCER; PLUS SILDENAFIL; IN-VITRO; CHEMOTHERAPY; DOXORUBICIN; CISPLATIN	The concepts of drug repurposing and Sildenafil or blue pill are tightly linked over the years. Indeed, in addition to its initial clinical application as an anti-hypertensive drug in the pulmonary system, Sildenafil is also known for its beneficial effects in erectile dysfunction. Moreover, evidence has been accumulated to support its value in anti-cancer therapy, either alone or in combination with other clinically efficient chemotherapy drugs. In this review, we focused on the old and recent in vitro and in vivo studies demonstrating the cellular and molecular rationale for the application of Sildenafil in combination therapy in various types of cancer. We emphasized on the different molecular targets as well as the different signaling pathways involved in cancer cells. The pro-apoptotic effect of Sildenafil through nitric oxide (NO)/ phosphodiesterase type 5 (PDE5)-dependent manner seems to be one of the most common mechanisms. However, the activation of autophagy, as well as the modulation of the anti-tumor immunity, constitutes the other pathways triggered by Sildenafil. Overall, the studies converged to reveal the complexity of the anti-cancer potential of Sildenafil. Thus, through our review, we aimed to present an updated and simplified picture of such repurposing of Sildenafil in the field of oncology.	[Iratni, Rabah; Ayoub, Mohammed Akli] United Arab Emirates Univ, Coll Sci, Dept Biol, POB 15551, Al Ain, U Arab Emirates		Iratni, R; Ayoub, MA (corresponding author), United Arab Emirates Univ, Coll Sci, Dept Biol, POB 15551, Al Ain, U Arab Emirates.	R_iratni@uaeu.ac.ae; mayoub@uaeu.ac.ae			Al Jalila FoundationAl Jalila Foundation (AJF) [AJF2018007-21S02]	The paper has been financially supported by Al Jalila Foundation grant (AJF2018007-21S02).	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Med. Chem.		2021	28	11					2248	2259		10.2174/0929867327666200730165338			12	Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Pharmacology & Pharmacy	RY0BS	WOS:000647580600010	32744956				2022-04-25	
J	Cui, JQ; Wei, CM; Deng, LL; Kuang, XY; Zhang, ZT; Pierides, C; Chi, JX; Wang, L				Cui, Jiaqi; Wei, Chunmei; Deng, Linli; Kuang, Xingyi; Zhang, Zengtie; Pierides, Chryso; Chi, Jianxiang; Wang, Li			MicroRNA-143 increases cell apoptosis in myelodysplastic syndrome through the Fas/FasL pathway both in vitro and in vivo	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						microRNA-143; myelodysplastic syndrome; cell apoptosis; lentivirus; xenograft	COLORECTAL-CANCER; TUMOR-SUPPRESSOR; INHIBITS GROWTH; GASTRIC-CANCER; EXPRESSION; LEUKEMIA; PROLIFERATION; DYSREGULATION; CHEMOTHERAPY; AUTOPHAGY	Whilst the role of microRNA-143 (miR-143) in myelodysplastic syndrome (MDS) remains unclear, abnormally expressed microRNA-143 has been detected in many types of cancer tissues. In this study, we describe a cohort study for the verification of miR-143 expression, as well as the investigation of the molecular mechanisms of miR-143 in MDS/acute myeloid leukaemia (AML). In a series of experiments, miR-143 recombinant lentiviral vectors transformed into SKM-1 cells were either overexpressed or knocked down, and the results illustrated that the overexpression of miR-143 inhibited SKM-1 cell growth, arrested the SKM-1 cells in the G0/G1 phase, interfered with cell proliferation and induced cell apoptosis via the Fas/FasL pathway. Conversely, miR-143 knockdown induced a decrease in the apoptosis and promoted the proliferation of SKM-1 cells. Moreover, miR-143 was shown to suppress MLLT3/AF9 expression by binding to its 3'-UTR. Taken together, the findings of this study indicate that miR-143 may be a critical regulator of MDS/AML cell carcinogenesis, acting as a potent antitumour molecular target for the diagnosis or treatment of cancers associated with the abnormal expression of MLLT3/AF9, hence facilitating the development of potential therapeutics against MDS/AML.	[Cui, Jiaqi; Wei, Chunmei; Deng, Linli; Wang, Li] Chongqing Med Univ, Affiliated Hosp 1, Dept Hematol, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Zhang, Zengtie] Xi An Jiao Tong Univ, Hlth Sci Ctr, Dept Pathol, Xian 710061, Shaanxi, Peoples R China; [Pierides, Chryso; Chi, Jianxiang] Karaiskakio Fdn, Ctr Study Haematol Malignancies, CY-2032 Nicosia, Cyprus		Wang, L (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Hematol, 1 Youyi Rd, Chongqing 400016, Peoples R China.	liwangls@yahoo.com	WEI, chunmei/AGX-9143-2022		Chongqing Education Commission Foundation [KJ1702017]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30971277, 81250034]	This study was supported by the Chongqing Education Commission Foundation (KJ1702017) and the National Natural Science Foundation of China (grant nos. 30971277 and 81250034).	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J. Oncol.	NOV	2018	53	5					2191	2199		10.3892/ijo.2018.4534			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	GX4LG	WOS:000447703300031	30132510	Bronze			2022-04-25	
J	Song, MQ; Yoon, G; Choi, JS; Kim, E; Liu, XJ; Oh, H; Chae, JI; Lee, MH; Shim, JH				Song, Mengqiu; Yoon, Goo; Choi, Joon-Seok; Kim, Eunae; Liu, Xuejiao; Oh, Ha-Na; Chae, Jung-Il; Lee, Mee-Hyun; Shim, Jung-Hyun			Janus kinase 2 inhibition by Licochalcone B suppresses esophageal squamous cell carcinoma growth	PHYTOTHERAPY RESEARCH			English	Article						esophageal squamous cell carcinoma; JAK2 inhibitor; Licochalcone B	IN-VITRO; COLORECTAL-CANCER; CYCLE PROGRESSION; JAK INHIBITOR; APOPTOSIS; AZD1480; SURVIVAL; STAT3; AUTOPHAGY; ACCURACY	Esophageal cancer (EC) is one of the leading causes to cancer death in the worldwide and major population of EC is esophageal squamous cell carcinoma (ESCC). Still, ESCC-targeted therapy has not been covered yet. In the present study we have identified that Licochalcone B (Lico B) inhibited the ESCC growth by directly blocking the Janus kinase (JAK) 2 activity and its downstream signaling pathway. Lico B suppressed KYSE450 and KYSE510 ESCC cell growth, arrested cell cycle at G2/M phase and induced apoptosis. Direct target of Lico B was identified by kinase assay and verified with in vitro and ex vivo binding. Computational docking model predicted for Lico B interaction to ATP-binding pocket of JAK2. Furthermore, treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B. Thus, JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl-1 expression was decreased with treatment of Lico B. Our results suggest that Lico B inhibits ESCC cell growth, arrests cell cycle and induces apoptosis, revealing the underlying mechanism involved in JAK2/STAT3 signaling pathways after Lico B treatment. It might provide potential role of Lico B in the treatment of ESCC.	[Song, Mengqiu; Liu, Xuejiao; Lee, Mee-Hyun] Zhengzhou Univ, Sch Basic Med Sci, Dept Pathophysiol, Zhengzhou, Peoples R China; [Song, Mengqiu; Liu, Xuejiao; Lee, Mee-Hyun] China US Henan Hormel Canc Inst, 127 Dongming Rd, Zhengzhou 450008, Henan, Peoples R China; [Yoon, Goo; Oh, Ha-Na; Shim, Jung-Hyun] Mokpo Natl Univ, Coll Pharm, Dept Pharm, Muan Gun 58554, Jeonnam, South Korea; [Choi, Joon-Seok] Daegu Catholic Univ, Coll Pharm, Gyongsan, South Korea; [Kim, Eunae] Chosun Univ, Coll Pharm, Gwangju, South Korea; [Chae, Jung-Il] Jeonbuk Natl Univ, BK21 Plus, Sch Dent, Dept Dent Pharmacol, Jeonju, South Korea; [Lee, Mee-Hyun] Dongshin Univ, Coll Korean Med, 85 Geonjae Ro, Naju Si 58245, Jeollanam Do, South Korea		Lee, MH (corresponding author), China US Henan Hormel Canc Inst, 127 Dongming Rd, Zhengzhou 450008, Henan, Peoples R China.; Shim, JH (corresponding author), Mokpo Natl Univ, Coll Pharm, Dept Pharm, Muan Gun 58554, Jeonnam, South Korea.; Lee, MH (corresponding author), Dongshin Univ, Coll Korean Med, 85 Geonjae Ro, Naju Si 58245, Jeollanam Do, South Korea.	mhlee@hci-cn.org; s1004jh@gmail.com		Shim, Jung-Hyun/0000-0002-4062-4016; Lee, Mee-Hyun/0000-0002-1216-0218	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC81972839] Funding Source: Medline; Basic Science Research program through the NRF Funded by the Ministry of Education [2019R1A2C1005899] Funding Source: Medline		Abraham M. 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Res.	AUG	2020	34	8					2032	2043		10.1002/ptr.6661			12	Chemistry, Medicinal; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	MV8PF	WOS:000556612000021	32144852				2022-04-25	
S	Maji, S; Panda, S; Samal, SK; Shriwas, O; Rath, R; Pellecchia, M; Emdad, L; Das, SK; Fisher, PB; Dash, R		Tew, KD; Fisher, PB		Maji, Santanu; Panda, Sanjay; Samal, Sabindra K.; Shriwas, Omprakash; Rath, Rachna; Pellecchia, Maurizio; Emdad, Luni; Das, Swadesh K.; Fisher, Paul B.; Dash, Rupesh			Bcl-2 Antiapoptotic Family Proteins and Chemoresistance in Cancer	ADVANCES IN CANCER RESEARCH, VOL 137	Advances in Cancer Research		English	Review; Book Chapter							FATTY-ACID SYNTHASE; CELL LUNG-CANCER; PHASE-II TRIAL; ADVANCED BREAST-CANCER; HUMAN NONSMALL CELL; STEM-LIKE CELLS; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; OVARIAN-CANCER; COLORECTAL-CANCER	Cancer is a daunting global problem confronting the world's population. The most frequent therapeutic approaches include surgery, chemotherapy, radiotherapy, and more recently immunotherapy. In the case of chemotherapy, patients ultimately develop resistance to both single and multiple chemotherapeutic agents, which can culminate in metastatic disease which is a major cause of patient death from solid tumors. Chemoresistance, a primary cause of treatment failure, is attributed to multiple factors including decreased drug accumulation, reduced drug-target interactions, increased populations of cancer stem cells, enhanced autophagy activity, and reduced apoptosis in cancer cells. Reprogramming tumor cells to undergo drug-induced apoptosis provides a promising and powerful strategy for treating resistant and recurrent neoplastic diseases. This can be achieved by downregulating dysregulated antiapoptotic factors or activation of proapoptotic factors in tumor cells. A major target of dysregulation in cancer cells that can occur during chemoresistance involves altered expression of Bcl-2 family members. Bcl-2 antiapoptotic molecules (Bcl-2, Bcl-xL, and Mcl-1) are frequently upregulated in acquired chemoresistant cancer cells, which block drug-induced apoptosis. We presently overview the potential role of Bcl-2 antiapoptotic proteins in the development of cancer chemoresistance and overview the clinical approaches that use Bcl-2 inhibitors to restore cell death in chemoresistant and recurrent tumors.	[Maji, Santanu; Samal, Sabindra K.; Shriwas, Omprakash; Dash, Rupesh] Inst Life Sci, Bhubaneswar, Odisha, India; [Maji, Santanu; Samal, Sabindra K.; Shriwas, Omprakash] Manipal Univ, Manipal, Karnataka, India; [Panda, Sanjay] HCG Panda Canc Ctr, Cuttack, Odisha, India; [Panda, Sanjay] Acharya Harihar Reg Canc Ctr, Cuttack, Odisha, India; [Rath, Rachna] Sriram Chandra Bhanj Dent Coll & Hosp, Cuttack, Odisha, India; [Pellecchia, Maurizio] Univ Calif Riverside, Riverside, CA 92521 USA; [Emdad, Luni; Das, Swadesh K.; Fisher, Paul B.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA; [Emdad, Luni; Das, Swadesh K.; Fisher, Paul B.] Virginia Commonwealth Univ, Sch Med, VCU Inst Mol Med, Richmond, VA USA; [Emdad, Luni; Das, Swadesh K.; Fisher, Paul B.] Virginia Commonwealth Univ, Sch Med, VCU Massey Canc Ctr, Richmond, VA USA		Dash, R (corresponding author), Inst Life Sci, Bhubaneswar, Odisha, India.	rupesh.dash@gmail.com	Pellecchia, Maurizio/Y-7072-2018	SAMAL, SABINDRA KUMAR/0000-0003-4785-1032	NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA168517] Funding Source: NIH RePORTER; 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J	Wu, HL; Hao, AX; Cui, HH; Wu, WB; Yang, HR; Hu, BH; Li, P				Wu, Hanli; Hao, Aixia; Cui, Honghong; Wu, Wenbin; Yang, Huanrong; Hu, Baohong; Li, Peng			TRAF6 expression is associated with poorer prognosis and high recurrence in urothelial bladder cancer	ONCOLOGY LETTERS			English	Article						TNF receptor-associated factor 6; recurrence; prognosis; metastasis; urothelial bladder cancer	KAPPA-B; COLORECTAL-CANCER; GROWTH-FACTOR; UBIQUITINATION; ACTIVATION; CARCINOMA; CHOLANGIOCARCINOMA; PROGRESSION; AUTOPHAGY; TBL1XR1	The aim of the present study was to investigate the clinical significance of TNF receptor-associated factor 6 (TRAF6) expression in urothelial bladder cancer. TRAF6 expression was detected by immunohistochemistry in 126 samples of patients with urothelial bladder cancer. The association between clinicopathological factors and TRAF6 expression was analyzed by chi(2) test. The association between TRAF6 expression, overall survival rate and the recurrence-free survival rate was evaluated in univariate analysis with Kaplan-Meier test and in multivariate analysis with Cox-regression model. In the cohort tested, the rate of high TRAF6 expression was 61.9% (78/126). TRAF6 expression was demonstrated to be significantly associated with positive metastasis (P=0.001) with chi(2) test. Furthermore, TRAF6 expression was demonstrated to be associated with overall survival rate (P=0.016) and recurrence-free survival rate (P=0.016). With Cox-regression model, it was indicate that TRAF6 high expression was an independent predictive factor of poor prognosis (P=0.037) and high recurrence (P=0.011). High TRAF6 expression may predict unfavorable prognosis and high recurrence in urothelial bladder cancer, indicating that TRAF6 may be a potential and promising therapeutic target in urothelial bladder cancer.	[Wu, Hanli; Hao, Aixia; Cui, Honghong; Wu, Wenbin; Yang, Huanrong] Yidu Cent Hosp Weifang, Dept Nephrol, Weifang 262500, Shandong, Peoples R China; [Hu, Baohong] Shandong Univ, East Dist Shandong Prov Hosp, Jinan 250014, Shandong, Peoples R China; [Hu, Baohong; Li, Peng] Qingdao Univ, Yantai Yuhuangding Hosp, Dept Med Oncol, 20 Yuhuangding East Rd, Yantai 264000, Shandong, Peoples R China		Hu, BH; Li, P (corresponding author), Qingdao Univ, Yantai Yuhuangding Hosp, Dept Med Oncol, 20 Yuhuangding East Rd, Yantai 264000, Shandong, Peoples R China.	khan2017@126.com; lipengyuhuangding@163.com			Science and Technology Project of Yantai City [2015WS018, 2016WS006]; Youth Research Initiation Foundation of Yuhuangding Hospital [201511]; Shandong Province Medical Science and Technology development project [2016WS0706]	The present study was supported by Science and Technology Project of Yantai City (grant nos. 2015WS018 and 2016WS006), Youth Research Initiation Foundation of Yuhuangding Hospital (grant no. 201511) and Shandong Province Medical Science and Technology development project (grant no. 2016WS0706).	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Lett.	AUG	2017	14	2					2432	2438		10.3892/ol.2017.6427			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FE0IS	WOS:000407904600173	28781679	Green Published, gold			2022-04-25	
J	Berdowska, I; Matusiewicz, M; Fecka, I				Berdowska, Izabela; Matusiewicz, Malgorzata; Fecka, Izabela			Punicalagin in Cancer Prevention-Via Signaling Pathways Targeting	NUTRIENTS			English	Review						punicalagin; pomegranate; ellagitannins; breast cancer; cervical cancer; ovarian cancer; colorectal cancer; thyroid cancer; apoptosis; autophagy	EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER; ELLAGIC ACID; CELL-LINE; POMEGRANATE JUICE; DRUG-RESISTANCE; OVARIAN-CANCER; ANNEXIN A1; BECLIN 1; EXPRESSION	The extract of pomegranate (Punica granatum) has been applied in medicine since ancient times due to its broad-spectrum health-beneficial properties. It is a rich source of hydrolyzable tannins and anthocyanins, exhibiting strong antioxidative, anti-inflammatory, and antineoplastic properties. Anticancer activities of pomegranate with reference to modulated signaling pathways in various cancer diseases have been recently reviewed. However, less is known about punicalagin (Pug), a prevailing compound in pomegranate, seemingly responsible for its most beneficial properties. In this review, the newest data derived from recent scientific reports addressing Pug impact on neoplastic cells are summarized and discussed. Its attenuating effect on signaling circuits promoting cancer growth and invasion is depicted. The Pug-induced redirection of signal-transduction pathways from survival and proliferation into cell-cycle arrest, apoptosis, senescence, and autophagy (thus compromising neoplastic progression) is delineated. Considerations presented in this review are based mainly on data obtained from in vitro cell line models and concern the influence of Pug on human cervical, ovarian, breast, lung, thyroid, colorectal, central nervous system, bone, as well as other cancer types.	[Berdowska, Izabela; Matusiewicz, Malgorzata] Wroclaw Med Univ, Dept Med Biochem, Chalubinskiego 10, PL-50368 Wroclaw, Poland; [Fecka, Izabela] Wroclaw Med Univ, Dept Pharmacognosy & Herbal Med, Borowska 211A, PL-50556 Wroclaw, Poland		Berdowska, I; Matusiewicz, M (corresponding author), Wroclaw Med Univ, Dept Med Biochem, Chalubinskiego 10, PL-50368 Wroclaw, Poland.	izabela.berdowska@umed.wroc.pl; malgorzata.matusiewicz@umed.wroc.pl; izabela.fecka@umed.wroc.pl	Berdowska, Izabela/AAZ-4016-2021; Fecka, Izabela/AAS-8974-2021	Fecka, Izabela/0000-0002-1139-4581; Berdowska, Izabela/0000-0002-0275-4522; Matusiewicz, Malgorzata/0000-0003-4624-0109			Adams LS, 2006, J AGR FOOD CHEM, V54, P980, DOI 10.1021/jf052005r; Al-Harbi SA, 2021, FRONT NUTR, V8, DOI 10.3389/fnut.2021.647582; Alzahrani AM, 2021, INT J MOL SCI, V22, DOI 10.3390/ijms22115465; Nieto MA, 2016, CELL, V166, P21, DOI 10.1016/j.cell.2016.06.028; Gimenez-Bastida JA, 2020, FOOD CHEM TOXICOL, V139, DOI 10.1016/j.fct.2020.111260; Arend RC, 2013, GYNECOL ONCOL, V131, P772, DOI 10.1016/j.ygyno.2013.09.034; 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J	Dai, W; Liu, XH				Dai, Wei; Liu, Xinghui			Circular RNA 0004904 promotes autophagy and regulates the fused in sarcoma/vascular endothelial growth factor axis in preeclampsia	INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE			English	Article						circular RNA 0004904; microRNA-570; invasion; autophagy; VEGF	COLORECTAL-CANCER; GASTRIC-CANCER; CIRCRNA; PATHOGENESIS; INVASION; PROGRESSION; METASTASIS; INHIBITION; PREDICTION; PLACENTAS	Circular (circ)RNA has been demonstrated to serve crucial roles in cell proliferation, differentiation and autophagy. However, to date, the function and mechanism of action of circRNA in preeclampsia have not been reported. The present study aimed to analyze the roles of circRNA-0004904 in preeclampsia and to clarify its underlying pathogenic mechanism. The expression levels of circ-0004904, microRNA (miR)-570 and autophagy-related 12 (ATG12) were detected by reverse transcription-quantitative (RT-q)PCR. In addition, the protein levels of ATG12, vascular endothelial growth factor (VEGF) and fused in sarcoma (FUS) were determined by western blot assay. The distribution of mRFP-GFP-LC3 in HTR8 and JEG3 cells was analyzed by confocal microscopy. Fluorescence in situ hybridization assay was utilized to identify the colocalization of circ-0004904 and miR-570. Cell proliferation was determined by 5-ethynyl-2 '-deoxyuridine assay, and invasion was evaluated by Matrigel invasion assay. The results of the present study demonstrated that the expression levels of circ-0004904 were elevated in the placental tissues and plasma samples of patients with preeclampsia compared with those in the control group samples. Ectopic expression of circ-0004904 promoted autophagy, but inhibited migration and proliferation of HTR8 cells compared with those in the negative control group. Silencing of circ-0004904 inhibited autophagy, and induced migration and proliferation in JEG3 cells compared with those in the negative control group. In addition, circ-0004904 regulated the levels of ATG12 via interaction with miR-570. Furthermore, circ-0004904 regulated the FUS/VEGF axis in HTR8 and JEG3 cells. In conclusion, circ-0004904 was abnormally expressed in the plasma and placental tissues of patients with preeclampsia. In addition, circ-0004904 was involved in the regulation of proliferation, invasion and autophagy in HTR8 and JEG3 cells. Thus, circ-0004904 may be used as a potential diagnostic biomarker and therapeutic target for preeclampsia.	[Dai, Wei; Liu, Xinghui] Sichuan Univ, Dept Obstet, West China Hosp, 1416 Sect 1,Chenglong Ave, Chengdu 610041, Sichuan, Peoples R China		Liu, XH (corresponding author), Sichuan Univ, Dept Obstet, West China Hosp, 1416 Sect 1,Chenglong Ave, Chengdu 610041, Sichuan, Peoples R China.	xinghuiliu@163.com					[Anonymous], 2019, Obstet Gynecol, V133, P1, DOI 10.1097/AOG.0000000000003018; Bai SH, 2020, SCI REP-UK, V10, DOI 10.1038/s41598-020-70484-2; Bakrania BA, 2022, AM J OBSTET GYNECOL, V226, pS973, DOI 10.1016/j.ajog.2020.10.025; Bao X, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0620-z; Bian LJ, 2018, BIOCHEM BIOPH RES CO, V505, P346, DOI 10.1016/j.bbrc.2018.09.073; Chen DS, 2018, CELL CYCLE, V17, P2080, DOI 10.1080/15384101.2018.1515553; Chen ZH, 2014, AM J PHYSIOL-LUNG C, V306, pL1016, DOI 10.1152/ajplung.00268.2013; Chilumula K, 2021, J ULTRASOUND, V24, P303, DOI 10.1007/s40477-020-00524-0; Cornelius DC, 2020, EBIOMEDICINE, V57, DOI 10.1016/j.ebiom.2020.102864; D'Ambra E, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20215477; Dai J, 2020, EUR REV MED PHARMACO, V24, P7963, DOI 10.26355/eurrev_202008_22479; Deepthi K, 2020, GENE, V762, DOI 10.1016/j.gene.2020.145040; Deng WG, 2007, CANCER RES, V67, P709, DOI 10.1158/0008-5472.CAN-06-3463; Ding CY, 2020, CANCER LETT, V479, P1, DOI 10.1016/j.canlet.2020.03.002; Dyess NF, 2021, J PEDIATR-US, V228, P11, DOI 10.1016/j.jpeds.2020.08.015; Gao L, 2015, J HYPERTENS, V33, P106, DOI 10.1097/HJH.0000000000000366; Garikipati VNS, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-11777-7; Gong G, 2020, CELL CYCLE, V19, P2139, DOI 10.1080/15384101.2020.1792636; Han D, 2017, HEPATOLOGY, V66, P1151, DOI 10.1002/hep.29270; Hu XP, 2018, CLIN EPIGENETICS, V10, DOI 10.1186/s13148-018-0482-3; Jia YH, 2020, FASEB J, V34, P13224, DOI 10.1096/fj.202000253RR; Jiang M, 2018, CELL PHYSIOL BIOCHEM, V46, P2576, DOI 10.1159/000489685; Lin L, 2021, IMMUNOL LETT, V230, P27, DOI 10.1016/j.imlet.2020.12.007; Livak KJ, 2001, METHODS, V25, P402, DOI 10.1006/meth.2001.1262; Murrow L, 2018, MOL CELL ONCOL, V5, DOI 10.1080/23723556.2015.1039191; Nakashima A, 2020, AUTOPHAGY, V16, P1771, DOI 10.1080/15548627.2019.1707494; Oh SY, 2008, REPROD SCI, V15, P912, DOI 10.1177/1933719108319159; Ou YH, 2019, TAIWAN J OBSTET GYNE, V58, P769, DOI 10.1016/j.tjog.2019.09.007; Panda AC, 2018, METHODS MOL BIOL, V1724, P43, DOI 10.1007/978-1-4939-7562-4_4; Reddy M, 2021, AM J OBSTET GYNECOL, V224, DOI 10.1016/j.ajog.2020.08.019; Saghafi N, 2018, INT J REPROD BIOMED, V16, P1, DOI 10.29252/ijrm.16.1.1; Sahay AS, 2018, MOL CELL BIOCHEM, V438, P141, DOI 10.1007/s11010-017-3121-y; Shang AQ, 2020, MOL CANCER, V19, DOI 10.1186/s12943-020-01235-0; Wang XY, 2020, MOL ONCOL, V14, P539, DOI 10.1002/1878-0261.12629; Wang YJ, 2019, BOSNIAN J BASIC MED, V19, P155, DOI 10.17305/bjbms.2019.3935; Wang Z, 2020, CANCER MANAG RES, V12, P6947, DOI 10.2147/CMAR.S254250; Wu YP, 2020, FRONT GENET, V11, DOI 10.3389/fgene.2020.00892; Xia LQ, 2020, BMC CANCER, V20, DOI 10.1186/s12885-020-07395-y; Xiao GH, 2020, J CLIN LAB ANAL, V34, DOI 10.1002/jcla.23252; Xin Y, 2020, BURNS TRAUMA, V8, DOI 10.1093/burnst/tkaa025; Xu YY, 2020, CANCER COMMUN, V40, P484, DOI 10.1002/cac2.12075; Yildiz DA, 2017, CELL MOL BIOL, V63, P51, DOI 10.14715/cmb/2017.63.12.12; Zhang HD, 2018, BIOMED PHARMACOTHER, V107, P1342, DOI 10.1016/j.biopha.2018.08.030; Zhang J, 2017, MOL CANCER, V16, DOI 10.1186/s12943-017-0719-3; Zhao HQ, 2020, EBIOMEDICINE, V56, DOI 10.1016/j.ebiom.2020.102813; Zhao YS, 2020, CANCER CELL INT, V20, DOI 10.1186/s12935-020-01390-w	46	2	2	2	6	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1107-3756	1791-244X		INT J MOL MED	Int. J. Mol. Med.	JUN	2021	47	6							111	10.3892/ijmm.2021.4944			10	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	RX7FR	WOS:000647386000001	33907824				2022-04-25	
J	Zhang, L; Cheng, X; Xu, SC; Bao, JD; Yu, HX				Zhang, Li; Cheng, Xian; Xu, Shichen; Bao, Jiandong; Yu, Huixin			Curcumin induces endoplasmic reticulum stress-associated apoptosis in human papillary thyroid carcinoma BCPAP cells via disruption of intracellular calcium homeostasis	MEDICINE			English	Article						apoptosis; curcumin; endoplasmic reticulum stress; human papillary thyroid carcinoma; intracellular calcium homeostasis	UNFOLDED PROTEIN RESPONSE; ER STRESS; COLORECTAL-CANCER; MITOCHONDRIA; INHIBITION; ACTIVATION; PREVENTION; ONCOGENES; AUTOPHAGY; TUMORS	Background: Thyroid cancer is the most common endocrine tumor. Our previous studies have demonstrated that curcumin can induce apoptosis in human papillary thyroid carcinoma BCPAP cells. However, the underlined mechanism has not been clearly elucidated. Endoplasmic reticulum (ER) is a major organelle for synthesis, maturation, and folding proteins as well as a large store for Ca2+. Overcoming chronically activated ER stress by triggering pro-apoptotic pathways of the unfolded protein response (UPR) is a novel strategy for cancer therapeutics. Our study aimed to uncover the ER stress pathway involved in the apoptosis caused by curcumin. Methods: BCPAP cells were treated with different doses of curcumin (12.5-50 mu M). Annexin V/PI double staining was used to determine cell apoptosis. Rhod-2/AM calcium fluorescence probe assay was performed to measure the calcium level of endoplasmic reticulum. Western blot was used to examine the expression of ER stress marker C/EBP homologous protein 10 (CHOP) and glucose-regulated protein 78 (GRP78). X-box binding protein1 (XBP-1) spliced form was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Curcumin significantly inhibited anchorage-independent cell growth and induced apoptosis in BCPAP cells. Curcumin induced ER stress and UPR responses in a dose-and time-dependent manner, and the chemical chaperone 4-phenylbutyrate (4-PBA) partially reversed the antigrowth activity of curcumin. Moreover, curcumin significantly increased inositol-requiring enzyme 1 alpha (IRE1 alpha) phosphorylation and XBP-1 mRNA splicing to induce a subsets of ER chaperones. Increased cleavage of activating transcription factor 6 (ATF6), which enhances expression of its downstream target CHOP was also observed. Furthermore, curcumin induced intracellular Ca2+ influx through inhibition of the sarco-endoplasmic reticulum ATPase 2A (SERCA2) pump. The increased cytosolic Ca2+ then bound to calmodulin to activate calcium/calmodulin-dependent protein kinase II (CaMKII) signaling, leading to mitochondrial apoptosis pathway activation. Ca2+ chelator BAPTA partially reversed curcumin-induced ER stress and growth suppression, confirming the possible involvement of calcium homeostasis disruption in this response. Conclusions: Curcumin inhibits thyroid cancer cell growth, at least partially, through ER stress-associated apoptosis. Our observations provoked that ER stress activation may be a promising therapeutic target for thyroid cancer treatment.	[Zhang, Li; Cheng, Xian; Xu, Shichen; Bao, Jiandong; Yu, Huixin] Jiangsu Inst Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Key Lab Nucl Med, 20 Qianrong Rd, Wuxi 214063, Jiangsu, Peoples R China		Zhang, L (corresponding author), Jiangsu Inst Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Key Lab Nucl Med, 20 Qianrong Rd, Wuxi 214063, Jiangsu, Peoples R China.	zhangli@jsinm.org			Science and Research Foundation of Health Bureau of Jiangsu Province [H2017032]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81602352, 81673436]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20171145, BK20151119]; Wuxi Municipal Commission of Health and Family Planning [Q201608]	This study was funded by the Science and Research Foundation of Health Bureau of Jiangsu Province (No. H2017032), the grants from the National Natural Science Foundation of China (Nos. 81602352 and 81673436), the Natural Science Foundation of Jiangsu Province (BK20171145 and BK20151119), and Wuxi Municipal Commission of Health and Family Planning (Q201608).	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J	Wang, J; Shao, L; Wang, CZ; Zhou, HH; Yuan, CS; Huang, WH				Wang, Jin; Shao, Li; Wang, Chong-Zhi; Zhou, Hong-Hao; Yuan, Chun-Su; Huang, Wei-Hua			Synergetic Inhibition of Human Colorectal Cancer Cells by Combining Polyyne-Enriched Fraction from Oplopanax elatus and Irinotecan	NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL			English	Article							QUANTITATIVE-ANALYSIS; CASPASES; CONSTITUENTS; FALCARINDIOL; CISPLATIN; AUTOPHAGY; HORRIDUS; DRUGS; LUNG	Although irinotecan is an important anticancer drug for treating colorectal cancer, its dose-dependent side effects limited its clinical application. Thus, it's important to develop low-toxic candidates to enhance the efficacy of irinotecan. Polyynes from genus Oplopanax were reported to possess potential anticancer effects on colorectal cancer. Hereby, we evaluated the synergetic inhibition of human colorectal cancer cells by combining polyyne-enriched fraction from Oplopanax elatus (the dichloromethane fraction of Oplopanax elatus, OED) and irinotecan. The results showed that 5 mu g/ml of OED combined with 40 mu M of irinotecan possessed significant synergetic inhibition on SW-480 cells with a combination index (CI) of 0.56. Besides, the percentage of apoptotic cells was significantly increased from 69.57% (40 mu M of irinotecan) or 72.7% (5 mu g/ml of OED) to 95.6% after treatment of OED combined with irinotecan (OCI), suggesting OED and irinotecan possess the synergistic apoptotic effect (P < 0.01). Furthermore, Caspase-3 was significantly activated in OCI group (P < 0.05). Besides, the percentage of apoptotic cells of OED or/and irinotecan significantly decreased after inhibition of caspase-3. These data indicated that OED could enhance antiproliferative effects of irinotecan on colorectal cancer cells, which was related with induction of apoptosis and regulations of activity of caspase-3.	[Wang, Jin; Zhou, Hong-Hao; Huang, Wei-Hua] Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410008, Hunan, Peoples R China; [Wang, Jin; Zhou, Hong-Hao; Huang, Wei-Hua] Cent S Univ, Inst Clin Pharmacol, Hunan Key Lab Pharmacogenet, Changsha, Hunan, Peoples R China; [Shao, Li] Hunan Univ Chinese Med, Sch Pharm, Dept Pharmacognosy, Changsha, Hunan, Peoples R China; [Wang, Chong-Zhi; Yuan, Chun-Su; Huang, Wei-Hua] Univ Chicago, Pritzker Sch Med, Tang Ctr Herbal Med Res, Chicago, IL 60637 USA		Huang, WH (corresponding author), Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410008, Hunan, Peoples R China.	endeavor34852@aliyun.com	Wang, Chong-Zhi/B-8337-2014	Wang, Chong-Zhi/0000-0002-0950-2109; Huang, Wei-Hua/0000-0003-4167-8304	National Natural Scientific Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31400306]; Hunan Provincial Natural Science Foundation of ChinaNatural Science Foundation of Hunan Province [2015JJ3156]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2015M570692]; fundamental research funds for the central universities of Central South University [1681-7608040003]	This work was supported by the National Natural Scientific Foundation of China (31400306), Hunan Provincial Natural Science Foundation of China (2015JJ3156), China Postdoctoral Science Foundation (2015M570692) and the fundamental research funds for the central universities of Central South University (1681-7608040003).	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Cancer	APR 3	2019	71	3					472	482		10.1080/01635581.2018.1516788			11	Oncology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Nutrition & Dietetics	HU9KZ	WOS:000465614600013	30372160				2022-04-25	
J	Scaioli, E; Biondi, R; Liverani, E; Sartini, A; Troiano, A; Fuccio, L; Muratori, R; Lombardi, G; Onorini, D; Dal Monte, P; Donati, M; Belluzzi, A				Scaioli, Eleonora; Biondi, Roberta; Liverani, Elisa; Sartini, Alessandro; Troiano, Antonella; Fuccio, Lorenzo; Muratori, Rosangela; Lombardi, Giulia; Onorini, Delia; Dal Monte, Paola; Donati, Manuela; Belluzzi, Andrea			Simkania negevensis in Crohn's Disease	DIGESTIVE DISEASES AND SCIENCES			English	Article						Simkania negevensis; Crohn's disease; Infective hypothesis	CHLAMYDIA-PNEUMONIAE; INFECTION; PREVALENCE; AUTOPHAGY; WATER; IGG	Background Simkania negevensis is an obligate intracellular Gram-negative bacterium ( family Simkaniaceae, order Chlamydiales) that has been isolated from domestic and mains water supplies, is able to infect human macrophages, and can induce an inflammatory response in the host. Methods From June to December 2016, in a single-center observational study, colonic Crohn's disease patients and controls (subjects undergoing screening for colorectal cancer) underwent blood tests to identify serum-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) to S. negevensis and a colonoscopy with biopsies for detection of S. negevensis DNA by polymerase chain reaction (PCR). Results Forty-three Crohn's disease patients and 18 controls were enrolled. Crohn's disease patients had higher prevalence of IgA antibodies to S. negevensis compared with controls (20.9% versus 0%, p = 0.04). Simkaniaceae negevensis DNA was detected in 34.9% and 5.6% of intestinal biopsies in Crohn's disease patients and controls, respectively (p = 0.02). All Crohn's disease patients with PCR-positive biopsies for S. negevensis were IgG seropositive, with specific IgA in 60% of them (p < 0.001). Immunosuppressive therapies, extraintestinal manifestations, or disease activity did not influence the presence of S. negevensis in the Crohn's disease population. Conclusions We identified S. negevensis in Crohn's disease patients by demonstrating the presence of S. negevensis mucosal DNA and seropositivity to the bacterium. These results could support the presence of an acute or persistent S. negevensis infection and suggest a possible role in the pathogenesis of Crohn's disease.	[Scaioli, Eleonora; Liverani, Elisa; Sartini, Alessandro; Troiano, Antonella; Fuccio, Lorenzo; Muratori, Rosangela; Belluzzi, Andrea] Univ Bologna, Gastroenterol Unit, Dept Med & Surg Sci, St Orsola Malpighi Hosp, Via Massarenti 9, I-40138 Bologna, Italy; [Biondi, Roberta; Lombardi, Giulia; Onorini, Delia; Dal Monte, Paola; Donati, Manuela] Univ Bologna, St Orsola Malpighi Hosp, Microbiol Unit, Dept Expt Diagnost & Specialty Med, I-40138 Bologna, Italy		Belluzzi, A (corresponding author), Univ Bologna, Gastroenterol Unit, Dept Med & Surg Sci, St Orsola Malpighi Hosp, Via Massarenti 9, I-40138 Bologna, Italy.	elescaio@gmail.com; roberta.biondi5@unibo.it; elisa.liverani@yahoo.it; ale.sartini@gmail.com; a.t.26101989@gmail.com; lorenzofuccio@gmail.com; rosangela.muratori@aosp.bo.it; giulia.lombardi@aosp.bo.it; delia.onorini@studio.unibo.it; paola.dalmonte@unibo.it; manuela.donati@unibo.it; andrea.belluzzi@aosp.bo.it	Sartini, Alessandro/AAN-3396-2020; Fuccio, Lorenzo/A-2557-2010	Sartini, Alessandro/0000-0003-1573-6451; Fuccio, Lorenzo/0000-0001-8618-2447; DAL MONTE, PAOLA/0000-0003-2326-7464			BEST WR, 1976, GASTROENTEROLOGY, V70, P439; Buisson A, 2016, INFLAMM BOWEL DIS, V22, P2943, DOI 10.1097/MIB.0000000000000946; Casson N, 2006, INT J ANTIMICROB AG, V27, P541, DOI 10.1016/j.ijantimicag.2006.03.009; Chen WX, 2002, J GASTROEN HEPATOL, V17, P987, DOI 10.1046/j.1440-1746.2002.02793.x; Daperno M, 2004, GASTROINTEST ENDOSC, V60, P505, DOI 10.1016/S0016-5107(04)01878-4; Donati M, 2015, J APPL MICROBIOL, V118, P1076, DOI 10.1111/jam.12761; Donati M, 2013, NEW MICROBIOL, V36, P303; Donati M, 2013, NEW MICROBIOL, V36, P85; Fasoli L, 2008, SCAND J INFECT DIS, V40, P269, DOI 10.1080/00365540701642146; Friedman MG, 1999, EPIDEMIOL INFECT, V122, P117, DOI 10.1017/S095026889800185X; FUKUSHI H, 1988, J CLIN MICROBIOL, V26, P675, DOI 10.1128/JCM.26.4.675-680.1988; Gordon SB, 2002, BRIT MED BULL, V61, P45, DOI 10.1093/bmb/61.1.45; Herweg JA, 2016, FEBS J, V283, P608, DOI 10.1111/febs.13609; Homer CR, 2010, GASTROENTEROLOGY, V139, P1630, DOI 10.1053/j.gastro.2010.07.006; Hugot JP, 2001, NATURE, V411, P599, DOI 10.1038/35079107; Kahane S, 1998, J INFECT DIS, V177, P1425, DOI 10.1086/517830; Kahane S, 2004, APPL ENVIRON MICROB, V70, P3346, DOI 10.1128/AEM.70.6.3346-3351.2004; KAHANE S, 1993, FEMS MICROBIOL LETT, V109, P329, DOI 10.1111/j.1574-6968.1993.tb06189.x; Kahane S, 2001, APPL ENVIRON MICROB, V67, P4789, DOI 10.1128/AEM.67.10.4789-4795.2001; Kahane Simona, 2007, J Infect, V55, pe13, DOI 10.1016/j.jinf.2007.03.002; Kahane S, 2008, FEMS IMMUNOL MED MIC, V52, P219, DOI 10.1111/j.1574-695X.2007.00361.x; Levine B, 2008, CELL, V132, P27, DOI 10.1016/j.cell.2007.12.018; Lieberman D, 2002, EUR J CLIN MICROBIOL, V21, P307, DOI 10.1007/s10096-002-0703-7; Liverani E, 2014, WORLD J GASTROENTERO, V20, P13060, DOI 10.3748/wjg.v20.i36.13060; Muller S, 2006, EUR J GASTROEN HEPAT, V18, P889, DOI 10.1097/00042737-200608000-00015; Petersen BT, 2011, GASTROINTEST ENDOSC, V73, P1075, DOI 10.1016/j.gie.2011.03.1183; Petrich A, 2002, CHLAM INF P 10 INT S; Vouga M, 2017, CRIT REV MICROBIOL, V43, P62, DOI 10.3109/1040841X.2016.1165650; Yang ZF, 2010, NAT CELL BIOL, V12, P814, DOI 10.1038/ncb0910-814	29	1	1	0	2	SPRINGER	DORDRECHT	VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS	0163-2116	1573-2568		DIGEST DIS SCI	Dig. Dis. Sci.	NOV	2019	64	11					3284	3290		10.1007/s10620-019-05632-4			7	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	JL4EL	WOS:000495483700034	31041636				2022-04-25	
J	Tian, F; Wang, JH; Zhang, ZH; Yang, J				Tian, Feng; Wang, Junhu; Zhang, Zhanhua; Yang, Jie			LncRNA SNHG7/miR-34a-5p/SYVN1 axis plays a vital role in proliferation, apoptosis and autophagy in osteoarthritis	BIOLOGICAL RESEARCH			English	Article						Osteoarthritis; SNHG7; miR-34a-5p; SYVN1; Cell growth; Autophagy	COLORECTAL-CANCER; DOWN-REGULATION; NONCODING RNAS; SNHG7 PROMOTES; PROGRESSION; CHONDROCYTE; EXPRESSION; CARTILAGE; CELLS; METASTASIS	Background Osteoarthritis (OA) is one of the most common rheumatic diseases of which clinical symptoms includes swelling, synovitis and inflammatory pain, affect patients' daily life. It was reported that non-coding RNAs play vital roles in OA. However, the regulation mechanism of ncRNA in OA pathogenesis has not been fully elucidated. Methods The expression of SNHG7, miR-34a-5p and SYVN1 was detected using qRT-PCR in tissues, serum and cells. The protein expression of SYVN1, PCNA, cleavage-caspase 3, beclin1 and LC3 were measured using western blot. The RNA immunoprecipitation (RIP), RNA pulldown, and luciferase reporter assays were used to verify the relationship between SNHG7, miR-34a-5p and SYVN1. The MTT and flow cytometry assay was performed to detected cell proliferation and cell apoptosis respectively. Results In this study, SNHG7 and SYVN1 expression were down-regulated, but miR-34a-5p was up-regulated in OA tissues and IL-1 beta treated cells compared with normal tissues and chondrocyte. Functional investigation revealed that up-regulated SNHG7 or down-regulated miR-34a-5p could promote cell proliferation and inhibit cell apoptosis and autophagy in OA cells. More than that, RIP, pulldown and luciferase reporter assay was applied to determine that miR-34a-5p was a target miRNA of SNHG7 and SYVN1 was a target mRNA of miR-34-5p. Rescue experiments showed that overexpression of miR-34a reversed high expression of SNHG7-mediated suppression of apoptosis and autophagy as well as promotion of proliferation, while its knockdown inhibited cell apoptosis and autophagy and promoted cell proliferation which could be impaired by silencing SYVN1. In addition, SNHG7 regulated SYVN1 through sponging miR-34a-5p. Conclusion SNHG7 sponged miR-34a-5p to affect cell proliferation, apoptosis and autophagy through targeting SYVN1 which provides a novel sight into the pathogenesis of OA.	[Tian, Feng; Wang, Junhu; Yang, Jie] Xi An Jiao Tong Univ, Honghui Hosp, Dept Foot & Ankle Surg, 555 East Youyi Rd, Xian 710054, Shaanxi, Peoples R China; [Zhang, Zhanhua] Xi An Jiao Tong Univ, Honghui Hosp, Dept Internal Med, Xian, Shaanxi, Peoples R China		Yang, J (corresponding author), Xi An Jiao Tong Univ, Honghui Hosp, Dept Foot & Ankle Surg, 555 East Youyi Rd, Xian 710054, Shaanxi, Peoples R China.	kcbgpf@163.com			Xi'an health and family planning commission [J20161008]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81200076]	This work was supported by Xi'an health and family planning commission. (Grant No. J20161008) and National Natural Science Foundation of China (Grant No. 81200076).	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Res.	FEB 17	2020	53	1							9	10.1186/s40659-020-00275-6			11	Biology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics	KN0OV	WOS:000514539300001	32066502	Green Published, gold			2022-04-25	
J	Jiang, ZY; Liu, JB; Chen, BA; Mani, R; Pugazhendhi, A; Shanmuganathan, R; Jacob, JA				Jiang, Ziyu; Liu, Jingbing; Chen, Baoan; Mani, Rajesh; Pugazhendhi, Arivalagan; Shanmuganathan, Rajasree; Jacob, Joe Antony			Cytotoxic effects of a sesquiterpene beta-elemene on THP-1 leukemia cells is mediated via crosstalk between beclin-1 mediated autophagy and caspase-dependent apoptosis	PROCESS BIOCHEMISTRY			English	Article						beta-elemene; Leukemia; Cytotoxicity; mRNA; Expressions; Crosstalk	COLORECTAL-CANCER; IN-VIVO; EXPRESSION; MECHANISM; LIFE; PCR	beta- elemene extracted from Curcuma zedoaria rhizome (commonly known as white turmeric) is an effective anticancer agent. There are limited reports on the use of this agent against THP-1 cells employing a mechanistic study. Therefore, as a foremost aim of the present study, the cytotoxic effect of elemene and its mechanism will be elucidated. For this aim, the method adopted was to treat THP-1 cells in a dose- and time- dependent manner with elemene and the cytotoxicity to be evaluated. The mRNA expressions of a set of autophagy and apoptosis related genes will be analyzed by quantitative PCR. The findings indicate that the IC50 values for 24, 48, 72 and 96 h of treated THP-1 cells were 64.71, 42.19, 25.29 and 20.21 mu g/mL respectively. The expressions of autophagy related genes such as Beclin-1, LC3II, ATG-5 and XBP-1 were upregulated. The expressions of anti-apoptotic Bcl2 was upregulated, whereas, the expression of pro-apoptotic Box was downregulated. Interestingly, the expressions of Caspase-3 and Caspase-8 were upregulated. To summarize, autophagy might have occurred in endoplasmic reticulum and there might be a crosstalk with apoptosis which could be the rationale behind the cytotoxic effects of elemene on THP-1 cells. Therefore, beta- elemene could be a potential therapeutic agent for leukemia.	[Jiang, Ziyu; Chen, Baoan; Jacob, Joe Antony] Southeast Univ, Sch Med, Zhongda Hosp, Dept Hematol & Oncol, Nanjing 210009, Jiangsu, Peoples R China; [Jiang, Ziyu; Liu, Jingbing] Nanjing Univ Chinese Med, Dept Oncol, Affiliated Hosp Integrated Tradit Chinese & Weste, Nanjing, Jiangsu, Peoples R China; [Mani, Rajesh] Jawaharlal Nehru Univ, Mol & Cell Biol Lab, Sch Biotechnol, New Delhi, India; [Pugazhendhi, Arivalagan] Ton Duc Thang Univ, Fac Environm & Labour Safety, Innovat Green Prod Synth & Renewable Environm Dev, Ho Chi Minh City, Vietnam; [Shanmuganathan, Rajasree] Duy Tan Univ, Inst Res & Dev, Da Nang 550000, Vietnam		Chen, BA (corresponding author), Southeast Univ, Sch Med, Zhongda Hosp, Dept Hematol & Oncol, Nanjing 210009, Jiangsu, Peoples R China.	cba8888@hotmail.com	Pugazhendhi, Arivalagan/F-5411-2018; Shanmuganathan, Rajasree/AAU-5295-2020	Pugazhendhi, Arivalagan/0000-0002-9529-3306; Mani, Rajesh/0000-0001-8649-0212	National natural science foundation of ChinaNational Natural Science Foundation of China (NSFC) [81973525]; Jiangsu Branch of China Academy of Chinese Medical Sciences [Y201803]	This work was supported by the National natural science foundation of China (Grant No. 81973525), Jiangsu Branch of China Academy of Chinese Medical Sciences (Grant No. Y201803, Nanjing 210028, China).	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DEC	2019	87						174	178		10.1016/j.procbio.2019.09.006			5	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Engineering, Chemical	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Engineering	JZ4WV	WOS:000505103600023					2022-04-25	
J	Cirone, M; Lotti, LV; Granato, M; Di Renzo, L; Biunno, I; Cattaneo, M; Verginelli, F; Vespa, S; Davies, D; Wells, V; Mariani-Costantini, R; Mallucci, L				Cirone, Mara; Lotti, Lavinia Vittoria; Granato, Marisa; Di Renzo, Livia; Biunno, Ida; Cattaneo, Monica; Verginelli, Fabio; Vespa, Simone; Davies, Derek; Wells, Valerie; Mariani-Costantini, Renato; Mallucci, Livio			Sourcing the immune system to induce immunogenic cell death in Kras-colorectal cancer cells	BRITISH JOURNAL OF CANCER			English	Article							GALACTOSIDE-BINDING PROTEIN; CALRETICULIN EXPOSURE; ER STRESS; BETA-GBP; AUTOPHAGY; PATHWAY; PI3K	BACKGROUND: Current approaches aimed at inducing immunogenic cell death (ICD) to incite an immune response against cancer neoantigens are based on the use of chemotherapeutics and other agents. Results are hampered by issues of efficacy, combinatorial approaches, dosing and toxicity. Here, we adopted a strategy based on the use of an immunomolecule that overcomes pharmachemical limitations. METHODS: Cytofluorometry, electron microscopy, RT-PCR, western blotting, apotome immunofluorescence, MLR and xenografts. RESULTS: We report that an ICD process can be activated without the use of pharmacological compounds. We show that in Krasmut/TP53-mut colorectal cancer cells the 15 kDa beta GBP cytokine, a T cell effector with onco-suppressor properties and a potential role in cancer immunosurveillance, induces key canonical events required for ICD induction. We document ER stress, autophagy that extends from cancer cells to the corresponding xenograft tumours, CRT cell surface shifting, ATP release and evidence of dendritic cell activation, a process required for priming cytotoxic T cells into a specific anticancer immunogenic response. CONCLUSIONS: Our findings provide experimental evidence for a rationale to explore a strategy based on the use of an immunomolecule that as a single agent couples oncosuppression with the activation of procedures necessary for the induction of long term response to cancer.	[Cirone, Mara; Lotti, Lavinia Vittoria; Granato, Marisa; Di Renzo, Livia] Univ Roma La Sapienza, Dipartimento Med Sperimentale, Viale Regina Elena 324, I-0061 Rome, Italy; [Biunno, Ida; Cattaneo, Monica] CNR, Ist Ric Genet & Biomed, Via Fantoli 15-16, I-20138 Milan, Italy; [Verginelli, Fabio] Univ G dAnnunzio, Dipartimento Farm, Via Vestini 1, I-66100 Chieti, Italy; [Vespa, Simone; Mariani-Costantini, Renato] Univ G DAnnunzio, Dipartimento Sci Med Orali & Biotechnol, Unita Patol Gen, Via Luigi Polacchi 11, I-66100 Chieti, Italy; [Vespa, Simone; Mariani-Costantini, Renato] Univ G DAnnunzio, Ctr Ateneo Ric Invecchiamento & Malattie Correlat, Via Luigi Polacchi 11, I-66100 Chieti, Italy; [Davies, Derek] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England; [Wells, Valerie] NYU London, 6 Bedford Sq, London WC1B 3RA, England; [Mallucci, Livio] Kings Coll London, Sch Canc & Pharmaceut Sci, Fac Life Sci & Med, Guys Campus, London SE1 1UL, England; [Cattaneo, Monica] MultiMedica, Via Fantoli 16-15, I-20138 Milan, Italy		Mallucci, L (corresponding author), Kings Coll London, Sch Canc & Pharmaceut Sci, Fac Life Sci & Med, Guys Campus, London SE1 1UL, England.	livio.mallucci@kcl.ac.uk	Granato, Marisa/K-6203-2014	Vespa, Simone/0000-0001-6146-9302; , IDA_2/0000-0002-1068-4763; /0000-0002-1866-5866; , Marisa/0000-0002-2758-5120; VERGINELLI, Fabio/0000-0002-8636-2517; Mariani-Costantini, Renato/0000-0002-4440-1848	King's College London; Universita' di Roma La Sapienza; G.d'Annunzio University Chieti	The work was supported by internal funding from King's College London, Universita' di Roma La Sapienza, and the G.d'Annunzio University Chieti.	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J. Cancer	OCT 29	2019	121	9					768	775		10.1038/s41416-019-0561-z			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	JI6GB	WOS:000493564700006	31558803	Green Submitted, Green Published, hybrid			2022-04-25	
J	Liu, KS; Guo, YM; Zheng, K; Zou, C; Wu, HX; Wang, SX; Ou, L; Wang, YF; Huang, BW; Wang, X				Liu, Kaisheng; Guo, Yaomin; Zheng, Kai; Zou, Chang; Wu, Haixiong; Wang, Shaoxiang; Ou, Ling; Wang, Yifei; Huang, Bowan; Wang, Xiao			Identification of the circRNA-miRNA-mRNA regulatory network of Hsp90 inhibitor-induced cell death in colorectal cancer by integrated analysis	GENE			English	Article						Colorectal cancer; SNX-2112; Cell death; mRNA; miRNA; circRNA	APOPTOSIS; AUTOPHAGY	Colorectal cancer (CRC) is a global disease with high incidence and mortality rate. Hsp90 inhibitors induce cell death in various cancers, including CRC. However, the underlying mechanisms need to be clarified further. In this study, Caco-2 cells were treated with 0.25 mu M SNX-2112, an Hsp90 inhibitor, for 48 h; subsequently, whole-transcriptome sequencing was performed. At the mRNA level in SNX-2112-treated Caco-2 cells, 1588 genes were upregulated, and 433 genes were downregulated. Six genes were found to be associated with necroptosis and apoptosis, and these 6 upregulated genes were validated by RT-qPCR. Hundred and six miRNAs were upregulated, and 48 miRNAs were downregulated in SNX-2112-treated Caco-2 cells. Eleven downregulated miRNAs were found to interact with the 6 upregulated genes. Moreover, 676 circRNAs were upregulated, and 291 circRNAs were downregulated in SNX-2112-treated Caco-2 cells. Among them, 126 circRNAs were found to be the target of the 11 downregulated miRNAs. The circRNA-miRNA-mRNA regulatory network of Hsp90 inhibitor-induced cell death in colorectal cancer was constructed. This regulatory network extends the underlying mechanism of Hsp90 and improves our understanding of Hsp90 inhibitors as potential targeted therapeutic agents.	[Liu, Kaisheng; Guo, Yaomin; Zou, Chang; Wu, Haixiong; Ou, Ling; Wang, Xiao] Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Southern Univ Sci & Technol,Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China; [Zheng, Kai; Wang, Shaoxiang] Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen 518060, Guangdong, Peoples R China; [Wang, Yifei] Jinan Univ, Coll Life Sci & Technol, Inst Biomed, Guangzhou 510632, Guangdong, Peoples R China; [Huang, Bowan] Cent Peoples Hosp Zhanjiang, Dept Anesthesiol, Zhanjiang 524000, Guangdong, Peoples R China		Wang, X (corresponding author), Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Southern Univ Sci & Technol,Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China.; Huang, BW (corresponding author), Cent Peoples Hosp Zhanjiang, Dept Anesthesiol, Zhanjiang 524000, Guangdong, Peoples R China.	bowanhuang@126.com; wangxiao0719@163.com	Zheng, Kai/AAT-8994-2021; Zou, Chang/AAS-3356-2021	Zheng, Kai/0000-0001-9275-1239; Zou, Chang/0000-0002-2003-7834; Wang, Xiao/0000-0001-8824-6280; Liu, Kaisheng/0000-0002-4755-0523	Cultivating Fund Project of Shenzhen People's Hospital [SYKYPY201928]; Science and Technology Foundation of Shenzhen [JCYJ20180301170047864, GJHZ20180928171802117]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81802749]	This research was funded by the Cultivating Fund Project of Shenzhen People's Hospital (SYKYPY201928), the Science and Technology Foundation of Shenzhen (JCYJ20180301170047864, GJHZ20180928171802117), and the National Natural Science Foundation of China (No. 81802749).	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J	Yassin, AM; El-Deeb, NM; Elsaid, FG; Shati, AA; Cioca, G; Tit, DM; Bungau, S; Popa, A; Hafez, EE				Yassin, Abdelrahman Mohamed; El-Deeb, Nehal Mohamed; Elsaid, Fahmy Gad; Shati, Ali Abdullah; Cioca, Gabriela; Tit, Delia Mirela; Bungau, Simona; Popa, Amorin; Hafez, Elsayed Elsayed			Lectin from Pisum fulvum Seeds as in vitro Anticancer and Apoptotic Gene Regulator	REVISTA DE CHIMIE			English	Article						lectin; Pisum fulvum; Fabaceae; cancer cell lines; antioxidant; anticancer	CONCANAVALIN-A; PURIFICATION; CELLS; POPULATION; AUTOPHAGY; ANTITUMOR; THERAPY; OBESITY	The lectins are non-immune origin carbohydrate-binding proteins. Plant's lectins are distributed in many species of medicinal plants, family Fabaceae. In this study the safety usage pattern of wild Pisum fulvum lectin was evaluated on different mammalian noncancerous cell types and the anticancer activity was examined on different cancer human cell lines: colorectal adenocarcinoma (Caco-2), hepatocellular carcinoma (HepG2), breast cancer cells (MCF7) and laryngeal carcinoma (Hep-2 cells). Moreover, both morphological and molecular evidence of apoptosis have been detected using both acridine orange/ethidium bromide (AO/EB) stain and RT-qPCR. The results revealed that IC50 of the wild lectin on the noncancerous cells ranged from 19.7 to 2.4 mu g protein/mL. In addition, lectin was more potent against HepG2 cells than the other used cells, with inhibition percentages ranged from 68.45 to 90.98 and with cancer cell selectivity index ranged 3.5 to 28.14. The treatment showed 67.6% inhibition of BrdU incorporation in the proliferated hepatocellular carcinoma cells. Furthermore, HepG2-lectin treated cells showed obvious nuclear condensation after 48 h of treatment with ability to down-regulate the expression of BCL2 and BAX and to up-regulate the expression of Ikab gene. The results obtained in this research work clearly indicated the Pisum fulvum lectin could be a promising potential anticancer agent.	[Yassin, Abdelrahman Mohamed; El-Deeb, Nehal Mohamed] City Sci Res & Technol Applicat, Genet Engn & Biotechnol Res Inst, Biopharmacet Prod Res Dept, Alexandria 21934, Egypt; [Elsaid, Fahmy Gad; Shati, Ali Abdullah] King Khalid Univ, RCAMS, Box 9004, Abha 61413, Saudi Arabia; [Elsaid, Fahmy Gad; Shati, Ali Abdullah] King Khalid Univ, Sci Coll, Biol Dept, Abha 61321, Saudi Arabia; [Elsaid, Fahmy Gad] Mansoura Univ, Fac Sci, Zool Dept, Mansoura 35516, Egypt; [Cioca, Gabriela] Lucian Blaga Univ Sibiu, Fac Med, 10 Victoriei Blvd, Sibiu 550024, Romania; [Tit, Delia Mirela; Bungau, Simona; Popa, Amorin] Univ Oradea, Fac Med & Pharm, Oradea 410028, Romania; [Hafez, Elsayed Elsayed] City Sci Res & Technol Applicat, ALCRI, Dept Plant Protect & Biomol Diag, Alexandria 21934, Egypt		Cioca, G (corresponding author), Lucian Blaga Univ Sibiu, Fac Med, 10 Victoriei Blvd, Sibiu 550024, Romania.; Popa, A (corresponding author), Univ Oradea, Fac Med & Pharm, Oradea 410028, Romania.	gabriela.cioca@ulbsibiu.ro; popa_amorin@yahoo.com	hafez, elsayed/ABG-2456-2021; Bungau, Simona Gabriela/C-1831-2015; Tit, Delia Mirela/AAT-5032-2020; Cioca, Gabriela/B-5504-2012	hafez, elsayed/0000-0003-4044-5103; Bungau, Simona Gabriela/0000-0003-3236-1292; Tit, Delia Mirela/0000-0002-0296-6592; Cioca, Gabriela/0000-0003-1165-1389; Yassin, Abdelrahman/0000-0001-6780-1521; Shati, Ali/0000-0003-1800-7238			Abdullaev FI, 1997, ARCH LATINOAM NUTR, V47, P195; AL-SOHAIMY A, 2007, AUST J BASIC APPL SC, V1, P213; Borenfreund E., 1985, J TISS CULT METHODS, V9, P7, DOI DOI 10.1007/BF01666038; Cagliari R, 2018, INT J BIOL MACROMOL, V119, P811, DOI 10.1016/j.ijbiomac.2018.07.156; Chang CP, 2007, HEPATOLOGY, V45, P286, DOI 10.1002/hep.21509; Cheung AHK, 2009, PHYTOMEDICINE, V16, P594, DOI 10.1016/j.phymed.2008.12.016; Coligan J, 1995, CURRENT PROTOCOLS IM; Faheina-Martins GV, 2012, TOXICOL IN VITRO, V26, P1161, DOI 10.1016/j.tiv.2012.06.017; Fang EF, 2010, J AGR FOOD CHEM, V58, P2221, DOI 10.1021/jf903964u; Fodor K, 2018, OXID MED CELL LONGEV, V2018, DOI 10.1155/2018/4147320; Gabius HJ, 2002, BBA-GEN SUBJECTS, V1572, P165, DOI 10.1016/S0304-4165(02)00306-9; Guja C, 2016, DIABETES RES CLIN PR, V120, pS101; Guja C, 2016, INT C INTERD MANAG D, P255; Guja C, 2015, INTERDISCIPLINARY APPROACHES IN DIABETIC CHRONIC KIDNEY DISEASE, P230; HAFEZ E. 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Chim.	APR	2019	70	4					1490	1495					6	Chemistry, Multidisciplinary; Engineering, Chemical	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry; Engineering	IA2JK	WOS:000469387200080					2022-04-25	
J	Manne, NDPK; Lima, M; Enos, RT; Wehner, P; Carson, JA; Blough, E				Manne, Nandini D. P. K.; Lima, M.; Enos, R. T.; Wehner, P.; Carson, J. A.; Blough, Eric			Altered cardiac muscle mTOR regulation during the progression of cancer cachexia in the Apc(Min/+) mouse	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						cachexia; Apc(Min/+); heart; Akt; AMPK; mTOR	PROTEIN-SYNTHESIS; SKELETAL-MUSCLE; AMPK ACTIVITY; CELL-DEATH; INTERLEUKIN-6; ATROPHY; MICE; PHOSPHORYLATION; TUMORIGENESIS; ACTIVATION	Cancer cachexia is a muscle wasting condition that occurs in response to a malignant growth in the body. The mechanisms regulating cardiac muscle mass with cachexia are not well understood. Using the Apc(Min/+) mouse model of colorectal cancer, we investigated how cachexia affects the regulation of 5'-adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (Akt) and mammalian target of rapamycin (mTOR) signaling in the heart. Compared to age-matched C57BL/6 (BL6) mice, Apc(Min/+) body mass and heart mass were lower at 12 (11+/-5 and 8+/-3%, respectively) and 20 weeks (26+/-3 and 6+/-4%, respectively) of age (P<0.05). Diminished heart mass in the 20-week-old Apc(Min/+) mice coincided with a decreased rate of myofibrillar protein synthesis and increased AMPK alpha phosphorylation. Cachexia decreased mTOR phosphorylation and the phosphorylation of the mTOR substrates, S6 ribosomal protein and 4EBP1 independent of Akt activation. These changes in mTOR-related protein signaling were accompanied by modest increases in the amount of Beclin1 but not protein ubiquitination or cardio-myocyte apoptosis. Taken together, these data suggest that loss of cardiac mass during cachexia progression in the Apc(Min/+) mouse is associated with an Akt-independent suppression of anabolic signaling and evidence of increased autophagy.	[Manne, Nandini D. P. K.; Blough, Eric] Marshall Univ, Ctr Diagnost Nanosyst, Huntington, WV 25755 USA; [Manne, Nandini D. P. K.; Blough, Eric] Marshall Univ, Dept Pharmacol Physiol & Toxicol, Huntington, WV 25755 USA; [Wehner, P.; Blough, Eric] Marshall Univ, Joan C Edwards Sch Med, Dept Cardiol, Huntington, WV 25755 USA; Marshall Univ, Sch Pharm, Dept Pharmaceut Sci & Res, Huntington, WV 25755 USA; [Lima, M.; Enos, R. T.; Carson, J. A.] Univ S Carolina, Appl Physiol Div Exercise Sci, Integrated Muscle Biol Lab, Columbia, SC 29208 USA		Blough, E (corresponding author), Marshall Univ, Ctr Diagnost Nanosyst, Dept Pharmaceut Sci & Res, Room 241N,Robert C Byrd Biotechnol Sci Ctr Bldg,1, Huntington, WV 25755 USA.	blough@marshall.edu	Manne, Nandini Durga Prasanna Kumar/ABD-5834-2021; Enos, Reilly/AFO-4814-2022; Carson, James/Q-5693-2019	Manne, Nandini Durga Prasanna Kumar/0000-0001-9159-0090; Enos, Reilly/0000-0001-5571-4586; Carson, James/0000-0003-3733-8796; Lima, Maria/0000-0002-0289-3477	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RO1CA121249]; DOEUnited States Department of Energy (DOE) [DE-PS02-09ER-01]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA121249] Funding Source: NIH RePORTER	This study was supported from NIH grant RO1CA121249 (to J.A.C), DOE grant (DE-PS02-09ER-01 to E.R.B). The authors would like to thank John W. Baynes and Suichi Sato for their technical input related to the heart protein synthesis measurements.	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J. Oncol.	JUN	2013	42	6					2134	2140		10.3892/ijo.2013.1893			7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	151WI	WOS:000319490700033	23589074	Green Submitted, Green Published, Bronze			2022-04-25	
J	Kawada, K; Toda, K; Sakai, Y				Kawada, Kenji; Toda, Kosuke; Sakai, Yoshiharu			Targeting metabolic reprogramming in KRAS-driven cancers	INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY			English	Review						KRAS; Cancer metabolism; Reprograming; Glycolysis; Glutaminolysis	AMINO-ACID TRANSPORTERS; F-18-FLUORODEOXYGLUCOSE ACCUMULATION; GLUTAMINE-METABOLISM; MAMMALIAN-CELLS; MUTATIONS; AUTOPHAGY; HYDROXYCHLOROQUINE; ADAPTATION; PATHWAY; TUMORS	Mutations of KRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. To date, no effective treatments that target mutant variants of KRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogene KRAS plays a critical role in controlling cancer metabolism by orchestrating multiple metabolic changes. One of the metabolic hallmarks of malignant tumor cells is their dependency on aerobic glycolysis, known as the Warburg effect. The role of KRAS signaling in the regulation of aerobic glycolysis has been reported in several types of cancer. KRAS-driven cancers are characterized by altered metabolic pathways involving enhanced nutrients uptake, enhanced glycolysis, enhanced glutaminolysis, and elevated synthesis of fatty acids and nucleotides. However, Just how mutated KRAS can coordinate the metabolic shift to promote tumor growth and whether specific metabolic pathways are essential for the tumorigenesis of KRAS-driven cancers are questions which remain to be answered. In this context, the aim of this review is to summarize current data on KRAS-related metabolic alterations in cancer cells. Given that cancer cells rely on changes in metabolism to support their growth and survival, the targeting of metabolic processes may be a potential strategy for treating KRAS-driven cancers.	[Kawada, Kenji; Toda, Kosuke; Sakai, Yoshiharu] Kyoto Univ, Grad Sch Med, Dept Surg, Sakyo Ku, 54 Shogoin Kawara Cho, Kyoto 6068507, Japan		Kawada, K (corresponding author), Kyoto Univ, Grad Sch Med, Dept Surg, Sakyo Ku, 54 Shogoin Kawara Cho, Kyoto 6068507, Japan.	kkawada@kuhp.kyoto-u.ac.jp					Aguilera O, 2016, ONCOTARGET, V7, P47954, DOI 10.18632/oncotarget.10087; Balasubramanian MN, 2013, AM J PHYSIOL-ENDOC M, V304, pE789, DOI 10.1152/ajpendo.00015.2013; Bhutia YD, 2016, BBA-MOL CELL RES, V1863, P2531, DOI 10.1016/j.bbamcr.2015.12.017; Bhutia YD, 2015, CANCER RES, V75, P1782, DOI 10.1158/0008-5472.CAN-14-3745; Bryant KL, 2014, TRENDS BIOCHEM SCI, V39, P91, DOI 10.1016/j.tibs.2013.12.004; Caicedo C, 2014, EUR J NUCL MED MOL I, V41, P2058, DOI 10.1007/s00259-014-2833-4; Cairns RA, 2011, NAT REV CANCER, V11, P85, DOI 10.1038/nrc2981; Chen SW, 2014, CLIN NUCL MED, V39, P685, DOI 10.1097/RLU.0000000000000481; Cohen R, 2015, ONCOTARGET, V6, P16832, DOI 10.18632/oncotarget.4160; Commisso C, 2013, NATURE, V497, P633, DOI 10.1038/nature12138; 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J. Clin. Oncol.	AUG	2017	22	4					651	659		10.1007/s10147-017-1156-4			9	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	FC2ST	WOS:000406689300007	28647837				2022-04-25	
J	Queiroz, KCS; Milani, R; Ruela-de-Sousa, RR; Fuhler, GM; Justo, GZ; Zambuzzi, WF; Duran, N; Diks, SH; Spek, CA; Ferreira, CV; Peppelenbosch, MP				Queiroz, Karla C. S.; Milani, Renato; Ruela-de-Sousa, Roberta R.; Fuhler, Gwenny M.; Justo, Giselle Z.; Zambuzzi, Willian F.; Duran, Nelson; Diks, Sander H.; Spek, C. Arnold; Ferreira, Carmen V.; Peppelenbosch, Maikel P.			Violacein Induces Death of Resistant Leukaemia Cells via Kinome Reprogramming, Endoplasmic Reticulum Stress and Golgi Apparatus Collapse	PLOS ONE			English	Article							CHROMOBACTERIUM-VIOLACEUM; COLORECTAL-CANCER; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; DAP-KINASE; APOPTOSIS; MECHANISM; CALPAIN; INHIBITION; EXPRESSION	It is now generally recognised that different modes of programmed cell death (PCD) are intimately linked to the cancerous process. However, the mechanism of PCD involved in cancer chemoprevention is much less clear and may be different between types of chemopreventive agents and tumour cell types involved. Therefore, from a pharmacological view, it is crucial during the earlier steps of drug development to define the cellular specificity of the candidate as well as its capacity to bypass dysfunctional tumoral signalling pathways providing insensitivity to death stimuli. Studying the cytotoxic effects of violacein, an antibiotic dihydro-indolone synthesised by an Amazon river Chromobacterium, we observed that death induced in CD34(+)/c-Kit(+)/P-glycoprotein(+)/MRP1(+) TF1 leukaemia progenitor cells is not mediated by apoptosis and/or autophagy, since biomarkers of both types of cell death were not significantly affected by this compound. To clarify the working mechanism of violacein, we performed kinome profiling using peptide arrays to yield comprehensive descriptions of cellular kinase activities. Pro-death activity of violacein is actually carried out by inhibition of calpain and DAPK1 and activation of PKA, AKT and PDK, followed by structural changes caused by endoplasmic reticulum stress and Golgi apparatus collapse, leading to cellular demise. Our results demonstrate that violacein induces kinome reprogramming, overcoming death signaling dysfunctions of intrinsically resistant human leukaemia cells.	[Fuhler, Gwenny M.; Peppelenbosch, Maikel P.] Erasmus MC Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands; [Queiroz, Karla C. S.; Ruela-de-Sousa, Roberta R.; Spek, C. Arnold] Univ Amsterdam, Acad Med Ctr, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, Netherlands; [Queiroz, Karla C. S.; Milani, Renato; Ruela-de-Sousa, Roberta R.; Ferreira, Carmen V.] Univ Estadual Campinas, Brazil UNICAMP, Dept Biochem, Inst Biol, Sao Paulo, Brazil; [Justo, Giselle Z.] Fed Univ Sao Paulo UNIFESP, Dept Biochem, Sao Paulo, Brazil; [Justo, Giselle Z.] Fed Univ Sao Paulo UNIFESP, Dept Cell Biol, Sao Paulo, Brazil; [Zambuzzi, Willian F.] Univ Grande Rio UNIGRANRIO, Heath Sci Sch, Multidisciplinary Lab Dent Res, Rio De Janeiro, Brazil; [Zambuzzi, Willian F.] Natl Inst Metrol Qual & Technol Inmetro, Biotechnol Lab, Bioengn Sect, Rio De Janeiro, Brazil; [Duran, Nelson] Univ Campinas UNICAMP, Inst Chem, Biol Chem Lab, Rio De Janeiro, Brazil; [Diks, Sander H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat Oncol, Beatrix Childrens Hosp, Groningen, Netherlands		Peppelenbosch, MP (corresponding author), Erasmus MC Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands.	M.Peppelenbosch@erasmusmc.nl	Fuhler, Gwenny/AAC-7122-2019; Milani, Renato/G-1037-2010; Inomat, Inct/H-9989-2013; Spek, Arnold/AAC-5866-2019; Zambuzzi, Willian/ABD-8339-2020; Peppelenbosch, Maikel P./U-5304-2019; Ruela de Sousa, Roberta/C-6825-2012; Queiroz, Karla/L-6438-2014; Zambuzzi, Willian Fernando/F-9519-2012	Fuhler, Gwenny/0000-0001-9221-4855; Milani, Renato/0000-0002-6902-6589; Spek, Arnold/0000-0002-2149-4068; Ruela de Sousa, Roberta/0000-0002-3762-2247; Zambuzzi, Willian Fernando/0000-0002-4149-5965; Duran, Nelson/0000-0001-8372-5143; Peppelenbosch, Maikel/0000-0001-9112-6028	TopInstitute pharma (The Netherlands)Netherlands Government; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ); Dutch Cancer SocietyKWF Kankerbestrijding [EMCR 2010-4737]	This work was supported by grants from TopInstitute pharma (The Netherlands), Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). CVF was supported by a research fellowship from CNPq. GMF was supported by the Dutch Cancer Society (grant EMCR 2010-4737). 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	Kim, MJ; Huang, YJ; Park, JI				Kim, Moon Jong; Huang, Yuanjian; Park, Jae-Il			Targeting Wnt Signaling for Gastrointestinal Cancer Therapy: Present and Evolving Views	CANCERS			English	Review						Wnt signaling; &#946; -catenin; cancer; gastrointestinal cancers; therapeutic targeting of Wnt signaling; &#946; -catenin paradox; molecular targeting	SMALL-MOLECULE INHIBITOR; BETA-CATENIN DEGRADATION; WNT/BETA-CATENIN; COLORECTAL-CANCER; STEM-CELLS; PHASE-I; AUTOPHAGY INHIBITION; TANKYRASE INHIBITOR; FRIZZLED HOMOLOGS; BREAST-CANCER	Simple Summary Therapeutic targeting of Wnt has long been suggested for gastrointestinal (GI) cancer treatment because deregulation of Wnt signaling is associated with GI cancers. However, therapeutic targeting of Wnt is still challenging because of the pleiotropic roles of Wnt signaling in the human body. Thus, targeting strategies of Wnt signaling are continuously evolving. The current flows of targeting Wnt signaling for cancer treatment are focused on increasing the specificity of drugs and combinatory treatment with other cancer drugs that minimize side effects and increase efficacy. Additionally, increased knowledge about the beta-catenin paradox has expanded the cases that can be treated with Wnt targeting therapy, not strictly considering Wnt upstream and downstream mutations. Here, we discuss these evolving views of targeting Wnt signaling and describe examples of current clinical trials. Wnt signaling governs tissue development, homeostasis, and regeneration. However, aberrant activation of Wnt promotes tumorigenesis. Despite the ongoing efforts to manipulate Wnt signaling, therapeutic targeting of Wnt signaling remains challenging. In this review, we provide an overview of current clinical trials to target Wnt signaling, with a major focus on gastrointestinal cancers. In addition, we discuss the caveats and alternative strategies for therapeutically targeting Wnt signaling for cancer treatment.	[Kim, Moon Jong; Huang, Yuanjian; Park, Jae-Il] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA; [Park, Jae-Il] Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci, Houston, TX 77030 USA; [Park, Jae-Il] Hlth Sci Ctr, Houston, TX 77030 USA; [Park, Jae-Il] Univ Texas MD Anderson Canc Ctr, Program Genet & Epigenet, Houston, TX 77030 USA		Park, JI (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA.; Park, JI (corresponding author), Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci, Houston, TX 77030 USA.; Park, JI (corresponding author), Hlth Sci Ctr, Houston, TX 77030 USA.; Park, JI (corresponding author), Univ Texas MD Anderson Canc Ctr, Program Genet & Epigenet, Houston, TX 77030 USA.	mkim312@mdanderson.org; yhuang14@mdanderson.org; jaeil@mdanderson.org	park, jaeil/AAS-5894-2021; Kim, Moon Jong/AAK-7406-2021	Kim, Moon Jong/0000-0002-7876-4639; PARK, JAE-IL/0000-0002-0737-2654	National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [2R01 CA193297]; Department of Defense Peer Reviewed Cancer Research ProgramUnited States Department of Defense [CA140572]; Specialized Program of Research Excellence (SPORE) grant in endometrial cancer [P50 CA83639]; ROSI Seed Award [00057597]; Institutional Research Grant (MD Anderson);  [RP140563];  [RP200315]	This work was supported by grants to the Cancer Prevention and Research Institute of Texas (RP140563 and RP200315 to J.-I.P.), the National Institutes of Health (2R01 CA193297 to J.-I.P.), the Department of Defense Peer Reviewed Cancer Research Program (CA140572 to J.-I.P.), an Institutional Research Grant (MD Anderson to J.-I.P.), a Specialized Program of Research Excellence (SPORE) grant in endometrial cancer (P50 CA83639), and an ROSI Seed Award (00057597 to M.J.K.).	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J	Liu, SH; Joshi, K; Denning, MF; Zhang, JW				Liu, Shanhui; Joshi, Kanak; Denning, Mitchell F.; Zhang, Jiwang			RIPK3 signaling and its role in the pathogenesis of cancers	CELLULAR AND MOLECULAR LIFE SCIENCES			English	Review						RIPK3 signaling; MLKL necroptosis; MLKL-independent signaling; Cancer pathogenesis	MIXED LINEAGE KINASE; NF-KAPPA-B; DOMAIN-LIKE PROTEIN; RECEPTOR-INTERACTING PROTEIN; NECROPTOSIS ADAPTER RIPK3; SHIKONIN-INDUCED NECROPTOSIS; INDUCED CELL-DEATH; PROGRAMMED NECROSIS; NUCLEAR TRANSLOCATION; PROGNOSTIC BIOMARKER	RIPK3 (receptor-interacting protein kinase 3) is a serine/threonine-protein kinase. As a key component of necrosomes, RIPK3 is an essential mediator of inflammatory factors (such as TNF alpha-tumor necrosis factor alpha) and infection-induced necroptosis, a programmed necrosis. In addition, RIPK3 signaling is also involved in the regulation of apoptosis, cytokine/chemokine production, mitochondrial metabolism, autophagy, and cell proliferation by interacting with and/or phosphorylating the critical regulators of the corresponding signaling pathways. Similar to apoptosis, RIPK3-signaling-mediated necroptosis is inactivated in most types of cancers, suggesting RIPK3 might play a critical suppressive role in the pathogenesis of cancers. However, in some inflammatory types of cancers, such as pancreatic cancers and colorectal cancers, RIPK3 signaling might promote cancer development by stimulating proliferation signaling in tumor cells and inducing an immunosuppressive response in the tumor environment. In this review, we summarize recent research progress in the regulators of RIPK3 signaling, and discuss the function of this pathway in the regulation of mixed lineage kinase domain-like (MLKL)-mediated necroptosis and MLKL-independent cellular behaviors. In addition, we deliberate the potential roles of RIPK3 signaling in the pathogenesis of different types of cancers and discuss the potential strategies for targeting this pathway in cancer therapy.	[Liu, Shanhui; Joshi, Kanak; Denning, Mitchell F.; Zhang, Jiwang] Loyola Univ Med Ctr, Dept Canc Biol, Inst Oncol, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA; [Zhang, Jiwang] Loyola Univ Med Ctr, Dept Pathol, Maywood, IL 60153 USA; [Zhang, Jiwang] Loyola Univ Med Ctr, Dept Radiat Oncol, Maywood, IL 60153 USA		Zhang, JW (corresponding author), Loyola Univ Med Ctr, Dept Canc Biol, Inst Oncol, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA.; Zhang, JW (corresponding author), Loyola Univ Med Ctr, Dept Pathol, Maywood, IL 60153 USA.; Zhang, JW (corresponding author), Loyola Univ Med Ctr, Dept Radiat Oncol, Maywood, IL 60153 USA.	jzhang@luc.edu		shanhui, liu/0000-0001-9254-5339	NIH through Loyola University Chicago [R01 HL133560-01, R01 CA223194-01]; Loyola program development funds	This work was supported by NIH Grants R01 HL133560-01 and R01 CA223194-01 through Loyola University Chicago, as well as Loyola program development funds to Jiwang Zhang.	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Mol. Life Sci.	DEC	2021	78	23					7199	7217		10.1007/s00018-021-03947-y		OCT 2021	19	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	XE9QL	WOS:000707516100001	34654937				2022-04-25	
J	Park, SY; Park, C; Park, SH; Hong, SH; Kim, GY; Hong, SH; Choi, YH				Park, Seon Young; Park, Cheol; Park, Shin-Hyung; Hong, Su-Hyun; Kim, Gi-Young; Hong, Sang Hoon; Choi, Yung-Hyun			Induction of apoptosis by ethanol extract of Evodia rutaecarpa in HeLa human cervical cancer cells via activation of AMP-activated protein kinase	BioScience Trends			English	Article						Evodia rutaecarpa; cervical cancer; apoptosis; caspase; AMPK	COLORECTAL-CANCER; UPSTREAM KINASE; TUMOR-CELLS; GROWTH; MITOCHONDRIA; METFORMIN; AUTOPHAGY; PATHWAYS; STRESS; EXPRESSION	The fruit of Evodia rutaecarpa (Juss.) Benth has been used widely in traditional medicine therapy. Although it has been shown to possess many pharmacological activities, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated. In the present study, we investigated the pro-apoptotic effects of an ethanol extract isolated from immature fruits of E. rutaecarpa (EEER) in HeLa human cervical cancer cells. EEER treatment decreased the cell viability of HeLa cells in a concentration-dependent manner, which was related to apoptotic cell death resulting from apoptotic body formation, DNA fragmentation, and an increased population of annexin V+-positive cells. EEER treatment significantly suppressed anti-apoptotic Bcl-2 expression, leading to subsequent loss of mitochondrial membrane potential (MMP), while it did not change expression levels of death receptor (DR)-related proteins. EEER treatment increased activity of caspase-3 and-9 but not caspase-8, and pretreatment of a caspase-3 inhibitor markedly attenuated EEER-induced apoptosis. Furthermore, EEER activated the AMP-activated protein kinase (AMPK) signaling pathway; however, inhibition of AMPK markedly abrogated EEER-induced apoptosis. Overall, the results suggest that the apoptotic activity of EEER may be associated with a caspase-dependent cascade through activation of the intrinsic signaling pathway connected with AMPK activation. E. rutaecarpa could be a prospective clinical application to treat human cervical cancer.	[Park, Seon Young; Hong, Sang Hoon] Dong Eui Univ, Coll Korean Med, Dept Internal Med, Busan 47227, South Korea; [Park, Cheol] Dong Eui Univ, Coll Nat Sci & Human Ecol, Dept Mol Biol, Busan, South Korea; [Park, Shin-Hyung] Dong Eui Univ, Coll Korean Med, Dept Pathol, Busan, South Korea; [Hong, Su-Hyun; Choi, Yung-Hyun] Dong Eui Univ, Coll Korean Med, Dept Biochem, Busan 47227, South Korea; [Kim, Gi-Young] Jeju Natl Univ, Sch Marine Biomed Sci, Dept Marine Life Sci, Jeju, South Korea; [Choi, Yung-Hyun] Dong Eui Univ, Antiaging Res Ctr, Busan, South Korea		Hong, SH (corresponding author), Dong Eui Univ, Coll Korean Med, Dept Internal Med, Busan 47227, South Korea.; Choi, YH (corresponding author), Dong Eui Univ, Coll Korean Med, Dept Biochem, Busan 47227, South Korea.	shhong@deu.ac.kr; choiyh@deu.ac.kr	Park, Shin-Hyung/U-9406-2017	Park, Shin-Hyung/0000-0002-4792-3393	Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [2014R1A1A1008460, 2015R1A2A2A01004633]	This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2014R1A1A1008460 and 2015R1A2A2A01004633).	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Trends	DEC	2016	10	6					467	476		10.5582/bst.2016.01170			10	Biology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics	EI9FS	WOS:000392813900006	27890875	Bronze			2022-04-25	
J	Kuan, YD; Lee, CH				Kuan, Yu-Diao; Lee, Che-Hsin			Salmonella overcomes tumor immune tolerance by inhibition of tumor indoleamine 2, 3-dioxygenase 1 expression	ONCOTARGET			English	Article						salmonella; tumor-targeting; indoleamine 2; 3-dioxygenase 1; immune tolerance	TYPHIMURIUM A1-R; COLORECTAL-CANCER; TARGETED THERAPY; STEM-LIKE; 2,3-DIOXYGENASE; AUTOPHAGY; BACTERIAL; CELLS; METASTASIS; EFFICACY	Over the past decades, Salmonella has been proven capable of inhibiting tumor growth. It can specifically target tumors and due to its facultative anaerobic property, can be more penetrative than other drug therapies. However, the molecular mechanism by which Salmonella inhibits tumor growth is still incompletely known. The antitumor therapeutic effect mediated by Salmonella is associated with an inflammatory immune response at the tumor site and a T cell-dependent immune response. Many tumors have been proven to have a high expression of indoleamine 2, 3-dioxygenase 1 (IDO), which is a rate-limiting enzyme that catalyzes tryptophan to kynurenine, thus causing immune tolerance within the tumor microenvironment. With decreased expression of IDO, increased immune response can be observed, which might be helpful when developing cancer immunotherapy. The expression of IDO was decreased after tumor cells were infected with Salmonella. In addition, Western blot analysis showed that the expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and phospho-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased after Salmonella infection. In conclusion, our results indicate that Salmonella inhibits IDO expression and plays a crucial role in anti-tumor therapy, which might be a promising strategy combined with other cancer treatments.	[Kuan, Yu-Diao; Lee, Che-Hsin] China Med Univ, Grad Inst Basic Med Sci, Sch Med, Taichung, Taiwan; [Lee, Che-Hsin] China Med Univ, Sch Med, Dept Microbiol, Taichung, Taiwan		Lee, CH (corresponding author), China Med Univ, Grad Inst Basic Med Sci, Sch Med, Taichung, Taiwan.; Lee, CH (corresponding author), China Med Univ, Sch Med, Dept Microbiol, Taichung, Taiwan.	chlee@mail.cmu.edu.tw			Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [MOST 104-2320-B-039-042-MY3]	This work was supported by grants from the Ministry of Science and Technology, Taiwan (MOST 104-2320-B-039-042-MY3).	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J	Mendez-Blanco, C; Fondevila, F; Fernandez-Palanca, P; Garcia-Palomo, A; van Pelt, J; Verslype, C; Gonzalez-Gallego, J; Mauriz, JL				Mendez-Blanco, Carolina; Fondevila, Flavia; Fernandez-Palanca, Paula; Garcia-Palomo, Andres; van Pelt, Jos; Verslype, Chris; Gonzalez-Gallego, Javier; Mauriz, Jose L.			Stabilization of Hypoxia-Inducible Factors and BNIP3 Promoter Methylation Contribute to Acquired Sorafenib Resistance in Human Hepatocarcinoma Cells	CANCERS			English	Article						BNIP3; hepatocarcinoma; HIF; hypoxia; resistance; sorafenib	HEPATOCELLULAR-CARCINOMA CELLS; COLORECTAL-CANCER; UP-REGULATION; PROTECTIVE AUTOPHAGY; EXPRESSION; APOPTOSIS; GENE; MECHANISMS; 5-AZA-2'-DEOXYCYTIDINE; CHEMORESISTANCE	Despite sorafenib effectiveness against advanced hepatocarcinoma (HCC), long-term exposure to antiangiogenic drugs leads to hypoxic microenvironment, a key contributor to chemoresistance acquisition. We aimed to study the role of hypoxia in the development of sorafenib resistance in a human HCC in vitro model employing the HCC line HepG2 and two variants with acquired sorafenib resistance, HepG2S1 and HepG2S3, and CoCl2 as hypoximimetic. Resistant cells exhibited a faster proliferative rate and hypoxia adaptive mechanisms, linked to the increased protein levels and nuclear translocation of hypoxia-inducible factors (HIFs). HIF-1 alpha and HIF-2 alpha overexpression was detected even under normoxia through a deregulation of its degradation mechanisms. Proapoptotic markers expression and subG1 population decreased significantly in HepG2S1 and HepG2S3, suggesting evasion of sorafenib-mediated cell death. HIF-1 alpha and HIF-2 alpha knockdown diminished resistant cells viability, relating HIFs overexpression with its prosurvival ability. Additionally, epigenetic silencing of Bcl-2 interacting protein 3 (BNIP3) was observed in sorafenib resistant cells under hypoxia. Demethylation of BNIP3 promoter, but not histone acetylation, restored BNIP3 expression, driving resistant cells' death. Altogether, our results highlight the involvement of HIFs overexpression and BNIP3 methylation-dependent knockdown in the development of sorafenib resistance in HCC. Targeting both prosurvival mechanisms could overcome chemoresistance and improve future therapeutic approaches.	[Mendez-Blanco, Carolina; Fondevila, Flavia; Fernandez-Palanca, Paula; Gonzalez-Gallego, Javier; Mauriz, Jose L.] Univ Leon, Inst Biomed IBIOMED, Campus Vegazana S-N, E-24071 Leon, Spain; [Mendez-Blanco, Carolina; Fondevila, Flavia; Fernandez-Palanca, Paula; Gonzalez-Gallego, Javier; Mauriz, Jose L.] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Av Monforte de Lemos 5, Madrid 28029, Spain; [Garcia-Palomo, Andres] Complejo Asistencial Univ Leon, Serv Oncol, Calle Altos de Nava S-N, Leon 24001, Spain; [van Pelt, Jos; Verslype, Chris] Katholieke Univ Leuven, Dept Oncol, Lab Clin Digest Oncol, B-3000 Leuven, Belgium; [van Pelt, Jos; Verslype, Chris] Univ Hosp Leuven, B-3000 Leuven, Belgium; [van Pelt, Jos; Verslype, Chris] Leuven Canc Inst LKI, B-3000 Leuven, Belgium		Mauriz, JL (corresponding author), Univ Leon, Inst Biomed IBIOMED, Campus Vegazana S-N, E-24071 Leon, Spain.; Mauriz, JL (corresponding author), Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Av Monforte de Lemos 5, Madrid 28029, Spain.	cmenb@unileon.es; ffonp@unileon.es; pferp@unileon.es; dfijmg@unileon.es; jos.vanpelt@kuleuven.be; chris.verslype@uzleuven.be; jgonga@unileon.es; jl.mauriz@unileon.es	Fernández-Palanca, Paula/AAH-1161-2019; Mauriz, Jose L/G-9970-2014; Pena, Flavia Fondevila/S-2788-2018; Blanco, Carolina Méndez/AAR-9136-2021; Blanco, Carolina Méndez/L-2569-2017; Gonzalez-Gallego, Javier/D-8219-2012	Fernández-Palanca, Paula/0000-0001-9765-9562; Mauriz, Jose L/0000-0003-3160-8599; Pena, Flavia Fondevila/0000-0003-2881-704X; Blanco, Carolina Méndez/0000-0001-6378-2554; Blanco, Carolina Méndez/0000-0001-6378-2554; Gonzalez-Gallego, Javier/0000-0002-4386-9342; van Pelt, Jos/0000-0001-6903-4338; Verslype, Chris/0000-0003-3857-466X	Instituto de Salud Carlos III, SpainInstituto de Salud Carlos III; Asociacion Espanola Contra el Cancer (AECC)-Junta Provincial de Leon; Ministry of Education of SpainSpanish Government [FPU16/05277, FPU17/01995]	CIBERehd is funded by Instituto de Salud Carlos III, Spain. C.M.B. is supported by the Asociacion Espanola Contra el Cancer (AECC)-Junta Provincial de Leon. F.F. and P.F.P. by the Ministry of Education of Spain (FPU16/05277 and FPU17/01995 grants).	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J	D'Alessandro, R; Refolo, MG; Lippolis, C; Giannuzzi, G; Carella, N; Messa, C; Cavallini, A; Carr, BI				D'Alessandro, Rosalba; Refolo, Maria G.; Lippolis, Catia; Giannuzzi, Grazia; Carella, Nicola; Messa, Caterina; Cavallini, Aldo; Carr, Brian I.			Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines	BMC CANCER			English	Article						Regorefenib; Platelets; HCC; Apoptosis; Growth; Invasion	CANCER-CELLS; MULTIDRUG-RESISTANCE; RAF/MEK/ERK PATHWAY; COLORECTAL-CANCER; ANTICANCER DRUGS; HEPATOMA-CELLS; THROMBOCYTOSIS; RECEPTOR; GROWTH; ANGIOGENESIS	Background: Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of Sorafenib or Regorafenib, two clinical HCC multikinase antagonists. Methods: Several human HCC cell lines were grown in the presence and absence of Sorafenib or Regorafenib, with or without hPL. Growth was measured by MTT assay, apoptosis was assessed by Annexin V and by western blot, and autophagy and MAPK growth signaling were also measured by western blot, and migration and invasion were measured by standard in vitro assays. Results: Both Sorafenib and Regorafenib-mediated inhibition of cell growth, migration and invasion were all antagonized by hPL. Drug-mediated apoptosis and decrease in phospho-ERK levels were both blocked by hPL, which also increased anti-apoptotic phospho-STAT, Bax and Bcl-xL levels. Preliminary data, obtained with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), included in hPL, revealed that these factors were able to antagonized Sorafenib in a proliferation assay, in particular when used in combination. Conclusions: Platelet factors can antagonize Sorafenib or Regorafenib-mediated growth inhibition and apoptosis in HCC cells. The modulation of platelet activity or numbers has the potential to enhance multikinase drug actions.	[D'Alessandro, Rosalba; Refolo, Maria G.; Lippolis, Catia; Carella, Nicola; Messa, Caterina; Cavallini, Aldo; Carr, Brian I.] IRCCS Saverio de Bellis, Natl Inst Digest Dis, Lab Biochem, I-70013 Castellana Grotte, BA, Italy; [Giannuzzi, Grazia] S Maria degli Angeli Hosp, Transfus Med Ctr, I-70017 Putignano, BA, Italy		Carr, BI (corresponding author), IRCCS Saverio de Bellis, Natl Inst Digest Dis, Lab Biochem, Via Turi 27, I-70013 Castellana Grotte, BA, Italy.	brianicarr@hotmail.com	D'Alessandro, Rosalba/J-2351-2018	Carr, Brian/0000-0002-6111-5077	NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA82723]; Ministry of Health of ItalyMinistry of Health, Italy; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA082723] Funding Source: NIH RePORTER	This research was supported in part by NIH grant CA82723 (BIC) and by Ministry of Health of Italy. The content is solely the responsibility of the authors and does not necessarily represent the official views of either NIH or Italian Ministry of Health.	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J	Palethorpe, HM; Tomita, Y; Smith, E; Pei, JV; Townsend, AR; Price, TJ; Young, JP; Yool, AJ; Hardingham, JE				Palethorpe, Helen M.; Tomita, Yoko; Smith, Eric; Pei, Jinxin V.; Townsend, Amanda R.; Price, Timothy J.; Young, Joanne P.; Yool, Andrea J.; Hardingham, Jennifer E.			The Aquaporin 1 Inhibitor Bacopaside II Reduces Endothelial Cell Migration and Tubulogenesis and Induces Apoptosis	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Article						angiogenesis; aquaporin-1 (AQP1); bacopaside II; endothelial cell migration	METASTATIC COLORECTAL-CANCER; TUMOR ANGIOGENESIS; BEVACIZUMAB; THERAPY; CAPECITABINE; OXALIPLATIN; COMBINATION; AUTOPHAGY; MONNIERA; PLANT	Expression of aquaporin-1 (AQP1) in endothelial cells is critical for their migration and angiogenesis in cancer. We tested the AQP1 inhibitor, bacopaside II, derived from medicinal plant Bacopa monnieri, on endothelial cell migration and tube-formation in vitro using mouse endothelial cell lines (2H11 and 3B11) and human umbilical vein endothelial cells (HUVEC). The effect of bacopaside II on viability, apoptosis, migration and tubulogenesis was assessed by a proliferation assay, annexin-V/propidium iodide flow cytometry, the scratch wound assay and endothelial tube-formation, respectively. Cell viability was reduced significantly for 2H11 at 15 mu M (p = 0.037), 3B11 at 12.5 mu M (p = 0.017) and HUVEC at 10 mu M (p < 0.0001). At 15 mu M, the reduced viability was accompanied by an increase in apoptosis of 38%, 50% and 32% for 2H11, 3B11 and HUVEC, respectively. Bacopaside II at >= 10 mu M significantly reduced migration of 2H11 (p = 0.0002) and 3B11 (p = 0.034). HUVECs were most sensitive with a significant reduction at 7.5 mu M (p = 0.037). Tube-formation was reduced with a 15 mu M dose for all cell lines and 10 mu M for 3B11 (p < 0.0001). These results suggest that bacopaside II is a potential anti-angiogenic agent.	[Palethorpe, Helen M.; Tomita, Yoko; Smith, Eric; Young, Joanne P.; Hardingham, Jennifer E.] Queen Elizabeth Hosp, Basil Hetzel Inst, Mol Oncol, Woodville South, SA 5011, Australia; [Tomita, Yoko; Smith, Eric; Pei, Jinxin V.; Townsend, Amanda R.; Price, Timothy J.; Young, Joanne P.; Yool, Andrea J.; Hardingham, Jennifer E.] Univ Adelaide, Adelaide Med Sch, Adelaide, SA 5005, Australia; [Townsend, Amanda R.; Price, Timothy J.] Queen Elizabeth Hosp, Med Oncol, Woodville South, SA 5011, Australia		Hardingham, JE (corresponding author), Queen Elizabeth Hosp, Basil Hetzel Inst, Mol Oncol, Woodville South, SA 5011, Australia.; Hardingham, JE (corresponding author), Univ Adelaide, Adelaide Med Sch, Adelaide, SA 5005, Australia.	helen.palethorpe@adelaide.edu.au; yoko.tomita@sa.gov.au; eric.smith@adelaide.edu.au; jinxin.pei@adelaide.edu.au; amanda.townsend@sa.gov.au; timothy.price@sa.gov.au; joanne.young@adelaide.edu.au; andrea.yool@adelaide.edu.au; jenny.hardingham@sa.gov.au	Palethorpe, Helen Marie/AAC-4219-2022; Smith, Eric/ABG-7104-2020; Smith, Eric/Y-1350-2019; Yool, Andrea/AAK-9907-2020	Palethorpe, Helen Marie/0000-0003-3803-5113; Smith, Eric/0000-0003-2958-3492; Yool, Andrea/0000-0003-1283-585X; Tomita, Yoko/0000-0001-7934-2203; Hardingham, Jennifer/0000-0001-8277-1199	Australian Research CouncilAustralian Research Council [ARC DP160104641]; Hospital Research Foundation	This study was partly funded by grants from the Australian Research Council to Andrea J. Yool and Jennifer E. Hardingham (ARC DP160104641) and from the Hospital Research Foundation to Amanda R. Townsend, Jennifer E. Hardingham and Timothy J. Price.	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J	Jahangiri, L; Ishola, T; Pucci, P; Trigg, RM; Pereira, J; Williams, JA; Cavanagh, ML; Gkoutos, GV; Tsaprouni, L; Turner, SD				Jahangiri, Leila; Ishola, Tala; Pucci, Perla; Trigg, Ricky M.; Pereira, Joao; Williams, John A.; Cavanagh, Megan L.; Gkoutos, Georgios V.; Tsaprouni, Loukia; Turner, Suzanne D.			The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells	CANCERS			English	Review						cancer stem cells (CSCs); tumour microenvironment; solid cancers; haematological malignancies; autophagy; LncRNAs	LONG NONCODING RNA; ACUTE MYELOID-LEUKEMIA; SIDE POPULATION CELLS; PANCREATIC-CANCER; COLORECTAL-CANCER; INITIATING CELLS; HYPOXIC STRESS; SELF-RENEWAL; OF-ORIGIN; C-MYC	Simple Summary Cancer stem cells (CSCs) represent a distinct cancer subpopulation that can influence the tumour microenvironment, in addition to cancer progression and relapse. A multitude of factors including CSC properties, long noncoding RNAs (lncRNAs), and autophagy play pivotal roles in maintaining CSCs. We discuss the methods of detection of CSCs and how our knowledge of regulatory and cellular processes, and their interaction with the microenvironment, may lead to more effective targeting of these cells. Autophagy and lncRNAs can regulate several cellular functions, thereby promoting stemness factors and CSC properties, hence understanding this triangle and its associated signalling networks can lead to enhanced therapy response, while paving the way for the development of novel therapeutic approaches. Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.	[Jahangiri, Leila; Ishola, Tala; Cavanagh, Megan L.; Tsaprouni, Loukia] Birmingham City Univ, Dept Life Sci, Birmingham B15 3TN, W Midlands, England; [Jahangiri, Leila; Pucci, Perla; Trigg, Ricky M.; Turner, Suzanne D.] Univ Cambridge, Dept Pathol, Div Cellular & Mol Pathol, Cambridge CB2 0QQ, England; [Trigg, Ricky M.] GlaxoSmithKline, Dept Funct Genom, Stevenage SG1 2NY, Herts, England; [Pereira, Joao] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA; [Williams, John A.; Gkoutos, Georgios V.] Univ Hosp Birmingham NHS Fdn Trust, Inst Translat Med, Birmingham B15 2TH, W Midlands, England; [Williams, John A.; Gkoutos, Georgios V.] Univ Birmingham, Coll Med & Dent Sci, Inst Canc & Genom Sci, Birmingham B15 2SY, W Midlands, England; [Gkoutos, Georgios V.] Med Res Council Harwell Inst, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England; [Gkoutos, Georgios V.] Univ Birmingham, MRC Hlth Data Res Midlands, Birmingham B15 2TT, W Midlands, England; [Gkoutos, Georgios V.] NIHR Expt Canc Med Ctr, Birmingham B15 2TT, W Midlands, England; [Gkoutos, Georgios V.] NIHR Surg Reconstruct & Microbiol Res Ctr, Birmingham B15 2TT, W Midlands, England; [Gkoutos, Georgios V.] NIHR Biomed Res Ctr, Birmingham B15 2TT, W Midlands, England; [Turner, Suzanne D.] Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic		Jahangiri, L (corresponding author), Birmingham City Univ, Dept Life Sci, Birmingham B15 3TN, W Midlands, England.; Jahangiri, L (corresponding author), Univ Cambridge, Dept Pathol, Div Cellular & Mol Pathol, Cambridge CB2 0QQ, England.; Gkoutos, GV (corresponding author), Univ Hosp Birmingham NHS Fdn Trust, Inst Translat Med, Birmingham B15 2TH, W Midlands, England.; Gkoutos, GV (corresponding author), Univ Birmingham, Coll Med & Dent Sci, Inst Canc & Genom Sci, Birmingham B15 2SY, W Midlands, England.; Gkoutos, GV (corresponding author), Med Res Council Harwell Inst, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England.; Gkoutos, GV (corresponding author), Univ Birmingham, MRC Hlth Data Res Midlands, Birmingham B15 2TT, W Midlands, England.; Gkoutos, GV (corresponding author), NIHR Expt Canc Med Ctr, Birmingham B15 2TT, W Midlands, England.; Gkoutos, GV (corresponding author), NIHR Surg Reconstruct & Microbiol Res Ctr, Birmingham B15 2TT, W Midlands, England.; Gkoutos, GV (corresponding author), NIHR Biomed Res Ctr, Birmingham B15 2TT, W Midlands, England.	leila.jahangiri@bcu.ac.uk; tala.ishola@bcu.ac.uk; pp504@cam.ac.uk; ricky.m.trigg@gsk.com; jtavaresdasilvapereira@mgh.harvard.edu; megan.cavanagh@mail.bcu.ac.uk; g.gkoutos@bham.ac.uk; loukia.tsaprouni@bcu.ac.uk; sdt36@cam.ac.uk	Turner, Suzanne Dawn/K-4405-2013	Turner, Suzanne Dawn/0000-0002-8439-4507; Tsaprouni, Loukia/0000-0002-4740-3099; Williams, John/0000-0002-0357-5454; Jahangiri, Leila/0000-0003-0235-8447; Pereira, Joao/0000-0002-5587-7593; Ishola, Dr. Tala/0000-0002-3067-0553; Pucci, Perla/0000-0003-1264-3487	NIHR Birmingham ECMC; NIHR Birmingham SRMRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC); Nanocommons Horizon 2020-EU [731032]; NIHR Birmingham Biomedical Research Centre; MRC HDR UKUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [HDRUK/CFC/01]; UK Research and Innovation, Department of Health and Social Care (England)	G.V.G. acknowledges support from the NIHR Birmingham ECMC, NIHR Birmingham SRMRC, Nanocommons Horizon 2020-EU (731032), the NIHR Birmingham Biomedical Research Centre, and the MRC HDR UK (HDRUK/CFC/01), an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Medical Research Council, or the Department of Health.	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J	Xiao, YZ; Sun, LQ; Fu, YM; Huang, Y; Zhou, RR; Hu, XW; Zhou, PC; Quan, J; Li, N; Fan, XG				Xiao, Yinzong; Sun, Lunquan; Fu, Yongming; Huang, Yan; Zhou, Rongrong; Hu, Xingwang; Zhou, Pengcheng; Quan, Jun; Li, Ning; Fan, Xue-Gong			High mobility group box 1 promotes sorafenib resistance in HepG2 cells and in vivo	BMC CANCER			English	Article						HCC; HMGB1; Sorafenib resistance; Mitochondria	HEPATOCELLULAR-CARCINOMA; HMGB1-MEDIATED AUTOPHAGY; REGULATES AUTOPHAGY; CANCER CELLS; LIVER-CANCER; HMGB1; APOPTOSIS; OSTEOSARCOMA; EXPRESSION; INVASION	Background: Primary liver cancer is a lethal malignancy with a high mortality worldwide. Currently, sorafenib is the most effective molecular-targeted drug against hepatocellular carcinoma (HCC). However, the sorafenib resistance rate is high. The molecular mechanism of this resistance has not been fully elucidated. High mobility group box 1 (HMGB1) is a multifaceted protein that plays a key role in the proliferation, apoptosis, metastasis and angiogenesis of HCC cells. In addition, HMGB1 has been suggested to contribute to chemotherapy resistance in tumours, including lung cancer, osteosarcoma, neuroblastoma, leukaemia, and colorectal cancer. This study investigated the association between HMGB1 and sorafenib resistance in HCC. Methods: HepG2 cells with HMGB1 knockdown or overexpression were generated. The efficacy of sorafenib in these cells was tested using flow cytometry and a cell counting assay. The subcellular localization of HMGB1 in HepG2 cells following sorafenib treatment was measured by western blotting and confocal microscopy. A murine subcutaneous HCC model was generated to examine the association between HMGB1 and the sensitivity of sorafenib treatment. Results: The HMGB1 knockdown cells exhibited a significantly higher apoptotic level and lower cell viability than the normal HMGB1 expressing cells following the sorafenib treatment. In addition, the cell viability observed in the HMGB1 overexpressing cells was higher than that observed in the control cells following the sorafenib intervention. Sorafenib had a better tumour inhibition effect in the HMGB1 knockdown group in vivo. The amount of mitochondrial HMGB1 decreased, while the amount of cytosolic HMGB1 increased following the exposure to sorafenib. Altogether, HMGB1 translocated from the mitochondria to the cytoplasm outside the mitochondria following the exposure of HepG2 cells to sorafenib. Conclusions: A novel potential role of HMGB1 in the regulation of sorafenib therapy resistance in HCC was observed. The knockdown of HMGB1 restores sensitivity to sorafenib and enhances HepG2 cell death, while HMGB1 overexpression blunts these effects. The translocation of HMGB1 from the mitochondria to the cytosol following sorafenib treatment provides new insight into sorafenib resistance in HCC.	[Xiao, Yinzong; Fu, Yongming; Huang, Yan; Zhou, Rongrong; Hu, Xingwang; Zhou, Pengcheng; Quan, Jun; Fan, Xue-Gong] Cent S Univ, Dept Infect Dis, Hunan Key Lab Viral Hepatitis, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China; [Sun, Lunquan] Cent S Univ, Ctr Mol Med, Key Lab Mol Radiat Oncol Hunan Prov, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China; [Li, Ning] Cent S Univ, Dept Blood Transfus, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China		Fan, XG (corresponding author), Cent S Univ, Dept Infect Dis, Hunan Key Lab Viral Hepatitis, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China.; Li, N (corresponding author), Cent S Univ, Dept Blood Transfus, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China.	nxli@hotmail.com	Hu, Xingwang/ABG-6400-2021	Xiao, Yinzong/0000-0001-8360-5352; Hu, Xingwang/0000-0002-2320-3279	Special National International Technology Cooperation of China [2015DFA31490]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272253, 81670538]; National Major Sciences Research Program of China (973 Program)National Basic Research Program of China [2013CB910502]	This study was supported by grants from the Special National International Technology Cooperation of China (2015DFA31490), the National Natural Science Foundation of China (No. 81272253) and the National Major Sciences Research Program of China (973 Program) (No. 2013CB910502) received by XGF. XGF supervised the design of the study and critically revised the manuscript. This study was supported by a grant from the National Natural Science Foundation of China (No. 81670538) received by NL; NL was involved in the study design and drafting the manuscript.	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J	Guan, YP; Fu, YY; Liu, Y; Wang, SY; Zhao, M; Jin, ZM; Jiang, FL; Hong, L; Huang, M; Li, M; Zhong, GP				Guan, Yanping; Fu, Yuanyuan; Liu, Yao; Wang, Siyi; Zhao, Man; Jin, Zhongming; Jiang, Fulin; Hong, Liang; Huang, Min; Li, Min; Zhong, Guoping			Quantitative bioanalytical LC-MS/MS assay for S130 in rat plasma - application to a pharmacokinetic study	BIOANALYSIS			English	Article						Atg4B inhibitor; bioavailability; LC-MS/MS; pharmacokinetics; PK; rat plasma; S130	COLORECTAL-CANCER; ATG4B; AUTOPHAGY	Aim: An innovative Atg4B inhibitor, S130, exhibited a negative influence on colorectal cancer cells in vitro and in vivo. To assist reliable toxicodynamic and pharmacokinetic evaluation, an LC-MS/MS assay of S130 in rat plasma must be necessary. Results: An LC-MS/MS assay for determination of S130 in rat plasma has been first developed and fully verifiedwhose valuesmet the admissible limits as per the US FDA guidelines. Chromatographic separation was achieved by using an isocratic elution after 3 min. MS was conducted under the ESI+ mode fitted with selected reaction monitoring. The calibration curve proved acceptable linearity over 0.50-800 ng/ml. Conclusion: The developed LC-MS/MS assay of S130 in rat plasma is easily applicable in pharmacokinetics study and the further toxicological evaluation.	[Guan, Yanping; Liu, Yao; Wang, Siyi; Jin, Zhongming; Jiang, Fulin; Huang, Min; Zhong, Guoping] Sun Yat Sen Univ, Sch Pharmaceut Sci, Inst Clin Pharmacol, Guangzhou 510006, Guangdong, Peoples R China; [Guan, Yanping; Fu, Yuanyuan; Liu, Yao; Wang, Siyi; Zhao, Man; Jin, Zhongming; Jiang, Fulin; Hong, Liang; Huang, Min; Li, Min; Zhong, Guoping] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Design & Evaluat, Guangzhou 510006, Guangdong, Peoples R China; [Guan, Yanping] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Pharm, Guangzhou 510120, Guangdong, Peoples R China; [Fu, Yuanyuan; Zhao, Man; Hong, Liang; Li, Min] Sun Yat Sen Univ, Sch Pharmaceut Sci, Natl & Local United Engn Lab Druggabil & New Drug, Guangzhou 510006, Guangdong, Peoples R China		Zhong, GP (corresponding author), Sun Yat Sen Univ, Sch Pharmaceut Sci, Inst Clin Pharmacol, Guangzhou 510006, Guangdong, Peoples R China.; Zhong, GP (corresponding author), Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Design & Evaluat, Guangzhou 510006, Guangdong, Peoples R China.	zhonggp@mail.sysu.edu.cn	管, 宴萍/AAL-5308-2020		National Key Research and Development Program [2017YFC0909303, 2016YFC0905001]; Guangdong Science and Technology Planning Project [2016A040403047]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31671437]; National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX09735010]; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2016A030313335]; Guangdong Provincial Key Laboratory of Construction Foundation [2017B030314030]	The authors appreciate the financial support provided by The National Key Research and Development Program (no. 2017YFC0909303), The Guangdong Science and Technology Planning Project (no. 2016A040403047); the National Key Research and Development Program (no. 2016YFC0905001); National Natural Science Foundation of China (no. 31671437); The National Science and Technology Major Project of the Ministry of Science and Technology of China (no. 2018ZX09735010); The Natural Science Foundation of Guangdong Province, China (no. 2016A030313335), and Guangdong Provincial Key Laboratory of Construction Foundation (no. 2017B030314030). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.	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J	Liu, Z; Wang, F; Ma, H; Xia, HC; Tian, JH; Sun, T				Liu, Zheng; Wang, Feng; Ma, Hui; Xia, Hechun; Tian, Jihui; Sun, Tao			Amentoflavone induces cell cycle arrest, apoptosis, and autophagy in BV-2 cells	FRONTIERS IN BIOSCIENCE-LANDMARK			English	Article						Epilepsy; Amentoflavone; BV-2 cells; Apoptosis; Cell cycle arrest; Autophagy	COLORECTAL-CANCER; EPILEPSY; PATHWAY; GROWTH; PROLIFERATION; INFLAMMATION; GENES; PHASE; NEUROPROTECTION; SUPPRESSION	Previous studies have shown that amentoflavone (AF) elicits anti-inflammatory and neuroprotective effects. To further investigate the effects of AF on the microglia cell line BV-2, proteomic analysis was performed to screen potential key regulators. The top 5 canonical pathways associated with AF treatment were EIF2 signaling, regulation of eIF4 and p70s6k signaling, mTOR signaling, protein ubiquitination pathway and phagosome maturation. The top up-regulated genes were DOCK2, SEC23A, ME1, UGGT1 and STOM, while the most down-regulated molecules were IGF2R, ATP5O, DDX47, WBP11 and IKBIP. AF significantly decreased BV-2 cell proliferation. It induced cell cycle arrest at G2/M, increased CDK2, p27Kip1 and p53/p-p53, and decreased CDK1/CDC2 and cyclin B1. Cell apoptosis was induced, with increased levels of BAX, c-caspase-3 and ccaspase-9, and decreased levels of BCL-XL. Increased level of autophagosome induced by AF was observed, and increased Beclin-1 and decreased phosphorylation of PI3K and Erk1 were found as well. In conclusion, AF induces cell cycle arrest at G2/M, promotes apoptosis and autophagy in BV-2 cells, which may account for the anti-inflammatory effect of AF in epilepsy.	[Liu, Zheng; Wang, Feng; Ma, Hui; Xia, Hechun; Tian, Jihui; Sun, Tao] Ningxia Med Univ, Dept Neurosurg, Gen Hosp, 804 South Shengli St, Yinchuan 750004, Ningxia, Peoples R China; [Liu, Zheng; Wang, Feng; Sun, Tao] Ningxia Med Univ, Incubat Base Natl Key Lab, Ningxia Key Lab Cerebrocranial Dis, Yinchuan 750004, Ningxia, Peoples R China		Sun, T (corresponding author), Ningxia Med Univ, Dept Neurosurg, Gen Hosp, 804 South Shengli St, Yinchuan 750004, Ningxia, Peoples R China.	ssldeng@sina.com		Sun, Tao/0000-0001-8062-3432	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81460208]; Ningxia Brain Project-the Basic and Clinical Research on the Temporal-insular Network, Epilepsy and Cognitive Function [2016BZ07]; Key Research and Development Projects of Ningxia Hui Autonomous Region [2018BEG03023]	The authors appreciate the financial support from the National Natural Science Foundation of China (Grant No.: 81460208), Ningxia Brain Project-the Basic and Clinical Research on the Temporal-insular Network, Epilepsy and Cognitive Function (Grant No.: 2016BZ07) and the Key Research and Development Projects of Ningxia Hui Autonomous Region (Grant No.: 2018BEG03023).	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Biosci.	JAN 1	2020	25						798	816		10.2741/4835			19	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	NG1TK	WOS:000563769400001	31585918				2022-04-25	
J	Lu, Y; Shi, CM; Qiu, SB; Fan, Z				Lu, Yang; Shi, Chunmei; Qiu, Songbo; Fan, Zhen			Identification and validation of COX-2 as a co-target for overcoming cetuximab resistance in colorectal cancer cells	ONCOTARGET			English	Article						EGFR; cetuximab; COX-2; COX-2 inhibitor; colorectal cancer	GROWTH-FACTOR-RECEPTOR; MONOCLONAL-ANTIBODY; K-RAS; ACQUIRED-RESISTANCE; MUTATION STATUS; EGF RECEPTOR; CYCLOOXYGENASE-2; INHIBITION; APOPTOSIS; CELECOXIB	Cetuximab, an epidermal growth factor receptor (EGFR)-blocking antibody, was approved for treatment of metastatic colorectal cancer over a decade ago; however, patients' responses to cetuximab vary substantially due to intrinsic and acquired resistance to cetuximab. Here, we report our findings using Affymetrix HG-U133A array to examine changes in global gene expression between DiFi, a human colorectal cancer cell line that is highly sensitive to cetuximab, and two other cell lines: DiFi5, a DiFi subline with acquired resistance to cetuximab, and DiFi-AG, a DiFi subline with acquired resistance to the EGFR tyrosine kinase inhibitor AG1478 but sensitivity to cetuximab. We identified prostaglandin-endoperoxide synthase 2 (PTGS2), which encodes cyclooxygenase-2 (COX-2), as the gene with the greatest difference between the cetuximab-resistant DiFi5 cells and the cetuximab-sensitive DiFi cells and DiFi-AG cells. Reverse transcription polymerase chain reaction and Western blotting validated upregulation of COX-2 in DiFi5 but not in DiFi or DiFi-AG cells. We developed COX-2 knockdown stable clones from DiFi5 cells and demonstrated that genetic knockdown of COX-2 partially re-sensitized DiFi5 cells to cetuximab. We further confirmed that cetuximab in combination with a COX-2 inhibitor led to cell death via apoptosis or autophagy not only in DiFi5 cells but also in another colorectal cancer cell line naturally resistant to cetuximab. Our findings support further evaluation of the strategy of combining cetuximab and a COX-2 inhibitor for treatment of metastatic colorectal cancer.	[Lu, Yang; Shi, Chunmei; Qiu, Songbo; Fan, Zhen] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA; [Shi, Chunmei] Fujian Med Univ, Union Hosp, Dept Oncol, Fuzhou 350001, Fujian, Peoples R China		Fan, Z (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.	zfan@mdanderson.org			US National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [CA129036, CA179015]; NIH through MD Anderson's Cancer Center Support Grant [CA016672]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA179015, R01CA129036, P30CA016672] Funding Source: NIH RePORTER	This work was supported in part by US National Institutes of Health (NIH) R01 awards CA129036 and CA179015. The work was also supported in part by the NIH through MD Anderson's Cancer Center Support Grant, CA016672. We thank the staff of the Flow Cytometry and Cellular Imaging Core Facility for technical assistance and thank Stephanie Deming of the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for editorial assistance.	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J	Tacar, O; Indumathy, S; Tan, ML; Baindur-Hudson, S; Friedhuber, AM; Dass, CR				Tacar, Oktay; Indumathy, Sivanjah; Tan, Mei Lin; Baindur-Hudson, Swati; Friedhuber, Anna M.; Dass, Crispin R.			Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: comparison with osteosarcoma cells	JOURNAL OF PHARMACY AND PHARMACOLOGY			English	Article						apoptosis; autophagy; Bax; Beclin-1; cardiotoxicity	DOWN-REGULATION; CANCER; CARDIOTOXICITY; MITOCHONDRIAL; CHEMOTHERAPY; ADRIAMYCIN; DELIVERY; THERAPY; STRESS; TARGET	ObjectiveDoxorubicin (Dox) is a frontline chemotherapeutic against osteosarcoma (OS) that is plagued by side effects, particularly in the heart. The specific objective of this article is to investigate whether low-dose Dox treatment had pro-autophagic effects in cardiomyocytes as well as osteosarcoma cells. MethodsThis study characterises apoptotic (Bax) and autophagic (Beclin-1) biomarker levels in human OS and cardiomyocyte cell lines as well as in various tissues when mice are exposed to low (1mg/kg, thrice weekly) and high (3mg/kg thrice weekly) dose Dox for a month. Key findingsThere was a decrease in Bax and increase in Beclin-1 in cardiac tissue in the high-dose group. Dox decreased Beclin-1 in the skin and liver, with no clear indication in the stomach, small intestine and testis. At low Dox doses of 10 and 100nm in cardiomyocytes and OS cells, there is a pro-apoptotic effect, with a quicker response in the 100-nm condition, and a slower but steady increase of a pro-apoptotic response at the lower 10-nm dose. However, electron microscopy images revealed changes to human OS cells that resembled autophagy. Human prostate, breast and colorectal cells treated with 10-nm Dox showed approximate to 40% reduction in cell viability after 24h. ConclusionIn culture, cells of both cardiomyocytes and OS revealed a predominant pro-apoptotic response at the expense of autophagy, although both seemed to be occurring in vivo.	[Tacar, Oktay; Indumathy, Sivanjah; Baindur-Hudson, Swati] Victoria Univ, Coll Hlth & Biomed, Melbourne, Vic 8001, Australia; [Tan, Mei Lin] St Vincents Hlth, Dept Orthopaed, Melbourne, Vic, Australia; [Friedhuber, Anna M.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia; [Dass, Crispin R.] Curtin Univ, Curtin Biosci Res Precinct, Perth, WA 6845, Australia; [Dass, Crispin R.] Curtin Univ, Sch Pharm, Perth, WA 6102, Australia		Dass, CR (corresponding author), Curtin Univ, Sch Pharm, Bldg 306,Brand Dr, Perth, WA 6102, Australia.	crispin.dass@curtin.edu.au			Academic50 grant	This study was supported by the Academic50 grant support to CRD.	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Pharm. Pharmacol.	FEB	2015	67	2					231	243		10.1111/jphp.12324			13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	AZ9BU	WOS:000348507100009	25208656				2022-04-25	
J	Rivas-Garcia, L; Quiles, JL; Varela-Lopez, A; Giampieri, F; Battino, M; Bettmer, J; Montes-Bayon, M; Llopis, J; Sanchez-Gonzalez, C				Rivas-Garcia, Lorenzo; Quiles, Jose Luis; Varela-Lopez, Alfonso; Giampieri, Francesca; Battino, Maurizio; Bettmer, Jorg; Montes-Bayon, Maria; Llopis, Juan; Sanchez-Gonzalez, Cristina			Ultra-Small Iron Nanoparticles Target Mitochondria Inducing Autophagy, Acting on Mitochondrial DNA and Reducing Respiration	PHARMACEUTICS			English	Article						nanotechnology; mitochondria; respiration; mtDNA deletions; copy number; metals		The application of metallic nanoparticles (materials with size at least in one dimension ranging from 1 to 100 nm) as a new therapeutic tool will improve the diagnosis and treatment of diseases. The mitochondria could be a therapeutic target to treat pathologies whose origin lies in mitochondrial dysfunctions or whose progression is dependent on mitochondrial function. We aimed to study the subcellular distribution of 2-4 nm iron nanoparticles and its effect on mitochondrial DNA (mtDNA), mitochondrial function, and autophagy in colorectal cell lines (HT-29). Results showed that when cells were exposed to ultra-small iron nanoparticles, their subcellular fate was mainly mitochondria, affecting its respiratory and glycolytic parameters, inducing the migration of the cellular state towards quiescence, and promoting and triggering the autophagic process. These effects support the potential use of nanoparticles as therapeutic agents using mitochondria as a target for cancer and other treatments for mitochondria-dependent pathologies.	[Rivas-Garcia, Lorenzo; Quiles, Jose Luis; Varela-Lopez, Alfonso; Llopis, Juan; Sanchez-Gonzalez, Cristina] Univ Granada, Fac Pharm, Dept Physiol Inst Nutr & Food Technol, Biomed Res Ctr, Avda Conocimiento S-N, Armilla 18071, Spain; [Rivas-Garcia, Lorenzo; Llopis, Juan; Sanchez-Gonzalez, Cristina] Univ Granada, Sport & Hlth Res Ctr, C Menendez Pelayo 32, Armilla 18016, Spain; [Quiles, Jose Luis] Univ Europea Atlantico UEA, Ctr Nutr & Hlth, Santander 39011, Spain; [Giampieri, Francesca; Battino, Maurizio] Polytech Univ Marche, Dept Clin Specialist & Odontostomatol Sci DISCO S, Biochem, I-60131 Ancona, Italy; [Giampieri, Francesca] King Abdulaziz Univ, Dept Biochem, Fac Sci, Jeddah 21589, Saudi Arabia; [Battino, Maurizio] Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China; [Bettmer, Jorg; Montes-Bayon, Maria] Univ Oviedo, Dept Analyt Chem, Fac Chem, Oviedo 33007, Spain; [Bettmer, Jorg; Montes-Bayon, Maria] Univ Oviedo, Inst Invest Sanitaria Principado Asturias ISPA, Oviedo 33007, Spain		Sanchez-Gonzalez, C (corresponding author), Univ Granada, Fac Pharm, Dept Physiol Inst Nutr & Food Technol, Biomed Res Ctr, Avda Conocimiento S-N, Armilla 18071, Spain.; Sanchez-Gonzalez, C (corresponding author), Univ Granada, Sport & Hlth Res Ctr, C Menendez Pelayo 32, Armilla 18016, Spain.	lorenrivas@ugr.es; jlquiles@ugr.es; alvarela@ugr.es; f.giampieri@staff.univpm.it; m.a.battino@staff.univpm.it; bettmerjorg@uniovi.es; montesmaria@uniovi.es; jllopis@ugr.es; crissg@ugr.es	Varela-López, Alfonso/F-8055-2016; García, Lorenzo Rivas/ABD-6217-2020; Battino, Maurizio/E-6103-2012; Giampieri, Francesca/I-1911-2015; Quiles, José L./C-6911-2013; Sanchez Gonzalez, Cristina/Q-6219-2017	Varela-López, Alfonso/0000-0002-0504-5086; Battino, Maurizio/0000-0002-7250-1782; Giampieri, Francesca/0000-0002-8151-9132; Quiles, José L./0000-0002-9048-9086; /0000-0002-0413-8432; Sanchez Gonzalez, Cristina/0000-0002-1044-4858	government of Asturias through the Science, Technology and Innovation Plan (PCTI) - FEDER funds [FC-GRUPIN-IDI/2018/000242]; Spanish Ministry of Economy, Industry and Competitiveness (MINECO) [CTQ2016-80069-C 2-1R, RTI2018-094605-B-I00]	Regional funding from the government of Asturias through the Science, Technology and Innovation Plan (PCTI) cofinanced by FEDER funds (FC-GRUPIN-IDI/2018/000242) and the funding from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) through projects CTQ2016-80069-C 2-1R and RTI2018-094605-B-I00.	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J	Bijnsdorp, IV; Peters, GJ				Bijnsdorp, I. V.; Peters, G. J.			DEOXYRIBOSE PROTECTS AGAINST RAPAMYCIN-INDUCED CYTOTOXICITY IN COLORECTAL CANCER CELLS IN VITRO	NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS			English	Article						Deoxyribose; thymidine phosphorylase; rapamycin	THYMIDINE PHOSPHORYLASE; DIHYDROPYRIMIDINE DEHYDROGENASE; SIGNALING PATHWAYS; ANGIOGENIC FACTORS; AUTOPHAGY; EXPRESSION; MIGRATION; SECRETION; MTOR	Thymidine phosphorylase (TPase) is also known as the platelet-derived endothelial cell growth factor (PD-ECGF) and plays a role in angiogenesis. Deoxyribose (dR; a downstream TPase-product) addition to endothelial cells may stimulate FAK and p70/S6k signaling, which can be inhibited by rapamycin. Rapamycin is a specific mammalian target of the rapamycin (mTOR) inhibitor, a kinase that lies directly upstream of p70/S6k. This suggests a role for TPase in the mTOR/p70/S6k pathway. In order to study this in more detail, we exposed cells with and without TPase expression to dR and rapamycin and determined the effect on cell growth. We observed protection in cytotoxicity in Colo320 cells, but not Colo320 TP1 cells. This was in part mediated by activation of p70/S6k and inhibition of autophagy. Further studies are recommended to elucidate the mechanism behind the protective effect of dR.	[Bijnsdorp, I. V.] Vrije Univ Amsterdam Med Ctr, Dept Urol, Amsterdam, Netherlands; [Bijnsdorp, I. V.; Peters, G. J.] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands		Peters, GJ (corresponding author), Boelelaan 1117,CCA 1-42, NL-1081 HV Amsterdam, Netherlands.	GJ.Peters@vumc.nl	Peters, Godefridus J/C-7562-2013	Peters, Godefridus J/0000-0002-5447-2877			Bijnsdorp IV, 2011, BRIT J CANCER, V104, P1185, DOI 10.1038/bjc.2011.74; Bijnsdorp IV, 2010, BIOCHEM PHARMACOL, V80, P786, DOI 10.1016/j.bcp.2010.05.009; Bronckaers A, 2009, MED RES REV, V29, P903, DOI 10.1002/med.20159; Brown NS, 2000, CANCER RES, V60, P6298; Chiang GG, 2007, TRENDS MOL MED, V13, P433, DOI 10.1016/j.molmed.2007.08.001; Hayashi T, 2008, HEPATO-GASTROENTEROL, V55, P403; Hotchkiss KA, 2003, J BIOL CHEM, V278, P19272, DOI 10.1074/jbc.M212670200; Kanazawa T, 2004, J BIOL CHEM, V279, P8452, DOI 10.1074/jbc.M306337200; KEEPERS YP, 1991, EUR J CANCER, V27, P897, DOI 10.1016/0277-5379(91)90142-Z; Levine B, 2005, J CLIN INVEST, V115, P2679, DOI 10.1172/JCI26390; Nakayama Y, 2005, ANTICANCER RES, V25, P3755; Seeliger H, 2004, CLIN CANCER RES, V10, P1843, DOI 10.1158/1078-0432.CCR-1176-3; Shigemitsu K, 1999, J BIOL CHEM, V274, P1058, DOI 10.1074/jbc.274.2.1058; White E, 2009, CLIN CANCER RES, V15, P5308, DOI 10.1158/1078-0432.CCR-07-5023	14	4	5	0	1	TAYLOR & FRANCIS INC	PHILADELPHIA	325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA	1525-7770			NUCLEOS NUCLEOT NUCL	Nucleosides Nucleotides Nucleic Acids		2011	30	12					1197	1202		10.1080/15257770.2011.602657			6	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	871LB	WOS:000298738500027	22132975				2022-04-25	
J	Scott, TA; Quintaneiro, LM; Norvaisas, P; Lui, PP; Wilson, MP; Leung, KY; Herrera-Dominguez, L; Sudiwala, S; Pessia, A; Clayton, PT; Bryson, K; Velagapudi, V; Mills, PB; Typas, A; Greene, NDE; Cabreiro, F				Scott, Timothy A.; Quintaneiro, Leonor M.; Norvaisas, Povilas; Lui, Prudence P.; Wilson, Matthew P.; Leung, Kit-Yi; Herrera-Dominguez, Lucia; Sudiwala, Sonia; Pessia, Alberto; Clayton, Peter T.; Bryson, Kevin; Velagapudi, Vidya; Mills, Philippa B.; Typas, Athanasios; Greene, Nicholas D. E.; Cabreiro, Filipe			Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans	CELL			English	Article							DNTP POOLS; 5-FLUOROURACIL; AUTOPHAGY; DEFECTS; THERAPY; GLYCINE; GENE	Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed three-way high-throughput screens that unraveled the complexity underlying host-microbe-drug interactions. We report that microbes can bolster or suppress the effects of fluoropyrimidines through metabolic drug interconversion involving bacterial vitamin B-6, B-9, and ribonucleotide metabolism. Also, disturbances in bacterial deoxynucleotide pools amplify 5-FU-induced autophagy and cell death in host cells, an effect regulated by the nucleoside diphosphate kinase ndk-1. Our data suggest a two-way bacterial mediation of fluoropyrimidine effects on host metabolism, which contributes to drug efficacy. These findings highlight the potential therapeutic power of manipulating intestinal microbiota to ensure host metabolic health and treat disease.	[Scott, Timothy A.; Quintaneiro, Leonor M.; Norvaisas, Povilas; Lui, Prudence P.; Cabreiro, Filipe] Univ Coll London & Birkbeck, Inst Struct & Mol Biol, London WC1E 6BT, England; [Quintaneiro, Leonor M.; Wilson, Matthew P.; Leung, Kit-Yi; Sudiwala, Sonia; Clayton, Peter T.; Mills, Philippa B.; Greene, Nicholas D. E.] UCL, Great Ormond St Inst Child Hlth, London WC1N 1EH, England; [Norvaisas, Povilas; Bryson, Kevin] UCL, Dept Comp Sci, London WC1E 6BT, England; [Herrera-Dominguez, Lucia; Typas, Athanasios] European Mol Biol Lab EMBL Heidelberg, Genome Biol, Meyerhofstr 1, D-69117 Heidelberg, Germany; [Pessia, Alberto; Velagapudi, Vidya] Univ Helsinki, Inst Mol Med Finland, Metabol Unit, FIN-00290 Helsinki, Finland		Cabreiro, F (corresponding author), Univ Coll London & Birkbeck, Inst Struct & Mol Biol, London WC1E 6BT, England.	f.cabreiro@ucl.ac.uk	Wilson, Matthew/ABA-8602-2021; Bryson, Kevin/AAZ-8177-2020; Pessia, Alberto/N-3072-2014; Velagapudi, Vidya/L-7278-2015	Wilson, Matthew/0000-0003-2252-8730; Pessia, Alberto/0000-0001-8607-9191; Velagapudi, Vidya/0000-0002-8261-7164; Herrera-Dominguez, Lucia/0000-0001-8276-2241; Scott, Timothy/0000-0001-7042-8609; Lui, Prudence/0000-0003-2562-5261; Mills, Philippa/0000-0002-9704-1268; Cabreiro, Filipe/0000-0002-3696-4843; Greene, Nicholas/0000-0002-4170-5248; Typas, Athanasios/0000-0002-0797-9018; Norvaisas, Povilas/0000-0003-4790-9820; Clayton, Peter/0000-0001-7592-4302	Wellcome Trust/Royal Society (Sir Henry Dale Fellowship) [102532/Z/12/Z]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MR/N003713/1]; Great Ormond Street Hospital Children's Charity; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MR/N003713/1, 1649908] Funding Source: researchfish; Wellcome TrustWellcome TrustEuropean Commission [102531/Z/13/Z] Funding Source: researchfish; Great Ormond Street Hospital Childrens Charity [V1273, V4115] Funding Source: researchfish	Worm strains were provided by the Caenorhabditis Genetics Center. F.C. acknowledges funding from the Wellcome Trust/Royal Society (Sir Henry Dale Fellowship-102532/Z/12/Z) and N.D.E.G. from the MRC (MR/N003713/1). N.D.E.G. is supported by Great Ormond Street Hospital Children's Charity. We thank Helena Cocheme, Andrew Osborne, and Jurg Bahler for critical reading of the manuscript.	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J	Koshkina, NV; Briggs, K; Palalon, F; Curley, SA				Koshkina, Nadezhda V.; Briggs, Katrina; Palalon, Flavio; Curley, Steven A.			Autophagy and Enhanced Chemosensitivity in Experimental Pancreatic Cancers Induced by Noninvasive Radiofrequency Field Treatment	CANCER			English	Article						noninvasive radiofrequency; pancreatic cancer; autophagy; gemcitabine; chemotherapy enhancer	COLORECTAL LIVER METASTASES; CELL-PROLIFERATION; COMBINED RESECTION/ABLATION; HEPATIC RESECTION; ABLATION; DEATH; GEMCITABINE; RECURRENCE; MODELS; GROWTH	BACKGROUNDPatients with pancreatic ductal adenocarcinoma (PDAC) have limited therapeutic options and poor response to the standard gemcitabine (GCB)-based chemotherapy. In the current study, the authors investigated the feasibility of noninvasive short-wave radiofrequency (RF) electric fields to improve the cytotoxic effect of GCB on PDAC cells and determined its mechanism of action. METHODSThe cytotoxicity of RF alone and in combination with GCB was studied in vitro on normal pancreatic human pancreatic ductal epithelial cells and different PDAC cell lines by flow cytometry, and in vivo on ectopic and orthotopic human PDAC xenograft models in mice. The mechanism of RF activity was studied by Western blot analysis and immunohistochemistry. Toxicity was determined by histopathology. RESULTSExposure of different PDAC cells to 13.56-megahertz radio waves resulted in a substantial cytotoxic effect, which was accompanied by the induction of autophagy but not apoptosis. These effects of RF were found to be absent in normal cells. Excessive numbers of autophagosomes in cancer cells persisted 24 to 48 hours after RF exposure and then declined. The addition of a subtoxic dose of GCB to RF treatment inhibited the recovery of cancer cells from the RF-induced autophagy and enhanced the cytotoxic effect of the latter on cancer cells. The treatment of PDAC in situ in mice with the combination of noninvasive RF and GCB was found to have a superior antitumor effect compared with the use of RF or GCB alone, yet there was no evidence of systemic toxicity. CONCLUSIONSNoninvasive RF treatment induced autophagy but not apoptosis in cancer cells and demonstrated potential as an enhancer of chemotherapy for treating patients with pancreatic cancer without toxicity to normal cells. Cancer 2014;120:480-491. (c) 2013 American Cancer Society.	[Koshkina, Nadezhda V.; Briggs, Katrina; Palalon, Flavio; Curley, Steven A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA; [Curley, Steven A.] Rice Univ, Dept Mech Engn & Mat Sci, Houston, TX 77251 USA		Koshkina, NV (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA.	nvkoshki@mdanderson.org			National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [U54CA143837]; National Institutes of Health University of Texas MD Anderson Cancer Center Support Grant [CA016672]; Kanzius Cancer Research Foundation; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [U54CA143837, P30CA016672] Funding Source: NIH RePORTER	Supported by the National Institutes of Health (grant U54CA143837), National Institutes of Health University of Texas MD Anderson Cancer Center Support Grant CA016672, and a research grant from the Kanzius Cancer Research Foundation (to Dr. Curley).	Abdalla EK, 2004, ANN SURG, V239, P818, DOI 10.1097/01.sla.0000128305.90650.71; Abedin MJ, 2007, CELL DEATH DIFFER, V14, P500, DOI 10.1038/sj.cdd.4402039; Adair ER, 2005, BIOELECTROMAGNETICS, V26, P448, DOI 10.1002/bem.20105; Arumugam T, 2006, J NATL CANCER I, V98, P1806, DOI 10.1093/jnci/djj498; Cuervo AM, 2004, TRENDS CELL BIOL, V14, P70, DOI 10.1016/j.tcb.2003.12.002; Glazer ES, 2010, CLIN CANCER RES, V16, P5712, DOI 10.1158/1078-0432.CCR-10-2055; Goldberg SN, 1996, ACAD RADIOL, V3, P929; Kabeya Y, 2000, EMBO J, V19, P5720, DOI 10.1093/emboj/19.21.5720; Kirson ED, 2007, P NATL ACAD SCI USA, V104, P10152, DOI 10.1073/pnas.0702916104; Klionsky DJ, 2012, AUTOPHAGY, V8, P445, DOI 10.4161/auto.19496; Laane E, 2009, CELL DEATH DIFFER, V16, P1018, DOI 10.1038/cdd.2009.46; Li M, 2006, CANCER-AM CANCER SOC, V106, P2284, DOI 10.1002/cncr.21862; Marchionni I, 2006, BBA-BIOMEMBRANES, V1758, P597, DOI 10.1016/j.bbamem.2006.03.014; Matsui Y, 2000, PANCREAS, V20, P14, DOI 10.1097/00006676-200001000-00002; MCGAHAN JP, 1990, INVEST RADIOL, V25, P267, DOI 10.1097/00004424-199003000-00011; Mizushima N, 2007, AUTOPHAGY, V3, P542, DOI 10.4161/auto.4600; Philip PA, 2010, J CLIN ONCOL, V28, P3605, DOI 10.1200/JCO.2009.25.7550; Renouf D, 2010, EXPERT REV ANTICANC, V10, P529, DOI [10.1586/era.10.21, 10.1586/ERA.10.21]; Taghi M, 2012, RECENT PATENTS ENDOC, V6, P251, DOI 10.2174/187221412802481757; Tang K, 2011, ONCOL REP, V25, P963, DOI 10.3892/or.2011.1139; Yang SH, 2011, GENE DEV, V25, P717, DOI 10.1101/gad.2016111; Yu L, 2004, CELL CYCLE, V3, P1124; Zimmerman JW, 2012, BRIT J CANCER, V106, P307, DOI 10.1038/bjc.2011.523	23	24	24	0	8	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0008-543X	1097-0142		CANCER-AM CANCER SOC	Cancer	FEB 15	2014	120	4					480	491		10.1002/cncr.28453			12	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	301UO	WOS:000330557800008	24496866	Bronze, Green Accepted			2022-04-25	
J	Liu, MP; Liao, M; Dai, C; Chen, JF; Yang, CJ; Liu, M; Chen, ZG; Yao, MC				Liu, Meng-ping; Liao, Min; Dai, Cong; Chen, Jie-feng; Yang, Chun-juan; Liu, Ming; Chen, Zuan-guang; Yao, Mei-cun			Sanguisorba officinalis L synergistically enhanced 5-fluorouracil cytotoxicity in colorectal cancer cells by promoting a reactive oxygen species-mediated, mitochondria-caspase-dependent apoptotic pathway	SCIENTIFIC REPORTS			English	Article							CYTOCHROME-C; PHASE-II; AUTOPHAGY; EXTRACT; GROWTH; ACID; 5-FU; COMBINATION; OXALIPLATIN; MECHANISMS	Sanguisorba officinalis L. radix is a widely used herb called DiYu (DY) in China and has an extensive range of bioactivities, including anti-cancer, anti-inflammatory, and anti-oxidative activities. However, there is little evidence to support its anti-cancer effects against colorectal cancer (CRC). The first-line chemotherapeutic agent 5-fluorouracil (5-FU) is used to treat CRC, but its efficiency is hampered by acquired drug resistance. This study found that a water extract of DY exerted anti-proliferative effects against two CRC cell lines (HCT-116 and RKO), and it sensitized CRC cells to 5-FU therapy by activating a reactive oxygen species (ROS)-mediated, mitochondria-caspase-dependent apoptotic pathway. Co-treatment of DY and 5-FU significantly elevated ROS levels, up-regulated Bax/Bcl-2 ratio and triggered mitochondrial dysfunction, followed by a release of cytochrome c and up-regulation of proteins such as cleaved-caspase-9/3 and cleaved-PARP. Additionally, the induction of autophagy may be involved in mediating synergism of DY in HCT-116 cells. Gallic acid (GA), catechinic acid (CA) and ellagic acid (EA) were identified as the potential chief constituents responsible for the synergistic effects of DY. In conclusion, co-treatment of DY, specifically GA, CA and EA, with 5-FU may be a potential alternative therapeutic strategy for CRC by enhancing an intrinsic apoptotic pathway.	[Liu, Meng-ping; Liao, Min; Dai, Cong; Chen, Jie-feng; Liu, Ming; Chen, Zuan-guang; Yao, Mei-cun] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China; [Yang, Chun-juan] Harbin Med Univ, Coll Pharm, Harbin 150081, Peoples R China		Yao, MC (corresponding author), Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.	yaomeicun@gmail.com	Liao, Min/L-7491-2018	Liao, Min/0000-0001-7050-0711	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81573551, 81573689]	We appreciate Kornberg lab (Sun Yat-sen University) to provide us experimental platform and National Natural Science Foundation of China (No. 81573551 and No. 81573689) to sponsor our study.	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J	Chen, SG; Wu, XZ; Hu, JW; Dai, GX; Rong, AH; Guo, G				Chen, Shengguang; Wu, Xianzheng; Hu, Jiawen; Dai, Guoxing; Rong, Aihong; Guo, Gang			PM2.5 exposure decreases viability, migration and angiogenesis in human umbilical vein endothelial cells and human microvascular endothelial cells	MOLECULAR MEDICINE REPORTS			English	Article						particulate matter; human umbilical vein endothelial cells; human microvascular endothelial cells; migration; angiogenesis	AMBIENT PARTICULATE MATTER; EPITHELIAL A549 CELLS; OXIDATIVE STRESS; COLORECTAL-CANCER; TENASCIN-C; EXPRESSION; INFLAMMATION; ADHESION; ATHEROSCLEROSIS; AUTOPHAGY	Previous studies have confirmed that exposure to particulate matter with a diameter of <= 2.5 mu m (PM2.5) is associated with inflammation. PM2.5 decreases cardiac cell viability and increases apoptosis through overproduction of reactive oxygen species (ROS). In the present study, the role of PM2.5 in ECs was investigated in vitro. Human umbilical vein endothelial cells and human microvascular endothelial cells (ECs) were incubated with PM2.5 (100-800 mu g/ml) to investigate the effects of PM2.5 on EC viability, migration, tube formation and intracellular levels of ROS. Cell viability and cell apoptosis were determined by MTT assay and flow cytometry analysis. Cell migration was assessed using a Boyden chamber assay, and tube formation was determined by matrigel assay. Tumor necrosis factor-a and interleukin-8 levels were measured by ELISA, and ROS levels were assessed with 2', 7' -dichlorofluorescin diacetate. The results indicated that PM2.5 decreases EC viability and increases EC apoptosis in a concentration-dependent manner. PM2.5 also decreased EC tube formation in a dose-dependent manner. The results also demonstrated that PM2.5 suppresses adhesion to EC extracellular matrix proteins. Furthermore, PM2.5 exposure significantly induced ROS generation, indicative of oxidative stress. Finally, it was demonstrated that PM2.5 decreased angiogenesis in vivo. These results suggested that repeated exposure to PM2.5 induces vascular inflammation.	[Chen, Shengguang; Wu, Xianzheng; Hu, Jiawen; Dai, Guoxing; Rong, Aihong; Guo, Gang] Tongji Univ, Tongji Hosp, Dept Emergency, 389 Xin Cun Rd, Shanghai 200333, Peoples R China		Wu, XZ (corresponding author), Tongji Univ, Tongji Hosp, Dept Emergency, 389 Xin Cun Rd, Shanghai 200333, Peoples R China.	xianzhengwubio@sohu.com					Aaron CP, 2016, ENVIRON HEALTH PERSP, V124, P1166, DOI 10.1289/ehp.1409451; Abdelrahim M, 2010, INT J ONCOL, V36, P5, DOI 10.3892/ijo_00000470; Amatullah H, 2012, INHAL TOXICOL, V24, P161, DOI 10.3109/08958378.2011.650235; Cui P, 2015, EUR J PUBLIC HEALTH, V25, P324, DOI 10.1093/eurpub/cku145; Cui YQ, 2015, CELL PHYSIOL BIOCHEM, V35, P353, DOI 10.1159/000369701; Deng XB, 2013, TOXICOL IN VITRO, V27, P1762, DOI 10.1016/j.tiv.2013.05.004; Favreau AJ, 2014, CANCER MED-US, V3, P265, DOI 10.1002/cam4.203; Fu JY, 2015, BMJ OPEN, V5, DOI 10.1136/bmjopen-2015-009452; Gimbrone MA, 2016, CIRC RES, V118, P620, DOI 10.1161/CIRCRESAHA.115.306301; Hessel M, 2009, CELL PHYSIOL BIOCHEM, V24, P201, DOI 10.1159/000233246; Hu H, 2013, BREAST CANCER RES TR, V139, P217, DOI 10.1007/s10549-013-2527-9; Ide M, 2007, ONCOL REP, V18, P1451; Li RJ, 2015, ENVIRON SCI POLLUT R, V22, P20167, DOI 10.1007/s11356-015-5222-z; Lin CP, 2013, BIOMED RES INT, V2013, DOI 10.1155/2013/845037; Madsen CD, 2007, J CELL BIOL, V177, P927, DOI 10.1083/jcb.200612058; Montiel-Davalos A, 2007, INHAL TOXICOL, V19, P91, DOI 10.1080/08958370701495212; Ostro B, 2014, ENVIRON RES, V132, P168, DOI 10.1016/j.envres.2014.03.042; Potera C, 2014, ENVIRON HEALTH PERSP, V122, pA29, DOI 10.1289/ehp.122-A29; Rui W, 2016, J APPL TOXICOL, V36, P48, DOI 10.1002/jat.3143; Thurston G, 2015, SEMIN RESP CRIT CARE, V36, P422, DOI 10.1055/s-0035-1549455; Tong GQ, 2015, ARCH ENVIRON CON TOX, V68, P31, DOI 10.1007/s00244-014-0077-8; Wang FF, 2016, BIOMED ENVIRON SCI, V29, P107, DOI 10.3967/bes2016.012; Wang YH, 2015, INT J CLIN EXP MED, V8, P58; Yang GZ, 2015, MOLECULES, V20, P6626, DOI 10.3390/molecules20046626; Yue HF, 2015, ENVIRON SCI TECHNOL, V49, P14484, DOI 10.1021/es506280c; Zhu GW, 2016, CELL PHYSIOL BIOCHEM, V39, P1665, DOI 10.1159/000447868	26	16	18	1	17	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1791-2997	1791-3004		MOL MED REP	Mol. Med. Rep.	SEP	2017	16	3					2425	2430		10.3892/mmr.2017.6877			6	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	FD3VX	WOS:000407461600009	28677750	Green Submitted, Green Published, hybrid			2022-04-25	
J	Hobbs, GA; Baker, NM; Miermont, AM; Thurman, RD; Pierobon, M; Tran, TH; Anderson, AO; Waters, AM; Diehl, JN; Papke, B; Hodge, RG; Klomp, JE; Goodwin, CM; DeLiberty, JM; Wang, JN; Ng, RWS; Gautam, P; Bryant, KL; Esposito, D; Campbell, SL; Petricoin, EF; Simanshu, DK; Aguirre, AJ; Wolpin, BM; Wennerberg, K; Rudloff, U; Cox, AD; Der, CJ				Hobbs, G. Aaron; Baker, Nicole M.; Miermont, Anne M.; Thurman, Ryan D.; Pierobon, Mariaelena; Tran, Timothy H.; Anderson, Andrew O.; Waters, Andrew M.; Diehl, J. Nathaniel; Papke, Bjoern; Hodge, Richard G.; Klomp, Jennifer E.; Goodwin, Craig M.; DeLiberty, Jonathan M.; Wang, Junning; Ng, Raymond W. S.; Gautam, Prson; Bryant, Kirsten L.; Esposito, Dominic; Campbell, Sharon L.; Petricoin, Emanuel F., III; Simanshu, Dhirendra K.; Aguirre, Andrew J.; Wolpin, Brian M.; Wennerberg, Krister; Rudloff, Udo; Cox, Adrienne D.; Der, Channing J.			Atypical KRAS(G12R) Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer	CANCER DISCOVERY			English	Article							GUANINE-NUCLEOTIDE EXCHANGE; ONCOGENIC KRAS; RAS-BINDING; PROTEIN; ACTIVATION; TRANSFORMATION; KINASE; TUMORIGENESIS; DEGRADATION; P110-ALPHA	Allele-specific signaling by different KRAS alleles remains poorly understood. The KRAS(G12R) mutation displays uneven prevalence among cancers that harbor the highest occurrence of KRAS mutations: It is rare (similar to 1%) in lung and colorectal cancers, yet relatively common (similar to 20%) in pancreatic ductal adenocarcinoma (PDAC), suggesting context-specific properties. We evaluated whether KRAS(G12R) is functionally distinct from the more common KRAS(G12D)- or KRAS(G12V)-mutant proteins (KRASG(12D/V)). We found that KRAS(G12D/V) but not KRAS(G12R) drives macropinocytosis and that MYC is essential for macropinocytosis in KRAS(G12D/V)- but not KRAS(G12R)-mutant PDAC. Surprisingly, we found that KRAS(G12R) is defective for interaction with a key effector, p110 alpha PI3K (PI3K alpha), due to structural perturbations in switch II. Instead, upregulated KRAS-independent P13K gamma activity was able to support macropinocytosis in KRAS(G12R)-mutant PDAC. Finally, we determined that KRAS(G12R)-mutant PDAC displayed a distinct drug sensitivity profile compared with KRAS(G12 D)-mutant PDAC but is still responsive to the combined inhibition of ERK and autophagy. SIGNIFICANCE: We determined that KRAS(G12R) is impaired in activating a key effector, p110 alpha PI3K. As such, KRAS(G12R) is impaired in driving macropinocytosis. However, overexpression of PI3K gamma in PDAC compensates for this deficiency, providing one basis for the prevalence of this otherwise rare KRAS mutant in pancreatic cancer but not other cancers.	[Hobbs, G. Aaron; Baker, Nicole M.; DeLiberty, Jonathan M.; Bryant, Kirsten L.; Cox, Adrienne D.; Der, Channing J.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27515 USA; [Miermont, Anne M.; Anderson, Andrew O.; Rudloff, Udo] NCI, Thorac & GI Oncol Branch, Bethesda, MD 20892 USA; [Thurman, Ryan D.; Campbell, Sharon L.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27515 USA; [Pierobon, Mariaelena; Petricoin, Emanuel F., III] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA; [Tran, Timothy H.; Esposito, Dominic; Simanshu, Dhirendra K.] NCI, RAS Initiat, Canc Res Technol Program, Frederick Natl Lab Canc Res,Leidos Biomed Res Inc, Frederick, MD 21701 USA; [Waters, Andrew M.; Papke, Bjoern; Hodge, Richard G.; Klomp, Jennifer E.; Goodwin, Craig M.; Campbell, Sharon L.; Cox, Adrienne D.; Der, Channing J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, CB7295, Chapel Hill, NC 27599 USA; [Diehl, J. Nathaniel; Der, Channing J.] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27515 USA; [Wang, Junning; Ng, Raymond W. S.; Aguirre, Andrew J.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA; [Gautam, Prson; Wennerberg, Krister] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland; [Aguirre, Andrew J.] Broad Inst MIT & Harvard, Cambridge, MA USA; [Wennerberg, Krister] Univ Copenhagen, BRIC, Copenhagen, Denmark; [Rudloff, Udo] NCI, Rare Tumor Initiat, Pediat Oncol Branch, Bethesda, MD 20892 USA; [Cox, Adrienne D.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA		Der, CJ (corresponding author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB7295, Chapel Hill, NC 27599 USA.; Rudloff, U (corresponding author), NCI, Ctr Canc Res, Bldg 10,Hatfield CRC,Room 2B-34D, Bethesda, MD 20892 USA.	rudloffu@mail.nih.gov	Wennerberg, Krister/AAH-2919-2022; Ariel, Pablo/AGJ-4118-2022	Wennerberg, Krister/0000-0002-1352-4220; DeLiberty, Jonathan/0000-0001-6001-6678; Diehl, John/0000-0002-7309-0903; Waters, Andrew/0000-0002-6058-5878; Gautam, Prson/0000-0002-1154-8501; Hodge, Richard/0000-0002-1920-1385; campbell, sharon/0000-0003-0311-409X; Simanshu, Dhirendra/0000-0002-9717-4618; Klomp, Jennifer/0000-0003-1781-648X; Esposito, Dominic/0000-0002-9987-1687; Hobbs, Aaron/0000-0002-4751-9681; Papke, Bjoern/0000-0001-8156-7508; Ng, Raymond/0000-0003-2573-8207	NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA42978, U01CA199235, P50CA196510, R35CA232113, P01CA203657, CA203657, K08CA218420-02, P50CA127003, U01CA224146, F32CA200313, T32CA009156, F31CA180628, F32CA221005, T32CA071341, HHSN261200800001E]; Department of DefenseUnited States Department of Defense [W81XWH-15-1-0611]; Lustgarten Pancreatic Cancer Foundation [388222]; 2015 Pancreatic Cancer Action Network-AACR Research Acceleration Network Grant [15-90-25-DER]; Lustgarten Foundation; Dana-Farber Cancer Institute Hale Center for Pancreatic Cancer Research; Doris Duke Charitable FoundationDoris Duke Charitable Foundation (DDCF) [2017066]; Pancreatic Cancer Action Network [18-35-AGUI]; DFCI Hale Family Center for Pancreatic Cancer Research; 2018 -Debbie's Dream Foundation-AACR Gastric Cancer Research Fellowship [18-40-41-HODG]; American Cancer SocietyAmerican Cancer Society [PF-18-061]; Slomo and Cindy Silvian Foundation; Intramural Research Program of the NIH, NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIA BC 011267]; Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [PA 3051/1-1]; Pancreatic Cancer Action Network/AACR Pathway to Leadership grant; Center for AIDS Research [5P30AI050410];  [P30CA016086]	C.J. Der and A.D. Cox were supported by grants from the NCI (R01CA42978, U01CA199235, P50CA196510, R35CA232113, and P01CA203657), the Department of Defense (W81XWH-15-1-0611), and the Lustgarten Pancreatic Cancer Foundation (388222). For C.J. Der and K. Wennerberg, research was supported by the 2015 Pancreatic Cancer Action Network-AACR Research Acceleration Network Grant, Grant Number 15-90-25-DER. K. Wennerberg was supported by NCI P01CA203657. S.L. Campbell and E.F. Petricoin III were supported by NCI CA203657. A.J. Aguirre was supported by the Lustgarten Foundation, the Dana-Farber Cancer Institute Hale Center for Pancreatic Cancer Research, the Doris Duke Charitable Foundation (2017066), the Pancreatic Cancer Action Network (18-35-AGUI), and NCI K08CA218420-02, P50CA127003, and U01CA224146. B.M. Wolpin was supported by the Lustgarten Foundation and DFCI Hale Family Center for Pancreatic Cancer Research. G.A. Hobbs was supported by NCI F32CA200313 and T32CA009156; N.M. Baker by NCI F31CA180628; R.D. Thurman, J.E. Klomp, and C.M. -Goodwin by NCI T32CA009156. C.M. Goodwin was supported by NCI F32CA221005. R.G. Hodge was supported by the 2018 -Debbie's Dream Foundation-AACR Gastric Cancer Research Fellowship, in memory of Sally Mandel, Grant Number 18-40-41-HODG. A.M. Waters was supported by a fellowship from the American Cancer Society (PF-18-061); J.N. Diehl by NCI T32CA071341 and a fellowship from the Slomo and Cindy Silvian Foundation. A.M. Miermont and U. Rudloff were supported by the Intramural Research Program of the NIH, NCI (ZIA BC 011267). B. Papke was supported by the Deutsche Forschungsgemeinschaft (DFG PA 3051/1-1). K.L. Bryant was supported by T32CA009156 and by a Pancreatic Cancer Action Network/AACR Pathway to Leadership grant. Support to T.H. Tran, D. Esposito, and D.K. Simanshu was provided by NCI under contract HHSN261200800001E. Structural work used Northeastern Collaborative Access Team beamline (GM103403) at the Advanced Photon Source (DE-AC02-06CH11357). The UNC Microscopy Services Laboratory and Flow Cytometry Core Facility were supported in part by P30CA016086. Research reported in this article was supported by the Center for AIDS Research award number 5P30AI050410. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.	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JAN	2020	10	1					104	123		10.1158/2159-8290.CD-19-1006			20	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	KB9TZ	WOS:000506831600025	31649109	Green Accepted			2022-04-25	
J	Novohradsky, V; Markova, L; Kostrhunova, H; Kasparkova, J; Hoeschele, J; Brabec, V				Novohradsky, Vojtech; Markova, Lenka; Kostrhunova, Hana; Kasparkova, Jana; Hoeschele, James; Brabec, Viktor			A [Pt(cis-1,3-diaminocycloalkane)Cl-2] analog exhibits hallmarks typical of immunogenic cell death inducers in model cancer cells	JOURNAL OF INORGANIC BIOCHEMISTRY			English	Article						Platinum; Cancer; Immunogenic cell death; Damage-associated molecular pattern; CT26 cell line	ANTICANCER THERAPY; AUTOPHAGY; DAMPS; CALRETICULIN; MECHANISMS; INDUCTION; PAMPS; DRUGS	The platinum drugs belong to prevailing chemotherapeutics used in the treatment of cancer. At present, however, the search for new anticancer metal-based drugs that operate by the mechanisms distinct from those of the conventional chemotherapeutics is very active. Furthermore, it has been demonstrated that cytotoxic chemotherapy and immunotherapy may exert a highly synergistic anticancer activity. Thus, the development of antitumor platinum and other metal-based drugs that exhibit cytostatic effects and concurrently elicit immunogenic cell death (ICD) has shown promise for cancer treatment. Notably, conventional platinum drug oxaliplatin ([Pt (1R,2R-DACH)(oxalate)], DACH = diaminocyclohexane) is a well-known agent that displays both cytostatic and immune responses. Moreover, it was also demonstrated that even minor derivatization of the unleaving cycloalkyl moiety in oxaliplatin might have a pronounced effect on its immunomodulatory activity. Here, we investigated how replacing the 1R,2R- diaminocyclohexane ring by 1,3-diaminocycloalkane (alkane = butane, pentane, or hexane) affects the ability to evoke secretion of damage-associated molecular patterns characteristic of ICD in model murine colorectal carcinoma cell line CT26. The results indicate that among the investigated [Pt (cis-1,3-diaminocycloalkane)Cl2] complexes, the complex containing the cyclobutyl moiety exhibits the hallmarks typical of ICD inducers. Thus, [Pt(cis-1,3-diaminocyclobutane)Cl2] may expand the spectrum of anticancer chemotherapeutics capable of inducing ICD in cancer cells and might be of interest for further (pre)clinical development.	[Novohradsky, Vojtech; Markova, Lenka; Kostrhunova, Hana; Kasparkova, Jana; Brabec, Viktor] Czech Acad Sci, Inst Biophys, Kralovopolska 135, CZ-61265 Brno, Czech Republic; [Hoeschele, James] Eastern Michigan Univ, Dept Chem, Ypsilanti, MI 48197 USA		Brabec, V (corresponding author), Czech Acad Sci, Inst Biophys, Kralovopolska 135, CZ-61265 Brno, Czech Republic.	brabec@ibp.cz	Kostrhunová, Hana/H-1934-2014	Kostrhunová, Hana/0000-0003-2706-6491			Ahmed A, 2020, MOL ONCOL, V14, P2994, DOI 10.1002/1878-0261.12851; Bianchi ME, 2007, J LEUKOCYTE BIOL, V81, P1, DOI 10.1189/jlb.0306164; Brabec V, 2017, COORDIN CHEM REV, V351, P2, DOI 10.1016/j.ccr.2017.04.013; Casares N, 2005, J EXP MED, V202, P1691, DOI 10.1084/jem.20050915; dos Santos-Rodrigues A, 2014, NEUROCHEM INT, V73, P229, DOI 10.1016/j.neuint.2014.03.014; Englinger B, 2019, CHEM REV, V119, P1519, DOI 10.1021/acs.chemrev.8b00396; FANIZZI FP, 1987, INORG CHIM A-BIOINOR, V137, P45, DOI 10.1016/S0020-1693(00)87114-5; Fucikova J, 2020, CELL DEATH DIS, V11, DOI 10.1038/s41419-020-03221-2; Galluzzi Lorenzo, 2020, J Immunother Cancer, V8, DOI 10.1136/jitc-2019-000337; Galluzzi L, 2015, CANCER CELL, V28, P690, DOI 10.1016/j.ccell.2015.10.012; Garg AD, 2016, CELL DEATH DIFFER, V23, P938, DOI 10.1038/cdd.2016.5; Gou HF, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0085789; Hanahan D, 2000, CELL, V100, P57, DOI 10.1016/S0092-8674(00)81683-9; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Hoeschele JD, 2020, J BIOL INORG CHEM, V25, P913, DOI 10.1007/s00775-020-01809-9; Johnstone TC, 2016, CHEM REV, V116, P3436, DOI 10.1021/acs.chemrev.5b00597; Johnstone TC, 2015, PHILOS T R SOC A, V373, DOI 10.1098/rsta.2014.0185; Jungwirth U, 2012, MOL PHARMACOL, V81, P719, DOI 10.1124/mol.111.077321; Kepp O, 2014, ONCOIMMUNOLOGY, V3, DOI 10.4161/21624011.2014.955691; Kroemer G, 2013, ANNU REV IMMUNOL, V31, P51, DOI 10.1146/annurev-immunol-032712-100008; Krysko DV, 2012, NAT REV CANCER, V12, P860, DOI 10.1038/nrc3380; Liu P, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-14848-1; Maiuri MC, 2007, NAT REV MOL CELL BIO, V8, P741, DOI 10.1038/nrm2239; Marino G, 2014, NAT REV MOL CELL BIO, V15, P81, DOI 10.1038/nrm3735; Martins I, 2014, CELL DEATH DIFFER, V21, P79, DOI 10.1038/cdd.2013.75; Mauthe M, 2018, AUTOPHAGY, V14, P1435, DOI 10.1080/15548627.2018.1474314; Michalak M, 2009, BIOCHEM J, V417, P651, DOI 10.1042/BJ20081847; Novohradsky V, 2020, INORG CHEM FRONT, V7, P4150, DOI 10.1039/d0qi00991a; Pfirschke C, 2016, IMMUNITY, V44, P343, DOI 10.1016/j.immuni.2015.11.024; Pitt JM, 2017, ADV EXP MED BIOL, V1036, P65, DOI 10.1007/978-3-319-67577-0_5; Rufo N, 2017, TRENDS CANCER, V3, P643, DOI 10.1016/j.trecan.2017.07.002; Serrano-del Valle A, 2019, FRONT CELL DEV BIOL, V7, DOI 10.3389/fcell.2019.00050; Stojanovska V, 2019, BIOMED RES INT, V2019, DOI 10.1155/2019/4650695; Stros M, 2010, BBA-GENE REGUL MECH, V1799, P101, DOI 10.1016/j.bbagrm.2009.09.008; Tang DL, 2012, IMMUNOL REV, V249, P158, DOI 10.1111/j.1600-065X.2012.01146.x; Terenzi A, 2016, J INORG BIOCHEM, V165, P71, DOI 10.1016/j.jinorgbio.2016.06.021; Tesniere A, 2010, ONCOGENE, V29, P482, DOI 10.1038/onc.2009.356; Tesniere A, 2008, CURR OPIN IMMUNOL, V20, P504, DOI 10.1016/j.coi.2008.05.007; Trautmann A, 2009, SCI SIGNAL, V2, DOI 10.1126/scisignal.256pe6; Venereau E., 2012, J GEN PHYSIOL, V140, pI6; Waldman AD, 2020, NAT REV IMMUNOL, V20, P651, DOI 10.1038/s41577-020-0306-5; Wong DYQ, 2015, ANGEW CHEM INT EDIT, V54, P6483, DOI 10.1002/anie.201500934; Zhao TS, 2015, ONCOTARGET, V6, P27816, DOI 10.18632/oncotarget.4816; Zhong WY, 2020, BMC GENOMICS, V21, DOI 10.1186/s12864-019-6344-3; Zhou JY, 2019, J CELL MOL MED, V23, P4854, DOI 10.1111/jcmm.14356; Zitvogel L, 2010, CLIN CANCER RES, V16, P3100, DOI 10.1158/1078-0432.CCR-09-2891	46	1	1	9	9	ELSEVIER SCIENCE INC	NEW YORK	STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA	0162-0134	1873-3344		J INORG BIOCHEM	J. Inorg. Biochem.	JAN	2022	226								111628	10.1016/j.jinorgbio.2021.111628		OCT 2021	8	Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Chemistry	WN7NV	WOS:000711955100001	34673378				2022-04-25	
J	Li, SX; Liu, FL; Xu, L; Li, C; Yang, X; Guo, B; Gu, JX; Wang, L				Li, Shuxuan; Liu, Fenglin; Xu, Ling; Li, Can; Yang, Xu; Guo, Bao; Gu, Jianxin; Wang, Lan			Wnt/beta-Catenin Signaling Axis Is Required for TFEB-Mediated Gastric Cancer Metastasis and Epithelial-Mesenchymal Transition	MOLECULAR CANCER RESEARCH			English	Article							TRANSCRIPTION FACTOR EB; ENDOLYSOSOMAL BIOGENESIS; COLORECTAL-CANCER; TGF-BETA; AUTOPHAGY; EXPRESSION; INHIBITOR; PHENOTYPE; LOX-1	Gastric cancer remains the third leading cause of cancer-related death, and tumor metastasis is the main risk factor for poor prognosis of patients with gastric cancer. Transcription factor EB (TFEB) is a MiT family member and has been found to drive tumorigenesis in a number of tissues, whereas few studies were focused on investigating its prometastasis role and mechanism in gastric cancer. Here, we found TFEB was upregulated in gastric cancer tissues compared with adjacent normal gastric epithelial tissues. IHC analysis from gastric cancer tissue microarray revealed that TFEB in gastric cancer was correlated with depth of tumor invasion, lymph node or distant metastasis, tumor tumor-nodemetastasis stage, and overall survival. Gastric cancer cells with TFEB overexpression presented an increased cell migration or invasion, and epithelial-mesenchymal transition (EMT). Furthermore, gene correlation analysis and gene set enrichment analysis enriched Wnt/beta-catenin signaling pathway members in TFEB high-expression group, and the TOP/FOPflash assay verified the effect of TFEB on beta-catenin transcription activity. Besides, we found that TFEB could trigger the aggregation of beta-catenin in nucleus and activate its transcription, as well as facilitate the expression of Wnt/beta-catenin target genes and EMT-related markers, which could be reversed by the Wnt/beta-catenin inhibitor XAV-939. Collectively, TFEB enhances gastric cancer metastatic potential by activating Wnt/ beta-catenin signaling pathway and may become a promising therapeutic target for gastric cancer metastasis.	[Li, Shuxuan; Xu, Ling; Li, Can; Yang, Xu; Guo, Bao; Gu, Jianxin; Wang, Lan] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, NHC Key Lab Glycoconjugate Res, Shanghai, Peoples R China; [Liu, Fenglin] Fudan Univ, Zhongshan Hosp, Dept Gen Surg, Shanghai, Peoples R China		Wang, L (corresponding author), Fudan Univ, Shanghai 200032, Peoples R China.	wanglan@fudan.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31870800, 31600648, 31842033]	This work was supported by the National Natural Science Foundation of China (31870800, 31600648, 31842033).	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Cancer Res.	NOV	2020	18	11					1650	1659		10.1158/1541-7786.MCR-20-0180			10	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	OQ4BC	WOS:000588729500004	32753474	Bronze			2022-04-25	
J	Feng, YQ; Zou, W; Hu, CH; Li, GY; Zhou, SH; He, Y; Ma, F; Deng, C; Sun, LL				Feng, Yeqian; Zou, Wen; Hu, Chunhong; Li, Guiyuan; Zhou, Shenghua; He, Yan; Ma, Fang; Deng, Chao; Sun, Lili			Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin	ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS			English	Article						CASC2; miR-21; PTEN; Cervical cancer; DDP; Chemoresistance	LONG NONCODING RNA; TUMOR-SUPPRESSOR GENE; CELL LUNG-CANCER; SIGNALING PATHWAY; MIR-21 PROMOTES; NEOADJUVANT CHEMOTHERAPY; INHIBITING AUTOPHAGY; COLORECTAL-CANCER; PTEN/AKT PATHWAY; CASC2 SUPPRESSES	Cisplatin (DDP)-based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (IncRNA) in tumor biology. However, the roles and regulatory mechanisms of the novel IncRNA, cancer susceptibility candidate 2 (CASC2), in cervical cancer tumorigenesis and chemoresistance are poorly understood. In this study, CASC2 expression was down-regulated in cervical cancer tissues, and was related to a shorter survival time and poorer clinicopathologic features. Exogenous CACS2 alone was sufficient to inhibit cervical cancer cell proliferation and amplified DDP-induced repression of cell proliferation. A lower expression of CACS2 was observed in the DDP-resistant cervical cancer tissues, compared to DDP-sensitive cancer tissues; CACS2 overexpression could sensitize DDP-resistant cervical cancer cell (HeLa/DDP and CaSki/DDP) to DDP. Further functional experiments indicate that CASC2 upregulated PTEN expression by direct inhibiting miR-21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AKT protein. In DDP-resistant cervical cancer tissues, miR-21 was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN as a ceRNA of miR-21 and plays an important role in cervical cancer sensitivity to DDP and may serve as a potential target for cancer diagnosis and treatment. (C) 2017 Elsevier Inc. All rights reserved.	[Feng, Yeqian; Zou, Wen; Hu, Chunhong; He, Yan; Ma, Fang; Deng, Chao] Cent S Univ, Dept Oncol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China; [Li, Guiyuan] Cent S Univ, Canc Res Inst, Changsha, Hunan, Peoples R China; [Zhou, Shenghua] Cent S Univ, Xiangya Hosp 2, Dept Cardiovascularol, Changsha 410011, Hunan, Peoples R China; [Sun, Lili] First Peoples Hosp YueYang, Dept Oncol, Yueyang, Hunan, Peoples R China		Zou, W; Hu, CH (corresponding author), Cent S Univ, Dept Oncol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China.	13507411313@139.com; huchunh@medmail.com.cn			Natural Science Fund Project of Hunan Province [2016JJ4096]	This study was supported by the Natural Science Fund Project of Hunan Province (project ID: 2016JJ4096).	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Biochem. Biophys.	JUN 1	2017	623						20	30		10.1016/j.abb.2017.05.001			11	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	EY1OT	WOS:000403735900003	28495512				2022-04-25	
J	Stoetzer, OJ; Wittwer, C; Lehner, J; Fahmueller, YN; Kohles, N; Fersching, DMI; Leszinski, G; Roessner, J; Holdenrieder, S				Stoetzer, Oliver J.; Wittwer, Christin; Lehner, Julia; Fahmueller, Yvonne N.; Kohles, Nikolaus; Fersching, Debora M. I.; Leszinski, Gloria; Roessner, Juliane; Holdenrieder, Stefan			Circulating nucleosomes and biomarkers of immunogenic cell death as predictive and prognostic markers in cancer patients undergoing cytotoxic therapy	EXPERT OPINION ON BIOLOGICAL THERAPY			English	Review						biomarkers; cancer; chemotherapy; DNAse; HMGB1; immunogenic cell death; nucleosomes; prediction; prognosis; RAGE; serum; SIRT; TACE	LUNG-CANCER; COLORECTAL-CANCER; IMMUNE-RESPONSES; TUMOR RESPONSE; CYFRA 21-1; HMGB1; SERUM; CHEMOTHERAPY; DNA; AUTOPHAGY	Introduction: Immunogenic cell death markers are released from apoptotic and necrotic cells upon pathologic or therapeutic causes and stimulate the innate and adaptive immune system. Cell death products such as nucleosomes, damage-associated molecular pattern (DAMP) molecules such as the high-mobility group box 1 protein (HMGB1) and its receptor of advanced glycation end products (sRAGE) are supposed to play an essential role in driving this process. However, this immunogenic activation may have dual effects, either by sensitizing the immune system for more efficient tumor cell removal or by creating a favorable tumor microenvironment that facilitates tumor growth, proliferation and invasiveness. Areas covered: Here, we review recent findings on the relevance of serum nucleosomes, DNAse activity, HMGB1 and sRAGE as biomarkers for the diagnosis, prognosis and therapy prediction in cancer disease. Expert opinion: In comparison with healthy controls, cancer patients demonstrated elevated serum levels of nucleosomes and HMGB1 while sRAGE levels were decreased. During locoregional and systemic cytotoxic therapies, a high release of nucleosomes and HMGB1 as well as low release of sRAGE before and during the initial phase of the treatment was found to be associated with poor response to the therapy and patient survival. Therefore, immunogenic cell death markers are promising tools for the prognosis, therapy prediction and monitoring in cancer patients.	[Holdenrieder, Stefan] Univ Hosp Bonn, Inst Clin Chem & Clin Pharmacol, D-53105 Bonn, Germany; [Wittwer, Christin; Lehner, Julia; Fahmueller, Yvonne N.; Kohles, Nikolaus; Fersching, Debora M. I.; Leszinski, Gloria; Roessner, Juliane; Holdenrieder, Stefan] Univ Hosp Munich, Inst Clin Chem, D-81366 Munich, Germany; [Stoetzer, Oliver J.] Outpatient Specialty Ctr, D-80638 Munich, Germany		Holdenrieder, S (corresponding author), Univ Hosp Bonn, Inst Clin Chem & Clin Pharmacol, Sigmund Freud Str 25, D-53105 Bonn, Germany.	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Biol. Ther.	JUN	2012	12			1			S217	S224		10.1517/14712598.2012.689280			8	Biotechnology & Applied Microbiology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Research & Experimental Medicine	947CY	WOS:000304405600026	22620489				2022-04-25	
J	Chi, YY; Xu, H; Wang, F; Chen, XL; Shan, ZZ; Sun, Y; Fan, QX				Chi, Yanyan; Xu, Han; Wang, Feng; Chen, Xiaoling; Shan, Zhengzheng; Sun, Yan; Fan, Qingxia			ZKSCAN3 promotes breast cancer cell proliferation, migration and invasion	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						ZKSCAN3; Breast cancer; Tumor progression; Akt; mTOR	COLORECTAL-CANCER; PROGRESSION; REPRESSOR; AUTOPHAGY; LOCALIZATION; PROTEINS; SURFACE; GROWTH	ZKSCAN3, a zinc-finger transcription factor, which has been shown to be upregulated in several human cancer. However, the expression level, function and mechanism of ZKSCAN3 in breast cancer remains unknown. In the current study, immunohistochemistry, western blot and quantitative real time polymerase chain reaction (qRT-PCR) results showed that ZKSCAN3 was overexpressed in breast cancer tissue compared with normal breast tissue. Through analyzing the clinicopathological characteristics, we demonstrated that positive ZKSCAN3 expression predicted poor prognosis of patients with breast cancer. The expression level of ZKSCAN3 protein/mRNA in breast cancer cells (MCF-7 and MDA-MB-231) was higher than its expression in normal breast cells (HBL-100). Knocking down ZKSCAN3 via its short hairpin RNA (shRNA) in MCF-7 and MDA-MB-231 inhibited cell viability, migration and invasion. Western blot analysis showed that ZKSCAN3 silencing lead to significant decreases in the expression of Cyclin D1, B-cell lymphoma-2 (Bcl-2), and matrix metalloproteinase (MMP)-2/MMP-9, as well as increases in the expression of Bcl2 Associated X Protein (Bax) in breast cancer cells. Additionally, ZKSCAN3-shRNA expression markedly suppressed tumor growth in breast cancer xenograft mice. Finally, we demonstrated that silencing of ZKSCAN3 was able to inhibit Akt/mTOR signaling pathway by blocking p-Akt and p-mTOR protein expression in breast cancer cells. These results demonstrate that ZKSCAN3 plays a significant role in the progression of breast cancer. Therefore, ZKSCAN3 is a potential therapeutic target for breast cancer. (C) 2018 Elsevier Inc. All rights reserved.	[Chi, Yanyan; Wang, Feng; Shan, Zhengzheng; Sun, Yan; Fan, Qingxia] Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, Zhengzhou 450052, Henan, Peoples R China; [Xu, Han] Zhengzhou Univ, Affiliated Hosp 1, Dept Breast Dis Surg, Zhengzhou 450052, Henan, Peoples R China; [Chen, Xiaoling] Wenzhou Med Univ, Zhejiang Prov Key Lab Med Genet, Sch Life Sci, Wenzhou 325035, Peoples R China		Sun, Y; Fan, QX (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, Zhengzhou 450052, Henan, Peoples R China.	YanSun1221@126.com; fqx1221@126.com					Akcakanat A, 2008, CANCER-AM CANCER SOC, V112, P2352, DOI 10.1002/cncr.23456; Brooks PC, 1996, CELL, V85, P683, DOI 10.1016/S0092-8674(00)81235-0; Chauhan S, 2013, MOL CELL, V50, P16, DOI 10.1016/j.molcel.2013.01.024; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Chua JP, 2014, HUM MOL GENET, V23, P1376, DOI 10.1093/hmg/ddt527; Dillon RL, 2007, ONCOGENE, V26, P1338, DOI 10.1038/sj.onc.1210202; Egeblad M, 2002, NAT REV CANCER, V2, P161, DOI 10.1038/nrc745; Evans AJ, 2004, AM J PATHOL, V164, P285, DOI 10.1016/S0002-9440(10)63118-5; Fullgrabe J, 2014, NAT REV MOL CELL BIO, V15, P65, DOI 10.1038/nrm3716; Kawahara T, 2016, ONCOTARGET, V7, P53599, DOI 10.18632/oncotarget.10679; Liu J. Y., 2018, SPAG5 PROMOTES PROLI; Lupo A, 2013, CURR GENOMICS, V14, P268, DOI 10.2174/13892029113149990002; McAuliffe PF, 2010, CLIN BREAST CANCER, V10, pS59, DOI 10.3816/CBC.2010.s.013; Saftig P, 2016, NAT CELL BIOL, V18, P1025, DOI 10.1038/ncb3409; Santos GC, 2007, J CLIN PATHOL, V60, P1, DOI 10.1136/jcp.2005.034389; Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387; Song MS, 2012, NAT REV MOL CELL BIO, V13, P283, DOI 10.1038/nrm3330; Takeha S, 1997, JPN J CANCER RES, V88, P72, DOI 10.1111/j.1349-7006.1997.tb00304.x; Urrutia R, 2003, GENOME BIOL, V4, DOI 10.1186/gb-2003-4-10-231; Yang L, 2011, ONCOGENE, V30, P1329, DOI 10.1038/onc.2010.515; Yang L, 2008, CANCER RES, V68, P4321, DOI 10.1158/0008-5472.CAN-08-0407; Yang L, 2008, J BIOL CHEM, V283, P35295, DOI 10.1074/jbc.M806965200; Yu Q, 1999, GENE DEV, V13, P35, DOI 10.1101/gad.13.1.35; Yu T, 2015, ONCOGENE, V34, P413, DOI 10.1038/onc.2013.574; Zhang XD, 2012, INT J BIOCHEM CELL B, V44, P1166, DOI 10.1016/j.biocel.2012.04.005	25	13	13	0	6	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.	SEP 18	2018	503	4					2583	2589		10.1016/j.bbrc.2018.07.019			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	GT8MM	WOS:000444791600058	30049438				2022-04-25	
J	Czerwinska, P; Shah, PK; Tomczak, K; Klimczak, M; Mazurek, S; Sozanska, B; Biecek, P; Korski, K; Filas, V; Mackiewicz, A; Andersen, JN; Wiznerowicz, M				Czerwinska, Patrycja; Shah, Parantu K.; Tomczak, Katarzyna; Klimczak, Marta; Mazurek, Sylwia; Sozanska, Barbara; Biecek, Przemyslaw; Korski, Konstanty; Filas, Violetta; Mackiewicz, Andrzej; Andersen, Jannik N.; Wiznerowicz, Maciej			TRIM28 multi-domain protein regulates cancer stem cell population in breast tumor development	ONCOTARGET			English	Article						TRIM28; KAP1; breast cancer stem cells; pluripotency; epigenetics	EPITHELIAL-MESENCHYMAL TRANSITION; DIFFERENTIAL EXPRESSION ANALYSIS; MITOCHONDRIAL BIOGENESIS; COLORECTAL-CANCER; PANCREATIC-CANCER; MOLECULAR SUBTYPE; SELF-RENEWAL; KAP1; PHENOTYPE; AUTOPHAGY	The expression of Tripartite motif-containing protein 28 (TRIM28)/Kruppel-associated box (KRAB)-associated protein 1 (KAP1), is elevated in at least 14 tumor types, including solid and hematopoietic tumors. High level of TRIM28 is associated with triple-negative subtype of breast cancer (TNBC), which shows higher aggressiveness and lower survival rates. Interestingly, TRIM28 is essential for maintaining the pluripotent phenotype in embryonic stem cells. Following on that finding, we evaluated the role of TRIM28 protein in the regulation of breast cancer stem cells (CSC) populations and tumorigenesis in vitro and in vivo. Downregulation of TRIM28 expression in xenografts led to deceased expression of pluripotency and mesenchymal markers, as well as inhibition of signaling pathways involved in the complex mechanism of CSC maintenance. Moreover, TRIM28 depletion reduced the ability of cancer cells to induce tumor growth when subcutaneously injected in limiting dilutions. Our data demonstrate that the downregulation of TRIM28 gene expression reduced the ability of CSCs to self-renew that resulted in significant reduction of tumor growth. Loss of function of TRIM28 leads to dysregulation of cell cycle, cellular response to stress, cancer cell metabolism, and inhibition of oxidative phosphorylation. All these mechanisms directly regulate maintenance of CSC population. Our original results revealed the role of the TRIM28 in regulating the CSC population in breast cancer. These findings may pave the way to novel and more effective therapies targeting cancer stem cells in breast tumors.	[Czerwinska, Patrycja; Tomczak, Katarzyna; Klimczak, Marta; Mazurek, Sylwia; Mackiewicz, Andrzej; Wiznerowicz, Maciej] Greater Poland Canc Ctr, Dept Diagnost & Canc Immunol, Lab Gene Therapy, Poznan, Poland; [Czerwinska, Patrycja; Tomczak, Katarzyna; Mackiewicz, Andrzej; Wiznerowicz, Maciej] Poznan Univ Med Sci, Dept Canc Immunol, Chair Med Biotechnol, Poznan, Poland; [Czerwinska, Patrycja; Tomczak, Katarzyna; Klimczak, Marta; Mazurek, Sylwia] Med Univ Warsaw, Postgrad Sch Mol Med, Warsaw, Poland; [Shah, Parantu K.; Andersen, Jannik N.] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77058 USA; [Sozanska, Barbara; Biecek, Przemyslaw] Warsaw Univ Technol, Fac Math & Informat Sci, Warsaw, Poland; [Biecek, Przemyslaw] Univ Warsaw, Fac Math Informat & Mech, Warsaw, Poland; [Korski, Konstanty; Filas, Violetta] Greater Poland Canc Ctr, Dept Canc Pathol, Poznan, Poland		Czerwinska, P; Wiznerowicz, M (corresponding author), Greater Poland Canc Ctr, Dept Diagnost & Canc Immunol, Lab Gene Therapy, Poznan, Poland.; Czerwinska, P; Wiznerowicz, M (corresponding author), Poznan Univ Med Sci, Dept Canc Immunol, Chair Med Biotechnol, Poznan, Poland.; Czerwinska, P (corresponding author), Med Univ Warsaw, Postgrad Sch Mol Med, Warsaw, Poland.	patrycja.czerwinska@wco.pl; maciej.wiznerowicz@wco.pl	Czerwinska, Patrycja/AAE-2419-2021	Czerwinska, Patrycja/0000-0003-2400-1174; Filas, Violetta/0000-0003-2028-877X; , Sylwia/0000-0002-5064-458X; Biecek, Przemyslaw/0000-0001-8423-1823	NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA16672]; PL-Grid Infrastructure; National Science CenterNational Science Centre, Poland [3342/B/P01/2010/39]; Greater Poland Cancer Center; MD Anderson Cancer Center; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA016672] Funding Source: NIH RePORTER	MD Anderson Cancer Center RPPA Core Facility is funded by NCI #CA16672. The MD Anderson Cancer Center Cancer Genomics Core Laboratory is a part of the NCI-funded Cancer Center Support Grant. This research was supported in part by PL-Grid Infrastructure. The research was supported by the National Science Center grant No: 3342/B/P01/2010/39 and by Greater Poland Cancer Center and MD Anderson Cancer Center intramural grants.	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Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	EH1DH	WOS:000391503300068	27845900	Green Published, gold, Green Submitted			2022-04-25	
J	Pajuelo-Reguera, D; Alan, L; Olejar, T; Jezek, P				Pajuelo-Reguera, David; Alan, Lukas; Olejar, Tomas; Jezek, Petr			Dichloroacetate stimulates changes in the mitochondrial network morphology via partial mitophagy in human SH-SY5Y neuroblastoma cells	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						dichloroacetate; mitochondria; mitophagy; neuroblastoma SH-SY5Y cells; mitochondrial network	COLORECTAL-CANCER CELLS; IN-VITRO; MEDIATED AUTOPHAGY; PINK1; FUSION; METABOLISM; APOPTOSIS; FISSION; PROTEIN; PARKIN	Dichloroacetate (DCA) is beneficial in cancer therapy because it induces apoptosis and decreases cancer growth in vitro and in vivo without affecting non-cancer cells. DCA stimulates the activity of the enzyme pyruvate dehydrogenase by inhibiting pyruvate dehydrogenase kinase. Consequently, DCA promotes oxidative phosphorylation after glycolysis. Therefore, DCA produces changes in energy metabolism that could affect the mitochondrial network and mitophagy. This investigation determined the effects of DCA treatment on mitophagy in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were cultured and distributed into 3 groups: control, NH4Cl and chloroquine. Each group was treated with DCA at 0, 5, 30 and 60 mM for 16 h. Samples were analyzed for cell viability, mtDNA copy number, mitochondrial network morphology and expression of key proteins involved in mitochondrial dynamics, such as LC3b, FIS1, OPA1, PARKIN and PINK1. In all groups, DCA caused a decrease in cell viability, an induction of autophagy in a dose-dependent manner and a decrease in Tim23, FIS1 and PARKIN protein expression, leading to profound morphological changes in the mitochondrial network resulting in shorter and more fragmented filaments. However, TFAM protein levels remained unchanged. Similarly, the mitochondrial copy number was not significantly different among the treatment groups. In conclusion, DCA induces mitophagy and remodeling of the mitochondrial network. In this remodeling, DCA induces a decrease in the expression of key proteins involved in protein degradation and mitochondrial dynamics but does not significantly affect the mtDNA density. Blocking late phase autophagy increases the effects of DCA, suggesting that autophagy protects the cell, at least partially, against DCA.	[Pajuelo-Reguera, David; Alan, Lukas; Olejar, Tomas; Jezek, Petr] Acad Sci Czech Republic, Inst Physiol, Dept Membrane Transport Biophys, Prague, Czech Republic		Pajuelo-Reguera, D (corresponding author), Acad Sci Czech Republic, Inst Physiol, Dept Membrane Transport Biophys, Prague, Czech Republic.	d.pajuel@outlook.com	Olejar, Tomas/E-3760-2017; Reguera, David Pajuelo/G-3814-2014; Jezek, Petr/B-9264-2012; Alán, Lukáš/H-9063-2013	Olejar, Tomas/0000-0002-0786-5029; Reguera, David Pajuelo/0000-0002-7715-9402; Jezek, Petr/0000-0002-2720-9395; Alán, Lukáš/0000-0001-7417-2620; olejar, tomas/0000-0002-6469-6970	Centre of Biomedical Research [CZ.1.07/2.3.00/30.0025]; European Social FundEuropean Social Fund (ESF); state budget of the Czech Republic	This study was supported within the project The Centre of Biomedical Research (CZ.1.07/2.3.00/30.0025). This study was also co-funded by the European Social Fund and the state budget of the Czech Republic.	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J. Oncol.	JUN	2015	46	6					2409	2418		10.3892/ijo.2015.2953			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	CI3QK	WOS:000354662300014	25846762	Bronze			2022-04-25	
J	Bachari, A; Piva, TJ; Salami, SA; Jamshidi, N; Mantri, N				Bachari, Ava; Piva, Terrence J.; Salami, Seyed Alireza; Jamshidi, Negar; Mantri, Nitin			Roles of Cannabinoids in Melanoma: Evidence from In Vivo Studies	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES			English	Review						medicinal herbs; apoptosis; THC; CBD; melanoma; cannabinoids	METASTATIC MELANOMA; CUTANEOUS MELANOMA; POTENTIAL ROLE; CANCER PAIN; CANNABIDIOL; VEMURAFENIB; RECEPTOR; THERAPY; GROWTH; CELLS	Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in the treatment of cancer in general, malignant melanoma, in particular, is resistant to existing medical therapies requiring an urgent need to develop effective treatments with lesser side effects. Several studies have shown that "cannabinoids", the major compounds of theCannabis sativaL.plant, can reduce cell proliferation and induce apoptosis in melanoma cells. Despite prohibited use ofCannabisin most parts of the world, in recent years there have been renewed interests in exploiting the beneficial health effects of theCannabisplant-derived compounds. Therefore, the aim of this study was in the first instance to review the evidence from in vivo studies on the effects of cannabinoids on melanoma. Systematic searches were carried out in PubMed, Embase, Scopus, and ProQuest Central databases for relevant articles published from inception. From a total of 622 potential studies, six in vivo studies assessing the use of cannabinoids for treatment of melanoma were deemed eligible for the final analysis. The findings revealed cannabinoids, individually or combined, reduced tumor growth and promoted apoptosis and autophagy in melanoma cells. Further preclinical and animal studies are required to determine the underlying mechanisms of cannabinoids-mediated inhibition of cancer-signaling pathways. Well-structured, randomized clinical studies on cannabinoid use in melanoma patients would also be required prior to cannabinoids becoming a viable and recognized therapeutic option for melanoma treatment in patients.	[Bachari, Ava; Mantri, Nitin] RMIT Univ, Sch Sci, Melbourne, Vic 3083, Australia; [Piva, Terrence J.; Jamshidi, Negar] RMIT Univ, Sch Hlth & Biomed Sci, POB 71, Melbourne, Vic 3083, Australia; [Salami, Seyed Alireza] Univ Tehran, Fac Agr Sci & Engn, Karaj 31587, Iran		Mantri, N (corresponding author), RMIT Univ, Sch Sci, Melbourne, Vic 3083, Australia.	Ava.Bachari@student.rmit.edu.au; terry.piva@rmit.edu.au; asalami@ut.ac.ir; negar.jamshidi@rmit.edu.au; nitin.mantri@rmit.edu.au	Salami, Seyed Alireza/AAC-7474-2022; Piva, Terrence/E-4129-2012	bachari, Ava/0000-0002-9864-2794; Piva, Terrence/0000-0003-0343-1781; Mantri, Nitin/0000-0002-7621-035X	MGC Pharmaceuticals Limited, Australia; RMIT University Scholarship	This research is funded by MGC Pharmaceuticals Limited, Australia. Ava Bachari is a Ph.D. student supported by an RMIT University Scholarship.	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J	Li, XY; Liu, QK; Wang, K; Luo, WZ; Liang, TS; Yuan, SP; Zhen, YW; Yan, DM				Li, Xueyuan; Liu, Qiankun; Wang, Kang; Luo, Wenzheng; Liang, Tiansong; Yuan, Shanpeng; Zhen, Yingwei; Yan, Dongming			RETRACTED: LncRNA SNHG5 regulates the cell viability and apoptosis of glioma cells by the miR-1297/KPNA2 axis (Retracted article. See vol. 11, pg. 6239, 2021)	RSC ADVANCES			English	Article; Retracted Publication							COLORECTAL-CANCER; MICRORNA-1297; PROLIFERATION; PROGNOSIS; PROMOTES; GROWTH; GLIOBLASTOMA; METASTASIS; MIGRATION; INVASION	Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) has been reported to participate in the occurrence and development of glioma. However, the function and underlying molecular mechanisms of SNHG5 in glioma remain largely unknown. The expressions of SNHG5, microRNA-1297 (miR-1297) and karyopherin subunit alpha 2 (KPNA2) in glioma tissues and cells were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) or western blot. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect cell viability and apoptosis, respectively. Western blot was also performed to detect the expressions of autophagy-associated proteins. The relationship among lncRNA SNHG5, miR-1297 and KPNA2 was verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. SNHG5 and KPNA2 were over expressed, and the level of miR-1297 was down-regulated in glioma tissues and cell lines. Knockdown of SHNG5 promoted apoptosis, while suppressing cell viability and autophagy of A172 and LN340 cells. Meanwhile, SHNG5 harbored the binding sites with miR-1297, and a negative correlation between the expression of SNHG5 and miR-1297 in glioma tissues was also observed. Interestingly, silencing of miR-1297 undermined the SHNG5 depletion-mediated effect on cell viability, apoptosis, and autophagy. KPNA2 was a direct target of miR-1297, and negatively regulated by miR-1297. More importantly, gain of KPNA2 mitigated the effect of SHNG5l knockdown on glioma cells. Silencing of SNHG5 had an implication in inhibiting apoptosis and stimulating cell viability and autophagy by the miR-1297/KPNA2 axis in glioma.	[Li, Xueyuan; Liu, Qiankun; Wang, Kang; Luo, Wenzheng; Yuan, Shanpeng; Zhen, Yingwei; Yan, Dongming] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurosurg, 1 Longhu Middle Ring Rd, Zhengzhou 450000, Henan, Peoples R China; [Liang, Tiansong] Zhengzhou Univ, Affiliated Hosp 1, Dept Radiotherapy, Zhengzhou, Henan, Peoples R China		Yan, DM (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Neurosurg, 1 Longhu Middle Ring Rd, Zhengzhou 450000, Henan, Peoples R China.	mrdmyan@163.com			Henan Science and Technology Research Project [172102410015]; Henan Province Higher Education Research Project [18A320077]; Medical Science and Technology Project of Henan Province [2018020043]	This work was supported by Henan Science and Technology Research Project (No. 172102410015), Henan Province Higher Education Research Project (No. 18A320077) and Medical Science and Technology Project of Henan Province (No. 2018020043).	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JAN 8	2020	10	3					1498	1506		10.1039/c9ra08693e			9	Chemistry, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	KC6PD	WOS:000507296300032		gold			2022-04-25	
J	Rrapaj, E; Trisolini, E; Bertero, L; Salvo, M; Indellicato, R; Andorno, S; Garcia-Manteiga, JM; Rena, O; Boldorini, RL				Rrapaj, Eltjona; Trisolini, Elena; Bertero, Luca; Salvo, Michela; Indellicato, Rossella; Andorno, Silvano; Garcia-Manteiga, Jose M.; Rena, Ottavio; Boldorini, Renzo L.			Expression analysis of HMGB1 in histological samples of malignant pleural mesothelioma	HISTOPATHOLOGY			English	Article						biomarker; high mobility group box 1; histological samples; malignant pleural mesothelioma; prognosis	GROUP BOX 1; MOBILITY GROUP BOX-1; REGULATES AUTOPHAGY; ASBESTOS EXPOSURE; COLORECTAL-CANCER; CHROMATIN PROTEIN; GENE-EXPRESSION; CELL; CARCINOMA; CARCINOGENESIS	AimsHigh mobility group box 1 (HMGB1) is a chromatin structural protein, expressed ubiquitously in the nuclei of mammalian cells. When transported extracellularly, it acts as a tumour suppressor and oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of HMGB1 have been related to a poor prognosis. Conversely, the significance of HMGB1 expression in MPM tissues is still unclear. Methods and resultsBiopsy samples from 170 patients with MPM were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semiquantitative system that sums the intensity (0-3) and the percentage (from 0 to 4) of positively stained cells in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated using the C-t method. High expression levels of HMGB1 as total (P = 0.0011) and cytoplasmic score (P = 0.0462) were related to a worse disease-specific survival (DSS) in the entire cohort and in the clinicopathological subgroups. No significant correlation was found between HMGB1 gene expression and DSS. ConclusionsThese findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also expressed in normal and reactive mesothelial cells, HMGB1 cannot be considered a diagnostic biomarker in histological samples of mesothelioma.	[Rrapaj, Eltjona; Trisolini, Elena; Salvo, Michela; Indellicato, Rossella; Andorno, Silvano; Boldorini, Renzo L.] Univ Piemonte Orientale, Dept Hlth Sci, Via Solaroli 17, I-28100 Novara, Italy; [Bertero, Luca] Univ Turin, Dept Med Sci, Div Pathol, Turin, Italy; [Garcia-Manteiga, Jose M.] IRCCS San Raffaele Hosp, Ctr Translat Genom & Bioinformat, Milan, Italy; [Rena, Ottavio] Maggiore della Carita Hosp, Unit Thorac Surg, Novara, Italy; [Boldorini, Renzo L.] Maggiore della Carita Hosp, Unit Pathol, Novara, Italy		Boldorini, RL (corresponding author), Univ Piemonte Orientale, Dept Hlth Sci, Via Solaroli 17, I-28100 Novara, Italy.	renzo.boldorini@med.uniupo.it	Rrapaj, Eltjona/AAW-1390-2020; Rrapaj, Eltjona/AAO-1526-2020; Bertero, Luca/N-5357-2017; Manteiga, Jose Manuel Garcia/AAN-1954-2020; Trisolini, Elena/J-2698-2017; BOLDORINI, Renzo Luciano/J-5330-2016	Rrapaj, Eltjona/0000-0003-3601-4888; Bertero, Luca/0000-0001-9887-7668; Manteiga, Jose Manuel Garcia/0000-0002-5481-040X; Trisolini, Elena/0000-0003-0919-3630; Andorno, Silvano/0000-0002-4207-2227; BOLDORINI, Renzo Luciano/0000-0003-1183-2737; Indellicato, Rossella/0000-0003-2134-4665	Department of Health Sciences, University of Eastern Piedmont, Novara (Italy)	This work was supported in part by the funds of Department of Health Sciences, University of Eastern Piedmont, Novara (Italy). The authors thank Fjona Zeneli MSc from the University of Porto (Portugal), Faculty of Economics for her assistance performing in part the statistical analysis of data. The authors also thank Professor Marco E. Bianchi, San Raffaele Institute who provided general support for this work.	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J	Honkala, AT; Tailor, D; Malhotra, SV				Honkala, Alexander T.; Tailor, Dhanir; Malhotra, Sanjay V.			Guanylate-Binding Protein 1: An Emerging Target in Inflammation and Cancer	FRONTIERS IN IMMUNOLOGY			English	Review						guanylate-binding protein 1; cytokine-induced GTPase; inflammation; interferon alpha (IFN alpha); infection; cancer	IFN-GAMMA; NUCLEOTIDE-BINDING; ENDOTHELIAL-CELLS; ALPHA-INTERFERON; GTPASE-ACTIVITY; GENE; HGBP1; IDENTIFICATION; GROWTH; PROLIFERATION	Guanylate-binding protein 1 (GBP1) is a large GTPase of the dynamin superfamily involved in the regulation of membrane, cytoskeleton, and cell cycle progression dynamics. In many cell types, such as endothelial cells and monocytes, GBP1 expression is strongly provoked by interferon gamma (IFN gamma) and acts to restrain cellular proliferation in inflammatory contexts. In immunity, GBP1 activity is crucial for the maturation of autophagosomes infected by intracellular pathogens and the cellular response to pathogen-associated molecular patterns. In chronic inflammation, GBP1 activity inhibits endothelial cell proliferation even as it protects from IFN gamma-induced apoptosis. A similar inhibition of proliferation has also been found in some tumor models, such as colorectal or prostate carcinoma mouse models. However, this activity appears to be context-dependent, as in other cancers, such as oral squamous cell carcinoma and ovarian cancer, GBP1 activity appears to anchor a complex, taxane chemotherapy resistance profile where its expression levels correlate with worsened prognosis in patients. This discrepancy in GBP1 function may be resolved by GBP1's involvement in the induction of a cellular senescence phenotype, wherein anti-proliferative signals coincide with potent resistance to apoptosis and set the stage for dysregulated proliferative mechanisms present in growing cancers to hijack GBP1 as a pro- chemotherapy treatment resistance (TXR) and pro-survival factor even in the face of continued cytotoxic treatment. While the structure of GBP1 has been extensively characterized, its roles in inflammation, TXR, senescence, and other biological functions remain under-investigated, although initial findings suggest that GBP1 is a compelling target for therapeutic intervention in a variety of conditions ranging from chronic inflammatory disorders to cancer.	[Honkala, Alexander T.; Tailor, Dhanir; Malhotra, Sanjay V.] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA		Malhotra, SV (corresponding author), Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA.	smalhotra@stanford.edu		Honkala, Alexander/0000-0002-7338-4039			Abdullah N, 2009, J MOL BIOL, V386, P690, DOI 10.1016/j.jmb.2008.12.060; Al-Zeer MA, 2013, AUTOPHAGY, V9, P50, DOI 10.4161/auto.22482; Ascierto ML, 2012, BREAST CANCER RES TR, V131, P871, DOI 10.1007/s10549-011-1470-x; Bai S, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-19401-2; Barz B, 2019, PLOS COMPUT BIOL, V15, DOI 10.1371/journal.pcbi.1007193; Bleiziffer O, 2012, BMC BIOTECHNOL, V12, DOI 10.1186/1472-6750-12-94; Britzen-Laurent N, 2018, CANCER RES, V78, DOI 10.1158/1538-7445.AM2018-4047; Britzen-Laurent N, 2016, WORLD J GASTROENTERO, V22, P6434, DOI 10.3748/wjg.v22.i28.6434; Britzen-Laurent N, 2013, CARCINOGENESIS, V34, P153, DOI 10.1093/carcin/bgs310; Capaldo CT, 2012, MUCOSAL IMMUNOL, V5, P681, DOI 10.1038/mi.2012.41; 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Immunol.	JAN 24	2020	10								3139	10.3389/fimmu.2019.03139			10	Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Immunology	KJ2AV	WOS:000511861200001	32117203	Green Published, gold			2022-04-25	
J	Ou, JJ; Peng, Y; Yang, WW; Zhang, Y; Hao, J; Li, F; Chen, YR; Zhao, Y; Xie, X; Wu, S; Zha, L; Luo, X; Xie, GF; Wang, LT; Sun, W; Zhou, Q; Li, JJ; Liang, HJ				Ou, Juanjuan; Peng, Yuan; Yang, Weiwen; Zhang, Yue; Hao, Jie; Li, Fu; Chen, Yanrong; Zhao, Yang; Xie, Xiong; Wu, Shuang; Zha, Lin; Luo, Xi; Xie, Ganfeng; Wang, Liting; Sun, Wei; Zhou, Qi; Li, Jianjun; Liang, Houjie			ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield	NATURE COMMUNICATIONS			English	Article							DNA MISMATCH REPAIR; ADJUVANT THERAPY; LYSOSOME FUSION; RNA DEGRADATION; MECHANISMS; PROTEIN; CHEMOTHERAPY; STRATEGIES; RESISTANCE; TARGET	The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.	[Ou, Juanjuan; Peng, Yuan; Yang, Weiwen; Zhang, Yue; Hao, Jie; Li, Fu; Chen, Yanrong; Zhao, Yang; Xie, Xiong; Wu, Shuang; Zha, Lin; Luo, Xi; Xie, Ganfeng; Li, Jianjun; Liang, Houjie] Army Med Univ, Southwest Hosp, Dept Oncol, Chongqing 400038, Peoples R China; [Ou, Juanjuan; Peng, Yuan; Yang, Weiwen; Zhang, Yue; Hao, Jie; Li, Fu; Chen, Yanrong; Zhao, Yang; Xie, Xiong; Wu, Shuang; Zha, Lin; Luo, Xi; Xie, Ganfeng; Li, Jianjun; Liang, Houjie] Army Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China; [Wang, Liting; Sun, Wei] Army Med Univ, Biomed Anal Ctr, Chongqing 400038, Peoples R China; [Zhou, Qi] Fuling Cent Hosp, Dept Oncol, Chongqing 408099, Peoples R China		Ou, JJ; Li, JJ; Liang, HJ (corresponding author), Army Med Univ, Southwest Hosp, Dept Oncol, Chongqing 400038, Peoples R China.; Ou, JJ; Li, JJ; Liang, HJ (corresponding author), Army Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China.	ojj521000@sina.com; leejjun2007@163.com; lianghoujie@sina.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772647, 81672856, 81672384, 81602628, 81602423]; Basic and Frontier Research Project of Chongqing [cstc2015jcyjB10001]; Social Science and Technology Innovation Project of Chongqing [cstc2015shmszx120058]; Health Bureau of Chongqing [2008-2-374];  [81370063]	This work was supported in part by grant numbers 81772647 (J.O.), 81672856 (J.L.), 81672384 (H.L.), 81602628 (X.L.) and 81602423 (L.Z.) from the National Natural Science Foundation of China, cstc2015jcyjB10001 (J.O.) from Basic and Frontier Research Project of Chongqing, cstc2015shmszx120058 (H.L.) from Social Science and Technology Innovation Project of Chongqing and 2008-2-374 (Q.Z.) from The Health Bureau of Chongqing. We got a writing assistance from Nature Research Editing Service, which is supported by grant 81370063 (J.O.). We thank the assistance from Shanghai Biotree Biotech Co., Ltd.	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Commun.	MAR 6	2019	10								1078	10.1038/s41467-019-08902-x			14	Multidisciplinary Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics	HN7YS	WOS:000460410300003	30842415	Green Published, gold			2022-04-25	
J	Han, HG; Moon, HW; Jeon, YJ				Han, Hye Gyeong; Moon, Hye Won; Jeon, Young Joo			ISG15 in cancer: Beyond ubiquitin-like protein	CANCER LETTERS			English	Review						Autophagy; Cancer; Cancer therapies; Exosomes; ISG15; Ubiquitin	INTERFERON-STIMULATED GENE; COLORECTAL-CANCER; PROGNOSTIC VALUE; MESSENGER-RNA; CRUCIAL ROLE; T-CELLS; CONJUGATION; EXPRESSION; ISGYLATION; USP18	ISG15, the product of interferon (IFN)-stimulated gene 15, is the first identified ubiquitin-like protein (Ubl), playing roles not only as an unconjugated form but also as a covalently conjugated form onto a target protein. ISG15 is not present in lower eukaryotes such as yeast, nematode (Caenorhabditis), or insect (Drosophila), indicating that the functions of ISG15 and ISG15 conjugation (ISGylation) are restricted to higher eukaryotes and have evolved with IFN signaling. Despite the highlighted complexity of ISG15 and ISGylation, increasing evidences have been emerging that ISG15 and ISGylation are implicated in a variety of pivotal cellular processes, involving protein translation, autophagy, exosome secretion, DNA repair, and immune modulation, which emphasizes the necessity of re-evaluation of ISG15 and ISGylation. In this review, we highlight current knowledge in the molecular understanding and physiological relevance of ISG15 and ISGylation and discuss new insights into how ISG15 is implicated in the pathogenesis of cancer, which could contribute to therapeutic intervention in cancer.	[Han, Hye Gyeong; Moon, Hye Won; Jeon, Young Joo] Chungnam Natl Univ, Coll Med, Dept Biochem, 266 Munhwa Ro, Daejeon 35015, South Korea; [Han, Hye Gyeong; Moon, Hye Won; Jeon, Young Joo] Chungnam Natl Univ, Coll Med, Dept Med Sci, 266 Munhwa Ro, Daejeon 35015, South Korea		Jeon, YJ (corresponding author), Chungnam Natl Univ, Coll Med, Dept Biochem, 266 Munhwa Ro, Daejeon 35015, South Korea.; Jeon, YJ (corresponding author), Chungnam Natl Univ, Coll Med, Dept Med Sci, 266 Munhwa Ro, Daejeon 35015, South Korea.	yjjeon@cnu.ac.kr	Jeon, Young Joo/AAB-7040-2021	Jeon, Young Joo/0000-0003-1004-5336	National Research Foundation of KoreaNational Research Foundation of Korea [NRF-2016R1A2B4006566]; BK21 Plus fellowship	This work was supported by grant from the National Research Foundation of Korea (NRF-2016R1A2B4006566). H.G. Han and H.W. Moon were the recipients of the BK21 Plus fellowship.	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J	Liang, JM; Zeng, F; Zhang, M; Pan, ZZ; Chen, YZ; Zeng, YN; Xu, Y; Xu, Q; Huang, YZ				Liang, Jianming; Zeng, Feng; Zhang, Meng; Pan, Zhenzhen; Chen, Yingzhi; Zeng, Yuaner; Xu, Yong; Xu, Qin; Huang, Yongzhuo			Green synthesis of hyaluronic acid-based silver nanoparticles and their enhanced delivery to CD44(+) cancer cells	RSC ADVANCES			English	Article							COLORECTAL-CANCER; IN-VIVO; APOPTOSIS; EXPRESSION; AUTOPHAGY; MONODANSYLCADAVERINE; PHOSPHATIDYLSERINE; INHIBITION; RESISTANCE; RELEASE	The potent antitumor activities of silver nanoparticles (AgNP) have attracted great attention. However, the application of AgNP is restricted by its non-specific delivery and poor cellular uptake. We developed a novel hyaluronic acid (HA)-based strategy for the green synthesis of AgNP, in which HA was used as the reducing agent and stabilizer. More importantly, HA is a ligand of CD44, and the HA-modified AgNP can target CD44 receptors that are overexpressed in many types of cancer cells. The CD44-dependent endocytosis can significantly increase the intracellular delivery of HA-AgNP, compared to the non-modified one. The antitumor efficacy was significantly improved by HA modification. Furthermore, we found that multiple mechanisms were involved for the enhanced anticancer activities of HA-AgNP, including the decline of mitochondrial membrane potential, cell-cycle arrest, apoptosis, and autophagy. The HA-based strategy for green synthesis and CD44-targeting delivery provided a promising solution for AgNP-mediated cancer treatment.	[Liang, Jianming; Zeng, Feng; Zhang, Meng; Pan, Zhenzhen; Chen, Yingzhi; Huang, Yongzhuo] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; [Liang, Jianming; Zeng, Feng; Xu, Qin] Guangzhou Univ Chinese Med, Inst Trop Med, Guangzhou 501450, Guangdong, Peoples R China; [Pan, Zhenzhen; Zeng, Yuaner] Guangzhou Univ Chinese Med, Sch Chinese Mat Med, Guangzhou 501450, Guangdong, Peoples R China; [Xu, Yong] Hubei Biol Med Ind Technol Inst Co Ltd, Wuhan 430075, Peoples R China		Huang, YZ (corresponding author), Chinese Acad Sci, Shanghai Inst Mat Med, 501 Hai Ke Rd, Shanghai 201203, Peoples R China.	xuqin@163.com; yzhuang@simm.ac.cn	Huang, Yongzhuo/A-4688-2013	Huang, Yongzhuo/0000-0001-7067-8915	973 Program, ChinaNational Basic Research Program of China [2014CB931900, 2013CB932503]; NSFC, ChinaNational Natural Science Foundation of China (NSFC) [81172996, 81373357, 81422048]	This work was supported by 973 Program, China (2014CB931900, 2013CB932503) and NSFC, China (81172996, 81373357, 81422048).	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J	Farzaei, MH; El-Senduny, FF; Momtaz, S; Parvizi, F; Iranpanah, A; Tewari, D; Naseri, R; Abdolghaffari, AH; Rezaei, N				Farzaei, Mohammad Hosein; El-Senduny, Fardous F.; Momtaz, Saeideh; Parvizi, Fatemeh; Iranpanah, Amin; Tewari, Devesh; Naseri, Rozita; Abdolghaffari, Amir Hossein; Rezaei, Nima			An update on dietary consideration in inflammatory bowel disease: anthocyanins and more	EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY			English	Review						Natural product; anthocyanins; IBD; cellular signaling pathways; natural dietary supplement; colorectal cancer	INTESTINAL ANTIINFLAMMATORY ACTIVITY; INDUCED ULCERATIVE-COLITIS; SODIUM-INDUCED COLITIS; TNBS-INDUCED COLITIS; COLORECTAL-CANCER; INHIBITS COLITIS; EPITHELIAL-CELLS; EXTRACT; L.; ACID	Introduction: Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder. A wealth of data pointed out that various aspects of chronic inflammation may be affected by several specific dietary factors. This paper calls attention to anthocyanins enriched plant food and anthocyanin dietary supplements, whose role in the management of IBD and its associated oncogenesis deems crucial. Area covered: We updated the most relevant dietary anthocyanins with potential anti-colitis and preventive effect on inflammatory associated colorectal cancer based on the recent animal and human researches along with revealing the major cellular and molecular mechanisms of action. Mounting evidence reported that anthocyanins enriched plant foods perform their protective role on IBD and inflammatory-induced colorectal cancer via different cellular transduction signaling pathways, including inflammatory transcription factors, SAPK/JNK and p38 MAPK cascade, JAK/STAT signaling, NF-kB/pERK/MAPK, Wnt signaling pathway, Nrf2 cytoprotective pathway as well as AMPK pathway and autophagy. Expert commentary: Combination of anthocyanins enriched dietary supplements with existing medications can provide new therapeutic options for IBD patients. Further, well-designed randomized control trials (RCTs) are essential to evaluate the role of anthocyanins enriched medicinal foods as well as isolated anthocyanin components as promising preventive and therapeutic dietary agents for IBD and its associated oncogenesis.	[Farzaei, Mohammad Hosein; Naseri, Rozita] Kermanshah Univ Med Sci, Pharmaceut Sci Res Ctr, Kermanshah, Iran; [El-Senduny, Fardous F.] Mansoura Univ, Biochem Div, Chem Dept, Mansoura, Egypt; [Momtaz, Saeideh; Abdolghaffari, Amir Hossein] Univ Tehran Med Sci, Fac Pharm & Pharmaceut Sci, Dept Toxicol & Pharmacol, Res Ctr, Tehran, Iran; [Momtaz, Saeideh; Abdolghaffari, Amir Hossein] Univ Tehran Med Sci, Fac Pharm & Pharmaceut Sci, Dept Toxicol & Pharmacol, Res Ctr, Tehran, Iran; [Parvizi, Fatemeh] Kermanshah Univ Med Sci, Med Biol Res Ctr, Kermanshah, Iran; [Iranpanah, Amin] Kermanshah Univ Med Sci, Students Res Comm, Fac Pharm, Kermanshah, Iran; [Iranpanah, Amin] USERN, PhytoPharmacol Interest Grp PPIG, Kermanshah, Iran; [Tewari, Devesh] Kumaun Univ, Fac Technol, Dept Pharmaceut Sci, Bhimtal Campus, Naini Tal, Uttarakhand, India; [Abdolghaffari, Amir Hossein] Islamic Azad Univ, Pharmaceut Sci Branch, Dept Pharmacol, Tehran, Iran; [Abdolghaffari, Amir Hossein] USERN, GPIG, Tehran, Iran; [Rezaei, Nima] Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Childrens Med Ctr, Tehran, Iran; [Rezaei, Nima] Univ Tehran Med Sci, Sch Med, Dept Immunol, Tehran, Iran; [Rezaei, Nima] USERN, NIIMA, Tehran, Iran		Rezaei, N (corresponding author), Childrens Med Ctr Hosp, Dr Qarib St,Keshavarz Blvd,POB 14194, Tehran, Iran.; Abdolghaffari, AH (corresponding author), ACECR, Inst Med Plants, Jahade Daneshgahi Res Soc, Karaj Qazvin Freeway,Supa Blvd,POB 141554364, Alborz, Karaj, Iran.	amirhosein172@hotmail.com; rezaei_nima@tums.ac.ir	Abdolghaffari, Amir Hossein/AAQ-1161-2021; El-Senduny, Fardous/E-3512-2019; Farzaei, Mohammad Hosein/M-5779-2017; Tewari, Devesh/P-9954-2019; Rezaei, Nima/B-4245-2008	El-Senduny, Fardous/0000-0002-4572-2061; Farzaei, Mohammad Hosein/0000-0001-7081-6521; Tewari, Devesh/0000-0002-5125-3791; Rezaei, Nima/0000-0002-3836-1827; Iranpanah, Amin/0000-0001-8422-6151; Abdolghaffari, Amir Hossein/0000-0001-9961-9097			Almeida LD, 2017, WORLD J GASTROENTERO, V23, P4369, DOI 10.3748/wjg.v23.i24.4369; Amin HP, 2015, MOL NUTR FOOD RES, V59, P1095, DOI 10.1002/mnfr.201400803; 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J	Koehler, BC; Scherr, AL; Lorenz, S; Urbanik, T; Kautz, N; Elssner, C; Welte, S; Bermejo, JL; Jager, D; Schulze-Bergkamen, H				Koehler, Bruno Christian; Scherr, Anna-Lena; Lorenz, Stephan; Urbanik, Toni; Kautz, Nicole; Elssner, Christin; Welte, Stefan; Bermejo, Justo Lorenzo; Jaeger, Dirk; Schulze-Bergkamen, Henning			Beyond Cell Death - Antiapoptotic Bcl-2 Proteins Regulate Migration and Invasion of Colorectal Cancer Cells In Vitro	PLOS ONE			English	Article							BREAST-CANCER; APOPTOSIS RESISTANCE; OBATOCLAX MESYLATE; METASTASIS; FAMILY; AUTOPHAGY; LIFE; XL; OVEREXPRESSION; PROGRESSION	Migration and invasion of malignant cells are prerequisites for cancer progression and metastasis. The Bcl-2 family of proteins consists of about 25 members and has been extensively studied in the context of apoptosis. Despite the fact that small molecules targeting Bcl-2 proteins have already entered clinical trials, very few studies investigated a role of antiapoptotic Bcl-2 proteins beside cell death in the context of metastasis. The aim of this study was to dissect a potential role of the antiapoptotic Bcl-2 proteins Mcl-1, Bcl-2 and Bcl-xL on migration and invasion of colorectal cancer cells independent of their cell death control function. We used migration and invasion assays as well as three dimensional cell cultures to analyze colorectal cancer cell lines (HT29 and SW480) after siRNA mediated knockdown or overexpression of Mcl-1, Bcl-2 or Bcl-xL. We observed neither spontaneous cell death induction nor impaired proliferation of cells lacking Mcl-1, Bcl-2 or Bcl-xL. In contrast, knockdown of Mcl-1 led to increased proliferation. Strikingly, we demonstrate a profound impairment of both, migration and invasion, of colorectal cancer cells after Mcl-1, Bcl-2 or Bcl-xL knockdown. This phenotype was completely revised in cells overexpressing Mcl-1, Bcl-2 or Bcl-xL. The most pronounced effect among the investigated proteins was observed for Bcl-2. The data presented indicate a pivotal role of Mcl-1, Bcl-2 and Bcl-xL for migration and invasion of colorectal cancer cells independent of their known antiapoptotic effects. Thus, our study illustrates novel antitumoral mechanisms of Bcl-2 protein targeting.	[Koehler, Bruno Christian; Scherr, Anna-Lena; Lorenz, Stephan; Urbanik, Toni; Kautz, Nicole; Elssner, Christin; Welte, Stefan; Jaeger, Dirk; Schulze-Bergkamen, Henning] Univ Heidelberg Hosp, Dept Med Oncol, Natl Ctr Tumor Dis, Heidelberg, Germany; [Bermejo, Justo Lorenzo] Univ Heidelberg Hosp, Inst Med Biometry & Informat, Heidelberg, Germany		Koehler, BC (corresponding author), Univ Heidelberg Hosp, Dept Med Oncol, Natl Ctr Tumor Dis, Heidelberg, Germany.	bruno.koehler@nct-heidelberg.de		Lorenzo Bermejo, Justo/0000-0002-6568-5333	Medical Faculty of the University of Heidelberg, Germany; German Research Foundation (Deutsche Forschungsgemeinschaft)German Research Foundation (DFG) [DFG SCHU 1443/4-1]; Merck Serono GmbH (Darmstadt, Germany)	This study was supported by a Postdoctoral-Fellowship granted to BCK from the Medical Faculty of the University of Heidelberg, Germany (http://www.medizinische-fakultaet-hd.uni-heidelberg.de), and grants to HSB from the German Research Foundation (Deutsche Forschungsgemeinschaft, http://www.dfg.de/, DFG SCHU 1443/4-1) and from Merck Serono GmbH (Darmstadt, Germany). 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, Q; Wang, BL; Sun, FR; Li, JQ; Cao, XP; Tan, L				Li, Quan; Wang, Bai-Ling; Sun, Fu-Rong; Li, Jie-Qiong; Cao, Xi-Peng; Tan, Lan			The role of UNC5C in Alzheimer's disease	ANNALS OF TRANSLATIONAL MEDICINE			English	Review						Alzheimer's disease (AD); apoptosis/autophagy; activating death-associated protein kinase 1 (activating DAPK1); tau; UNC5C	AMYLOID PRECURSOR PROTEIN; COLORECTAL-CANCER; RECEPTORS UNC5H; RARE MUTATION; CELL-DEATH; KINASE 1; NETRIN-1; APOPTOSIS; GENE; EXPRESSION	Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease in adults characterized by the deposition of extracellular plaques of beta-amyloid protein (A beta), intracellular neurofibrillary tangles (NFTs), synaptic loss and neuronal apoptosis. AD has a strong and complex genetic component that involving into multiple genes. With recent advances in whole-exome sequencing (WES) and whole-genome sequencing (WGS) technology, UNC5C was identified to have association with AD. Emerging studies on cell and animal models identified that aberrant UNC5C may contribute to AD by activating death-associated protein kinase 1 (DAPK1) which is a new component involved in AD pathogenesis with an extensive involvement in aberrant tau, A beta and neuronal apoptosis/autophagy. In this review, we briefly summarize the biochemical properties, genetics, epigenetics, and the speculative role of UNC5C in AD. We hope our review would bring comprehensive understandings of AD pathogenesis and provide new therapeutic targets for AD.	[Li, Quan; Sun, Fu-Rong; Li, Jie-Qiong; Tan, Lan] Qingdao Univ, Qingdao Municipal Hosp, Dept Neurol, Qingdao 266071, Peoples R China; [Wang, Bai-Ling] Qingdao Mental Hlth Ctr, Dept Geriatr, Qingdao 266034, Peoples R China; [Cao, Xi-Peng] Qingdao Univ, Qingdao Municipal Hosp, Clin Res Ctr, Qingdao 266071, Peoples R China		Tan, L (corresponding author), Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, 5 Donghai Middle Rd, Qingdao 266071, Peoples R China.	dr.tanlan@163.com			Shandong Taishan Scholar; Qingdao Key Health Discipline Development Fund; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders	This work was supported by grants from the Shandong Taishan Scholar, Qingdao Key Health Discipline Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.	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TRANSL. MED.	MAY	2018	6	10							178	10.21037/atm.2018.04.43			10	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	GH3SK	WOS:000433322300010	29951500	Green Published			2022-04-25	
J	Xavier, S; Gilbert, V; Rastaldi, MP; Krick, S; Kollins, D; Reddy, A; Bottinger, E; Cohen, CD; Schlondorff, D				Xavier, Sandhya; Gilbert, Victoria; Rastaldi, Maria Pia; Krick, Stefanie; Kollins, Dmitrij; Reddy, Anand; Bottinger, Erwin; Cohen, Clemens D.; Schlondorff, Detlef			BAMBI Is Expressed in Endothelial Cells and Is Regulated by Lysosomal/Autolysosomal Degradation	PLOS ONE			English	Article							GROWTH-FACTOR-BETA; MEMBRANE-BOUND INHIBITOR; ISOLATED RAT HEPATOCYTES; TGF-BETA; GENE-EXPRESSION; PSEUDORECEPTOR BAMBI; PROTEIN-DEGRADATION; COLORECTAL-CANCER; MESANGIAL CELLS; AUTOPHAGY	Background: BAMBI (BMP and Activin Membrane Bound Inhibitor) is considered to influence TGF beta and Wnt signaling, and thereby fibrosis. Surprisingly data on cell type-specific expression of BAMBI are not available. We therefore examined the localization, gene regulation, and protein turnover of BAMBI in kidneys. Methodology/Principal Findings: By immunofluorescence microscopy and by mRNA expression, BAMBI is restricted to endothelial cells of the glomerular and some peritubular capillaries and of arteries and veins in both murine and human kidneys. TGF beta upregulated mRNA of BAMBI in murine glomerular endothelial cells (mGEC). LPS did not downregulate mRNA for BAMBI in mGEC or in HUVECs. BAMBI mRNA had a half-life of only 60 minutes and was stabilized by cycloheximide, indicating post-transcriptional regulation due to AU-rich elements, which we identified in the 3' untranslated sequence of both the human and murine BAMBI gene. BAMBI protein turnover was studied in HUVECs with BAMBI overexpression using a lentiviral system. Serum starvation as an inducer of autophagy caused marked BAMBI degradation, which could be totally prevented by inhibition of lysosomal and autolysosomal degradation with bafilomycin, and partially by inhibition of autophagy with 3-methyladenine, but not by proteasomal inhibitors. Rapamycin activates autophagy by inhibiting TOR, and resulted in BAMBI protein degradation. Both serum starvation and rapamycin increased the conversion of the autophagy marker LC3 from LC3-I to LC3-II and also enhanced co-staining for BAMBI and LC3 in autolysosomal vesicles. Conclusions/Significance: 1. BAMBI localizes to endothelial cells in the kidney and to HUVECs. 2. BAMBI mRNA is regulated by post-transcriptional mechanisms. 3. BAMBI protein is regulated by lysosomal and autolysosomal degradation. The endothelial localization and the quick turnover of BAMBI may indicate novel, yet to be defined functions of this modulator for TGF beta and Wnt protein actions in the renal vascular endothelium in health and disease.	[Xavier, Sandhya; Gilbert, Victoria; Krick, Stefanie; Kollins, Dmitrij; Reddy, Anand; Bottinger, Erwin; Schlondorff, Detlef] Mt Sinai Sch Med, Dept Med, New York, NY USA; [Cohen, Clemens D.] Univ Hosp, Div Nephrol, Zurich, Switzerland; [Cohen, Clemens D.] Univ Hosp, Inst Physiol, Ctr Integrat Human Physiol, Zurich, Switzerland; [Cohen, Clemens D.] Univ Zurich, Zurich, Switzerland; [Rastaldi, Maria Pia] Fdn DAmico Ric Malattie Renali, Renal Immunopathol Lab, Milan, Italy		Xavier, S (corresponding author), Mt Sinai Sch Med, Dept Med, New York, NY USA.	detlef.schlondorff@mssm.edu			National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01-DK081420-01]; Else Kroener-Fresenius Foundation [A62/04]; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [32-122439/1]; Fondazione IRCCS Policlinico; 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) [R01DK056077, R01DK081420, R01DK060043] Funding Source: NIH RePORTER	This work was supported by the National Institutes of Health ( National Institute of Diabetes and Digestive and Kidney Diseases R01-DK081420-01 to D. S.) and in part by the Else Kroener-Fresenius Foundation (A62/04 to C. D. C.) and the Swiss National Science Foundation (32-122439/1 to C. D. C.), and Progetto a concorso 2009/2010 Fondazione IRCCS Policlinico to M. P. R. 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	Lu, W; Fu, DL; Kong, XX; Huang, ZH; Hwang, M; Zhu, YS; Chen, LB; Jiang, K; Li, XL; Wu, YH; Li, J; Yuan, Y; Ding, KF				Lu, Wei; Fu, Dongliang; Kong, Xiangxing; Huang, Zhiheng; Hwang, Maxwell; Zhu, Yingshuang; Chen, Liubo; Jiang, Kai; Li, Xinlin; Wu, Yihua; Li, Jun; Yuan, Ying; Ding, Kefeng			FOLFOX treatment response prediction in metastatic or recurrent colorectal cancer patients via machine learning algorithms	CANCER MEDICINE			English	Article						colorectal cancer; FOLFOX; machine learning algorithm; microarray meta-analysis	POOR RESPONSE; R PACKAGE; OXALIPLATIN; MICROARRAY; FOLFIRI; EXPRESSION; SIGNATURE; THERAPY; FLUOROURACIL; CHEMOTHERAPY	Early identification of metastatic or recurrent colorectal cancer (CRC) patients who will be sensitive to FOLFOX (5-FU, leucovorin and oxaliplatin) therapy is very important. We performed microarray meta-analysis to identify differentially expressed genes (DEGs) between FOLFOX responders and nonresponders in metastatic or recurrent CRC patients, and found that the expression levels of WASHC4, HELZ, ERN1, RPS6KB1, and APPBP2 were downregulated, while the expression levels of IRF7, EML3, LYPLA2, DRAP1, RNH1, PKP3, TSPAN17, LSS, MLKL, PPP1R7, GCDH, C19ORF24, and CCDC124 were upregulated in FOLFOX responders compared with nonresponders. Subsequent functional annotation showed that DEGs were significantly enriched in autophagy, ErbB signaling pathway, mitophagy, endocytosis, FoxO signaling pathway, apoptosis, and antifolate resistance pathways. Based on those candidate genes, several machine learning algorithms were applied to the training set, then performances of models were assessed via the cross validation method. Candidate models with the best tuning parameters were applied to the test set and the final model showed satisfactory performance. In addition, we also reported that MLKL and CCDC124 gene expression were independent prognostic factors for metastatic CRC patients undergoing FOLFOX therapy.	[Lu, Wei; Fu, Dongliang; Kong, Xiangxing; Huang, Zhiheng; Hwang, Maxwell; Zhu, Yingshuang; Chen, Liubo; Jiang, Kai; Li, Xinlin; Li, Jun; Ding, Kefeng] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Colorectal Surg, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China; [Lu, Wei; Fu, Dongliang; Kong, Xiangxing; Huang, Zhiheng; Hwang, Maxwell; Zhu, Yingshuang; Chen, Liubo; Jiang, Kai; Li, Xinlin; Li, Jun; Yuan, Ying; Ding, Kefeng] Zhejiang Univ, Affiliated Hosp 2, Key Lab Canc Prevent & Intervent China Natl Minis, Key Lab Mol Biol Med Sci,Sch Med,Canc Inst, Hangzhou, Zhejiang, Peoples R China; [Yuan, Ying] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Med Oncol, Hangzhou, Zhejiang, Peoples R China; [Wu, Yihua] Zhejiang Univ, Sch Publ Hlth, Dept Toxicol, Hangzhou, Zhejiang, Peoples R China		Ding, KF (corresponding author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Colorectal Surg, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China.; Ding, KF (corresponding author), Zhejiang Univ, Sch Med, China Natl Minist Educ, Key Lab Canc Prevent & Intervent, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China.	dingkefeng@zju.edu.cn			Key Technology Research and Development Program of Zhejiang Province [2017C03017]	This work was supported by the Key Technology Research and Development Program of Zhejiang Province (2017C03017).	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FEB	2020	9	4					1419	1429		10.1002/cam4.2786		JAN 2020	11	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	KK2ZX	WOS:000504965800001	31893575	Green Published, gold			2022-04-25	
J	Bergamin, LS; Figueiro, F; Dietrich, F; Manica, FD; Filippi-Chiela, EC; Mendes, FB; Jandrey, EHF; Lopes, DV; Oliveira, FH; Nascimento, IC; Ulrich, H; Battastini, AMO				Bergamin, Leticia Scussel; Figueiro, Fabricio; Dietrich, Fabricia; Manica, Fabiana de Mattos; Filippi-Chiela, Eduardo C.; Mendes, Franciane Brackman; Farias Jandrey, Elisa Helena; Lopes, Daniela Vasconcelos; Oliveira, Francine H.; Nascimento, Isis C.; Ulrich, Henning; Oliveira Battastini, Ana Maria			Interference of ursolic acid treatment with glioma growth: An in vitro and in vivo study	EUROPEAN JOURNAL OF PHARMACOLOGY			English	Article						Ursolic acid; Glioma; Glioma cell death; In vivo glioma model	NF-KAPPA-B; PROSTATE-CANCER CELLS; GLIOBLASTOMA CELLS; COLORECTAL-CANCER; INDUCED APOPTOSIS; INDUCE APOPTOSIS; INHIBITS GROWTH; OLEANOLIC ACID; AUTOPHAGY; PATHWAYS	Glioblastoma multiforme is the most devastating tumor in the brain. Ursolic acid (UA) is found in a variety of plants, and exhibits several pharmacological activities. In this study, we investigated the effects of UA in vitro, clarifying the mechanisms that mediate its toxicity and the long-lasting actions of UA in C6 glioma cells. We also evaluated the antitumor activity of UA in an in vivo orthotopic glioma model. Cell numbers were assessed using the Trypan blue exclusion test, and the cell cycle was characterized by flow cytometry using propidium iodide staining. Apoptosis was analyzed using an Annexin V kit and by examining caspase-3. Akt immunocontent was verified by Western blot and the long-lasting actions of UA were measured by cumulative population doubling (CPD). In vivo experiments were performed in rats to measure the effects on tumor size, malignant features and toxicological parameters. In vitro results showed that UA decreased glioma cell numbers, increased the sub-G1 fraction and induced apoptotic death, accompanied by increased active caspase-3 protein levels. Akt phosphorylation/activation in cells was also diminished by UA. With regard to CPD, cell proliferation was almost completely restored upon single UA treatments, but when the UA was added again, the majority of cells died, demonstrating the importance of re-treatment cycles with chemotherapeutic agents for abolishing tumor growth. In vivo, ursolic acid slightly reduced glioma tumor size but did not decrease malignant features. Ursolic acid may be a potential candidate as an adjuvant for glioblastoma therapy.	[Bergamin, Leticia Scussel; Figueiro, Fabricio; Dietrich, Fabricia; Mendes, Franciane Brackman; Oliveira Battastini, Ana Maria] Univ Fed Rio Grande do Sul, Programa Posgrad Ciencias Biol Bioquim, Inst Ciencias Basicas Saude, Porto Alegre, RS, Brazil; [Bergamin, Leticia Scussel; Nascimento, Isis C.; Ulrich, Henning] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, Brazil; [Manica, Fabiana de Mattos; Farias Jandrey, Elisa Helena; Lopes, Daniela Vasconcelos; Oliveira Battastini, Ana Maria] Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Bioquim, Rua Ramiro Barcelos 2600 Anexo, BR-90035003 Porto Alegre, RS, Brazil; [Filippi-Chiela, Eduardo C.] Univ Fed Rio Grande do Sul, Programa Posgrad Gastroenterol & Hepatol, Fac Med, Porto Alegre, RS, Brazil; [Oliveira, Francine H.] Univ Fed Rio Grande do Sul, Serv Patol, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil		Battastini, AMO (corresponding author), Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Bioquim, Rua Ramiro Barcelos 2600 Anexo, BR-90035003 Porto Alegre, RS, Brazil.	abattastini@gmail.com	Nascimento, Isis C/A-2725-2017; Figueiró, Fabrício/M-3625-2016; Dietrich, Fabrícia/F-8658-2019; Filippi-Chiela, Eduardo/F-1959-2014; Battastini, Ana M/E-2809-2012; Jandrey, Elisa Helena Farias/ABA-8577-2020; Ulrich, Henning/C-5245-2013	Figueiró, Fabrício/0000-0003-0899-6407; Filippi-Chiela, Eduardo/0000-0001-8192-3779; Battastini, Ana M/0000-0001-6068-3278; Jandrey, Elisa Helena Farias/0000-0003-0750-7552; Ulrich, Henning/0000-0002-2114-3815; Nascimento, Isis/0000-0002-2633-8216; Dietrich, Fabricia/0000-0002-6458-2359	CNPq-BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [303264/2013-4]; FAPERGS/PRONEXFundacao de Amparo a Ciencia e Tecnologia do Estado do Rio Grande do Sul (FAPERGS) [16/2551-0000473-0]; Sao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/50880-4, 2015/18730-0]; CNPqConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [157647/2013-7, 150410/2016-6]	This work was supported by CNPq-Brazil (Project No 303264/2013-4), FAPERGS/PRONEX (Project No: 16/2551-0000473-0); L.S.B. PhD fellowship supported by CNPq (Project No: 157647/2013-7) and postdoctoral fellowship supported by CNPq (Project No: 150410/2016-6). H.U. acknowledges grant support from the Sao Paulo Research Foundation (FAPESP project No. 2012/50880-4). I.C.N. is supported by a postdoctoral fellowship granted by FAPESP (project No. 2015/18730-0).	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J. Pharmacol.	SEP 15	2017	811						268	275		10.1016/j.ejphar.2017.06.030			8	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	FH1EF	WOS:000410881800032	28663034				2022-04-25	
J	Liu, W; Phang, JM				Liu, Wei; Phang, James M.			Proline dehydrogenase (oxidase) in cancer	BIOFACTORS			English	Review						proline dehydrogenase; oxidase; reactive oxygen species; tumor suppressor; oncogene; metabolic stress	INDUCED APOPTOSIS; PPAR-GAMMA; P53-INDUCED GENE-6; COLORECTAL-CANCER; TUMOR-SUPPRESSOR; METABOLISM; EXPRESSION; PATHWAY; STRESS; RISK	Proline dehydrogenase (oxidase, PRODH/POX), the first enzyme in the proline degradative pathway, plays a special role in tumorigenesis and tumor development. Proline metabolism catalyzed by PRODH/POX is closely linked with the tricarboxylic acid (TCA) cycle and urea cycle. The proline cycle formed by the interconversion of proline and ?1-pyrroline-5-carboxylate (P5C) between mitochondria and cytosol interlocks with pentose phosphate pathway. Importantly, by catalyzing proline to P5C, PRODH/POX donates electrons into the electron transport chain to generate ROS or ATP. In earlier studies, we found that PRODH/POX functions as a tumor suppressor to initiate apoptosis, inhibit tumor growth, and block the cell cycle, all by ROS signaling. It also suppresses hypoxia inducible factor signaling by increasing a-ketoglutarate. During tumor progression, PRODH/POX is under the control of various tumor-associated factors, such as tumor suppressor p53, inflammatory factor peroxisome proliferator-activated receptor gamma (PPAR?), onco-miRNA miR-23b*, and oncogenic transcription factor c-MYC. Recent studies revealed the two-sided features of PRODH/POX-mediated regulation. Under metabolic stress such as oxygen and glucose deprivation, PRODH/POX can be induced to serve as a tumor survival factor through ATP production or ROS-induced autophagy. The paradoxical roles of PRODH/POX can be understood considering the temporal and spatial context of the tumor. Further studies will provide additional insights into this protein and on its metabolic effects in tumors, which may lead to new therapeutic strategies.(C) 2012 International Union of Biochemistry and Molecular Biology, Inc.	[Liu, Wei; Phang, James M.] NIH, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD USA		Phang, JM (corresponding author), Frederick Natl Lab, 1050 Boyles St,Bldg 538,Rm 144, Frederick, MD 21702 USA.	phangj@mail.nih.gov	liu, wei/E-7340-2012		Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer ResearchUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI); National Cancer Institute, NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [HHSN27612080001]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [ZIABC010744, ZIABC010743] Funding Source: NIH RePORTER	The work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project also has been funded in part with Federal funds from the National Cancer Institute, NIH, under contract no. HHSN27612080001. The content of this review does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. government. The authors thank Dr. Ziqiang Zhu for his reading of the manuscript.	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J	Wang, C; Luo, J; Chen, ZH; Ye, ML; Hong, YH; Liu, JL; Nie, JY; Zhao, Q; Chang, Y				Wang, Chun; Luo, Jie; Chen, Zhihang; Ye, Mingliang; Hong, Yinghui; Liu, Jialiang; Nie, Jiayan; Zhao, Qiu; Chang, Ying			MiR-375 Impairs the Invasive Capabilities of Hepatoma Cells by Targeting HIF1 alpha Under Hypoxia	DIGESTIVE DISEASES AND SCIENCES			English	Article						HIF1 alpha; MiR-375; Hypoxia; Hepatocellular carcinoma	HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; LIVER-DISEASE; EXPRESSION; METASTASIS; LENVATINIB; MICRORNAS; AUTOPHAGY	Background and Aims Hypoxia represents one of the most pervasive microenvironmental stresses in HCC due to the overwhelming growth and inadequate blood supply. HIF1 alpha as an important transcription factor participates in the regulation of various biological behaviors of HCC cells under hypoxia. Our previous study indicated that miR-375 is a hypoxia-associated miRNA. However, the interaction between miR-375 and HIF1 alpha remains unclear. Methods Bioinformatic analysis was performed for miRNA screening. qRT-PCR, western blotting, and immunohistochemical staining were used to detect the expression of related molecules. Bioinformatic analysis and dual luciferase assay were used to predict and further confirm the target association. Transwell chamber assay and flow cytometry were, respectively, used to detect migration, invasion and apoptosis of hepatoma cells. Results MiR-375 presented an obviously differential expression in human HCCs versus background livers (BLs) and HCCs versus normal liver tissues (NLTs). In rat models, miR-375 was gradually declined during hepatocarcinogenesis. HIF1 alpha was remarkably upregulated at protein level rather than at mRNA level in human HCCs versus BLs, HCCs versus NLTs, BLs versus NLTs, and in rat fibrotic livers versus NLTs. HIF1 alpha was determined to be a target of miR-375. MiR-375 inhibitor induced the migration and invasive capabilities and attenuated apoptosis of hepatoma cells under hypoxia. Depriving HIF1 alpha by siRNA could partially reverse the function of miR-375 inhibitor under hypoxia. Conclusions MiR-375 impairs the invasive capabilities of HCC cells by targeting HIF1 alpha under hypoxia.	[Wang, Chun; Luo, Jie; Ye, Mingliang; Hong, Yinghui; Liu, Jialiang; Nie, Jiayan; Zhao, Qiu; Chang, Ying] Wuhan Univ, Dept Gastroenterol, Zhongnan Hosp, Wuhan 430071, Peoples R China; [Wang, Chun; Luo, Jie; Ye, Mingliang; Hong, Yinghui; Liu, Jialiang; Nie, Jiayan; Zhao, Qiu; Chang, Ying] Hubei Clin Ctr, Wuhan, Peoples R China; [Wang, Chun; Luo, Jie; Ye, Mingliang; Hong, Yinghui; Liu, Jialiang; Nie, Jiayan; Zhao, Qiu; Chang, Ying] Key Lab Intestinal & Colorectal Dis, Wuhan, Peoples R China; [Chen, Zhihang] Guangxi Med Univ, Affiliated Hosp 1, Dept Coloproctol Surg, Nanning, Peoples R China		Chang, Y (corresponding author), Wuhan Univ, Dept Gastroenterol, Zhongnan Hosp, Wuhan 430071, Peoples R China.; Chang, Y (corresponding author), Hubei Clin Ctr, Wuhan, Peoples R China.; Chang, Y (corresponding author), Key Lab Intestinal & Colorectal Dis, Wuhan, Peoples R China.	changying@whu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81670554, 81302112, 81870390]; Natural Science Fund for Distinguished Young Scholar of Hubei Province [2017CFA068]; National Key R&D Program of China [2017YFC0112302]; Ministry of Public Health in Hubei Province of China [XF2012-8]	This work was supported by research grants from the National Natural Science Foundation of China (Nos. 81670554, 81302112, 81870390); the Natural Science Fund for Distinguished Young Scholar of Hubei Province (No. 2017CFA068); the National Key R&D Program of China (No. 2017YFC0112302); and the Ministry of Public Health in Hubei Province of China (No. XF2012-8).	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J	Chen, HT; Li, RR; Zhang, F; Yao, QH; Guo, Y				Chen, Haitao; Li, Rongrong; Zhang, Fan; Yao, Qinghua; Guo, Yong			A Scientometric Visualization Analysis for Natural Products on Cancer Research from 2008 to 2020	FRONTIERS IN PHARMACOLOGY			English	Article						natural product; cancer; bibliometric; citation analysis; molecular docking; gut microbiota; immune checkpoint	CHEMOTHERAPY; MODULATION; INDUCTION; APOPTOSIS; AUTOPHAGY; CELLS; ACID	Background: An increasing number of studies have shown that natural products have anti-tumor effects, and it has become a hotspot in cancer research. However, few bibliometric analyses have been examined in this field systematically. The current study aimed to explore the status and provide the developing trends in the natural products on cancer research. Methods: Publications on natural products in cancer research were extracted from the Web of Science core collection database. CiteSpace (5.6.R3) software and GraphPad prism 6 were used to analyze and plot the references. Results: On February 1, 2021, 34,611 records of natural products in cancer research published from 2008 to 2020 were collected. The United States was the driving force, with a strong academic reputation in this area. The top-contributing institution was the Chinese Academy of Sciences. Most publications were published in Molecules. Efferth Thomas was the most prolific author, while Newman DJ was the most cited and frequently co-cited author. Flavonoid, curcumin, and polyphenol were the most widely studied natural products. Oleanolic acid and rosmarinic acid have gradually become research hotspots recently. Breast cancer, prostate cancer, and colorectal cancer were the most common types of cancer in this field. "Natural killer cell" was the leading research hotspot. The keywords of "leaf extract," "molecular docking" and "gold nanoparticle" appeared most recently as research frontiers. Conclusion: Our results provided a general overview of the major research directions of natural products research in cancer. The mechanisms of natural products, especially those related to molecular docking, gold nanoparticle, gut microbiota, and immune checkpoints may soon become hotspots and should be closely monitored.	[Chen, Haitao; Zhang, Fan] Zhejiang Chinese Med Univ, Clin Coll 1, Hangzhou, Peoples R China; [Li, Rongrong] Zhejiang Chinese Med Univ, Clin Coll 3, Hangzhou, Peoples R China; [Yao, Qinghua] Univ Chinese Acad Sci, Dept Integrated Tradit Chinese & Western Med, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China; [Guo, Yong] Zhejiang Chinese Med Univ, Dept Oncol, Affiliated Hosp 1, Hangzhou, Peoples R China		Yao, QH (corresponding author), Univ Chinese Acad Sci, Dept Integrated Tradit Chinese & Western Med, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China.; Guo, Y (corresponding author), Zhejiang Chinese Med Univ, Dept Oncol, Affiliated Hosp 1, Hangzhou, Peoples R China.	yaoqh@zjcc.org.cn; guoyong1047@zcmu.edu.cn					Al-Ani LA, 2019, PLOS ONE, V14, DOI 10.1371/journal.pone.0216725; Anwar A, 2018, MOL BIOL REP, V45, P1339, DOI 10.1007/s11033-018-4294-5; Bian Y, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21020684; Blagden SP, 2020, LANCET ONCOL, V21, P969, DOI 10.1016/S1470-2045(20)30218-7; Boss A, 2016, NUTRIENTS, V8, DOI 10.3390/nu8080513; Brandt CS, 2009, J EXP MED, V206, P1495, DOI 10.1084/jem.20090681; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Chen HT, 2020, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.588079; Chen LX, 2016, INT IMMUNOPHARMACOL, V37, P65, DOI 10.1016/j.intimp.2016.02.005; Chen YX, 2020, LANCET GASTROENTEROL, V5, P267, DOI 10.1016/S2468-1253(19)30409-1; Cheung MK, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.00744; Cueva C, 2020, NUTRIENTS, V12, DOI 10.3390/nu12030625; Deng R, 2020, MINI-REV MED CHEM, V20, P161, DOI 10.2174/1389557519666191011154923; Dobrzynska M, 2020, BIOMOLECULES, V10, DOI 10.3390/biom10091268; Farhood B, 2019, J CELL PHYSIOL, V234, P5728, DOI 10.1002/jcp.27442; Farkkila N., 2019, ACTA ONCOL, V58, P1062, DOI [10.1080/0284186X.2019.1592218, DOI 10.1080/0284186X.2019.1592218]; Feng XL, 2020, EUR J CANCER PREV, V29, P493, DOI 10.1097/CEJ.0000000000000561; Hallajzadeh J, 2020, MED ONCOL, V37, DOI 10.1007/s12032-020-01367-9; Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013; Hayakawa T, 2020, CANCER SCI, V111, P4326, DOI 10.1111/cas.14675; Kim SY, 2017, NUTRIENTS, V9, DOI 10.3390/nu9090938; Lanier LL, 2008, NAT IMMUNOL, V9, P495, DOI 10.1038/ni1581; Lin Y, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.00764; Martins F, 2019, NAT REV CLIN ONCOL, V16, P563, DOI 10.1038/s41571-019-0218-0; Meng X, 2018, NUTRIENTS, V10, DOI 10.3390/nu10101457; Merigo JM, 2019, TOURISM GEOGR, V21, P881, DOI 10.1080/14616688.2019.1666913; Moradi M, 2020, N-S ARCH PHARMACOL, V393, P2145, DOI 10.1007/s00210-020-01917-y; Mulet-Forteza C, 2019, INT J CONTEMP HOSP M, V31, P4574, DOI 10.1108/IJCHM-10-2018-0828; Najmuddin SUFS, 2016, BMC COMPLEM ALTERN M, V16, DOI 10.1186/s12906-016-1290-y; Narozna M, 2021, PHARMACEUTICALS-BASE, V14, DOI 10.3390/ph14010032; Naveed S, 2019, INDIAN J DERMATOL, V64, P122, DOI 10.4103/ijd.IJD_129_17; Newman DJ, 2016, J NAT PROD, V79, P629, DOI 10.1021/acs.jnatprod.5b01055; Newman DJ, 2012, J NAT PROD, V75, P311, DOI 10.1021/np200906s; Patel SA, 2018, IMMUNITY, V48, P417, DOI 10.1016/j.immuni.2018.03.007; Perng DS, 2016, J DRUG TARGET, V24, P624, DOI 10.3109/1061186X.2015.1132221; Qin JJ, 2017, CHIN J NAT MEDICINES, V15, P401, DOI 10.1016/S1875-5364(17)30062-6; Rodriguez-Garcia C, 2019, ANTIOXIDANTS-BASEL, V8, DOI 10.3390/antiox8050137; Rodriguez-Luna A, 2019, MAR DRUGS, V17, DOI 10.3390/md17080451; Rosado-Perez J, 2018, CURR PHARM DESIGN, V24, P4807, DOI 10.2174/1381612824666190114164758; Schnipper LE, 2015, J CLIN ONCOL, V33, P2563, DOI 10.1200/JCO.2015.61.6706; Shafabakhsh R., 2019, PHARMACOL RES, V147, P104353, DOI [10.1016/j.phrs.2019.104353, DOI 10.1016/j.phrs.2019.104353]; Shahwar D, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20082010; Siegel RL, 2020, CA-CANCER J CLIN, V70, P7, DOI 10.3322/caac.21590; Sinha D, 2016, SEMIN CANCER BIOL, V40-41, P209, DOI 10.1016/j.semcancer.2015.11.001; Song YL, 2017, CELL BIOL INT, V41, P1367, DOI 10.1002/cbin.10868; Stout NL, 2018, JNCI-J NATL CANCER I, V110, P815, DOI 10.1093/jnci/djy108; Tan HD, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.01504; Troselj KG, 2020, MOLECULES, V25, DOI 10.3390/molecules25225240; Wang YS, 2018, PROTEIN CELL, V9, P568, DOI 10.1007/s13238-018-0513-z; Xu XL, 2017, J GLOB HEALTH, V7, DOI 10.7189/jogh.07.010414; Yamamoto S, 2017, BREAST CANCER-TOKYO, V24, P783, DOI 10.1007/s12282-017-0779-7; Yang MM, 2021, J CANCER RES CLIN, V147, P1101, DOI 10.1007/s00432-021-03510-z; Yeung Andy Wai Kan, 2018, Critical Reviews in Oncogenesis, V23, P347, DOI 10.1615/CritRevOncog.2018027566; Zeng Y, 2019, CURR MED CHEM, V26, P1849, DOI 10.2174/0929867324666170523123655; Zhang Y, 2018, J BUON, V23, P763; Zhang YY, 2019, ONCOTARGETS THER, V12, P5457, DOI 10.2147/OTT.S200161	56	0	0	9	20	FRONTIERS MEDIA SA	LAUSANNE	AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND		1663-9812		FRONT PHARMACOL	Front. Pharmacol.	AUG 6	2021	12									10.3389/fphar.2021.650141			12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	UM6DE	WOS:000693420100001	34421584	gold, Green Published			2022-04-25	
J	Chekhonin, VP; Shein, SA; Korchagina, AA; Gurina, OI				Chekhonin, Vladimir P.; Shein, Sergey A.; Korchagina, Anna A.; Gurina, Olga I.			VEGF in Tumor Progression and Targeted Therapy	CURRENT CANCER DRUG TARGETS			English	Article						Antiangiogenic therapy; bevacizumab; cell invasion; glioma; target therapy; tumor resistance; VEGF	ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; BEVACIZUMAB PLUS IRINOTECAN; HIGH-GRADE GLIOMAS; CANCER STEM-CELLS; PHASE-II TRIAL; BREAST-CANCER; RECURRENT GLIOBLASTOMA; IN-VIVO; MONOCLONAL-ANTIBODIES	Progression of solid tumors depends on vascularization and angiogenesis in a malignant tissue. Among a whole range of proangiogenic factors, a vascular endothelial growth factor A (VEGF-A) plays a key role. Blockade of VEGF may lead to regression of vascular network and inhibition of a tumor growth. In the present time, bevacizumab has been introduced into wide clinical practice in therapy of breast cancer, colorectal cancer and recurrent high-grade gliomas (HGGs). Coadministration of antiangiogenic therapy with irinotecan may increase probability of the response to the treatment and prolong progression-free survival rate (PFS). Moreover, bevacizumab is well tolerated and significantly improves patient's quality of life. However, in the case of brain tumors, the efficiency of such an approach is controversial. The antiangiogenic therapy can slightly delay tumor growth and does not lead to complete recovery. In addition, it contributes to enhanced tumor cell invasion into the normal brain. The mechanisms of resistance include activation of alternative proangiogenic signaling pathways, of an invasive population of tumor cells, metabolic change toward glycolysis and recruitment of myeloid bone marrow-derived cells to tumors. Obviously, that anti-VEGF therapy as monotherapy was not effective against HGGs. To enhance the antitumor treatment efficacy, it is necessary to develop a multi-target strategy to inhibit critical processes in malignancy progression such as angiogenesis, invasion, autophagy, metastatic spread, recruitment of bone marrow-derived endothelial cells and tumor stem-like cells. In addition, anti-VEGF antibodies have shown a promising result as a tumor-targeting vector for delivery therapeutic and diagnostic drugs in brain tumors.	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Cancer Drug Targets	MAY	2013	13	4					423	443		10.2174/15680096113139990074			21	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	144XV	WOS:000318976500006	23167597				2022-04-25	
J	Guo, ZZ; Meng, MJ; Geng, SN; Du, ZH; Zheng, YQ; Yao, JJ; Li, ZB; Han, G; Lin, HH; Du, GJ				Guo, Zhenzhen; Meng, Mingjing; Geng, Shengnan; Du, Zhenhua; Zheng, Yaqiu; Yao, Jingjing; Li, Zibo; Han, Guang; Lin, Haihong; Du, Gangjun			The optimal dose of arsenic trioxide induced opposite efficacy in autophagy between K562 cells and their initiating cells to eradicate human myelogenous leukemia	JOURNAL OF ETHNOPHARMACOLOGY			English	Article						Arsenic trioxide; Chronic myelogenous leukemia (CML); Leukemiainitiating cells (LICs); Autophagy; Senescence	ACUTE PROMYELOCYTIC LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; DIFFERENTIATION; CANCER; DEGRADATION; CONTRIBUTES; INHIBITION; MUTATION; AS2O3; AGENT	Ethnopharmacological relevance: Arsenic trioxide (As2O3), a main component of arsenolite which is a common traditional Chinese medicine (TCM) wildly used as a therapeutic agent for more than 2400 years in china, has been accepted as a standard treatment for the patients with acute promyelocytic leukemia (APL) based on the principle in TCM of "using a poison to fight against other poisons or malignancy illnesses". However, it remains unknown that which mechanism is actually responsible for the therapeutic effects against these blood malignancies. Aim of the study: The purpose of this study was to explore the actual mechanism that ATO exerts its effects in K562 cells and their initiating cells (K562s). Materials and methods: K562s cells were separated and enriched for CD34+/CD38- cells using magnetic microbeads. Cell proliferation was determined by incorporation of BrdU. Cell apoptosis was evaluated by Annexin-V binding and PI uptake. Autophagy was estimated by acridine orange and immunofluorescence staining of LC3-B and p62. MC colonic formation was used to examine cell self-renew. ROS generation inside living cells was measured by DCFH-DA. Cell differentiation was assessed by the benzidine staining. The SA-beta-gal assay was used to detect cell senescence. Protein expression was examined by western blotting and immunohistochemical staining. Results: K562s cells were stronger in self-renew and resistance to ATO cytotoxicity and starvation-induced apoptosis than K562 cells. Unexpectedly, we found that ATO at a dose of 0.5 mu M which had no effect on cell proliferation resulted in maximum suppression on self-renew in both cells and maximum starvation-induced apoptosis in K562s cells but minimum starvation-induced apoptosis in K562 cells. Next, we found that ATO no more than 0.5 mu M selectively induced K562s cell differentiation indicated by benzidine staining, gamma-globin and CD235a expression. More importantly, we found that ATO no more than 0.5 mu M led to opposite efficacy in autophagy between K562 and K562s cells, and the opposite autophagy could induced late-phase senescence in both cells. Finally, we used the optimal dose of ATO to eradicate leukemia cells and obtained a satisfied therapeutic outcomes in vivo. Conclusions: Our results suggest that the used dose of ATO may determine the fate of cell differentiation senescence or malignant transformation, and the optimal dose of ATO induced opposite efficacy in autophagy between K562 cells and their initiating cells and ultimately leads both cells to late-phase senescence.	[Guo, Zhenzhen; Meng, Mingjing; Geng, Shengnan; Du, Zhenhua; Zheng, Yaqiu; Yao, Jingjing; Li, Zibo; Han, Guang; Lin, Haihong; Du, Gangjun] Henan Univ, Inst Pharm, Coll Pharm, Kaifeng 475004, Henan Province, Peoples R China		Lin, HH; Du, GJ (corresponding author), Henan Univ, Inst Pharm, Coll Pharm, Kaifeng 475004, Henan Province, Peoples R China.	1070417690@qq.com; 2272352627@qq.com; 1017172540@qq.com; 1256747886@qq.com; 2388756645@qq.com; yaojingjing123456@qq.com; 963235757@qq.com; hang@henu.edu.cn; linhaihong369@126.com; 724200@henu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81173094, 81373974]	This work was supported by National Natural Science Foundation of China (No. 81173094, 81373974).	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Ethnopharmacol.	JAN 20	2017	196						29	38		10.1016/j.jep.2016.12.010			10	Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine	EJ9ER	WOS:000393529900004	27965050				2022-04-25	
J	Jin, CL; Yuan, P				Jin, Chunlai; Yuan, Peng			Implications of lipid droplets in lung cancer: Associations with drug resistance	ONCOLOGY LETTERS			English	Review						lung cancer; non-small cell lung cancer; drug resistance; epidermal growth factor receptor; tyrosine kinase inhibitors; lipid droplet	FATTY-ACID OXIDATION; TYROSINE KINASE INHIBITORS; HORMONE-SENSITIVE LIPASE; GROWTH-FACTOR; COLORECTAL-CANCER; CELL-SURVIVAL; MITOCHONDRIAL-FUNCTION; ENDOPLASMIC-RETICULUM; INCREASED EXPRESSION; REGULATES AUTOPHAGY	Cancer cells usually show different metabolic patterns compared with healthy cells due to the reprogramming of metabolic processes. The process of lipid metabolism undergoes notable changes, leading to the accumulation of lipid droplets in cells. Additionally, this phenotype is considered an important marker of cancer cells. Lipid droplets are a highly dynamic type of organelle in the cell, which is composed of a neutral lipid core, a monolayer phospholipid membrane and lipid droplet-related proteins. Lipid droplets are involved in several biological processes, including cell proliferation, apoptosis, lipid metabolism, stress, immunity, signal transduction and protein trafficking. Epidermal growth factor receptor (EGFR)-activating mutations are currently the most effective therapeutic targets for non-small cell lung cancer. Several EGFR tyrosine kinase inhibitors (EGFR-TKIs) that target these mutations, including gefitinib, erlotinib, afatinib and osimertinib, have been widely used clinically. However, the development of acquired resistance has a major impact on the efficacy of these drugs. A number of previous studies have reported that the expression of lipid droplets in the tumor tissues of patients with lung cancer are elevated, whereas the association between elevated numbers of lipid droplets and drug resistance has received little attention. The present review describes the potential association between lipid droplets and drug resistance. Furthermore, the mechanisms and implications of lipid droplet accumulation in cancer cells are analyzed, as wells as the mechanism by which lipid droplets suppress endoplasmic reticulum stress and apoptosis, which are essential for the development and treatment of lung cancer.	[Jin, Chunlai; Yuan, Peng] First Peoples Hosp Jinan, Dept Surg, 132 Ming Lake St, Jinan 250011, Shandong, Peoples R China		Yuan, P (corresponding author), First Peoples Hosp Jinan, Dept Surg, 132 Ming Lake St, Jinan 250011, Shandong, Peoples R China.	pengyuan_dr@126.com			College of Animal Science, Huazhong Agricultural University	The authors of the present study would like to thank Dr Yi Jin, from the College of Animal Science, Huazhong Agricultural University (Wuhan, China) for his help in researching the progress of lipid droplets and oxidative stress.	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J	Subramaniam, S; Jeet, V; Clements, JA; Gunter, JH; Batra, J				Subramaniam, Sugarniya; Jeet, Varinder; Clements, Judith A.; Gunter, Jennifer H.; Batra, Jyotsna			Emergence of MicroRNAs as Key Players in Cancer Cell Metabolism	CLINICAL CHEMISTRY			English	Review							INHIBITS TUMOR-GROWTH; PYRUVATE-DEHYDROGENASE; COLORECTAL-CANCER; PROSTATE-CANCER; LACTATE-DEHYDROGENASE; FATTY-ACID; AEROBIC GLYCOLYSIS; CERVICAL-CANCER; BLADDER-CANCER; PROLIFERATION	BACKGROUND: Metabolic reprogramming is a hallmark of cancer. MicroRNAs (miRNAs) have been found to regulate cancer metabolism by regulating genes involved in metabolic pathways. Understanding this layer of complexity could lead to the development of novel therapeutic approaches. CONTENT: miRNAs are noncoding RNAs that have been implicated as master regulators of gene expression. Studies have revealed the role of miRNAs in the metabolic reprogramming of tumor cells, with several miRNAs both positively and negatively regulating multiple metabolic genes. The tricarboxylic acid (TCA) cycle, aerobic glycolysis, de novo fatty acid synthesis, and altered autophagy allow tumor cells to survive under adverse conditions. In addition, major signaling molecules, hypoxiainducible factor, phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin/phosphatase and tensin homolog, and insulin signaling pathways facilitate metabolic adaptation in tumor cells and are all regulated by miRNAs. Accumulating evidence suggests that miRNA mimics or inhibitors could be used to modulate the activity of miRNAs that drive tumor progression via altering their metabolism. Currently, several clinical trials investigating the role of miRNA-based therapy for cancer have been launched that may lead to novel therapeutic interventions in the future. SUMMARY: In this review, we summarize cancer-related metabolic pathways, including glycolysis, TCA cycle, pentose phosphate pathway, fatty acid metabolism, amino acid metabolism, and other metabolism-related oncogenic signaling pathways, and their regulation by miRNAs that arc known to lead to tumorigenesis. Fur- ther, we discuss the current state of miRNA therapeutics in the clinic and their future potential. (C) 2019 American Association for Clinical Chemistry	[Subramaniam, Sugarniya; Jeet, Varinder; Clements, Judith A.; Gunter, Jennifer H.; Batra, Jyotsna] Queensland Univ Technol, Fac Hlth, Sch Biomed Sci, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia; [Subramaniam, Sugarniya; Jeet, Varinder; Clements, Judith A.; Gunter, Jennifer H.; Batra, Jyotsna] Queensland Univ Technol, APCRC Q, Translat Res Inst, Brisbane, Qld, Australia		Batra, J (corresponding author), Translat Res Inst, 37 Kent St, Brisbane, Qld 4102, Australia.	jyotsna.batra@qut.edu.au	Gunter, Jennifer H/B-8960-2016	Gunter, Jennifer H/0000-0003-2447-5732; Jeet, Varinder/0000-0003-3765-5310	QUT Postgraduate Research Award (QUTPRA); QUT HDR Tuition Fee Sponsorship; Movember Foundation; Prostate Cancer Foundation of Australia; Queensland Government; Cancer Council AustraliaCancer Council Australia; Cure Cancer Australia; Cancer Australia; National Health and Medical Research Council (NHMRC)National Health and Medical Research Council (NHMRC) of Australia	S. Subramaniam, QUT Postgraduate Research Award (QUTPRA) and QUT HDR Tuition Fee Sponsorship; J. Gunter, the Movember Foundation, the Prostate Cancer Foundation of Australia, a Queensland Government Advance Queensland Fellowship; J. Batra, Cancer Council Australia and Cure Cancer and Cancer Australia Young Investigator award, National Health and Medical Research Council (NHMRC) Career Development Fellowship.	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Chem.	SEP	2019	65	9					1090	1101		10.1373/clinchem.2018.299651			12	Medical Laboratory Technology	Science Citation Index Expanded (SCI-EXPANDED)	Medical Laboratory Technology	IV6HS	WOS:000484370100008	31101638	Green Submitted, Bronze			2022-04-25	
J	Kosmidou, V; Vlassi, M; Anagiotos, K; Raftopoulou, S; Kalogerakou, E; Skarmalioraki, S; Aggeli, C; Choreftaki, T; Zografos, G; Pintzas, A				Kosmidou, Vivian; Vlassi, Margarita; Anagiotos, Kyriakos; Raftopoulou, Sofia; Kalogerakou, Eirini; Skarmalioraki, Salomi; Aggeli, Chrysanthi; Choreftaki, Theodosia; Zografos, George; Pintzas, Alexander			Noxaupregulation and 5-gene apoptotic biomarker panel in colorectal cancer	EUROPEAN JOURNAL OF CLINICAL INVESTIGATION			English	Article						apoptosis; CRC; novel 5-biomarker panel; Noxa early detection	TARGETING MCL-1; IAP PROTEINS; NOXA; INHIBITOR; EXPRESSION; ACTIVATION; AUTOPHAGY; PATHWAYS; MEK/ERK; MARKERS	Background NOXA and MCL1 are involved in the intrinsic pathway of apoptosis, where Noxa selectively binds to MCL1 and prevents it from inhibiting apoptosis. Both factors are considered as potential tumour biomarkers, while MCL1 has attracted interest as target in cancer. The purpose of this study was to investigate the expression of NOXA and MCL1 in 160 CRC tumour samples, to investigate their significance, also in combination with IAPs, DR5 expression andKRASgene mutations in CRC. Materials and methods Fresh frozen colorectal tissue was obtained from patients undergoing surgery for CRC. Real-time quantitative PCR was performed for the determination of mRNA expression levels. Protein expression was determined immunohistochemically. Differences in the mRNA expression profile were evaluated with the nonparametric Wilcoxon signed ranks test. Statistical analysis was performed with the use of Mann-WhitneyUtest and receiver-operating characteristic (ROC) curve. Results NOXAwas found to be overexpressed in CRC tumours (P < .0001), even from early stage. Moreover,NOXA/MCL1mRNA expression was significantly elevated in tumour samples compared to normal pairs (P < .0001). ROC curve analysis showed that bothNOXAexpression and its combination withMcl1expression have fair discriminatory value between CRC and normal colorectal tissue. Combinatorial ROC analysis revealed the most significant discriminatory value ofNOXA, MCL1withcIAP1andcIAP2(AUC = 0.834,P < .0001) as a 5-gene panel of markers. Conclusion Noxa, Mcl1, DR5,cIAP1andcIAP2mRNA expressions are significantly deregulated in CRC and could provide a panel of markers with significant discriminatory value between CRC and normal colorectal tissue.	[Kosmidou, Vivian; Vlassi, Margarita; Anagiotos, Kyriakos; Raftopoulou, Sofia; Kalogerakou, Eirini; Skarmalioraki, Salomi; Pintzas, Alexander] Natl Hellen Res Fdn, Inst Chem Biol, Lab Signal Mediated Gene Express, Athens, Greece; [Aggeli, Chrysanthi; Zografos, George] Gen Hosp Athens G Gennimatas, Dept Surg 3, Athens, Greece; [Choreftaki, Theodosia] Gen Hosp Athens G Gennimatas, Dept Pathol, Athens, Greece		Pintzas, A (corresponding author), Natl Hellen Res Fdn, Inst Chem Biol, Athens, Greece.	apint@eie.gr			General Secretariat for Research and TechnologyGreek Ministry of Development-GSRT [11SYN1-485]	General Secretariat for Research and Technology, Grant/Award Number: SYNERGASIA "THERACAN" 11SYN1-485	Abraha AM, 2016, WORLD J GASTRO ONCOL, V8, P583, DOI 10.4251/wjgo.v8.i8.583; Bai YH, 2018, CELL PHYSIOL BIOCHEM, V48, P1755, DOI 10.1159/000492317; Chen L, 2005, MOL CELL, V17, P393, DOI 10.1016/j.molcel.2004.12.030; Conti A, 2015, ONCOTARGET, V6, P10994, DOI 10.18632/oncotarget.3552; de Almagro M. 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J. Clin. Invest.	JAN	2021	51	1							e13353	10.1111/eci.13353		AUG 2020	17	Medicine, General & Internal; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine; Research & Experimental Medicine	PH0JP	WOS:000558012900001	32682341				2022-04-25	
J	Helmy, MW; Ghoneim, AI; Katary, MA; Elmahdy, RK				Helmy, Maged W.; Ghoneim, Asser, I; Katary, Mohamed A.; Elmahdy, Rana K.			The synergistic anti-proliferative effect of the combination of diosmin and BEZ-235 (dactolisib) on the HCT-116 colorectal cancer cell line occurs through inhibition of the PI3K/Akt/mTOR/NF-kappa B axis	MOLECULAR BIOLOGY REPORTS			English	Article						Colorectal cancer; BEZ-235; Diosmin; PI3K; NF-kappa b	NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; RAPAMYCIN INHIBITOR; PATHWAY COMPONENTS; SIGNALING PATHWAYS; MAMMALIAN TARGET; DUAL INHIBITOR; PI3K PATHWAY; FACTOR-ALPHA	One of the most lethal malignancies worldwide is colorectal cancer (CRC). Alterations in various signalling pathways, including PI3K-mTOR and NF-kappa B, have been reported in CRC with subsequent dysregulation of proliferation, apoptosis, angiogenesis and, questionably, autophagy processes. BEZ-235 (dactolisib) is a dual PI3K-mTOR inhibitor with potent anti-tumour activity. However, the observed toxicity of BEZ-235 necessitated the termination of its clinical trials. Hence, we aimed to evaluate the potential long-lasting anti-carcinogenic effects of adding diosmin (DIO, a natural NF-kappa B inhibitor) to BEZ-235 in HCT-116 CRC cells. The median inhibitory concentrations (IC50s) of BEZ-235 and/or DIO were evaluated in the HCT-116 CRC cell line. Caspase-3 activity was assessed colorimetrically, and p-Akt, NF-kappa B, CD1, VEGF and LC3B levels were assessed by ELISA. Additionally, LC3-II and P62 gene expression were assessed using qRT-PCR. The observed CIs (combination indices) and DRIs (dose reduction indices) confirmed the synergistic effect of DIO and BEZ-235. Co-administration of both drugs either in combination-1 (1 mu M for BEZ-235, 250 mu M for DIO) or in combination-2 (0.51 mu M for BEZ-235 + 101.99 mu M for DIO) inhibited the PI3K/Akt/mTOR/NF-kappa B axis, leading to the induction of apoptosis (via active caspase-3), and the inhibition of proliferation marker (CD1), angiogenesis marker (VEGF), autophagy protein (LC3B) and altered effects on LC3-IIandP62 gene expression. Our results reveal the synergistic chemotherapeutic effects of DIO combined with BEZ-235 in the HCT-116 CRC cell line and encourage future preclinical and clinical studies of this combination with reduced BEZ-235 concentrations to avoid its reported toxicity. [GRAPHICS] .	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Biol. Rep.	MAR	2020	47	3					2217	2230		10.1007/s11033-020-05327-4		FEB 2020	14	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	LG1EV	WOS:000516374900001	32088816				2022-04-25	
J	Guo, LL; Ma, LL; Liu, C; Lei, Y; Tang, N; Huang, YX; Huang, G; Li, DZ; Wang, Q; Liu, GL; Tang, MS; Jing, ZL; Deng, YJ				Guo, Lili; Ma, Lili; Liu, Chao; Lei, Yan; Tang, Na; Huang, Yingxin; Huang, Guan; Li, Dazhou; Wang, Qi; Liu, Guanglong; Tang, Minshan; Jing, Zhiliang; Deng, Yongjian			ERp29 counteracts the suppression of malignancy mediated by endoplasmic reticulum stress and promotes the metastasis of colorectal cancer	ONCOLOGY REPORTS			English	Article						endoplasmic reticulum protein 29; endoplasmic reticulum stress; colorectal cancer cells; CUL5; metastasis	UNFOLDED PROTEIN RESPONSE; ER-STRESS; UP-REGULATION; APOPTOSIS; EXPRESSION; CELLS; GENE; INFLAMMATION; ACTIVATION; AUTOPHAGY	Endoplasmic reticulum protein 29 (ERp29), an endoplasmic reticulum (ER) protein, participates in ER stress (ERS), but little is known about the association of ERp29 with ERS in the metastasis and prognosis of cancerous diseases. The present study revealed that ERp29 was important to ERS and interfered with the malignant behaviors of colorectal cancer (CRC). Experiments in in vitro and in animal models revealed that ERS inhibited the cell growth and suppressed the metastatic capacity of CRC cells, but ERp29 counteracted these effects. Furthermore, it was demonstrated that ERp29 recovered the migration and metastatic behaviors of CRC cells suppressed by ERS, mediated only when it combined with cullin5 (CUL5). ERp29 also relied on CUL5 to promote epithelial-mesenchymal transition. From the immunohistochemical examination of CRC tissues, the high expression of ERp29 was revealed to predict the poor prognosis of 457 CRC cases. The retrospective analysis of the clinicopathological data of patients with CRC was consistent with the results of the in vitro and in vivo experiments. Thus, ERp29 protected CRC cells from ERS-mediated reduction of malignancy to promote metastasis and may be a potential target of medical intervention for CRC therapy.	[Guo, Lili; Ma, Lili; Lei, Yan; Huang, Yingxin; Huang, Guan; Li, Dazhou; Wang, Qi; Liu, Guanglong; Tang, Minshan; Jing, Zhiliang; Deng, Yongjian] Southern Med Univ, Nanfang Hosp, Dept Pathol, 1838 North Guangzhou Rd, Guangzhou 510515, Guangdong, Peoples R China; [Guo, Lili; Ma, Lili; Lei, Yan; Huang, Yingxin; Huang, Guan; Li, Dazhou; Wang, Qi; Liu, Guanglong; Tang, Minshan; Jing, Zhiliang; Deng, Yongjian] Southern Med Univ, Sch Basic Med Sci, 1838 North Guangzhou Rd, Guangzhou 510515, Guangdong, Peoples R China; [Guo, Lili; Ma, Lili; Lei, Yan; Huang, Yingxin; Huang, Guan; Li, Dazhou; Wang, Qi; Liu, Guanglong; Tang, Minshan; Jing, Zhiliang; Deng, Yongjian] Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou 510515, Guangdong, Peoples R China; [Ma, Lili] Taishan City Peoples Hosp, Dept Cardiothorac Surg, Taishan 529200, Guangdong, Peoples R China; [Liu, Chao] Guangdong Gen Hosp, Dept Pathol & Lab Med, Guangzhou 510080, Guangdong, Peoples R China; [Liu, Chao] Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China; [Tang, Na] Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Pathol, Shenzhen 518020, Guangdong, Peoples R China		Deng, YJ (corresponding author), Southern Med Univ, Nanfang Hosp, Dept Pathol, 1838 North Guangzhou Rd, Guangzhou 510515, Guangdong, Peoples R China.; Deng, YJ (corresponding author), Southern Med Univ, Sch Basic Med Sci, 1838 North Guangzhou Rd, Guangzhou 510515, Guangdong, Peoples R China.	dengyj@smu.edu.cn			National Key Research and Development Program of China [2016YFC1201801]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672453, 81372584, 81201970, 81702359]; Guangdong Provincial Natural Science Foundation of ChinaNational Natural Science Foundation of Guangdong Province [2015A030313243, 2015A030310089, C1051156]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2017M622736]; Guangdong Medical Science and Technology Research Foundation [A2017403]	The present study was supported by the National Key Research and Development Program of China (grant no. 2016YFC1201801), the National Natural Science Foundation of China (grant nos. 81672453, 81372584, 81201970 and 81702359), the Guangdong Provincial Natural Science Foundation of China (grant nos. 2015A030313243, 2015A030310089 and C1051156), the China Postdoctoral Science Foundation (grant no. 2017M622736) and the Guangdong Medical Science and Technology Research Foundation (grant no. A2017403).	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Rep.	MAR	2019	41	3					1603	1615		10.3892/or.2018.6943			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	HM5ZB	WOS:000459552700015	30569094	Green Published, hybrid, Green Submitted			2022-04-25	
J	Bodmer, WF; Crouch, DJM				Bodmer, Walter F.; Crouch, Daniel J. M.			Somatic selection of poorly differentiating variant stem cell clones could be a key to human ageing	JOURNAL OF THEORETICAL BIOLOGY			English	Article						Ageing; Tissue stem cells; Somatic mutation; Cellular differentiation; Natural selection	COLONIC CRYPT; CANCER; MUTATIONS; HEMATOPOIESIS; POPULATION; SENESCENCE; PRECURSORS; MECHANISM; EVOLUTION; AUTOPHAGY	Any replicating system in which heritable variants with differing replicative potentials can arise is subject to a Darwinian evolutionary process. The continually replicating adult tissue stem cells that control the integrity of many tissues of long-lived, multicellular, complex vertebrate organisms, including humans, constitute such a replicating system. Our suggestion is that somatic selection for mutations (or stable epigenetic changes) that cause an increased rate of adult tissue stem cell proliferation, and their long-term persistence, at the expense of normal differentiation, is a major key to the ageing process. Once an organism has passed the reproductive age, there is no longer any significant counterselection at the organismal level to this inevitable cellular level Darwinian process. (C) 2020 Elsevier Ltd. All rights reserved.	[Bodmer, Walter F.] Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, Dept Oncol,Canc & Immunogenet Lab, Oxford, England; [Crouch, Daniel J. M.] Univ Oxford, JDRF Wellcome Trust Diabet & Inflammat Lab, Wellcome Ctr Human Genet, Old Rd Campus, Oxford, England		Bodmer, WF (corresponding author), Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, Dept Oncol,Canc & Immunogenet Lab, Oxford, England.	walter.bodmer@hertford.ox.ac.uk; daniel.crouch@well.ox.ac.uk			JDRFJuvenile Diabetes Research Foundation [5-SRA-2015-130-A-N]; Wellcome TrustWellcome TrustEuropean Commission [107212/Z/15/Z, 203131/Z/16/Z]	This work was supported by JDRF Grant 5-SRA-2015-130-A-N and Wellcome Trust Grants 107212/Z/15/Z and 203131/Z/16/Z.	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Theor. Biol.	MAR 21	2020	489								110153	10.1016/j.jtbi.2020.110153			10	Biology; Mathematical & Computational Biology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology	KL2ZB	WOS:000513296000007	31935413	Green Submitted			2022-04-25	
J	Subasi, E; Atalay, EB; Erdogan, D; Sen, B; Pakyapan, B; Kayali, HA				Subasi, Elif; Atalay, Esra Bulut; Erdogan, Duygu; Sen, Betill; Pakyapan, Bilge; Kayali, Hulya Ayar			Synthesis and characterization of thiosemicarbazone-functionalized organoruthenium (II)-arene complexes: Investigation of antitumor characteristics in colorectal cancer cell lines	MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS			English	Article						Organoruthenium (II)-arene complexes; Thiosemicarbazone; Antitumor activity; Colorectal cancer cell lines; Crystal structure	CRYSTAL-STRUCTURE; DNA-BINDING; RUTHENIUM; MEDICINE	In the current study, organoruthenium(II)-arene complexes (I-IV) have been prepared by the reaction of ({(eta(6)-pcym)RuCl}(2)(mu-Cl)(2)] with new thiosemicarbazones (TSC1-4).The isolate was analyzed using elemental analysis, FT-IR, H-1 and C-13 NMR spectroscopy and single-crystal XRD. Subsequently, the complexes and TSC ligands were assessed for anticancer properties in vitro against three different colorectal cancer stage's cell lines (Caco-2, DLD-1, and SW620) and a noncancerous cell line (CCD18Co). The complexes (I-IV) showed higher cytotoxicity with low IC50 values as 0.1-0.33 mu M in colorectal cell lines except for SW620 (47.4-84.20 mu M) than in a noncancerous cell. Complex I was 2.8 and 24.5-fold more active against Caco-2 and DLD-1 than CCD18Co, respectively. The complexes (I-IV) accumulated at a high concentration in the cell nuclei and caused cell cycle arrest by affecting the G0/G1 and/or G2/M phase and showed high binding affinity with CT-DNA (Kb = 10(4) M-1). The expression of Caspase-3 and Caspase-9 apoptosis-related protein levels was slightly upregulated and Atg5 autophagy-related protein level was clearly downregulated according to control and 5-FU-treated cells after complex I and II treatment. Furthermore, it was observed that cytotoxicity of the complexes is decreased while cancer progresses. Altogether, this study indicates that all organoruthenium (II)-arene complexes (particularly complex I) can be a promising alternative to platinum counterparts in cancer treatment.	[Subasi, Elif] Dokuz Eylul Univ, Fac Sci, Dept Chem, TR-35160 Izmir, Turkey; [Atalay, Esra Bulut; Erdogan, Duygu] Dokuz Eylul Univ, Izmir Int Biomed & Genome Inst, TR-35340 Izmir, Turkey; [Sen, Betill] Dokuz Eylul Univ, Fac Sci, Dept Phys, TR-35160 Izmir, Turkey; [Pakyapan, Bilge] Ege Univ, Inst Sci & Technol, TR-35100 Izmir, Turkey; [Kayali, Hulya Ayar] Izmir Biomed & Genome Ctr, TR-35340 Izmir, Turkey; [Kayali, Hulya Ayar] Dokuz Eylul Univ, Fac Sci, Div Biochem, Dept Chem, TR-35160 Izmir, Turkey		Subasi, E; Kayali, HA (corresponding author), Dokuz Eylul Univ, Fac Sci, Dept Chem, TR-35160 Izmir, Turkey.	elif.subasi@deu.edu.tr; hulya.ayarkayali@gmail.com		Erdogan, Duygu/0000-0002-4930-7017	TUBITAK (The Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215Z663]; Dokuz Eylul UniversityDokuz Eylul University [2010.KB.FEN.13]	This study was financed by project number 215Z663 TUBITAK (The Scientific and Technological Research Council of Turkey). The authors acknowledge Dokuz Eylul University for the use of the Oxford Rigaku Xcalibur Eos Diffractometer (purchased under University Research Grant No: 2010.KB.FEN.13) and Izmir Biomedicine and Genome Center. We also gratefully thank Zehra Taysan for her help in vitro part.	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Sci. Eng. C-Mater. Biol. Appl.	JAN	2020	106								110152	10.1016/j.msec.2019.110152			15	Materials Science, Biomaterials	Science Citation Index Expanded (SCI-EXPANDED)	Materials Science	JU3ZA	WOS:000501616000021	31753399				2022-04-25	
J	Lu, M; Sun, LHR; Zhou, J; Zhao, Y; Deng, X				Lu, Min; Sun, Luhaoran; Zhou, Jin; Zhao, Yan; Deng, Xin			Dihydroartemisinin-Induced Apoptosis is Associated with Inhibition of Sarco/Endoplasmic Reticulum Calcium ATPase Activity in Colorectal Cancer	CELL BIOCHEMISTRY AND BIOPHYSICS			English	Article						Colorectal cancer; Dihydroartemisinin; Endoplasmic reticulum stress; Mitochondrial apoptosis pathway; Sarco/endoplasmic reticulum calcium ATPase	ENDOPLASMIC-RETICULUM; IN-VITRO; STRESS; CELLS; MITOCHONDRIA; EXPRESSION; AUTOPHAGY; CA2+	Dihydroartemisinin (DHA) is a promising anti-cancer compound capable of inhibiting proliferation and inducing apoptosis of various cancer cells, including colorectal cancer. However, the molecular mechanisms have not been well understood. This study aimed to explore the underlying mechanism of DHA-induced apoptosis in HCT-116 cells. Cell counting kit-8 assay and flow cytometry analysis confirmed that DHA inhibited proliferation, arrested cell cycle at G0/G1 phase, and enhanced apoptosis in HCT-116 cells. Fluo-3/AM-stained flow cytometry assay revealed that the intracellular Ca2+ concentration of HCT-116 cells was increased significantly after DHA treatment. Meanwhile, the activity of sarco/endoplasmic reticulum calcium ATPase (SERCA) was appeared to be reduced in a dose-dependent manner. We further detected the upregulated expression of CAAT/enhancer binding protein homologous protein (CHOP) in DHA-treated HCT-116 cells. Conversely, silencing CHOP resulted in a decrease of DHA-induced apoptosis. In addition, the expression of Bax in cytoplasm was elevated significantly along with the sharply decline of Bcl-2 expression in DHA-treated HCT-116 cells. Moreover, the distributions of Bid on mitochondria were increased, accompanied by the activation of caspase-3 in the presence of DHA. Overall, our data indicated that DHA triggered endoplasmic reticulum (ER) stress through inhibiting SERCA activity to release intracellular Ca2+ from ER, the upregulated expression of CHOP activated mitochondrial apoptosis pathway to induce apoptosis of HCT-116 cells. Therefore, our findings provide a theoretical foundation for DHA as a potential candidate in treatment of colorectal cancer.	[Lu, Min; Zhou, Jin] China Med Univ, Affiliated Hosp 1, Dept Colorectal Surg, Shenyang 110001, Peoples R China; [Sun, Luhaoran] China Med Univ, Dept Clin Med, Year Syst 7, Shenyang 110001, Peoples R China; [Zhao, Yan] China Med Univ, Sch Pharm, Dept Pharmaceut, Shenyang 110013, Peoples R China; [Deng, Xin] China Med Univ, Coll Basic Med Sci, Expt Ctr Funct Subjects, Shenyang 110013, Peoples R China		Lu, M (corresponding author), China Med Univ, Affiliated Hosp 1, Dept Colorectal Surg, 155 North Nanjing St, Shenyang 110001, Peoples R China.	minlu1@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81250020]	This study was supported by a Grant from the National Natural Science Foundation of China (Grant No.: 81250020).	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Biophys.	SEP	2015	73	1					137	145		10.1007/s12013-015-0643-3			9	Biochemistry & Molecular Biology; Biophysics; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics; Cell Biology	CP3WD	WOS:000359812500023	25701954				2022-04-25	
J	Ayan, IC; Cetinkaya, S; Dursun, HG; Suntar, I				Ayan, Ilknur Cnar; Cetinkaya, Sumeyra; Dursun, Hatice Gul; Suntar, Ipek			Bioactive Compounds of Rheum ribes L. and its Anticancerogenic Effect via Induction of Apoptosis and miR-200 Family Expression in Human Colorectal Cancer Cells	NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL			English	Article							ANTIOXIDANT ACTIVITY; MICRORNA-200 FAMILY; IN-VITRO; PROLIFERATION; CYTOTOXICITY; COMBINATION; AUTOPHAGY; EXTRACTS; PROMOTES; TARGETS	Rheum ribes L. is a widespread plant species in the eastern part of our country and is consumed as a vegateble by the folk people. In our study, we investigated whether R. ribeshas anti-cancerogenic effect on colorectal cancer cell lines. Six different extracts were obtained from R. ribes. Total phenolic, flavonoid contents, antioxidant activities, and cytotoxic effects of all extracts on colorectal cancer cells were determined. Differences in expression levels of the miR-200 family and target genes were assessed by real-time qPCR in cells. Antiproliferative effect was determined by TUNEL, Annexin V, cell cycle, invasion analysis; and levels of BCL-2, ZEB1, GATA4 and FAS/CD95 proteins were determined by ELISA. According to the results of miRNA expression analysis, the only dose group with a significant increase (p < 0,05) in the expression level of all of miRNAs in both cell lines was RM (Root methanol) extract alone. Our results showed that, RM caused a significant increase in the expressions of miR-200a/b/c and miR-141, and it suppressed BCL-2, ZEB1, GATA4 expressions, with this way. Thus, it has been suggested that the treatment of RM alone, or combined treatment of RM with 5-FU result in a better response than cancer cells treated with 5-FU alone.	[Ayan, Ilknur Cnar; Dursun, Hatice Gul] Necmettin Erbakan Univ, Med Fac, Dept Med Biol, Konya, Turkey; [Cetinkaya, Sumeyra] Minist Agr & Forestry, Biotechnol Res Ctr, Ankara, Turkey; [Suntar, Ipek] Gazi Univ, Dept Pharmacognosy, Fac Pharm, Ankara, Turkey		Ayan, IC (corresponding author), Necmettin Erbakan Univ, Dept Med Biol, Med Fac, TR-42090 Meram, Konya, Turkey.	ilknurcinar@msn.com	cetinkaya, sumeyra/ABG-9815-2020		scientific research projects foundation of Necmettin Erbakan university [161418001]	This work was supported by scientific research projects foundation of Necmettin Erbakan university (Grant number: 161418001).	Abdulla K. 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Cancer	JUN 10	2021	73	7					1228	1243		10.1080/01635581.2020.1792947		JUL 2020	16	Oncology; Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Nutrition & Dietetics	SO3SE	WOS:000550551300001	32691634				2022-04-25	
J	Akhtar, MF; Saleem, A; Rasul, A; Baig, MMFA; Bin-Jumah, M; Daim, MMA				Akhtar, Muhammad Furqan; Saleem, Ammara; Rasul, Azhar; Baig, Mirza Muhammad Faran Ashraf; Bin-Jumah, May; Daim, Mohamed M. Abdel			Anticancer natural medicines: An overview of cell signaling and other targets of anticancer phytochemicals	EUROPEAN JOURNAL OF PHARMACOLOGY			English	Article						Apoptosis; Autophagy; Cell cycle; mTOR pathway; Angiogenesis; Epigenetics	EPITHELIAL-MESENCHYMAL TRANSITION; IN-VITRO; CANCER-CELLS; COLORECTAL-CANCER; OXIDATIVE STRESS; DIHYDROFOLATE-REDUCTASE; ANTIMUTAGENIC ACTIVITY; INDUCED APOPTOSIS; DNA METHYLATION; GENE-EXPRESSION	Therapies of cancer are as diverse as multifaceted the cancer is. Anticancer drugs include, but not limited to synthetic, semisynthetic and natural drugs and monoclonal antibodies. A recent decline in new drug development has led to the rebirth of herbal therapeutics in the form of dietary supplements and botanical preparations. Medicinal plants comprise of complex phytochemicals due to vast biosynthetic capacity. A wide array of phytochemicals has been pharmacologically evaluated for their chemo-preventive and chemotherapeutic potential for several decades. These phytochemicals target cancer at diverse sites such as apoptotic pathways, genetic and epigenetic mutations, damage to deoxyribonucleic acid, production of reactive oxygen species, autophagy, invasion and metastasis of cancer cells, and modulation of cell signaling through Janus-activated kinase/Signal transducer and activator of transcription, Notch, mitogen-activated protein kinase/Extracellular signal-regulated kinase, phosphatidylinositol 3-kinase/Protein kinase B/mammalian target of rapamycin, Nuclear factor kappa B, Wingless-related integration site and Transforming growth factor beta pathways. This review focuses on the therapeutic targets of anticancer and chemo-preventive phytochemicals and their mode of action.	[Akhtar, Muhammad Furqan] Riphah Int Univ, Riphah Inst Pharmaceut Sci, Lahore Campus, Lahore, Pakistan; [Saleem, Ammara] Govt Coll Univ Faisalabad, Fac Pharmaceut Sci, Dept Pharmacol, Faisalabad, Pakistan; [Rasul, Azhar] Govt Coll Univ Faisalabad, Dept Zool, Faisalabad, Pakistan; [Baig, Mirza Muhammad Faran Ashraf] Nanjing Univ, Sch Chem & Chem Engn, Nanjing, Peoples R China; [Bin-Jumah, May] Princess Nourah Bint Abdulrahman Univ, Coll Sci, Biol Dept, Riyadh, Saudi Arabia; [Daim, Mohamed M. Abdel] King Saud Univ, Coll Sci, Dept Zool, Riyadh 11451, Saudi Arabia; [Daim, Mohamed M. Abdel] Suez Canal Univ, Fac Vet Med, Pharmacol Dept, Ismailia 41522, Egypt		Akhtar, MF (corresponding author), Riphah Int Univ, Riphah Inst Pharmaceut Sci, Lahore Campus, Lahore, Pakistan.	furqan.pharmacist@gmail.com	Saleem, Ammara/AAD-3227-2022; Bin-Jumah, May Nasser/I-1646-2018; Akhtar, Muhammad Furqan/O-8793-2019; Baig, Mirza Muhammad Faran Ashraf/N-8128-2014; Abdel-Daim, Mohamed M./B-2545-2013; Akhtar, Muhmmmad Furqan/T-8811-2017; Rasul, Azhar/AAF-5253-2021; Akhtar, Muhammad Furqan/ABI-7498-2020	Bin-Jumah, May Nasser/0000-0002-3017-9924; Akhtar, Muhammad Furqan/0000-0002-2407-1503; Baig, Mirza Muhammad Faran Ashraf/0000-0003-4791-9594; Abdel-Daim, Mohamed M./0000-0002-4341-2713; Akhtar, Muhmmmad Furqan/0000-0002-2407-1503; Rasul, Azhar/0000-0001-9669-7364; Akhtar, Muhammad Furqan/0000-0003-2270-6242	Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program	This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program.	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J. Pharmacol.	DEC 5	2020	888								173488	10.1016/j.ejphar.2020.173488			14	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	OV7QD	WOS:000592398600007	32805253				2022-04-25	
J	Wang, R; Liu, HW; Shao, YY; Wang, KL; Yin, SS; Qiu, YL; Wu, HH; Liu, EW; Wang, T; Gao, XM; Yu, HY				Wang, Rui; Liu, Hongwei; Shao, Yingying; Wang, Kailong; Yin, Shuangshuang; Qiu, Yuling; Wu, Honghua; Liu, Erwei; Wang, Tao; Gao, Xiumei; Yu, Haiyang			Sophoridine Inhibits Human Colorectal Cancer Progression via Targeting MAPKAPK2	MOLECULAR CANCER RESEARCH			English	Article							NATURAL-PRODUCTS; NETWORK PHARMACOLOGY; DRUG DISCOVERY; MATRINE; KINASE; OPPORTUNITIES; MECHANISMS	Radian Sophorae flavescentis is a traditional Chinese medicine commonly used to treat cancer in China. However, its active components and underlying mechanism remain ambiguous. In this study, we have screened the pharmacokinetic parameters of the main chemical constituents of Radian Sophorae flavescentis by Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform and have found that Sophoridine is one of the best antitumor active ingredients. We have found that MAPKAPK2 is a potential target for Sophoridine by the PharmMapper and KEGG datab-Xase analysis. Moreover, we have found that Sophoridine selectively inactivates phospho-MAPKAPK2 (Thr222) and directly binds into the ATP site of MAPKAPK2 by molecular docking. Furthermore, we have found out a direct binding between MAPKAPK2 and Sophoridine by cellular thermal shift assay and drug affinity responsive targets stability assay. The inhibition effects are further confirmed by Western blot: Sophoridine significantly decreases phospho-MAPKAPK2 (Thr222) in a time-dependent manner, but there is no obvious change in its total expression in colorectal cancer cells. Clinical studies have shown that a higher level of MAPKAPK2 is associated with a poorer percent survival rate (prognosis). Furthermore, a higher level of MAPKAPK2 is positively associated with the enrichment of downregulation of apoptosis and autophagy by gene set enrichment analysis, as well as upregulation of proliferation and cell-cycle arrest. Taken together, our results suggest that the MAPKAPK2 plays a key role in Sophoridine-inhibited growth and invasion in colorectal cancers.	[Wang, Rui; Liu, Hongwei; Shao, Yingying; Wang, Kailong; Yin, Shuangshuang; Wu, Honghua; Liu, Erwei; Wang, Tao; Gao, Xiumei; Yu, Haiyang] Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, Tianjin, Peoples R China; [Qiu, Yuling] Tianjin Med Univ, Sch Pharm, Tianjin, Peoples R China		Yu, HY (corresponding author), Tianjin Univ Tradit Chinese Med, 312 Anshan Rd, Tianjin 300193, Peoples R China.	hyyu@tjutcm.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81603253, 21711540293, 81873089, 81602614, 81973570]; Important Drug Development Fund, Ministry of Science and Technology of China [2018ZX09735-002]; Natural Science Foundation of Tianjin CityNatural Science Foundation of Tianjin [15PTCYSY00030]	This work was supported by grants from National Natural Science Foundation of China (81603253, 21711540293, and 81873089 to H. Yu, and 81602614 and 81973570 to Y. Qiu), Important Drug Development Fund, Ministry of Science and Technology of China (2018ZX09735-002 to T. Wang), and Natural Science Foundation of Tianjin City (No. 15PTCYSY00030 to Z. Li).	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Cancer Res.	DEC	2019	17	12					2469	2479		10.1158/1541-7786.MCR-19-0553			11	Oncology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology	JT4HH	WOS:000500951800011	31575657	Bronze			2022-04-25	
J	Novohradsky, V; Pracharova, J; Kasparkova, J; Imberti, C; Bridgewater, HE; Sadler, PJ; Brabec, V				Novohradsky, Vojtech; Pracharova, Jitka; Kasparkova, Jana; Imberti, Cinzia; Bridgewater, Hannah E.; Sadler, Peter J.; Brabec, Viktor			Induction of immunogenic cell death in cancer cells by a photoactivated platinum(iv) prodrug	INORGANIC CHEMISTRY FRONTIERS			English	Article							IMMUNE-SYSTEM; EXPOSURE; CHEMOTHERAPY; GENERATION; AUTOPHAGY; RESPONSES; THERAPY; AGENTS; DRUGS; DNA	The platinum(iv) prodrug trans,trans,trans-[Pt(N-3)(2)(OH)(2)(py)(2)] (1) is stable and non-toxic in the dark, but potently cytotoxic to cancer cells when irradiated by visible light, including cisplatin-resistant cells. On irradiation with visible light, it generates reactive Pt(ii) species which can attack DNA, and produces reactive oxygen species (ROS) and reactive nitrogen species (RNS) which exert unusual effects on biochemical pathways. We now show that its novel mechanism of action includes induction of immunogenic cell death (ICD). Treatment of cancer cells with 1 followed by photoirradiation with visible light induces calreticulin (CRT) expression at the surface of dying cancer cells. This is accompanied by release of high mobility group protein-1B (HMGB1) and the secretion of ATP. Autophagy appears to play a key role in this chemotherapeutically-stimulated ICD. The observed uneven distribution of ecto-CRT promotes phagocytosis, confirmed by the observation of engulfment of photoirradiated CT26 colorectal cancer cells treated with 1 by J774.A1 macrophages. The photoactivatable prodrug 1 has a unique mechanism of action which distinguishes it from other platinum drugs due to its immunomodulating properties, which may enhance its anticancer efficacy.	[Novohradsky, Vojtech; Pracharova, Jitka; Kasparkova, Jana; Brabec, Viktor] Czech Acad Sci, Inst Biophys, Kralovopolska 135, CZ-61265 Brno, Czech Republic; [Pracharova, Jitka] Palacky Univ, Ctr Reg Hana Biotechnol & Agr Res, Dept Biophys, Slechtitelu 27, Olomouc 78371, Czech Republic; [Imberti, Cinzia; Bridgewater, Hannah E.; Sadler, Peter J.] Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England		Brabec, V (corresponding author), Czech Acad Sci, Inst Biophys, Kralovopolska 135, CZ-61265 Brno, Czech Republic.	brabec@ibp.cz	Imberti, Cinzia/N-2717-2018; Brabec, Viktor/H-1946-2014	Imberti, Cinzia/0000-0003-1187-7951; Brabec, Viktor/0000-0002-8233-1393; Bridgewater, Hannah/0000-0003-1769-9025	Czech Science FoundationGrant Agency of the Czech Republic [18-09502S]; Wellcome TrustWellcome TrustEuropean Commission [209173/Z/17/Z]; EPSRCUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [EP/F034210/1, EP/P030572/1]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [G0701062] Funding Source: UKRI	This work was supported by the Czech Science Foundation (Grant 18-09502S), the Wellcome Trust (Grant 209173/Z/17/Z, Fellowship for C. I.), EPSRC (Grants EP/F034210/1 and EP/P030572/1) and Anglo American Platinum Mike and Enfys Bagguley (PhD Studentship for H. E. B).	Apetoh L, 2008, CANCER RES, V68, P4026, DOI 10.1158/0008-5472.CAN-08-0427; Apetoh L, 2007, NAT MED, V13, P1050, DOI 10.1038/nm1622; Bednarski PJ, 2007, ANTI-CANCER AGENT ME, V7, P75, DOI 10.2174/187152007779314053; Brabec V, 2017, COORDIN CHEM REV, V351, P2, DOI 10.1016/j.ccr.2017.04.013; Du J, 2018, INORG CHEM, V57, P5575, DOI 10.1021/acs.inorgchem.8b00529; Dudek AM, 2013, CYTOKINE GROWTH F R, V24, P319, DOI 10.1016/j.cytogfr.2013.01.005; Englinger B, 2019, CHEM REV, V119, P1519, DOI 10.1021/acs.chemrev.8b00396; Farrer N. 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Chem. Front.	NOV 7	2020	7	21					4150	4159		10.1039/d0qi00991a			10	Chemistry, Inorganic & Nuclear	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	OM1XY	WOS:000585823500011	34540235	Green Accepted			2022-04-25	
J	Lim, EG; Kim, GT; Kim, BM; Kim, EJ; Kim, SY; Kim, YM				Lim, Eun Gyeong; Kim, Guen Tae; Kim, Bo Min; Kim, Eun Ji; Kim, Sang-Yong; Kim, Young Min			Ethanol extract from Cnidium monnieri (L.) Cusson induces cell cycle arrest and apoptosis via regulation of the p53-independent pathway in HepG2 and Hep3B hepatocellular carcinoma cells	MOLECULAR MEDICINE REPORTS			English	Article						apoptosis; Akt/GSK-3 beta signaling pathway; cell cycle arrest; CME; hepatocellular carcinoma cells; p53-independent pathway	COLORECTAL-CANCER CELLS; SIGNALING PATHWAY; A549 CELLS; IN-VITRO; P21; P53; MITOCHONDRIAL; EXPRESSION; COUMARINS; AUTOPHAGY	Cnidium monnieri (L.) Cusson is a frequently used traditional Chinese medicine that treats gynecological diseases and carbuncles. However, the mechanism of action of C. monnieri remains to be fully elucidated. The present study examined the cell cycle arrest and apoptotic effects resulting from ethanol extract of C. monnieri (CME) in HepG2 (wild-type p53) and Hep3B (p53-null) hepatocellular carcinoma cells. An MTT assay was used to confirm the anti-proliferative effect of CME. The cells were stained with Hoechst 33342 or propidium iodide. It was demonstrated that proliferation of HepG2 cells was suppressed by CME. Cell cycle arrest occurred in the G1 phase following treatment with CME and the number of apoptotic bodies was increased. The expression levels of cell cycle-associated proteins, including protein kinase B (Akt), glycogen synthase kinase-3 beta (GSK-3 beta), p53, cyclin E and cyclin-dependent kinase 2 (CDK2) were determined by western blot analysis. The protein levels of phosphorylated (p)-Akt, p-GSK-3 beta, p-MDM2 and cyclin E were decreased, whereas the protein levels of p53, p21 and p-CDK2 (Thr14/Tyr15) were increased following treatment with CME. Furthermore, treatment or co-treatment with LY294002 (phosphoinositide-3-kinase/Akt inhibitor) or Pifithrin-alpha (p53 inhibitor) with CME resulted in CME-induced G1 arrest which occurred through the p53-independent signaling pathway in hepatocellular carcinoma cells. In conclusion, CME induces G1 arrest and apoptosis via the Akt/GSK-3 beta signaling pathway which is regulated by MDM2-induced degradation of p21, rather than p53.	[Lim, Eun Gyeong; Kim, Guen Tae; Kim, Bo Min; Kim, Eun Ji; Kim, Young Min] Hannam Univ, Coll Life Sci & Nanotechnol, Dept Biol Sci & Biotechnol, Yuseong Dero 1646, Daejeon 34054, South Korea; [Kim, Sang-Yong] Shinansan Univ, Dept Food Sci & Biotechnol, Ansan 425792, Gyeonggi Do, South Korea		Kim, YM (corresponding author), Hannam Univ, Coll Life Sci & Nanotechnol, Dept Biol Sci & Biotechnol, Yuseong Dero 1646, Daejeon 34054, South Korea.	kym@hnu.kr					Abbas T, 2009, NAT REV CANCER, V9, P400, DOI 10.1038/nrc2657; Byambaragchaa M, 2013, ASIAN PAC J CANCER P, V14, P5397, DOI 10.7314/APJCP.2013.14.9.5397; Chien SY, 2009, HUM EXP TOXICOL, V28, P493, DOI 10.1177/0960327109107002; Choi EJ, 2013, CHINESE J CANCER RES, V25, P536, DOI 10.3978/j.issn.1000-9604.2013.10.02; Esposti MD, 2003, BIOCHEM BIOPH RES CO, V304, P455, DOI 10.1016/S0006-291X(03)00617-X; Gartel AL, 2002, MOL CANCER THER, V1, P639; Grizzi F, 2007, J TRANSL MED, V5, DOI 10.1186/1479-5876-5-3; Hsu SC, 2007, ANTICANCER RES, V27, P2415; Jiang GQ, 2016, J ETHNOPHARMACOL, V193, P368, DOI 10.1016/j.jep.2016.08.045; Karimian A, 2016, DNA REPAIR, V42, P63, DOI 10.1016/j.dnarep.2016.04.008; Kim Eun Ji, 2015, Korean Society for Biotechnology and Bioengineering Journal, V30, P175; Kulikov R, 2005, MOL CELL BIOL, V25, P7170, DOI 10.1128/MCB.25.16.7170-7180.2005; Li HB, 2005, J SEP SCI, V28, P268, DOI 10.1002/jssc.200400002; Meng J, 2012, ONCOL REP, V28, P384, DOI 10.3892/or.2012.1793; Nicholson KM, 2002, CELL SIGNAL, V14, P381, DOI 10.1016/S0898-6568(01)00271-6; Park C, 2016, ASIAN PAC J TROP MED, V9, P336, DOI 10.1016/j.apjtm.2016.03.003; Prakash O., 2013, J PHARMACOL SCI, V1, P104, DOI [10.12691/ajps-1-6-1, DOI 10.12691/AJPS-1-6-1]; Romorini L, 2016, SCI REP-UK, V6, DOI 10.1038/srep35660; Rossig L, 2002, J BIOL CHEM, V277, P9684, DOI 10.1074/jbc.M106157200; Shen GX, 2006, CANCER CHEMOTH PHARM, V57, P317, DOI 10.1007/s00280-005-0050-3; Sun Y, 2016, ONCOTARGETS THER, V9, P2845, DOI 10.2147/OTT.S99770; Sutherland C., 2011, INT J ALZHEIMERS DIS, V2011; Tai Y, 2016, EXP THER MED, V12, P2681, DOI 10.3892/etm.2016.3630; Tan J, 2005, CANCER RES, V65, P9012, DOI 10.1158/0008-5472.CAN-05-1226; Thotala DK, 2012, CELL DEATH DIFFER, V19, P387, DOI 10.1038/cdd.2011.94; Wang R, 2016, SCI REP-UK, V6, DOI 10.1038/srep27071; Wang Y, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2767-2; Watcharasit P, 2003, J BIOL CHEM, V278, P48872, DOI 10.1074/jbc.M305870200; Yang LL, 2003, PLANTA MED, V69, P1091, DOI 10.1055/s-2003-45188; 이세희, 2012, [Journal of Cancer Prevention, 대한암예방학회지], V17, P244; Yuan L, 2015, MOL MED REP, V11, P2459, DOI 10.3892/mmr.2014.3100; Zhang RW, 2014, J BIOL CHEM, V289, P6394, DOI 10.1074/jbc.M113.513960; Zhang Z, 2004, J BIOL CHEM, V279, P16000, DOI 10.1074/jbc.M312264200; Zhao T, 2016, EXP THER MED, V12, P3301, DOI 10.3892/etm.2016.3765; Zhu YP, 1998, CHINESE MAT MED CHEM, P624	35	7	7	1	8	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1791-2997	1791-3004		MOL MED REP	Mol. Med. Rep.	FEB	2018	17	2					2572	2580		10.3892/mmr.2017.8183			9	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	FT5WP	WOS:000423224300061	29207130	Bronze			2022-04-25	
J	Jin, SG; Li, XP; Dai, Y; Li, C; Wang, DX				Jin, Shiguang; Li, Xueping; Dai, Yan; Li, Cheng; Wang, Daxin			NF-kappa B-mediated miR-650 plays oncogenic roles and activates AKT/ERK/NF-kappa B pathways by targeting RERG in glioma cells	CELLULAR ONCOLOGY			English	Article						Glioma; miR-650; RERG; PHLPP2; NF-kappa B; AKT; ERK	COLORECTAL-CANCER; LUNG-CANCER; PROLIFERATION; PROMOTES; GLIOBLASTOMA; EXPRESSION; PROTEIN; PROGRESSION; MICRORNAS; INVASION	Purpose Glioma is the most common cancer in the central nervous system and has a high mortality rate. Despite advances that have been made in the treatment of glioma, its prognosis still remains poor. Dysregulation of miRNAs has been reported in many cancers, including glioma. Here, we set out to assess the role of miR-650 in glioma, including its diagnostic and therapeutic potential. Methods miR-650 and RAS-like estrogen-regulated growth inhibitor (RERG) expression levels were analyzed using qRT-PCR in primary glioma tissues and cell lines. Cell Counting Kit-8, 5-ethynyl-2 '-deoxyuridine, colony formation, Western blotting, scratch wound healing, Transwell, adhesion, autophagy, immunofluorescence, luciferase reporter, electrophoretic mobility shift, tumor xenograft and flow cytometry assays were employed to investigate the mechanisms underlying the effect of miR-650 and RERG on glioma development. Results miR-650 was found to be up-regulated in glioma tissues and cell lines compared to non-cancerous brain tissues and neural progenitor cells, respectively. We also found that miR-650 promoted cell proliferation, migration and invasion in glioma cells, and enhanced glioma tumor formation and growth in vivo. We identified and validated RERG as a direct target of miR-650. RERG was shown to act as a tumor suppressor in glioma cells, and its suppressor roles were rescued by miR-650. We found that nuclear factor (NF)-kappa B bound to the promoter of miR-650 and enhanced its expression. PH domain and leucine rich repeat protein phosphatase 2 (PHLPP2), as a co-factor of the RERG/PHLPP2 complex, mediated miR-650-induced activation of the protein kinase B/extracellular-signal-regulated kinase/NF-kappa B signaling pathways. Conclusions Our data revealed novel functional roles for miR-650 in glioma development and may provide new avenues for future clinical applications.	[Jin, Shiguang; Dai, Yan; Li, Cheng; Wang, Daxin] Yangzhou Univ, Clin Med Coll, Yangzhou 225001, Jiangsu, Peoples R China; [Jin, Shiguang] Cent South Univ, Xiangya Hosp 2, Changsha 410008, Hunan, Peoples R China; [Li, Xueping] Nanjing Med Univ, Hosp Nanjing 1, Nanjing Hosp, Nanjing 210029, Jiangsu, Peoples R China		Wang, DX (corresponding author), Yangzhou Univ, Clin Med Coll, Yangzhou 225001, Jiangsu, Peoples R China.	Daxinw2002@sina.com			Yangzhou Natural Science Foundation [YZ2016125]; Jiangsu Provincial "333 Engineering" Project [BRA2015171]; Self-help Research Project of Postdoctor in Jiangsu	This work was supported partially by the Yangzhou Natural Science Foundation (YZ2016125), Jiangsu Provincial "333 Engineering" Project (BRA2015171) and The Self-help Research Project of Postdoctor in Jiangsu.	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Oncol.	DEC	2020	43	6					1035	1048		10.1007/s13402-020-00533-5		SEP 2020	14	Oncology; Cell Biology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology; Pathology	PA6VA	WOS:000573418300001	32986146				2022-04-25	
J	Khan, GJ; Rizwan, M; Abbas, M; Naveed, M; Yu, BY; Naeem, MA; Khan, S; Yuan, ST; Baig, MMFA; Sun, L				Khan, Ghulam Jilany; Rizwan, Mohsin; Abbas, Muhammad; Naveed, Muhammad; Yu Boyang; Naeem, Muhammad Ahsan; Khan, Sara; Yuan, Shengtao; Baig, Mirza Muhammad Faran Ashraf; Sun, Li			Pharmacological effects and potential therapeutic targets of DT-13	BIOMEDICINE & PHARMACOTHERAPY			English	Review						DT-13; Anti-cancer; Anti-metastasis; Cardio protective; Pharmacological effects	DWARF LILYTURF TUBER; RADIX-OPHIOPOGON-JAPONICUS; CANCER-CELL-MIGRATION; LIRIOPE-MUSCARI; SAPONIN MONOMER; AQUEOUS EXTRACT; STEROIDAL SAPONINS; CALCIUM CURRENTS; LUNG-CANCER; HYPOXIA	DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies. In vivo and in vitro studies show that the drug regulates multiple cellular functions for its several pharmacological effects including, anti-adhesive effects via regulation of tissue factor and transforming growth factor; anti-migratory effects through indirect regulation of NM-IIA in the tumor microenvironment, Tissue factor, down-regulation of CCR5-CCL5 axis and MMP-2/9 inhibition; anti-metastatic effects via regulation of MMPs and tissue factor; proapoptotic effects by modulation of endocytosis of EGF receptor; anti-angiogenic effects via regulation of HIF1a, ERK, Akt signalling and autophagy inducing characteristics by regulating PI3K/Akt/mTOR signalling pathway. In addition to anti-tumor activities, DT-13 has significant anti-inflammatory, cardioprotective, hepatoprotective and immunomodulating effects. Pharmaceutical dosage form and targeted drug delivery system for DT-13 has not been established yet. Moreover, DT-13, has not been studied for its action on brain, colorectal, hepatic, pancreatic, prostate and blood cancers. Similarly the effects of drug on carbohydrate and glucose metabolism is another niche yet to be explored. In some traditional therapies, crude drug from the plant is used against diabetic and neurological disorders that are not reported in scientific literature, however due to profound	[Khan, Ghulam Jilany; Sun, Li] China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing 210009, Jiangsu, Peoples R China; [Khan, Ghulam Jilany] Univ Cent Punjab, Fac Pharm, Dept Pharmacol, Lahore, Pakistan; [Khan, Ghulam Jilany; Yuan, Shengtao] China Pharmaceut Univ, Jiangsu Ctr Pharmacodynam Res & Evaluat, Nanjing 210009, Jiangsu, Peoples R China; [Rizwan, Mohsin; Naeem, Muhammad Ahsan] Univ Engn & Technol, Dept Mechatron & Control Engn, Lahore, Pakistan; [Abbas, Muhammad; Naveed, Muhammad] China Pharmaceut Univ, Dept Clin Pharm, Sch Basic Med & Clin Pharm, Sch Pharm, Nanjing 211198, Jiangsu, Peoples R China; [Abbas, Muhammad] Affiliated Nanjing Med Univ, Dept Med Oncol, Jiangsu Canc Hosp, Nanjing 211198, Jiangsu, Peoples R China; [Abbas, Muhammad] Jiangsu Inst Canc & Res, Nanjing 211198, Jiangsu, Peoples R China; [Yu Boyang] China Pharmaceut Univ, Dept Complex Prescript Tradit Chinese Med, Sch Chinese Mat Med, Nanjing 210009, Jiangsu, Peoples R China; [Khan, Sara] Univ Punjab, Univ Coll Pharm, Dept Pharmaceut Chem, Lahore, Pakistan; [Baig, Mirza Muhammad Faran Ashraf] Nanjing Univ, State Key Lab Coordinat Chem, Sch Chem & Chem Engn, Nanjing 210023, Jiangsu, Peoples R China		Sun, L (corresponding author), China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing 210009, Jiangsu, Peoples R China.; Yuan, ST (corresponding author), China Pharmaceut Univ, Jiangsu Ctr Pharmacodynam Res & Evaluat, Nanjing 210009, Jiangsu, Peoples R China.	U4574904@hotmail.com; U4574904@aol.com; tanoliabbass7@yahoo.com; navedO4@yahoo.com; boyangyu59@163.com; mahsan.naeem@gmail.com; Pharmacist_pu@hotmail.com; 13914798635@163.com; u4574904@gmail.com; Sunli@cpu.edu.cn	Khan, Ghulam Jilany/C-2135-2017; Baig, Mirza Muhammad Faran Ashraf/N-8128-2014; Abbas, Muhammad/AAY-1430-2020; Naveed, Muhammad/Y-3856-2018	Khan, Ghulam Jilany/0000-0002-2748-5314; Baig, Mirza Muhammad Faran Ashraf/0000-0003-4791-9594; Abbas, Muhammad/0000-0002-4453-0981; Naveed, Muhammad/0000-0002-2193-9266	National natural science foundation of chinaNational Natural Science Foundation of China (NSFC) [81573456, 81773766]	The work is supported by National natural science foundation of china (Grant No.< gn1 > 81573456 < /gn1 > and Grant no.< gn1 > 81773766 < /gn1 >)	Abbas M, 2017, BIOMED PHARMACOTHER, V95, P1082, DOI 10.1016/j.biopha.2017.09.032; [Anonymous], 2015, DT 13 PUBCHE7 COMP D; Beach JR, 2011, P NATL ACAD SCI USA, V108, P17991, DOI 10.1073/pnas.1106499108; Boyang Y., 1995, CHIN TRADIT HERB DRU, V4; Chen Chao-yang, 2013, COMPLEMENTARY ALTERN, V2013, P14; Chen LL, 2011, J PHARMACEUT BIOMED, V56, P650, DOI 10.1016/j.jpba.2011.07.003; CHEN M, 1990, ACTA PHARM SINIC, V11, P161; Conti MA, 2008, J CELL SCI, V121, P11, DOI 10.1242/jcs.007112; Coukell AJ, 1999, PHARMACOECONOMICS, V15, P405, DOI 10.2165/00019053-199915040-00008; Du HZ, 2016, ONCOL REP, V36, P721, DOI 10.3892/or.2016.4890; Duan CL, 2010, HELV CHIM ACTA, V93, P227, DOI 10.1002/hlca.200900165; FANG XC, 1990, J CHROMATOGR, V514, P287, DOI 10.1016/S0021-9673(01)89400-0; Feng Y., 2014, APPL DWARF LILYTURF; Guan T, 2013, EUR J PHARMACOL, V714, P303, DOI 10.1016/j.ejphar.2013.07.036; Herben VMM, 1996, CLIN PHARMACOKINET, V31, P85, DOI 10.2165/00003088-199631020-00001; Huang YL, 2008, J PHARMACOL SCI, V108, P198, DOI 10.1254/jphs.08083FP; Ishibashi H, 2001, BRIT J PHARMACOL, V132, P461, DOI 10.1038/sj.bjp.0703818; Jiang L, 2012, WORLD J GASTROENTERO, V18, P2035, DOI 10.3748/wjg.v18.i17.2035; Jilany K. 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JAN	2018	97						255	263		10.1016/j.biopha.2017.10.101			9	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	FR4NC	WOS:000419041300034	29107216				2022-04-25	
J	Polato, F; Rusconi, P; Zangrossi, S; Morelli, F; Boeri, M; Musi, A; Marchini, S; Castiglioni, V; Scanziani, E; Torri, V; Broggini, M				Polato, Federica; Rusconi, Paolo; Zangrossi, Stefano; Morelli, Federica; Boeri, Mattia; Musi, Alberto; Marchini, Sergio; Castiglioni, Vittoria; Scanziani, Eugenio; Torri, Valter; Broggini, Massimo			DRAGO (KIAA0247), a New DNA Damage-Responsive, p53-Inducible Gene That Cooperates With p53 as Oncosupprossor	JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE			English	Article							COLORECTAL-CANCER; ACTIVATION; BINDING; PROTEIN; ACETYLATION; METHYLATION; SUPPRESSION; MEDIATOR; INNATE; FAMILY	Background p53 influences genomic stability, apoptosis, autophagy, response to stress, and DNA damage. New p53-target genes could elucidate mechanisms through which p53 controls cell integrity and response to damage. Methods DRAGO (drug-activated gene overexpressed, KIAA0247) was characterized by bioinformatics methods as well as by real-time polymerase chain reaction, chromatin immunoprecipitation and luciferase assays, time-lapse microscopy, and cell viability assays. Transgenic mice (94 p53(-/-) and 107 p53(+/-) mice on a C57BL/6J background) were used to assess DRAGO activity in vivo. Survival analyses were performed using Kaplan-Meier curves and the Mantel-Haenszel test. All statistical tests were two-sided. Results We identified DRAGO as a new p53-responsive gene induced upon treatment with DNA-damaging agents. DRAGO is highly conserved, and its ectopic overexpression resulted in growth suppression and cell death. DRAGO(-/-) mice are viable without macroscopic alterations. However, in p53(-/-) or p53(+/-) mice, the deletion of both DRAGO alleles statistically significantly accelerated tumor development and shortened lifespan compared with p53(-/-) or p53(+/-) mice bearing wild-type DRAGO alleles (p53(-/-), DRAGO(-/-) mice: hazard ratio [HR] = 3.25, 95% confidence interval [CI] = 1.7 to 6.1, P < .001; p53(+/-), DRAGO(-/-) mice: HR = 2.35, 95% CI = 1.3 to 4.0, P < .001; both groups compared with DRAGO(+/+) counterparts). DRAGO mRNA levels were statistically significantly reduced in advanced-stage, compared with early-stage, ovarian tumors, but no mutations were found in several human tumors. We show that DRAGO expression is regulated both at transcriptional-through p53 (and p73) and methylation-dependent control-and post-transcriptional levels by miRNAs. Conclusions DRAGO represents a new p53-dependent gene highly regulated in human cells and whose expression cooperates with p53 in tumor suppressor functions.	[Polato, Federica; Rusconi, Paolo; Zangrossi, Stefano; Morelli, Federica; Boeri, Mattia; Musi, Alberto; Marchini, Sergio; Broggini, Massimo] IRCCS Ist Ric Farmacol Mario Negri, Mol Pharmacol Lab, Dept Oncol, I-20156 Milan, Italy; [Torri, Valter] IRCCS Ist Ric Farmacol Mario Negri, Lab Methodol Biomed Res, Dept Oncol, I-20156 Milan, Italy; [Castiglioni, Vittoria; Scanziani, Eugenio] Univ Milan, Dipartimento Patol Anim Igiene & Sanita Pubbl Vet, Milan, Italy; [Castiglioni, Vittoria; Scanziani, Eugenio] Fdn Filarete, Mouse & Anim Pathol Lab, Milan, Italy		Broggini, M (corresponding author), IRCCS Ist Ric Farmacol Mario Negri, Via G La Masa 19, I-20156 Milan, Italy.	massimo.broggini@marionegri.it	Torri, Valter/H-7550-2015; Boeri, Mattia/L-4393-2013; Marchini, sergio/J-3968-2018; broggini, massimo/AAA-6460-2020; Polato, Federica/Q-1803-2018; Scanziani, Eugenio/G-8046-2017	Torri, Valter/0000-0001-9541-9354; Boeri, Mattia/0000-0001-7106-3138; Marchini, sergio/0000-0003-1783-7651; Scanziani, Eugenio/0000-0003-3996-5048; BROGGINI, MASSIMO/0000-0002-8138-9358			Appella E, 2001, EUR J BIOCHEM, V268, P2764, DOI 10.1046/j.1432-1327.2001.02225.x; Aylon Y, 2011, CURR OPIN GENET DEV, V21, P86, DOI 10.1016/j.gde.2010.10.002; Burbee DG, 2001, JNCI-J NATL CANCER I, V93, P691, DOI 10.1093/jnci/93.9.691; Chuikov S, 2004, NATURE, V432, P353, DOI 10.1038/nature03117; DENG CX, 1995, CELL, V82, P675, DOI 10.1016/0092-8674(95)90039-X; ELDEIRY WS, 1993, CELL, V75, P817, DOI 10.1016/0092-8674(93)90500-P; Flores ER, 2005, CANCER CELL, V7, P363, DOI 10.1016/j.ccr.2005.02.019; Gostissa M, 1999, EMBO J, V18, P6462, DOI 10.1093/emboj/18.22.6462; Gu W, 1997, CELL, V90, P595, DOI 10.1016/S0092-8674(00)80521-8; HARPER JW, 1993, CELL, V75, P805; Heintz APM, 2006, INT J GYNECOL OBSTET, V95, pS161, DOI 10.1016/S0020-7292(06)60033-7; Huang CJ, 2011, J TRANSL MED, V9, DOI 10.1186/1479-5876-9-82; Kodach LL, 2010, CARCINOGENESIS, V31, P1567, DOI 10.1093/carcin/bgq147; Lane D, 2010, CSH PERSPECT BIOL, V2, DOI 10.1101/cshperspect.a000893; Lang GA, 2004, CELL, V119, P861, DOI 10.1016/j.cell.2004.11.006; Li H, 2011, CELL CYCLE, V10, P3346, DOI 10.4161/cc.10.19.17630; Lu X, 2005, CURR OPIN GENET DEV, V15, P27, DOI 10.1016/j.gde.2004.12.008; Luo JY, 2004, P NATL ACAD SCI USA, V101, P2259, DOI 10.1073/pnas.0308762101; Marchini S, 2001, EXPERT OPIN INV DRUG, V10, P1703, DOI 10.1517/13543784.10.9.1703; Menendez D, 2009, NAT REV CANCER, V9, P724, DOI 10.1038/nrc2730; Munoz-Fontela C, 2011, J IMMUNOL, V187, P6428, DOI 10.4049/jimmunol.1101459; Nagase T, 1996, DNA Res, V3, P321, DOI 10.1093/dnares/3.5.321; Nakano K, 2001, MOL CELL, V7, P683, DOI 10.1016/S1097-2765(01)00214-3; Oda E, 2000, SCIENCE, V288, P1053, DOI 10.1126/science.288.5468.1053; Rigatti MJ, 2012, MOL CARCINOGEN, V51, P363, DOI 10.1002/mc.20795; SAH VP, 1995, NAT GENET, V10, P175, DOI 10.1038/ng0695-175; Schwanzer-Pfeiffer D, 2010, CELL IMMUNOL, V263, P65, DOI 10.1016/j.cellimm.2010.02.017; Shieh SY, 1997, CELL, V91, P325, DOI 10.1016/S0092-8674(00)80416-X; SHIOHARA M, 1994, BLOOD, V84, P3781, DOI 10.1182/blood.V84.11.3781.bloodjournal84113781; Staib F, 2005, CANCER RES, V65, P10255, DOI 10.1158/0008-5472.CAN-05-1714; Vousden KH, 2009, NAT REV CANCER, V9, P691, DOI 10.1038/nrc2715; Vousden KH, 2009, CELL, V137, P413, DOI 10.1016/j.cell.2009.04.037; Vousden KH, 2002, NAT REV CANCER, V2, P594, DOI 10.1038/nrc864; Wang YM, 2007, CLIN CANCER RES, V13, P4111, DOI 10.1158/1078-0432.CCR-07-0408; Wu GS, 1997, NAT GENET, V17, P141, DOI 10.1038/ng1097-141	35	11	14	0	2	OXFORD UNIV PRESS INC	CARY	JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA	0027-8874	1460-2105		JNCI-J NATL CANCER I	JNCI-J. Natl. Cancer Inst.	APR	2014	106	4							dju053	10.1093/jnci/dju053			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	AF4OA	WOS:000334691500028	24652652	Green Published, Bronze			2022-04-25	
J	Abraham, D; Jackson, N; Gundara, JS; Zhao, JT; Gill, AJ; Delbridge, L; Robinson, BG; Sidhu, SB				Abraham, Deepak; Jackson, Nicole; Gundara, Justin S.; Zhao, JingTing; Gill, Anthony J.; Delbridge, Leigh; Robinson, Bruce G.; Sidhu, Stan B.			MicroRNA Profiling of Sporadic and Hereditary Medullary Thyroid Cancer Identifies Predictors of Nodal Metastasis, Prognosis, and Potential Therapeutic Targets	CLINICAL CANCER RESEARCH			English	Article							RET PROTOONCOGENE; COLORECTAL-CANCER; SOMATIC MUTATIONS; CARCINOMA; EXPRESSION; DISSECTION; ONCOGENE; CELLS	Purpose: While the molecular basis of hereditary medullary thyroid cancer (HMTC) has been well defined, little is known about the molecular pathogenesis of sporadic medullary thyroid cancer (SMTC). In addition, microRNAs (miRNAs) have been shown to be important diagnostic and prognostic markers in cancer but have not been defined in MTC. Our aim was to study the miRNA profile of MTC to identify prognostic biomarkers and potential therapeutic targets. Experimental Design: MiRNA microarray profiling was carried out in fresh frozen tissues from patients with SMTC (n = 12) and HMTC (n = 7). Differential expression of three miRNAs was confirmed in a validation cohort of SMTC and HMTC samples (n = 45) using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. The functional role of a selected miRNA was investigated in vitro in the human medullary thyroid carcinoma cell line (TT cells) using cell proliferation assays and Western blotting analysis. Results: MiRs-183 and 375 were overexpressed (P = 0.001; 0.031) and miR-9* was under-expressed (P = 0.011) in SMTC versus HMTC. Overexpression of miRs-183 and 375 in MTC predicted lateral lymph node metastases (P < 0.001; P = 0.001) and was associated with residual disease (P = 0.001; 0.003), distant metastases (P = 0.003; 0.001), and mortality (P = 0.01; 0.011). Knock down of miR-183 expression in the TT cell line induced a significant decrease in the viable cell count and upregulation of the protein LC3B, which is associated with autophagy. Conclusions: Our data indicate that miRNAs play a pivotal role in the biology of MTC and represent an important class of prognostic biomarkers and therapeutic targets warranting further investigation. Clin Cancer Res; 17(14); 4772-81. (C)2011 AACR.	[Abraham, Deepak; Jackson, Nicole; Gundara, Justin S.; Zhao, JingTing; Robinson, Bruce G.; Sidhu, Stan B.] Univ Sydney, Kolling Inst Med Res, Royal N Shore Hosp, Sydney, NSW 2006, Australia; [Abraham, Deepak; Gundara, Justin S.; Delbridge, Leigh; Sidhu, Stan B.] Univ Sydney, Royal N Shore Hosp, Dept Endocrine Surg Unit, Sydney, NSW 2006, Australia		Sidhu, SB (corresponding author), Level 2,69 Christie St, St Leonards, NSW 2065, Australia.	stansidhu@nebsc.com.au	Sidhu, Stan/K-1555-2015; Gill, Anthony J/D-4215-2015; Gill, Anthony J./M-5015-2019	Gill, Anthony J/0000-0002-9447-1967; Delbridge, leigh/0000-0001-8281-8831	NSW Cancer Institute; Endeavour International Postgraduate Research ScholarshipAustralian Government	This work was supported by a NSW Cancer Institute Research Innovation Grant. D. Abraham is an Endeavour International Postgraduate Research Scholarship recipient. S. Sidhu is a NSW Cancer Institute Fellow.	ABRAHAM DT, 2010, ANN SURG ONCOL; Bandres E, 2009, INT J CANCER, V125, P2737, DOI 10.1002/ijc.24638; Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; Bastian BC, 1998, CANCER RES, V58, P2170; Calin GA, 2004, P NATL ACAD SCI USA, V101, P11755, DOI 10.1073/pnas.0404432101; Chen YT, 2008, MODERN PATHOL, V21, P1139, DOI 10.1038/modpathol.2008.105; Clayman GL, 2003, OTOLARYNG CLIN N AM, V36, P91, DOI 10.1016/S0030-6665(02)00136-6; desSouza Rocha Simonini P, 2010, CANC RE, V70, P9175; Dvorakova S, 2008, MOL CELL ENDOCRINOL, V284, P21, DOI 10.1016/j.mce.2007.12.016; Elisei R, 2008, J CLIN ENDOCR METAB, V93, P682, DOI 10.1210/jc.2007-1714; Gimm O, 1997, J CLIN ENDOCR METAB, V82, P3902, DOI 10.1210/jc.82.11.3902; HAZARD JB, 1959, J CLIN ENDOCR METAB, V19, P152, DOI 10.1210/jcem-19-1-152; Hundahl SA, 1998, CANCER-AM CANCER SOC, V83, P2638, DOI 10.1002/(SICI)1097-0142(19981215)83:12<2638::AID-CNCR31>3.0.CO;2-1; Jiang JM, 2005, NUCLEIC ACIDS RES, V33, P5394, DOI 10.1093/nar/gki863; Kebebew E, 2000, CANCER-AM CANCER SOC, V88, P1139, DOI 10.1002/(SICI)1097-0142(20000301)88:5<1139::AID-CNCR26>3.0.CO;2-Z; Kloos RT, 2009, THYROID, V19, P565, DOI 10.1089/thy.2008.0403; Leboulleux S, 2004, CLIN ENDOCRINOL, V61, P299, DOI 10.1111/j.1365-2265.2004.02037.x; Li JP, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-354; Lin WM, 2008, CANCER RES, V68, P664, DOI 10.1158/0008-5472.CAN-07-2615; Lu J, 2005, NATURE, V435, P834, DOI 10.1038/nature03702; Machens A, 2008, BRIT J SURG, V95, P586, DOI 10.1002/bjs.6075; Machens A, 2010, J CLIN ENDOCR METAB, V95, P2655, DOI 10.1210/jc.2009-2368; Marsh DJ, 1996, CLIN ENDOCRINOL, V44, P249, DOI 10.1046/j.1365-2265.1996.681503.x; Meyer-Rochow GY, 2010, ENDOCR-RELAT CANCER, V17, P835, DOI 10.1677/ERC-10-0142; Motoyama K, 2009, INT J ONCOL, V34, P1069, DOI 10.3892/ijo_00000233; Pelizzo MR, 2007, EJSO-EUR J SURG ONC, V33, P493, DOI 10.1016/j.ejso.2006.10.021; Sarver AL, 2010, CANCER RES, V70, P9570, DOI 10.1158/0008-5472.CAN-10-2074; Scollo C, 2003, J CLIN ENDOCR METAB, V88, P2070, DOI 10.1210/jc.2002-021713; Soon PSH, 2009, CLIN CANCER RES, V15, P7684, DOI 10.1158/1078-0432.CCR-09-1587; Uchino S, 1998, JPN J CANCER RES, V89, P411, DOI 10.1111/j.1349-7006.1998.tb00579.x; Volinia S, 2006, P NATL ACAD SCI USA, V103, P2257, DOI 10.1073/pnas.0510565103; Wang GF, 2008, FEBS LETT, V582, P3663, DOI 10.1016/j.febslet.2008.09.051; Weber T, 2001, SURGERY, V130, P1044, DOI 10.1067/msy.2001.118380a	33	109	119	0	15	AMER ASSOC CANCER RESEARCH	PHILADELPHIA	615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA	1078-0432	1557-3265		CLIN CANCER RES	Clin. Cancer Res.	JUL 15	2011	17	14					4772	4781		10.1158/1078-0432.CCR-11-0242			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	793JI	WOS:000292816900016	21622722				2022-04-25	
J	Wang, Y; Wang, Y; Wang, J; Lei, W; Li, K; Wu, DC; Wang, XJ				Wang, Ying; Wang, Ya; Wang, Ji; Lei, Wan; Li, Ke; Wu, Daocheng; Wang, Xiaojuan			Pharmacokinetics, biodistribution, and bioavailability of gossypol-loaded Pluronic (R) F127 nanoparticles	JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY			English	Article						Gossypol; Pluronic (R) F127; Nanoparticle; Pharmacokinetics; Biodistribution	COLORECTAL-CARCINOMA CELLS; BLOCK-COPOLYMER MICELLES; PROSTATE-CANCER; DRUG-DELIVERY; INHIBITOR; (-)-GOSSYPOL; AUTOPHAGY; GROWTH; BCL-2; PROLIFERATION	To enhance the water solubility and improve the bioavailability of gossypol, gossypol-loaded Pluronic (R) F127 nanoparticles (GLPFNs) for intravenous (i.v.) administration were prepared through thin-film hydration. The morphological characteristics of the GLPFNs were determined by transmission electron microscopy and particle size analysis. Pharmacokinetic and biodistribution studies were performed using Kun Ming (KM) mice by measuring gossypol concentrations in plasma and tissue samples of the mice using ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC- ESI-MS/MS). The GLPFNs exhibited uniform spherical shapes with a dynamic size of 70 +/- 2.4 nm. The encapsulation and drug-loading efficiencies of the GLPFNs were 91.2% +/- 3.1% and 9.1% +/- 0.42%, respectively. The particles further exhibited sustained drug release for about 200 h. The UHPLC-ESI-MS/MS method used in this work for plasma and tissue sample analysis was fully validated. The pharmacokinetics of the GLPFNs was studied after intravenous (i.v.) and intragastric (i.g.) administration to KM mice, and tissue distribution studies of the GLPFNs were performed. The AUC (0-inf) of the GLPFNs exhibited five- and sixfold increases. The clearance of GLPFNs decreased up to 5.6-fold when the gossypol entrapped in GLPFNs was i.g. administered. The absolute bioavailability of GLPFNs, which was 44.32%, increased by threefold compared with that of gossypol alone. The relative bioavailability of the GLPFNs after intravenous (i.v.) and intragastric (i.g.) administration was 192.38% and 560.75%, respectively. The concentration of GLPFNs was higher than that of gossypol, especially in reticuloendothelial cell-containing organs. Thus, the GLPFNs improved the bioavailability of the lipophilic drug gossypol. The gossypol-loaded Pluronic (R) F127 nanoparticles exhibited high biocompatibility and tunable drug release characteristics for treating cancer.	[Wang, Ying; Wang, Ji; Lei, Wan; Wang, Xiaojuan] Fourth Mil Med Univ, State Key Lab Mil Stomatol, Sch Stomatol, Xian 710032, Shaanxi, Peoples R China; [Wang, Ying; Wang, Ji; Lei, Wan; Wang, Xiaojuan] Fourth Mil Med Univ, Natl Clin Res Ctr Oral Dis, Sch Stomatol, Xian 710032, Shaanxi, Peoples R China; [Wang, Ying; Wang, Ji; Lei, Wan; Wang, Xiaojuan] Fourth Mil Med Univ, Shaanxi Engn Res Ctr Dent Mat & Adv Manufacture, Sch Stomatol, Dept Pharm, Xian 710032, Shaanxi, Peoples R China; [Wang, Ya; Li, Ke; Wu, Daocheng] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Educ Minist, Xian 710049, Shaanxi, Peoples R China		Wang, XJ (corresponding author), Fourth Mil Med Univ, State Key Lab Mil Stomatol, Sch Stomatol, Xian 710032, Shaanxi, Peoples R China.; Wang, XJ (corresponding author), Fourth Mil Med Univ, Natl Clin Res Ctr Oral Dis, Sch Stomatol, Xian 710032, Shaanxi, Peoples R China.; Wang, XJ (corresponding author), Fourth Mil Med Univ, Shaanxi Engn Res Ctr Dent Mat & Adv Manufacture, Sch Stomatol, Dept Pharm, Xian 710032, Shaanxi, Peoples R China.; Wu, DC (corresponding author), Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Educ Minist, Xian 710049, Shaanxi, Peoples R China.	wudaocheng@mail.xjtu.edu.cn; wxjyh231@fmmu.edu.cn		Wu, Daocheng/0000-0002-6183-539X	Shan xi province science and technology and innovation project [2011KTCL03-07, 2011KTCL03-01]	This study was supported by the grants of Shan xi province science and technology and innovation project (Nos. 2011KTCL03-07 and 2011KTCL03-01).	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Drug Deliv. Sci. Technol.	JUN	2018	45						388	396		10.1016/j.jddst.2018.04.002			9	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	GM8QQ	WOS:000438498100044					2022-04-25	
J	Wang, ZG; Chen, K; Li, DC; Chen, MD; Li, AQ; Wang, J				Wang, Zhengguang; Chen, Ke; Li, Dongchang; Chen, Mengding; Li, Angqing; Wang, Jian			miR-140-3p is involved in the occurrence and metastasis of gastric cancer by regulating the stability of FAM83B	CANCER CELL INTERNATIONAL			English	Article						Gastric cancer; miR-140-3p; SNHG12; RNA-binding protein HuR; FAM38B; Proliferation; Nuclear transportation; Metastasis; mRNA stability	NONCODING RNA SNHG12; GENE-EXPRESSION; COLORECTAL-CANCER; SIGNALING PATHWAY; PROLIFERATION; PROGRESSION; AUTOPHAGY	Background Gastric cancer (GC) is a malignant tumor and microRNAs (miRNAs) are closely connected to GC development. The purpose of this study is to investigate the effect of miR-140-3p on the occurrence and metastasis of GC. Methods We detected miR-140-3p expression in GC cells and tissues. The correlation between miR-140-3p and prognosis and clinicopathological features in GC was analyzed. The role of miR-140-3p in GC cell migration, invasion, and proliferation was analyzed. The model of tumor transplantation and metastasis in nude mice was established, and the effect of miR-140-3p on the development and metastasis of GC was assessed. The relation between miR-140-3p and SNHG12 and the relations among HuR, SNHG12, and FAM83B were analyzed. Results miR-140-3p was poorly expressed in GC. GC patients with low miR-140-3p expression had a poor prognosis and unfavorable clinicopathologic features. Overexpression of miR-140-3p inhibited GC cell migration, invasion, and proliferation, and inhibited the development and metastasis of GC. miR-140-3p directly bound to SNHG12 in GC tissues and downregulated SNHG12 expression. SNHG12 overexpression induced HuR nuclear transportation. HuR can bind to FAM83B and up-regulate the mRNA level of FAM83B. Overexpression of SNHG12 or FAM83B reduced the inhibition of overexpression of miR-140-3p on GC. Conclusion miR-140-3p directly bound to SNHG12 in GC and down-regulated the expression of SNHG12, reduced the binding of SNHG12 and HuR, thus inhibiting the nuclear transportation of HuR and the binding of HuR and FAM83B, and reducing the transcription of FAM83B, and finally inhibiting the growth and metastasis of GC.	[Wang, Zhengguang; Chen, Ke] Anhui Med Univ, Dept Gen Surg, Affiliated Hosp 1, 218 Jixi Rd, Hefei 230022, Anhui, Peoples R China; [Li, Dongchang; Chen, Mengding; Li, Angqing; Wang, Jian] Anhui Med Univ, Hefei 230001, Anhui, Peoples R China		Wang, ZG (corresponding author), Anhui Med Univ, Dept Gen Surg, Affiliated Hosp 1, 218 Jixi Rd, Hefei 230022, Anhui, Peoples R China.	wangzhengguang0401@163.com			Anhui Provincial Natural Science FoundationNatural Science Foundation of Anhui Province [2008085MH294]	This work was supported by Anhui Provincial Natural Science Foundation [2008085MH294].	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OCT 16	2021	21	1							537	10.1186/s12935-021-02245-8			19	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	WH5ED	WOS:000707699900001	34656115	gold, Green Published			2022-04-25	
J	Eloranta, K; Cairo, S; Liljestrom, E; Soini, T; Kyronlahti, A; Judde, JG; Wilson, DB; Heikinheimo, M; Pihlajoki, M				Eloranta, Katja; Cairo, Stefano; Liljestrom, Emmi; Soini, Tea; Kyronlahti, Antti; Judde, Jean-Gabriel; Wilson, David B.; Heikinheimo, Markku; Pihlajoki, Marjut			Chloroquine Triggers Cell Death and Inhibits PARPs in Cell Models of Aggressive Hepatoblastoma	FRONTIERS IN ONCOLOGY			English	Article						liver cancer; hepatoblastoma; pediatric oncology; poly(ADP)-ribose polymerase; metabolomics; aspartate; NAD(+)	COLORECTAL-CANCER CELLS; BREAST-CANCER; STEM-CELLS; IN-VITRO; AUTOPHAGY; TUMOR; APOPTOSIS; GROWTH; HYDROXYCHLOROQUINE; POLY(ADP-RIBOSE)	Background:Hepatoblastoma (HB) is the most common pediatric liver malignancy. Despite advances in chemotherapeutic regimens and surgical techniques, the survival of patients with advanced HB remains poor, underscoring the need for new therapeutic approaches. Chloroquine (CQ), a drug used to treat malaria and rheumatologic diseases, has been shown to inhibit the growth and survival of various cancer types. We examined the antineoplastic activity of CQ in cell models of aggressive HB. Methods:Seven human HB cell models, all derived from chemoresistant tumors, were cultured as spheroids in the presence of relevant concentrations of CQ. Morphology, viability, and induction of apoptosis were assessed after 48 and 96 h of CQ treatment. Metabolomic analysis and RT-qPCR based Death Pathway Finder array were used to elucidate the molecular mechanisms underlying the CQ effect in a 2-dimensional cell culture format. Quantitative western blotting was performed to validate findings at the protein level. Results:CQ had a significant dose and time dependent effect on HB cell viability both in spheroids and in 2-dimensional cell cultures. Following CQ treatment HB spheroids exhibited increased caspase 3/7 activity indicating the induction of apoptotic cell death. Metabolomic profiling demonstrated significant decreases in the concentrations of NAD(+)and aspartate in CQ treated cells. In further investigations, oxidation of NAD(+)decreased as consequence of CQ treatment and NAD(+)/NADH balance shifted toward NADH. Aspartate supplementation rescued cells from CQ induced cell death. Additionally, downregulated expression of PARP1 and PARP2 was observed. Conclusions:CQ treatment inhibits cell survival in cell models of aggressive HB, presumably by perturbing NAD(+)levels, impairing aspartate bioavailability, and inhibiting PARP expression. CQ thus holds potential as a new agent in the management of HB.	[Eloranta, Katja; Liljestrom, Emmi; Soini, Tea; Kyronlahti, Antti; Heikinheimo, Markku; Pihlajoki, Marjut] Univ Helsinki, Helsinki Univ Hosp, Childrens Hosp, Pediat Res Ctr, Helsinki, Finland; [Cairo, Stefano; Judde, Jean-Gabriel] Xentech, Evry, France; [Soini, Tea] Karolinska Inst, Ctr Infect Med, Dept Med, Stockholm, Sweden; [Wilson, David B.; Heikinheimo, Markku] Washington Univ, Sch Med, Dept Pediat, St Louis Childrens Hosp, St Louis, MO 63110 USA; [Wilson, David B.] Washington Univ, Dept Dev Biol, Sch Med, St Louis, MO USA		Pihlajoki, M (corresponding author), Univ Helsinki, Helsinki Univ Hosp, Childrens Hosp, Pediat Res Ctr, Helsinki, Finland.	marjut.pihlajoki@helsinki.fi	Wilson, David/K-7433-2014	Wilson, David/0000-0002-1826-7745; Eloranta, Katja/0000-0002-0396-5137	Cancer Foundation Finland; Finska Lakaresallskapet; Helsinki University Central Hospital Research Grants; Paivikki, and Sakari Sohlberg Foundation; Sigrid Juselius FoundationSigrid Juselius Foundation; Doctoral Program in Clinical Research at University of Helsinki Funds	This study was supported by the Cancer Foundation Finland, Finska Lakaresallskapet, Helsinki University Central Hospital Research Grants, Paivikki, and Sakari Sohlberg Foundation, Sigrid Juselius Foundation, and Doctoral Program in Clinical Research at University of Helsinki Funds.	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Oncol.	JUL 17	2020	10								1138	10.3389/fonc.2020.01138			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	NA8UD	WOS:000560093100001	32766148	Green Published, gold			2022-04-25	
J	Wei, B; Wang, YY; Wang, JW; Cai, XM; Xu, LY; Wu, JJ; Wang, Y; Liu, W; Gu, YH; Guo, WJ; Xu, Q				Wei, Bin; Wang, Yuanyuan; Wang, Jiawei; Cai, Xiaomin; Xu, Lingyan; Wu, Jingjing; Wang, Ying; Liu, Wen; Gu, Yanhong; Guo, Wenjie; Xu, Qiang			Apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer via the Akt/beta-catenin pathway	CANCER CELL INTERNATIONAL			English	Article						Apatinib; Esophageal cancer; Tumor progression; Cisplatin sensitivity; VEGFR2; Akt/beta-catenin pathway	COLORECTAL-CANCER; SIGNALING PATHWAY; EXPRESSION; SURVIVAL; EFFICACY; AUTOPHAGY; SAFETY	Background: Esophageal cancer is the sixth leading cause of cancer-related mortality worldwide, which is partially due to limited progress of therapy. Apatinib, an inhibitor of VEGFR2, has a promising antitumor effect on malignancies. However, the underlying mechanism of its antitumor effect on esophageal cancer remains poorly understood. Materials and methods: Eighteen pairs of frozen esophageal cancer and their para-cancer samples and 25 paraffin specimens from advanced esophageal cancer patients treated with cisplatin-based regimen were collected. The effects of apatinib on cell growth, cell apoptosis, cell cycle and invasion/migration of esophageal cancer cells were assessed. Bioinformatics, luciferase reporter, immunoprecipitation and immunofluorescence assays were conducted for mechanic investigation. Quantitative RT-PCR, western blotting and immunohistochemistry were used to measure the expression of functional genes. Xenograft tumor growth of mice was performed. Results: We found that VEGFR2 was highly expressed in esophageal cancer and associated with poor efficacy of cisplatin-based treatment. Apatinib displayed profound actions against tumor cell growth of human esophageal cancer via promoting cell apoptosis and cell cycle arrest. Also, apatinib displayed the inhibitory effects on cell migration and invasion. Moreover, apatinib strongly suppressed the growth of esophageal cancer xenografts in mice. The effects of apatinib on esophageal cancer were partially dependent on its block of the VEGFR2/Akt/beta-catenin pathway. Specifically, apatinib induced the degradation of beta-catenin and decreased its transcriptional activity through Akt/GSK-3 beta repression. Further in vitro and in vivo studies revealed that low dose apatinib had a synergistic antitumor effect with cisplatin on esophageal cancer. Conclusion: Our study indicates that apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer by deactivating the Akt/beta-catenin pathway. These findings provide a theoretical foundation for using apatinib as an effective therapeutic drug for esophageal cancer.	[Wei, Bin; Wang, Yuanyuan; Wang, Jiawei; Cai, Xiaomin; Xu, Lingyan; Wang, Ying; Gu, Yanhong] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, 300 Guangzhou Rd, Nanjing 210029, Peoples R China; [Wei, Bin; Wu, Jingjing] Nanjing Med Univ, Dept Oncol, Affiliated Huaian Peoples Hosp 1, Huaian, Peoples R China; [Liu, Wen; Guo, Wenjie; Xu, Qiang] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, 22 Hankou Rd, Nanjing 210093, Peoples R China		Gu, YH (corresponding author), Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, 300 Guangzhou Rd, Nanjing 210029, Peoples R China.; Guo, WJ; Xu, Q (corresponding author), Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, 22 Hankou Rd, Nanjing 210093, Peoples R China.	guyhphd@163.com; guowj@nju.edu.cn; molpharm@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81871944, 81572389]; Jiangsu 333 project [BRA2016517]; Jiangsu province key medical talents [ZDRCA2016026]; Science and Technology Development Foundation of Nanjing Medical University [NMUB2018151, NMUB2019346]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [020814380114]	This study was supported by National Natural Science Foundation of China (81871944, 81572389), Jiangsu 333 project (BRA2016517), Jiangsu province key medical talents (ZDRCA2016026), Science and Technology Development Foundation of Nanjing Medical University (NMUB2018151, NMUB2019346) and Fundamental Research Funds for the Central Universities (020814380114).	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MAY 27	2020	20	1							198	10.1186/s12935-020-01290-z			13	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	LW0HW	WOS:000538828800001	32514243	Green Published, gold			2022-04-25	
J	Kuo, KK; Hsiao, PJ; Chang, WT; Chuang, SC; Yang, YH; Wuputra, K; Ku, CC; Pan, JB; Li, CP; Kato, K; Liu, CJ; Wu, DC; Yokoyama, KK				Kuo, Kung-Kai; Hsiao, Pi-Jung; Chang, Wen-Tsan; Chuang, Shih-Chang; Yang, Ya-Han; Wuputra, Kenly; Ku, Chia-Chen; Pan, Jia-Bin; Li, Chia-Pei; Kato, Kohsuke; Liu, Chung-Jung; Wu, Deng-Chyang; Yokoyama, Kazunari K.			Therapeutic Strategies Targeting Tumor Suppressor Genes in Pancreatic Cancer	CANCERS			English	Review						BRCA1; BRCA2; clinical trial; pancreatic cancer; p53; translational research; tumor suppressor gene	MUTANT P53 REACTIVATION; WILD-TYPE; DUCTAL ADENOCARCINOMA; GERMLINE MUTATIONS; SIGNALING PATHWAYS; INDUCE APOPTOSIS; BREAST-CANCER; IN-VIVO; PHASE-I; CELLS	Simple Summary Tumor suppressor genes are critical in the control of many biological functions. They can be classified based on their roles in proliferation, cell-cycle progression, DNA repair/damage, and crucial signaling functions, including apoptosis, autophagy, and necrosis. The absence of functional tumor suppressor genes entails a higher risk of dysfunction of cell growth, differentiation, cell death, and cancer development. Loss of function or mutations of such genes has been identified in many types of cancer, such as breast, bladder, colorectal, head and neck, lung, ovarian, uterine, and pancreatic cancers. Familial cancer syndromes, such as Li-Fraumeni syndrome, are associated with loss of TP53 function. Extensive studies have been carried out to clarify the roles of the products of these genes, as well as their mechanistic link to cancers, to identify novel targets for specific cancer types. Here, we introduce the roles of tumor suppressor gene products in pancreatic cancer development and its therapeutics for tumorigenesis prevention. The high mortality of pancreatic cancer is attributed to the insidious progression of this disease, which results in a delayed diagnosis and advanced disease stage at diagnosis. More than 35% of patients with pancreatic cancer are in stage III, whereas 50% are in stage IV at diagnosis. Thus, understanding the aggressive features of pancreatic cancer will contribute to the resolution of problems, such as its early recurrence, metastasis, and resistance to chemotherapy and radiotherapy. Therefore, new therapeutic strategies targeting tumor suppressor gene products may help prevent the progression of pancreatic cancer. In this review, we discuss several recent clinical trials of pancreatic cancer and recent studies reporting safe and effective treatment modalities for patients with advanced pancreatic cancer.	[Kuo, Kung-Kai; Chang, Wen-Tsan; Chuang, Shih-Chang; Yang, Ya-Han] Kaohsiung Med Univ Hosp, Dept Surg, Div Gen & Digest Surg, Kaohsiung 80756, Taiwan; [Kuo, Kung-Kai; Yang, Ya-Han; Wuputra, Kenly; Ku, Chia-Chen; Pan, Jia-Bin; Li, Chia-Pei; Liu, Chung-Jung; Wu, Deng-Chyang; Yokoyama, Kazunari K.] Kaohsiung Med Univ, Regenerat Med & Cell Therapy Res Ctr, Kaohsiung 80708, Taiwan; [Kuo, Kung-Kai; Chang, Wen-Tsan; Chuang, Shih-Chang; Yang, Ya-Han] Kaohsiung Med Univ, Coll Med, Dept Surg, Kaohsiung 80708, Taiwan; [Hsiao, Pi-Jung] I Shou Univ, Dept Internal Med, Div Endocrinol & Metab, EDA Hosp,Coll Med, Kaohsiung 82445, Taiwan; [Wuputra, Kenly; Ku, Chia-Chen; Pan, Jia-Bin; Li, Chia-Pei; Yokoyama, Kazunari K.] Kaohsiung Med Univ, Grad Inst Med, Kaohsiung 80708, Taiwan; [Kato, Kohsuke] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Infect Biol, Tsukuba, Ibaraki 3058577, Japan; [Liu, Chung-Jung; Wu, Deng-Chyang] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Gastroenterol, Kaohsiung 80756, Taiwan; [Liu, Chung-Jung; Wu, Deng-Chyang; Yokoyama, Kazunari K.] Kaohsiung Med Univ Hosp, Cell Therapy & Res Ctr, Kaohsiung 80756, Taiwan		Yokoyama, KK (corresponding author), Kaohsiung Med Univ, Regenerat Med & Cell Therapy Res Ctr, Kaohsiung 80708, Taiwan.; Yokoyama, KK (corresponding author), Kaohsiung Med Univ, Grad Inst Med, Kaohsiung 80708, Taiwan.; Yokoyama, KK (corresponding author), Kaohsiung Med Univ Hosp, Cell Therapy & Res Ctr, Kaohsiung 80756, Taiwan.	kkkuo@kmu.edu.tw; ed112609@edah.org.tw; wtchang@kmu.edu.tw; chuangsc@kmu.edu.tw; R030126@kmu.edu.tw; r020017@kmu.edu.tw; r991046@gap.kmu.edu.tw; r060139@gap.kmu.edu.tw; 1100058@kmuh.org.tw; kkato@md.tsukuba.ac.jp; 1020590@ms.kmuh.org.tw; dechwu@kmu.edu.tw; Kazu@kmu.edu.tw	Ku, Chiachen/AAA-2868-2022; Liu, Chung-Jung/AAX-1889-2021	Ku, Chiachen/0000-0002-1496-3081; Liu, Chung-Jung/0000-0002-2657-565X; Chang, Wen-Tsan/0000-0001-5622-8299; Yokoyama, Kazunari/0000-0001-8508-7587	Ministry of Science and Technology [MOST 109-2314-B-037-119, MOST 109-2320-B-037-033]; National Health Research InstitutesNational Health Research Institutes, Japan [NHRI-EX109-10720SI]; Kaohsiung Medical University Hospital [SA10803C]; Kaohsiung Medical University Research Center [KMU-TC109A02, KMU-TC109A02-0, KMU-TC109A02-3]	This work was supported by grants from the Ministry of Science and Technology (MOST 109-2314-B-037-119; MOST 109-2320-B-037-033), the National Health Research Institutes (NHRIEX109-10720SI), Kaohsiung Medical University Hospital (SA10803C), and Kaohsiung Medical University Research Center (KMU-TC109A02; KMU-TC109A02-0, KMU-TC109A02-3).	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J	Choy, YY; Fraga, M; Mackenzie, GG; Waterhouse, AL; Cremonini, E; Oteiza, PI				Choy, Ying Yng; Fraga, Magdalena; Mackenzie, Gerardo G.; Waterhouse, Andrew L.; Cremonini, Eleonora; Oteiza, Patricia I.			The PI3K/Akt pathway is involved in procyanidin-mediated suppression of human colorectal cancer cell growth	MOLECULAR CARCINOGENESIS			English	Article						apoptosis; proanthocyanidin; autophagy; cell cycle arrest	GRAPE SEED EXTRACT; NF-KAPPA-B; IN-VITRO; APPLE PROCYANIDINS; OXIDANT PRODUCTION; DIETARY FIBER; AKT INHIBITOR; CACO-2 CELLS; RISK; ACTIVATION	Colorectal cancer (CRC) has the third highest incidence worldwide. Epidemiological studies showed that the consumption of fruit and vegetables containing procyanidins (PCA), polymers of flavan-3-ols, is associated with lower CRC risk. However, the molecular mechanisms supporting this positive association are unclear. This study investigated the capacity of PCA with different degrees of polymerization to reduce CRC cell growth, characterizing the underlying mechanisms. Compared to the monomer ((-)-epicatechin) and the trimer, the hexamer (Hex) was the most active at reducing CRC cell viability. Hex caused a concentration- (2.5-50M) and time- (24-72h) dependent decrease in the viability of six human CRC cell lines in culture. Hex caused CRC apoptotic Caco-2 cell death within 24h, as evidenced by caspase 3 and caspase 9 activation, DNA fragmentation, and changes in nuclear morphology/staining. Hex-induced apoptosis occurs through the mitochondrial pathway, as evidenced by an increased Bad mitochondrial translocation, and cytochrome c release from the mitochondria to the cytosol. Hex also arrested the Caco-2 cell cycle at G(2)/M phase and upregulated genes involved in autophagy. Mechanistically, in Caco-2 cells Hex inhibited the PI3K/Akt signaling pathway, causing the downstream downregulation of proteins involved in the regulation of cell survival (Bad, GSK-3). Accordingly, the Akt inhibitor MKK-2206 decreased Bad and GSK-3 phosphorylation. MKK-2206 decreased cell growth, having an additive effect with Hex. In conclusion, our results show that large PCA can inhibit CRC cell growth via the Akt kinase pathway, demonstrating a mechanism to explain the epidemiological evidence linking PCA-rich diets with lower CRC risk. (c) 2016 Wiley Periodicals, Inc.	[Choy, Ying Yng; Waterhouse, Andrew L.] Univ Calif Davis, Dept Viticulture & Enol, Davis, CA 95616 USA; [Fraga, Magdalena; Cremonini, Eleonora; Oteiza, Patricia I.] Univ Calif Davis, Dept Nutr, One Shields Ave, Davis, CA 95616 USA; [Fraga, Magdalena; Cremonini, Eleonora; Oteiza, Patricia I.] Univ Calif Davis, Dept Environm Toxicol, One Shields Ave, Davis, CA 95616 USA; [Mackenzie, Gerardo G.] SUNY Stony Brook, Dept Prevent Med, Stony Brook Canc Ctr, Stony Brook, NY 11794 USA		Oteiza, PI (corresponding author), Univ Calif Davis, Dept Nutr, One Shields Ave, Davis, CA 95616 USA.; Oteiza, PI (corresponding author), Univ Calif Davis, Dept Environm Toxicol, One Shields Ave, Davis, CA 95616 USA.	poteiza@ucdavis.edu	Mackenzie, Gerardo G/AAW-5114-2020; Waterhouse, Andrew/F-6719-2011	Waterhouse, Andrew/0000-0002-5088-7442	NIFA-USDAUnited States Department of Agriculture (USDA) [CA-D*-xxx-7244-H]; Stony Brook Cancer Center	Grant sponsor: NIFA-USDA; Grant number: CA-D*-xxx-7244-H; Grant sponsor: Stony Brook Cancer Center	Adamson GE, 1999, J AGR FOOD CHEM, V47, P4184, DOI 10.1021/jf990317m; Agarwal E, 2014, BMC CANCER, V14, DOI 10.1186/1471-2407-14-145; Aune D, 2011, GASTROENTEROLOGY, V141, P106, DOI 10.1053/j.gastro.2011.04.013; Ben QW, 2014, GASTROENTEROLOGY, V146, P689, DOI 10.1053/j.gastro.2013.11.003; BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3; Carnero A, 2010, CURR PHARM DESIGN, V16, P34, DOI 10.2174/138161210789941865; Carnesecchi S, 2002, CANCER LETT, V175, P147, DOI 10.1016/S0304-3835(01)00731-5; Chan DSM, 2011, PLOS ONE, V6, DOI [10.1371/journal.pone.0020456, 10.1371/journal.pone.0027218]; Chappell WH, 2011, ONCOTARGET, V2, P135, DOI 10.18632/oncotarget.240; Choy YY, 2014, FOOD FUNCT, V5, P2298, DOI [10.1039/c4fo00325j, 10.1039/C4FO00325J]; Choy YY, 2013, J AGR FOOD CHEM, V61, P121, DOI 10.1021/jf301939e; Da Silva M, 2012, FREE RADICAL BIO MED, V52, P151, DOI 10.1016/j.freeradbiomed.2011.10.436; Danielsen SA, 2015, BBA-REV CANCER, V1855, P104, DOI 10.1016/j.bbcan.2014.09.008; Eferl R, 2003, NAT REV CANCER, V3, P859, DOI 10.1038/nrc1209; Engelbrecht AM, 2007, CANCER LETT, V258, P144, DOI 10.1016/j.canlet.2007.08.020; Erlejman AG, 2008, ARCH BIOCHEM BIOPHYS, V476, P186, DOI 10.1016/j.abb.2008.01.024; Forester SC, 2010, J AGR FOOD CHEM, V58, P5320, DOI 10.1021/jf9040172; Gosse F, 2005, CARCINOGENESIS, V26, P1291, DOI 10.1093/carcin/bgi074; Hammerstone JF, 2000, J NUTR, V130, p2086S, DOI 10.1093/jn/130.8.2086S; Harwood AJ, 2001, CELL, V105, P821, DOI 10.1016/S0092-8674(01)00412-3; Hirai H, 2010, MOL CANCER THER, V9, P1956, DOI 10.1158/1535-7163.MCT-09-1012; Jiang BH, 2008, BBA-PROTEINS PROTEOM, V1784, P150, DOI 10.1016/j.bbapap.2007.09.008; Kaur M, 2006, CLIN CANCER RES, V12, P6194, DOI 10.1158/1078-0432.CCR-06-1465; Kerr D, 2003, NAT REV CANCER, V3, P615, DOI 10.1038/nrc1147; Lizarraga D, 2007, FEBS J, V274, P4802, DOI 10.1111/j.1742-4658.2007.06010.x; Mackenzie GG, 2008, INT J CANCER, V123, P56, DOI 10.1002/ijc.23477; Mai W, 2006, ONCOLOGY-BASEL, V71, P297, DOI 10.1159/000106429; Maiti D, 2001, J BIOL CHEM, V276, P329, DOI 10.1074/jbc.M002650200; Manning BD, 2007, CELL, V129, P1261, DOI 10.1016/j.cell.2007.06.009; Miura T, 2008, CARCINOGENESIS, V29, P585, DOI 10.1093/carcin/bgm198; Muzny DM, 2012, NATURE, V487, P330, DOI 10.1038/nature11252; Noguchi M, 2014, BBA-REV CANCER, V1846, P342, DOI 10.1016/j.bbcan.2014.07.013; Pierini R, 2008, MOL NUTR FOOD RES, V52, P1399, DOI 10.1002/mnfr.200700513; Prasad R, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0043064; Rossi M, 2010, CANCER CAUSE CONTROL, V21, P243, DOI 10.1007/s10552-009-9455-3; Rubinsztein DC, 2012, NAT REV DRUG DISCOV, V11, P709, DOI 10.1038/nrd3802; Shakoori A, 2005, BIOCHEM BIOPH RES CO, V334, P1365, DOI 10.1016/j.bbrc.2005.07.041; Suman S, 2014, MOL CARCINOGEN, V53, pE151, DOI 10.1002/mc.22076; Terry P, 2001, JNCI-J NATL CANCER I, V93, P525, DOI 10.1093/jnci/93.7.525; Terzic J, 2010, GASTROENTEROLOGY, V138, P2101, DOI 10.1053/j.gastro.2010.01.058; Theodoratou E, 2007, CANCER EPIDEM BIOMAR, V16, P684, DOI 10.1158/1055-9965.EPI-06-0785; Tsang C, 2005, BRIT J NUTR, V94, P170, DOI 10.1079/BJN20051480; Verstraeten SV, 2013, BBA-BIOMEMBRANES, V1828, P2646, DOI 10.1016/j.bbamem.2013.07.023; Verstraeten SV, 2003, FREE RADICAL BIO MED, V34, P84, DOI 10.1016/S0891-5849(02)01185-1; Wang W. 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J	Choroba, K; Machura, B; Szlapa-Kula, A; Malecki, JG; Raposo, L; Roma-Rodrigues, C; Cordeiro, S; Baptista, PV; Fernandes, AR				Choroba, Katarzyna; Machura, Barbara; Szlapa-Kula, Agata; Malecki, Jan G.; Raposo, Luis; Roma-Rodrigues, Catarina; Cordeiro, Sandra; Baptista, Pedro, V; Fernandes, Alexandra R.			Square planar Au(III), Pt(II) and Cu(II) complexes with quinoline-substituted 2,2 ':6 ',2 ''-terpyridine ligands: From in vitro to in vivo biological properties	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY			English	Article						Square planar metal complexes; Apoptosis; Autophagy induction; Mitochondrial membrane potential changes; Intracellular reactive oxygen species; Ex-ovo chorioallantoic membrane in vivo assay	LUMINESCENT PLATINUM(II) COMPLEXES; PI STACKING INTERACTIONS; DNA-BINDING PROPERTIES; TERPYRIDINE COMPLEXES; METAL-COMPLEXES; CRYSTAL-STRUCTURE; PHOTOPHYSICAL PROPERTIES; COPPER(II) COMPLEXES; GOLD(III) COMPLEXES; SOLUTION CHEMISTRY	Cancer is the second leading cause of death worldwide. Cisplatin has challenged cancer treatment; however, resistance and side effects hamper its use. New agents displaying improved activity and more reduced side effects relative to cisplatin are needed. In this work we present the synthesis, characterization and biological activities of three complexes with quinoline-substituted 2,2':6',2 ''-terpyridine ligand: [Pt(4'-(2-quin)-terpy)Cl](SO3CF3) (1), [Au(4 '-(2-quin)-terpy)Cl](PF6)(2)center dot CH3CN (2) and [Cu(4'-(2-quin)-terpy)Cl](PF6) (3). The three complexes displayed a high antiproliferative activity in ovarian carcinoma cell line (A2780) and even more noticeable in a colorectal carcinoma cell line (HCT116) following the order 3 > 2 > 1. The complexes IC50 are at least 20 x lower than the IC50 displayed by cisplatin (15.4 mu M) in HCT116 cell line while displaying at the same time, much reduced cytotoxicity in a normal dermal fibroblast culture. These cytotoxic activities seem to be correlated with the inclination angles of 2-quin unit to the central pyridine. Interestingly, all complexes can interact with calf-thymus DNA (CT-DNA) in vitro via different mechanisms, although intercalation seems to be the preferred mechanism at least for 2 and 3 at higher concentrations of DNA. Moreover, circular dichroism (CD) data seems to indicate that complex 3, more planar, induces a high destabilization of the DNA double helix (shift from B-form to Z-form). Higher the deviation from planar, the lower the cytotoxicity displayed by the complexes. Cellular uptake may be also responsible for the different cytotoxicity exhibited by complexes with 3 > 2 > 1. Complex 2 seems to enter cells more passively while complex 1 and 3 might enter cells via energy-dependent and -independent mechanisms. Complexes 1-3 were shown to induce ROS are associated with the increased apoptosis and autophagy. Moreover, all complexes dissipate the mitochondrial membrane potential leading to an increased BAX/BCL-2 ratio that triggered apoptosis. Complexes 2 and 3 were also shown to exhibit an anti-angiogenic effect by significantly reduce the number of newly formed blood vessel in a CAM model with no toxicity in this in vivo model. Our results seem to suggest that the increased cytotoxicity of complex 3 in HCT116 cells and its potential interest for further translation to pre-clinical mice xenografts might be associated with: 1) higher % of internalization of HCT116 cells via energy-dependent and -independent mechanisms; 2) ability to intercalate DNA and due to its planarity induced higher destabilization of DNA; 3) induce intracellular ROS that trigger apoptosis and autophagy; 4) low toxicity in an in vivo model of CAM; 5) potential anti-angiogenic effect. (c) 2021 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).	[Choroba, Katarzyna; Machura, Barbara; Szlapa-Kula, Agata; Malecki, Jan G.] Univ Silesia, Inst Chem, Szkolna 9, PL-40006 Katowice, Poland; [Raposo, Luis; Roma-Rodrigues, Catarina; Cordeiro, Sandra; Baptista, Pedro, V; Fernandes, Alexandra R.] NOVA Sch Sci & Technol, Dept Ciencias Vida, UCIBIO, Campus Caparica, P-2829516 Caparica, Portugal		Choroba, K (corresponding author), Univ Silesia, Inst Chem, Szkolna 9, PL-40006 Katowice, Poland.; Fernandes, AR (corresponding author), NOVA Sch Sci & Technol, Dept Ciencias Vida, UCIBIO, Campus Caparica, P-2829516 Caparica, Portugal.	katarzyna.choroba@us.edu.pl; ma.fernandes@fct.unl.pt	Raposo, Luís/AAX-1610-2021; Roma-Rodrigues, Catarina/S-6144-2016; Roma-Rodrigues, Catarina/AAT-5658-2021; Raposo, Luís R/T-3754-2017; Baptista, Pedro/A-1237-2009; Malecki, Jan Grzegorz/M-4022-2017; Fernandes, Alexandra/C-7465-2011	Raposo, Luís/0000-0002-8637-346X; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Roma-Rodrigues, Catarina/0000-0002-8676-6562; Raposo, Luís R/0000-0002-8637-346X; Szlapa-Kula, Agata/0000-0001-6539-5419; Cordeiro, Sandra/0000-0002-3825-1695; Choroba, Katarzyna/0000-0003-0168-5753; Machura, Barbara/0000-0001-7688-6491; Baptista, Pedro/0000-0001-5255-7095; Malecki, Jan Grzegorz/0000-0001-5571-3196; Fernandes, Alexandra/0000-0003-2054-4438	Applied Molecular Biosciences Unit - UCIBIO - FCT [UIDP/04378/2020, UIDB/04378/2020, SFRH/BPD/124612/2016, PTDC/CVT-EPI/6685/2014]	This work was supported by the Applied Molecular Biosciences Unit - UCIBIO which is financed by national funds from FCT (UIDP/04378/2020, UIDB/04378/2020 and fellowships SFRH/BPD/124612/2016 (C. Roma-Rodrigues), and PTDC/CVT-EPI/6685/2014 (L R. Raposo)).	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J. Med. Chem.	JUN 5	2021	218								113404	10.1016/j.ejmech.2021.113404		APR 2021	19	Chemistry, Medicinal	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	RW0EA	WOS:000646195900027	33823390	hybrid, Green Published			2022-04-25	
J	Zheng, L; Chen, JT; Zhou, ZY; He, ZK				Zheng, Li; Chen, Jiangtao; Zhou, Zhongyong; He, Zhikuan			miR-195 enhances the radiosensitivity of colorectal cancer cells by suppressing CARM1	ONCOTARGETS AND THERAPY			English	Article						miR-195; CARM1; colorectal cancer; radiosensitivity	UP-REGULATION; RADIORESISTANCE; EXPRESSION; MICRORNAS; RADIATION; AUTOPHAGY; RESISTANCE	Background: microRNAs (miRNAs) can regulate the sensitivity of cancer cells to chemotherapy and radiotherapy. Aberrant expression of miR-195 has been found to be involved in colorectal cancer (CRC); however, its function and underlying mechanism in the radioresistance of CRC remains unclear. Methods: The levels of miR-195 and CARM1 were detected by quantitative reverse transcription-polymerase chain reaction and Western blot analysis in HCT-116 and HT-29 cells, respectively. Colony survival and apoptosis were determined by clonogenic assay and flow cytometry analysis, respectively. The apoptosis-related proteins Bax, Bcl-2, and gamma-H2AX were detected using Western blot. The targets of miR-195 were identified by bioinformatic prediction and luciferase reporter assays. CRC cells in vitro and in vivo were exposed to different doses of X-ray radiations. Results: miR-195 was downregulated, and CARM1 was upregulated in HCT-116 and HT-29 cells. miR-195 overexpression or CARM1 knockdown suppressed colony survival, induced apoptosis, promoted expression of Bax and gamma-H2AX, and inhibited Bcl-2 expression in CRC cells. CARM1 was identified and validated to be a functional target of miR-195. Moreover, restored expression of CARM1 reversed the enhanced radiosensitivity of CRC cells induced by miR-195. Furthermore, miR-195 increased the sensitivity of CRC cells to radiation in vivo. Conclusion: miR-195 enhances radiosensitivity of CRC cells through suppressing CARM1. Therefore, miR-195 acts as a potential regulator of radioresistance for CRC cells and as a promising therapeutic target for CRC patients.	[Zheng, Li; Chen, Jiangtao; Zhou, Zhongyong; He, Zhikuan] Henan Univ, Huaihe Hosp, Dept Gen Surg, 8 Baobei Rd, Gulou Dist 475000, Kaifeng, Peoples R China		Zheng, L (corresponding author), Henan Univ, Huaihe Hosp, Dept Gen Surg, 8 Baobei Rd, Gulou Dist 475000, Kaifeng, Peoples R China.	lizhengccn@163.com					Ahmed MAH, 2009, J CLIN PATHOL, V62, P1117, DOI 10.1136/jcp.2009.069310; Al-Dhaheri M, 2011, CANCER RES, V71, P2118, DOI 10.1158/0008-5472.CAN-10-2426; Ambros V, 2004, NATURE, V431, P350, DOI 10.1038/nature02871; An W, 2004, CELL, V117, P735, DOI 10.1016/j.cell.2004.05.009; Bartel DP, 2004, CELL, V116, P281, DOI 10.1016/S0092-8674(04)00045-5; Beskow C, 2009, BRIT J CANCER, V101, P816, DOI 10.1038/sj.bjc.6605201; Chaachouay H, 2011, RADIOTHER ONCOL, V99, P287, DOI 10.1016/j.radonc.2011.06.002; Chiu SJ, 2010, BIOCHEM BIOPH RES CO, V394, P774, DOI 10.1016/j.bbrc.2010.03.068; Covic M, 2005, EMBO J, V24, P85, DOI 10.1038/sj.emboj.7600500; Deng XB, 2013, J NEURO-ONCOL, V114, P263, DOI 10.1007/s11060-013-1179-2; Duan WM, 2013, J RADIAT RES, V54, P611, DOI 10.1093/jrr/rrs136; Dumont FJ, 2012, CURR CANCER DRUG TAR, V12, P899; Francescone RA, 2011, J BIOL CHEM, V286, P15332, DOI 10.1074/jbc.M110.212514; Garzon R, 2009, ANNU REV MED, V60, P167, DOI 10.1146/annurev.med.59.053006.104707; Hung PS, 2008, J PATHOL, V214, P368, DOI 10.1002/path.2280; Kim YR, 2010, BMC CANCER, V10, DOI 10.1186/1471-2407-10-197; Li D, 2011, CLIN CANCER RES, V17, P1722, DOI 10.1158/1078-0432.CCR-10-1800; Lin J, 2013, J CELL BIOCHEM, V114, P606, DOI 10.1002/jcb.24398; Liu L, 2010, BIOCHEM BIOPH RES CO, V400, P236, DOI 10.1016/j.bbrc.2010.08.046; Liu YJ, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0062383; Metheetrairut C, 2013, CURR OPIN GENET DEV, V23, P12, DOI 10.1016/j.gde.2013.01.002; Moncharmont C, 2012, CANCER LETT, V322, P139, DOI 10.1016/j.canlet.2012.03.024; Gutierrez JJP, 2011, COLORECTAL DIS, V13, pE145, DOI 10.1111/j.1463-1318.2011.02577.x; Rundle AG, 2008, GASTROENTEROLOGY, V134, P1311, DOI 10.1053/j.gastro.2008.02.032; Sun QQ, 2015, INT J CANCER, V136, P1003, DOI 10.1002/ijc.29065; Vu LP, 2010, BLOOD, V116, P1494, DOI 10.1182/blood.V116.21.3632.3632; Wang L, 2015, SCI ADV, V1, DOI 10.1126/sciadv.1500463; Wang L, 2014, CANCER CELL, V25, P21, DOI 10.1016/j.ccr.2013.12.007; Wang P, 2013, GASTROENTEROLOGY, V145, P1133, DOI 10.1053/j.gastro.2013.07.048; Wang XQ, 2012, MED ONCOL, V29, P919, DOI 10.1007/s12032-011-9880-5; Xiao SH, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0108810; Xue Q, 2013, WORLD J GASTROENTERO, V19, P9307, DOI 10.3748/wjg.v19.i48.9307; Yang XD, 2015, AM J CANCER RES, V5, P545; Yaromina A, 2007, RADIOTHER ONCOL, V83, P304, DOI 10.1016/j.radonc.2007.04.020; Zhang YH, 2015, CHIN J INTEGR MED, V10, P10, DOI DOI 10.1371/J0URNAL.P0NE.0131597; Zhang Y, 2014, CELL BIOCHEM BIOPHYS, V69, P303, DOI 10.1007/s12013-013-9799-x; Zhang Yin, 2014, EURASIP J ADV SIG PR, V2014, P1, DOI DOI 10.1016/J.ENGGE0.2014.08.024; Zheng L, 2015, J TRANSL MED, V13, DOI 10.1186/s12967-015-0592-z; Zhu J, 2015, INT J CLIN EXP MED, V8, P9142	39	31	38	1	9	DOVE MEDICAL PRESS LTD	ALBANY	PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND	1178-6930			ONCOTARGETS THER	OncoTargets Ther.		2017	10						1027	1038		10.2147/OTT.S125067			12	Biotechnology & Applied Microbiology; Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	EL3JH	WOS:000394514900001	28255246	Green Published, Green Submitted, gold			2022-04-25	
J	Li, SY; Chen, S; Wang, BX; Zhang, L; Su, YN; Zhang, XP				Li, Shuyuan; Chen, Shuo; Wang, Boxue; Zhang, Lin; Su, Yinan; Zhang, Xipeng			A Robust 6-lncRNA Prognostic Signature for Predicting the Prognosis of Patients With Colorectal Cancer Metastasis	FRONTIERS IN MEDICINE			English	Article						colorectal cancer; metastasis; prognosis; long non-coding RNAs; prognostic signature	NONCODING RNA SIGNATURE; EXPRESSION; SURVIVAL; CERNA; SET	Objective: Our study aimed to construct a robust long non-coding RNA (lncRNA) prognostic signature for colorectal cancer (CRC) metastasis. Methods: Differentially expressed lncRNAs were identified between metastatic CRC and non-metastatic CRC samples from The Cancer Genome Atlas Database (TCGA) using the edgeR package. The differentially expressed lncRNAs with prognosis of patients with CRC metastasis were identified by univariate Cox regression analysis, followed by a stepwise multivariate Cox regression model. The survminer package in R was used to identify the optimal cutoff point for high-risk and low-risk groups. The receiver operating characteristic (ROC) curves were plotted to assess this signature. To explore potential signaling pathways associated with these lncRNAs, Gene Set Enrichment Analysis (GSEA) was performed. Results: A 6-lncRNA signature was built based on the lncRNA expression profile for CRC metastasis. The optimal cutoff value was used to classify high-risk and low-risk groups using the survminer package. The high-risk groups could have poorer survival time than the low-risk groups. ROC curve result indicated that this lncRNA signature had high sensitivity and accuracy. GSEA analysis results showed that the six lncRNAs were significantly enriched in several CRC metastasis-related signaling pathways such as "cell cycle," "DNA replication," "mismatch repair," "oxidative phosphorylation," "regulation of autophagy," and "insulin signaling pathway." Conclusion: Our study constructed a 6-lncRNA model for predicting the survival outcomes of patients with CRC metastasis, which could become potential prognostic biomarkers, and therapeutic targets for CRC metastasis.	[Li, Shuyuan; Chen, Shuo; Wang, Boxue; Zhang, Lin; Su, Yinan; Zhang, Xipeng] Tianjin Union Med Ctr, Dept Colorectal Surg, Tianjin, Peoples R China		Zhang, XP (corresponding author), Tianjin Union Med Ctr, Dept Colorectal Surg, Tianjin, Peoples R China.	zhangxipeng2016@sina.com			Foundation of Tianjin Union Medical Center [2016RMNK002]	This work was funded by The Foundation of Tianjin Union Medical Center (2016RMNK002).	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Med.	MAR 6	2020	7								56	10.3389/fmed.2020.00056			10	Medicine, General & Internal	Science Citation Index Expanded (SCI-EXPANDED)	General & Internal Medicine	LC3MK	WOS:000525228800001	32211413	Green Published, gold			2022-04-25	
J	Yan, SY; Li, QQ; Zhang, DR; Wang, XW; Xu, Y; Zhang, C; Guo, DL; Bao, YH				Yan, Siyuan; Li, Qianqian; Zhang, Deru; Wang, Xiaowen; Xu, Yang; Zhang, Cong; Guo, Dongli; Bao, Yonghua			Necroptosis pathway blockage attenuates PFKFB3 inhibitor-induced cell viability loss and genome instability in colorectal cancer cells	AMERICAN JOURNAL OF CANCER RESEARCH			English	Article						PFKFB3; necroptosis; genome instability; colorectal cancer; cell viability	MIXED LINEAGE KINASE; MOLECULAR-MECHANISMS; RIP1 KINASE; DNA-REPAIR; DEATH; AUTOPHAGY; APOPTOSIS; CASPASE-8; GROWTH	Cancer cells prone to utilize aerobic glycolysis other than oxidative phosphorylation to sustain its continuous cell activity in the stress microenvironment. Meanwhile, cancer cells generally suffer from genome instability, and both radiotherapy and chemotherapy may arouse DNA strand break, a common phenotype of genome instability. Glycolytic enzyme PFKFB3 (6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3), plays essential roles in variety physiology and pathology processes, and generally maintain high level in cancer cells. Although this protein has been reported to involve in genome instability, its role remains unclear and controversial. Here, we showed that PFK-15, a PFKFB3 inhibitor, obviously induced apoptosis, cell viability loss, and inhibited cell proliferation/migration. Besides, PFK-15 was also found to induce necroptosis, as it not only up-regulated the phosphorylated RIP1, RIP3 and MLKL, but also enhanced the interaction between RIP3 and RIP1/MLKL, all of which are characterization of necroptosis induction. Both genetically and pharmacologically deprivation of necroptosis attenuated the cytotoxic effect of PFK-15. Besides, PFK-15 increased the gamma-H2AX level and micronuclei formation, markers for genome instability, and inhibition of necroptosis attenuated these phenotypes. Collectively, the presented data demonstrated that PFK-15 induced genome instability and necroptosis, and deprivation of necroptosis attenuated cytotoxicity and genotoxicity of PFK-15 in colorectal cancer cells, thereby revealing a more intimate relationship among PFKFB3, necroptosis and genome instability.	[Yan, Siyuan; Li, Qianqian; Zhang, Deru; Wang, Xiaowen; Xu, Yang; Zhang, Cong; Bao, Yonghua] Jining Med Univ, Inst Precis Med, Key Lab Precis Oncol Shandong Higher Educ, Jining 272067, Peoples R China; [Guo, Dongli] Jining Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp, Jining 272000, Peoples R China		Yan, SY (corresponding author), Jining Med Univ, Inst Precis Med, Key Lab Precis Oncol Shandong Higher Educ, Jining 272067, Peoples R China.				National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31801169]; Faculty Startup Funds from Jining Medical University; Teacher Research Support Foundation in Jining medical university [JYFC2018KJ065]; Student Innovation Training Program in Jining Medical University [cx2019-010, 201702010332]	This work was supported by grants from the National Natural Science Foundation of China (31801169 to Yan S.) , The Faculty Startup Funds from Jining Medical University (to Yan S.) , the Teacher Research Support Foundation in Jining medical university (JYFC2018KJ065 to Yan S.) , and The Student Innovation Training Program in Jining Medical University (cx2019-010, 201702010332) .	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J. Cancer Res.		2021	11	5					2062	+					27	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	SI3FY	WOS:000654712200001	34094669				2022-04-25	
J	Jin, GY; Liu, YH; Zhang, J; Bian, ZH; Yao, SR; Fei, BJ; Zhou, LY; Yin, Y; Huang, ZH				Jin, Guoying; Liu, Yuhang; Zhang, Jia; Bian, Zehua; Yao, Surui; Fei, Bojian; Zhou, Leyuan; Yin, Yuan; Huang, Zhaohui			A panel of serum exosomal microRNAs as predictive markers for chemoresistance in advanced colorectal cancer	CANCER CHEMOTHERAPY AND PHARMACOLOGY			English	Article						Colorectal cancer; Chemoresistance; Exosome; MicroRNAs	PROMOTES CELL-PROLIFERATION; DRUG-RESISTANCE; SENSITIVITY; STATISTICS; BIOMARKERS; DIAGNOSIS; INVASION; TARGETS; MIRNAS	BackgroundChemoresistance is a common problem for cancer treatment worldwide. Circulating exosomal microRNAs (miRNAs) have been considered as promising biomarkers of cancers. However, few studies have assessed the relationship between serum/plasma exosomal microRNAs and chemoresistance in colorectal cancer (CRC).MethodsBased on previous microarray analysis, we selected 30 miRNAs which are aberrantly expressed during CRC progression and then detected their expression levels in three pairs of oxaliplatin/5-fluorouracil-resistant CRC cell lines and the corresponding secreted exosomes. Six candidate exosomal miRNAs were identified for further evaluating potential value in predicting chemotherapeutic effect in advanced CRC patients. Finally, the molecular mechanisms of these miRNAs in drug resistance were explored by bioinformatics preliminarily.ResultsWe observed that the expression of 14 miRNAs was significantly higher in three drug-resistant CRC cells comparing with their parental cells. Among these miRNAs, miR-21-5p, miR-1246, miR-1229-5p, miR-135b, miR-425 and miR-96-5p are also up-regulated in exosomes from culture media of resistant cells. Clinical sample analysis confirmed that the expression levels of miR-21-5p, miR-1246, miR-1229-5p and miR-96-5p in serum exosomes were significantly higher in chemoresistant patients in contrast with chemosensitive controls. ROC curve showed that the combination of the four miRNAs had an area of under the curve (AUC) of 0.804 (P<0.05). In addition, GO analysis and KEGG pathway analysis revealed that these miRNAs were enriched in PI3K-Akt signaling pathway, FoxO signaling pathway and autophagy pathway.ConclusionsOur study demonstrates that a panel of serum exosomal miRNAs containing miR-21-5p, miR-1246, miR-1229-5p and miR-96-5p could significantly distinguish the chemotherapy-resistant group from advanced colorectal cancer patients. Targeting these miRNAs may promote chemosensitivity to oxaliplatin and 5-fluorouracil, and might be promising strategy for CRC treatment.	[Jin, Guoying; Liu, Yuhang; Zhang, Jia; Bian, Zehua; Yao, Surui; Yin, Yuan; Huang, Zhaohui] Jiangnan Univ, Affiliated Hosp, Wuxi Canc Inst, 200 Huihe Rd, Wuxi 214062, Jiangsu, Peoples R China; [Jin, Guoying; Liu, Yuhang; Zhang, Jia; Bian, Zehua; Yao, Surui; Yin, Yuan; Huang, Zhaohui] Jiangnan Univ, Wuxi Sch Med, Canc Epigenet Program, Wuxi 214122, Jiangsu, Peoples R China; [Fei, Bojian] Jiangnan Univ, Affiliated Hosp, Dept Surg Oncol, Wuxi 214062, Jiangsu, Peoples R China; [Zhou, Leyuan] Jiangnan Univ, Affiliated Hosp, Dept Radiat Oncol, Wuxi 214062, Jiangsu, Peoples R China		Yin, Y; Huang, ZH (corresponding author), Jiangnan Univ, Affiliated Hosp, Wuxi Canc Inst, 200 Huihe Rd, Wuxi 214062, Jiangsu, Peoples R China.; Yin, Y; Huang, ZH (corresponding author), Jiangnan Univ, Wuxi Sch Med, Canc Epigenet Program, Wuxi 214122, Jiangsu, Peoples R China.	yinyuandiana@163.com; hzhwxsy@126.com	Yin, Yuan/AAG-1707-2020; Huang, Zhaohui/S-9410-2019	Huang, Zhaohui/0000-0002-0117-9976	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672328, 81772636]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [NOJUSRP51619B, JUSRP51710A]; Medical Key Professionals Program of Jiangsu Province [AF052141]; Medical Youth Professionals Program of Jiangsu Province [QNRC2016162]; Medical Innovation Team Program of Wuxi [CXTP003]; National First-class Discipline Program of Food Science and Technology [JUFSTR20180101]; Project of the Wuxi Health and Family Planning Commission [Z201806]	This study was partially supported by grants from the National Natural Science Foundation of China (81672328 and 81772636), Fundamental Research Funds for the Central Universities (NOJUSRP51619B and JUSRP51710A), Medical Key Professionals Program of Jiangsu Province (AF052141), Medical Youth Professionals Program of Jiangsu Province (QNRC2016162), Medical Innovation Team Program of Wuxi (CXTP003), National First-class Discipline Program of Food Science and Technology (JUFSTR20180101), Project of the Wuxi Health and Family Planning Commission (Z201806).	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Pharmacol.	AUG	2019	84	2					315	325		10.1007/s00280-019-03867-6			11	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	IJ1VG	WOS:000475686400010	31089750				2022-04-25	
J	Deshpande, NP; Wilkins, MR; Castano-Rodriguez, N; Bainbridge, E; Sodhi, N; Riordan, SM; Mitchell, HM; Kaakoush, NO				Deshpande, Nandan P.; Wilkins, Marc R.; Castano-Rodriguez, Natalia; Bainbridge, Emily; Sodhi, Nidhi; Riordan, Stephen M.; Mitchell, Hazel M.; Kaakoush, Nadeem O.			Campylobacter concisus pathotypes induce distinct global responses in intestinal epithelial cells	SCIENTIFIC REPORTS			English	Article							INFLAMMATORY-BOWEL-DISEASE; COMPARATIVE GENOMICS; COLORECTAL-CANCER; INDUCED APOPTOSIS; TIGHT JUNCTIONS; VIBRIO-CHOLERAE; ASSOCIATION; MICROBIOTA; INFECTION; AUTOPHAGY	The epithelial response to the opportunistic pathogen Campylobacter concisus is poorly characterised. Here, we assessed the intestinal epithelial responses to two C. concisus strains with different virulence characteristics in Caco-2 cells using RNAseq, and validated a subset of the response using qPCR arrays. C. concisus strains induced distinct response patterns from intestinal epithelial cells, with the toxigenic strain inducing a significantly more amplified response. A range of cellular functions were significantly regulated in a strain-specific manner, including epithelial-to-mesenchymal transition (NOTCH and Hedgehog), cytoskeletal remodeling, tight junctions, inflammatory responses and autophagy. Pattern recognition receptors were regulated, including TLR3 and IFI16, suggesting that nucleic acid sensing was important for epithelial recognition of C. concisus. C. concisus zonula occludens toxin (ZOT) was expressed and purified, and the epithelial response to the toxin was analysed using RNAseq. ZOT upregulated PAR2 expression, as well as processes related to tight junctions and cytoskeletal remodeling. C. concisus ZOT also induced upregulation of TLR3, pro-inflammatory cytokines IL6, IL8 and chemokine CXCL16, as well as the executioner caspase CASP7. Here, we characterise distinct global epithelial responses to C. concisus strains, and the virulence factor ZOT, and provide novel information on mechanisms by which this bacterium may affect the host.	[Deshpande, Nandan P.; Wilkins, Marc R.] UNSW Australia, Sch Biotechnol & Biomol Sci, Syst Biol Initiat, Sydney, NSW 2052, Australia; [Wilkins, Marc R.; Castano-Rodriguez, Natalia; Bainbridge, Emily; Sodhi, Nidhi; Mitchell, Hazel M.] UNSW Australia, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia; [Wilkins, Marc R.] UNSW Australia, Ramaciotti Ctr Gene Funct Anal, Sydney, NSW 2052, Australia; [Riordan, Stephen M.] Prince Wales Hosp, Gastrointestinal & Liver Unit, Randwick, NSW 2031, Australia; [Kaakoush, Nadeem O.] UNSW Australia, Sch Med Sci, Sydney, NSW 2052, Australia		Kaakoush, NO (corresponding author), UNSW Australia, Sch Med Sci, Sydney, NSW 2052, Australia.	n.kaakoush@unsw.edu.au	Kaakoush, Nadeem/ABG-9499-2020	Kaakoush, Nadeem Omar/0000-0003-4017-1077; Castano-Rodriguez, Natalia/0000-0001-8819-8872	Cancer Institute NSW Career Development Fellowship [15/CDF/1-11]; Australian Federal Government NCRIS SchemeAustralian GovernmentDepartment of Industry, Innovation and Science; New South Wales State Government RAAP Scheme; University of New South Wales; Ministry of Higher Education, MalaysiaMinistry of Education, Malaysia [UM.C/625/HIR/MOHE/CHAN/13/1]	This work was supported by a Cancer Institute NSW Career Development Fellowship (15/CDF/1-11 to N.O.K.). M.R.W. and N.P.D. acknowledge funding from the Australian Federal Government NCRIS Scheme, the New South Wales State Government RAAP Scheme and the University of New South Wales. H.M.M. receives funding from the Ministry of Higher Education, Malaysia (UM.C/625/HIR/MOHE/CHAN/13/1).	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J	Friedhuber, AM; Chandolu, V; Manchun, S; Donkor, O; Sriamornsak, P; Dass, CR				Friedhuber, Anna M.; Chandolu, Vijay; Manchun, Somkamon; Donkor, Osaana; Sriamornsak, Pornsak; Dass, Crispin R.			Nucleotropic doxorubicin nanoparticles decrease cancer cell viability, destroy mitochondria, induce autophagy and enhance tumour necrosis	JOURNAL OF PHARMACY AND PHARMACOLOGY			English	Article						cancer; doxorubicin; efficacy; nanoparticle; nucleus	EPITHELIUM-DERIVED FACTOR; DELIVERY-SYSTEMS; CHITOSAN NANOPARTICLES; DRUG-RESISTANCE; GENE DELIVERY; MURINE MODEL; C-JUN; OSTEOSARCOMA; GROWTH; THERAPY	Objective Doxorubicin (Dox) is used clinically against various neoplasias, but suffers from serious side effects, and for the past three decades, this shortcoming has spurred research towards finding better drug delivery systems (DDSs) for this frontline drug. Methods A non-targeted nucleotropic Dox-loaded nanoparticle (DNP) DDS is described, which has a simple chemical design, is easy to formulate and administer, is inexpensive, non-biohazardous and may prove to be useful clinically. Key findings The DNP formulated via vortex-assisted complex coarcevation enhanced (300-fold) cell-inhibitory activity of the drug in a panel of human cancer cells (osteosarcoma, breast, prostate and colorectal cancer) and enhanced (10-fold) efficacy against osteosarcoma (OS) in vivo. The slow-release DNPs localised to the endoplasmic reticulum disrupted the mitochondria and entered the nucleus. Prominent cytosolic vacuolisation, budding off of portions of the cytoplasm, both suggestive of autophagy, were observed. Mice that were administered with DNPs intratumorally had the smallest tumours at the end of the study, with more necrotic hotspots. Conclusion This promising nucleotropic DDS enhances the cell delivery and activity of Dox against a variety of human cancer cell lines and in OS tumours in mice.	[Friedhuber, Anna M.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia; [Chandolu, Vijay] Victoria Univ, Canc Res Lab, Melbourne, Vic 8001, Australia; [Donkor, Osaana] Victoria Univ, Coll Hlth & Biomed, Melbourne, Vic 8001, Australia; [Dass, Crispin R.] Curtin Univ, Sch Pharm, Perth, WA 6845, Australia; [Dass, Crispin R.] Curtin Univ, Perth, WA 6845, Australia; [Manchun, Somkamon; Sriamornsak, Pornsak] Silpakorn Univ, Dept Pharmaceut Technol, Nakhon Pathom, Thailand; [Sriamornsak, Pornsak] Silpakorn Univ, Pharmaceut Biopolymer Grp PBiG, Nakhon Pathom, Thailand		Dass, CR (corresponding author), Curtin Univ, Sch Pharm, Bldg 306, Perth, WA 6102, Australia.	crispin.dass@curtin.edu.au	Sriamornsak, Pornsak/F-5850-2010	Sriamornsak, Pornsak/0000-0002-5525-1494	Curtin Academic50 scheme; Australia/New Zealand (ANZ) Bank grant; Thailand Research FundThailand Research Fund (TRF)	The authors acknowledge the support of a Curtin Academic50 scheme to CRD, an Australia/New Zealand (ANZ) Bank grant to CRD, and a Thailand Research Fund allowance to PS and SM.	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Pharm. Pharmacol.	JAN	2015	67	1					68	77		10.1111/jphp.12322			10	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	AX5ZU	WOS:000347004100007	25208603				2022-04-25	
J	Pan, L; Li, Y; Jin, L; Li, J; Xu, AX				Pan, Li; Li, Yi; Jin, Li; Li, Jing; Xu, Aixiang			TRPM2-AS promotes cancer cell proliferation through control of TAF15	INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY			English	Article						TRPM2-AS; TAF15; TRPM2; Colorectal cancer	UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; APOPTOSIS; AUTOPHAGY; DOCETAXEL; PATHWAY; RNA	Background: Colorectal cancer (CRC) ranks the third among all common malignancy worldwide. Long noncoding RNAs (lncRNAs) have been demonstrated as implicated in CRC, but the roles of many lncRNAs in CRC remain unclear. Exploration of lncRNA TRMP2-AS and its nearby gene in CRC progress was the focus of current study. Methods: The expression of TRPM2-AS and its nearby mRNA TRPM2 was measured by using RT-qPCR. The protein levels of TRPM2 and TAF15 were determined using western blot. Cell proliferation was detected by using CCK-8, colony formation and EdU assays. The interaction between TAF15 and TRPM2-AS or TRPM2 was evaluated by RNA pull-down and RIP assays. The TRPM2 mRNA stability was probed using the transcriptional inhibitor Actinomycin D. Results: TRPM2-AS was significantly upregulated in CRC cells. Knock-down of TRPM2-AS inhibited CRC cell proliferation. Mechanically, TRPM2-AS directly interacted with RNA-binding protein (RBP) TAF15 and thus maintained the mRNA stability of TRPM2. TRPM2 was a prerequisite for TRPM2-AS to exert its promoting function in CRC cell proliferation. Conclusion: This research demonstrated that TRPM2-AS facilitated proliferation of CRC cells by enhancing TAF15-mediated mRNA stability of TRPM2, unmasking the role of TRPM2-AS in CRC.	[Pan, Li; Jin, Li] Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sch Med, Radiotherapy Dept, Chengdu, Peoples R China; [Li, Yi] Univ Elect Sci & Technol China, Acad Med Sci, Dept Gastroenterol & Hepatol, Affiliated Hosp, Chengdu 610000, Sichuan, Peoples R China; [Li, Yi] Univ Elect Sci & Technol China, Acad Med Sci, Sichuan Prov Peoples Hosp, Chengdu 610000, Sichuan, Peoples R China; [Li, Jing] Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sch Med, Dept Gen Internal Med, Chengdu, Peoples R China; [Xu, Aixiang] Zaozhuang Tradit Chinese Med Hosp, Dept Outpatient, 2666 Taihang Mt Rd, Zaozhuang 277000, Shandong, Peoples R China		Xu, AX (corresponding author), Zaozhuang Tradit Chinese Med Hosp, Dept Outpatient, 2666 Taihang Mt Rd, Zaozhuang 277000, Shandong, Peoples R China.; Li, J (corresponding author), Univ Elect Sci & Technol China, Dept Gen Internal Med, Sichuan Canc Hosp & Inst, 55,Sect 4,Renmin South Rd, Chengdu, Peoples R China.; Li, J (corresponding author), Univ Elect Sci & Technol China, Sch Med, 55,Sect 4,Renmin South Rd, Chengdu, Peoples R China.	ligu637279897@163.com; zai47077303962@163.com					Ballarino M, 2013, ONCOGENE, V32, P4646, DOI 10.1038/onc.2012.490; Bertuzzi M, 2015, BMC CANCER, V15, DOI 10.1186/s12885-015-1058-7; Bester AC, 2018, CELL, V173, P649, DOI 10.1016/j.cell.2018.03.052; Chan THM, 2014, GUT, V63, P832, DOI 10.1136/gutjnl-2012-304037; Cheng X, 2018, CANCER LETT, V431, P105, DOI 10.1016/j.canlet.2018.05.046; Cubillos-Ruiz JR, 2017, CELL, V168, P692, DOI 10.1016/j.cell.2016.12.004; Davila-Gonzalez D, 2018, CLIN CANCER RES, V24, P1152, DOI 10.1158/1078-0432.CCR-17-1437; Fatica A, 2014, NAT REV GENET, V15, P7, DOI 10.1038/nrg3606; Frakes AE, 2017, MOL CELL, V66, P761, DOI 10.1016/j.molcel.2017.05.031; Galluzzi L, 2017, NAT REV CLIN ONCOL, V14, P247, DOI 10.1038/nrclinonc.2016.183; Hetz C, 2012, NAT REV MOL CELL BIO, V13, P89, DOI 10.1038/nrm3270; Heymach JV, 2014, ANN ONCOL, V25, P1941, DOI 10.1093/annonc/mdu269; Ibrahim S, 2019, CANCERS, V11, DOI 10.3390/cancers11040561; Igder S., 2019, KRAS MUTATION ABNORM; Jiang DD, 2015, SEMIN CANCER BIOL, V33, P48, DOI 10.1016/j.semcancer.2015.04.010; Lebedeva S, 2011, MOL CELL, V43, P340, DOI 10.1016/j.molcel.2011.06.008; Loktionov A, 2019, EUR J GASTROEN HEPAT, V31, P1220, DOI 10.1097/MEG.0000000000001535; Senft D, 2015, TRENDS BIOCHEM SCI, V40, P141, DOI 10.1016/j.tibs.2015.01.002; Walter P, 2011, SCIENCE, V334, P1081, DOI 10.1126/science.1209038; Wang C, 2019, ONCOGENE, V38, P1611, DOI 10.1038/s41388-018-0548-x; Wang JW, 2018, AUTOPHAGY, V14, P2007, DOI 10.1080/15548627.2018.1501133; Wang YH, 2017, CANCER LETT, V393, P8, DOI 10.1016/j.canlet.2017.01.036; Wu XC, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-1699-6; Yarom N., 2019, CLIN COLORECTAL CANC, DOI [10.1016/j.cicc.2019.05.004, DOI 10.1016/J.CICC.2019.05.004]; Zhang W, 2019, MOL ONCOL, V13, P2194, DOI 10.1002/1878-0261.12560; Zhu XL, 2017, CELL DEATH DISCOV, V3, DOI 10.1038/cddiscovery.2017.59	26	19	19	2	8	PERGAMON-ELSEVIER SCIENCE LTD	OXFORD	THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND	1357-2725	1878-5875		INT J BIOCHEM CELL B	Int. J. Biochem. Cell Biol.	MAR	2020	120								105683	10.1016/j.biocel.2019.105683			8	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	KO0AR	WOS:000515208900006	31887411				2022-04-25	
J	Wu, XY; Chen, J; Cao, QH; Dong, M; Lin, Q; Fan, XJ; Xia, Q; Chen, ZH; Liu, QT; Wan, XB				Wu, Xiang-Yuan; Chen, Jie; Cao, Qing-Hua; Dong, Min; Lin, Qu; Fan, Xin-Juan; Xia, Qing; Chen, Zhan-Hong; Liu, Quentin; Wan, Xiang-Bo			Beclin 1 activation enhances chemosensitivity and predicts a favorable outcome for primary duodenal adenocarcinoma	TUMOR BIOLOGY			English	Article						Autophagy; Beclin 1; HIF-1 alpha; Prognostic biomarker; PDA	POOR-PROGNOSIS; MALIGNANT PHENOTYPE; COLORECTAL-CANCER; GASTRIC-CANCER; AUTOPHAGY; EXPRESSION; CELLS; FLUOROURACIL; OXALIPLATIN; LEUCOVORIN	We and others had proven that hypoxia-induced autophagy was essential to regulate cancer cell destiny under anticancer therapeutic stress. Here, we addressed the clinicopathologic effect of HIF-1 alpha and autophagic Beclin 1 in primary duodenal adenocarcinoma (PDA). HIF-1 alpha and Beclin 1 expression level were semi-quantitatively evaluated using tissue microarrays and immunohistochemistry (IHC) staining in 141 PDA patients. Among these patients, 77 acted as training set to select HIF-1 alpha and Beclin 1 IHC cutoff score for patient outcome, and 64 cases were used as testing set to evaluate their prognostic effect. We found that Beclin 1 was cytoplasmic overexpressed, defined by training set fixed cutoff point, in 49.6 % PDA tissue, compared to 46.8 % patients had HIF-1 alpha high expression. In testing set, Beclin 1 overexpression predicted a superior 5-year overall survival (OS) in both univariate (P = 0.010) and multivariate (P = 0.017) analyses. However, we did not detect any correlation between HIF-1 alpha level and patient prognosis (P = 0.989). Significantly, among Beclin 1 overexpressed patients, radical surgery plus adjuvant chemotherapy had a 23.1-month OS improvement than given radical surgery alone (59.2 vs 36.1 months; P = 0.01). For Beclin 1 lowly expressed patients, radical surgery plus adjuvant chemotherapy and given radical surgery alone had the similar OS (P = 0.283). Contrary to previous studies, we failed to detect any correlation between Beclin 1 and HIF-1 alpha levels in PDA (correlation coefficient 0.217, P = 0.099). In conclusions, our results confirmed that Beclin 1 was a favorable prognostic biomarker for PDA, and might be used to identify particular patients for more selective therapy.	[Wu, Xiang-Yuan; Chen, Jie; Dong, Min; Lin, Qu; Chen, Zhan-Hong; Wan, Xiang-Bo] Sun Yat Sen Univ, Dept Med Oncol, Affiliated Hosp 3, Guangzhou 510630, Guangdong, Peoples R China; [Cao, Qing-Hua] Sun Yat Sen Univ, Dept Pathol, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China; [Fan, Xin-Juan] Sun Yat Sen Univ, Dept Pathol, Gastrointestinal Inst, Affiliated Hosp 6, Guangzhou 510655, Guangdong, Peoples R China; [Xia, Qing; Liu, Quentin] Sun Yat Sen Univ, State Key Lab Oncol South China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China		Wu, XY (corresponding author), Sun Yat Sen Univ, Dept Med Oncol, Affiliated Hosp 3, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China.	wuxiangy@mail.sysu.edu.cn; wanxbo@mail.sysu.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81000934]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities; Science and Technology Foundation of Guangdong Province [2009B060700024, 2011B03180076]	This work was supported by National Natural Science Foundation of China (No. 81000934 to X. B. Wan), the Fundamental Research Funds for the Central Universities (to X. B. Wan), Science and Technology Foundation of Guangdong Province (2009B060700024 to X.Y. Wu and 2011B03180076 to Q. Lin).	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APR	2013	34	2					713	722		10.1007/s13277-012-0599-5			10	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	109JX	WOS:000316364500013	23225331				2022-04-25	
J	Cui, FC; Chen, Y; Wu, XY; Hu, M; Qin, WS				Cui, F. -C.; Chen, Y.; Wu, X. -Y.; Hu, M.; Qin, W. -S.			MicroRNA-493-5p suppresses colorectal cancer progression via the PI3K-Akt-FoxO3a signaling pathway	EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES			English	Article						MiR-493-5p; Colorectal cancer; PI3K-Akt-FoxO3a signaling pathway; Migration; Progression	CELLS; PROMOTES; INVASION; METASTASIS; PROLIFERATION; GLYCOLYSIS; AUTOPHAGY; MIGRATION; GROWTH; PI3K	OBJECTIVE: MicroRNA493-5p (miR-493-5p) appears to have an essential role in the abnormal cell proliferation and migration observed in the development and progression of various cancers. However, the function and mechanism of action of miR-493-5p in colorectal cancer (CRC) is unclear. PATIENTS AND METHODS: MiR-493-5p expression was analyzed in CRC patient tissue samples and cell lines by fluorescence quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). SW480 and Caco-2 cells were transfected with miR-493-5p mimics or treated with the phosphoinositide 3-kinase (PI3K) agonist 740Y-P. Cell proliferation was determined by colony formation and cell proliferation assays and cell migration and invasion by transwell migration and wound-healing assays. The Luciferase reporter assay was used to verify the association between the expression of miR-493-5p and PI3K activity. Expression levels of PI3K, protein kinase B(Akt). and forkhead box O 3a (FoxO3a) proteins were measured by Western blot analysis and immunofluorescence assay. RESULTS: MiR-493-5p expression was significantly downregulated in CRC tissue samples and cell lines which was associated with progression of CRC. The proliferation, migration, and invasion of CRC cells were inhibited by miR-493-5p overexpression, The finding that miR-493-5p upregulation decreased PI3K. Akt, and FoxO3a protein expression revealed that it directly targets PI3K. Additionally, the miR-493-5p-mediated suppression of CRC cell proliferation, migration and invasion was counteracted by the PI3K agonist, indicating that miR-493-5p suppresses CRC progression by inhibiting the PI3K-Akt-FoxO3a signaling pathway. CONCLUSIONS: MiR-493-5p suppresses the proliferation, migration, invasion, and progression of CRC via the PI3K-Akt-FoxO3a signaling pathway.	[Cui, F. -C.; Wu, X. -Y.; Hu, M.; Qin, W. -S.] Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Clin Lab, Peoples Hosp, Zhengzhou, Henan, Peoples R China; [Chen, Y.] Zhengzhou Univ, Dept Pathol, Affiliated Tumor Hosp, Zhengzhou, Henan, Peoples R China		Cui, FC (corresponding author), Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Clin Lab, Peoples Hosp, Zhengzhou, Henan, Peoples R China.	facaichn@163.com					Ain A, 2015, CANC LETT, V359, P47; ar FM, 2016, CHIN CLIN ONCOL, V5, P76; Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI 10.3322/caac.21492; Challagundla KB, 2014, EXPERT REV MOL DIAGN, V14, P565, DOI 10.1586/14737159.2014.922879; Cui ZH, 2019, ONCOTARGETS THER, V12, P11531, DOI 10.2147/OTT.S229104; Deng FL, 2019, THERANOSTICS, V9, P1001, DOI 10.7150/thno.30056; DeSantis CE, 2014, CA-CANCER J CLIN, V64, P252, DOI 10.3322/caac.21235; Dijkers PF, 2002, J CELL BIOL, V156, P531; Engelman JA, 2009, NAT REV CANCER, V9, P550, DOI 10.1038/nrc2664; Garrido-Laguna I, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0038033; Ji X, 2019, J CELL BIOCH; Kopetz S, 2009, J CLIN ONCOL, V27, P3677, DOI 10.1200/JCO.2008.20.5278; Kudo-Saito C, 2009, CANCER CELL, V15, P195, DOI 10.1016/j.ccr.2009.01.023; Li Z, 2013, MOL CELL BIOCHEM, V381, P233, DOI 10.1007/s11010-013-1707-6; Liang CC, 2019, INT J CLIN EXP PATHO, V12, P4011; Liang Z, 2017, ONCOTARGET, V8, P47389, DOI 10.18632/oncotarget.17650; Liao RF, 2017, MOL NEUROBIOL, V54, P6931, DOI 10.1007/s12035-016-0211-x; Luo H, 2013, CELL DEATH DIS, V4, DOI 10.1038/cddis.2013.3; Pan S, 2020, LIFE SCI, V244; Sbarouni E, 2018, J THORAC DIS, V10, P1256, DOI 10.21037/jtd.2018.03.27; Stacey DW, 2003, CURR OPIN CELL BIOL, V15, P158, DOI 10.1016/S0955-0674(03)00008-5; Sun L, 2020, J CANCER, V11, P630, DOI 10.7150/jca.33022; Syed DN, 2014, BIOCHEM PHARMACOL, V89, P349, DOI 10.1016/j.bcp.2014.03.007; Tenbaum SP, 2012, NAT MED, V18, P892, DOI 10.1038/nm.2772; Vannini I, 2018, CURR OPIN GENET DEV, V48, P128, DOI 10.1016/j.gde.2018.01.001; Vara JAF, 2004, CANCER TREAT REV, V30, P193, DOI 10.1016/j.ctrv.2003.07.007; Vucicevic L, 2011, AUTOPHAGY, V7, P40, DOI 10.4161/auto.7.1.13883; Wang GN, 2018, INT J MOL MED, V41, P1740, DOI 10.3892/ijmm.2018.3358; Wang K, 2016, AUTOPHAGY, V12, P2498, DOI 10.1080/15548627.2016.1231494; Wang S, 2017, ONCOTARGET, V8, P82303, DOI 10.18632/oncotarget.19398; Wei QD, 2019, INT J CLIN EXP PATHO, V12, P1565; Wu FL, 2018, INT J CLIN EXP PATHO, V11, P3943; Yan S, 2019, MEDIATORS INFLAMM 20, V2019; Yasukawa K, 2020, CANCER SCI, V111, P869, DOI 10.1111/cas.14292; Zhang Y, 2019, CANCER CELL INT, V19, DOI 10.1186/s12935-019-1053-1; Zhang ZQ, 2019, J CELL PHYSIOL, V234, P13525, DOI 10.1002/jcp.28030; Zhao LF, 2016, ONCOL REP, V36, P1007, DOI 10.3892/or.2016.4882	37	4	5	0	1	VERDUCI PUBLISHER	ROME	VIA GREGORIO VII, ROME, 186-00165, ITALY	1128-3602			EUR REV MED PHARMACO	Eur. Rev. Med. Pharmacol. Sci.	APR	2020	24	8					4212	4223					12	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	LO7BQ	WOS:000533783000027	32373957				2022-04-25	
J	Hsu, YC; Huang, TY; Chen, MJ				Hsu, Y-C; Huang, T-Y; Chen, M-J			Therapeutic ROS targeting of GADD45 gamma in the induction of G2/M arrest in primary human colorectal cancer cell lines by cucurbitacin E	CELL DEATH & DISEASE			English	Article						Cucurbitacin E; Colorectal cancer (CRC); G2/M arrest; Growth arrest and DNA damage 45 (GADD45)	NF-KAPPA-B; CYCLE ARREST; APOPTOSIS; AUTOPHAGY; ACTIN; PHOSPHORYLATION; MITOSIS; STRESS; INHIBITORS; TRITERPENE	Cucurbitacin E (CuE) or alpha-elaterin is a natural compound previously shown to be an antifeedant as well as a potent chemopreventive agent against several types of cancer. The present study investigated the anticancer effects of CuE on colorectal cancer (CRC) using primary cell lines isolated from five CRC patients in Taiwan, Specifically, we explored the anti-proliferation and cell cycle G2/M arrest induced by CuE in CRC cells. MPM-2 flow cytometry tests show that CuE-treated cells accumulated in metaphase (CuE 2.5-7.5 mu M). Results further indicate that CuE produced G(2)/M arrest as well as the downregulation of CDC2 and cyclin B1 expression and dissociation. Both effects increased proportionally with the dose of CuE; however, the inhibition of proliferation, arrest of mitosis, production of reactive oxygen species (ROS), and loss of mitochondrial membrane potential (Delta Psi m) were found to be dependent on the quantity of CuE used to treat the cancer cells. In addition, cell cycle arrest in treated cells coincided with the activation of the gene GADD45(alpha, beta, gamma). Incubation with CuE resulted in the binding of GADD45 gamma to CDC2, which suggests that the delay in CuE-induced mitosis is regulated by the overexpression of GADD45 gamma. Our findings suggest that, in addition to the known effects on cancer prevention, CuE may have antitumor activities in established CRC.	[Hsu, Y-C] Chang Jung Christian Univ, Grad Inst Med Sci, Coll Hlth Sci, Tainan 71101, Taiwan; [Hsu, Y-C] Chang Jung Christian Univ, Coll Hlth Sci, Innovat Res Ctr Med, Tainan 71101, Taiwan; [Huang, T-Y] Tainan Sin Lau Hosp, Dept Neurosurg, Tainan, Taiwan; [Chen, M-J] Chi Mei Med Ctr, Dept Surg, Div Traumatol, Tainan, Taiwan; [Chen, M-J] Chia Nan Univ Pharm & Sci, Coll Leisure & Recreat Management, Dept Sports Management, Tainan, Taiwan		Hsu, YC (corresponding author), Chang Jung Christian Univ, Grad Inst Med Sci, 1 Changda Rd, Tainan 71101, Taiwan.	d8702008@tmu.edu.tw	Hsu, Yi-Chiang/AAX-5470-2021; Hsu, Yi-Chiang/AGZ-2083-2022	Hsu, Yi-Chiang/0000-0002-6256-9521; 	National Science Council (Taiwan)Ministry of Science and Technology, Taiwan [NSC100-2313-B-309-001, NSC101-2313-B-309-001]	The authors appreciate the funding support provided by the National Science Council (Taiwan) (grant NSC100-2313-B-309-001) and (NSC101-2313-B-309-001). The authors are also grateful to the technical assistance provided by Ms Ai-Jie Han of Innovative Research Center of Medicine.	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APR	2014	5								e1198	10.1038/cddis.2014.151			8	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	AG5HP	WOS:000335450400044	24763055	Green Published, gold			2022-04-25	
J	Huang, WS; Lin, CT; Chen, CN; Chang, SF; Chang, HI; Lee, KC				Huang, Wen-Shih; Lin, Chien-Tsong; Chen, Cheng-Nan; Chang, Shun-Fu; Chang, Hsin-I; Lee, Ko-Chao			Metformin increases the cytotoxicity of oxaliplatin in human DLD-1 colorectal cancer cells through down-regulating HMGB1 expression	JOURNAL OF CELLULAR BIOCHEMISTRY			English	Article						colorectal cancer; HMGB1; metformin; NF-b; oxaliplatin	NF-KAPPA-B; BOX 1 HMGB1; DRUG-RESISTANCE; PATHWAY; APOPTOSIS; AUTOPHAGY; CHEMOTHERAPY; SENSITIVITY; METASTASIS; INHIBITION	Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide. Chemotherapy has been the major strategy for treating patients with advanced CRC. Oxaliplatin (OXA) is used as both an adjuvant and neoadjuvant anticancer agent available to treat advanced CRC. High-mobility group box 1 protein (HMGB1) is a critical regulator of cell death and survival. HMGB1 overexpression has been shown to be resistant to cytotoxic agents. In addition, Metformin, a widely used drug for diabetes, has emerged as a potential anticancer agent. In this study, we examined whether HMGB1 plays a role in the OXA- and/or metformin-induced cytotoxic effect on CRC cells. The results showed that treatment with OXA increased HMGB1 expression in the ERK1/2- and Akt-dependent manners in DLD-1 cells. HMGB1 gene knockdown enhanced the cytotoxicity and cell growth inhibition of OXA. Moreover, OXA-increased HMGB1 expression was by inducing NF-B-DNA-binding activity to in DLD-1 cells. Compared to a single agent, OXA combined with metformin administration resulted in cytotoxicity and cell growth inhibition synergistically, accompanied with reduced HMGB1 level. These findings may have implications for the rational design of future drug regimens incorporating OXA and metformin for the treatment of CRC. The results of this study suggest that decreasing HMGB1 expression may enhance the therapeutic effect of OXA in patients with CRC and the concept of metformin combined with OXA seems to present a therapeutic strategy for the treatment of CRC.	[Huang, Wen-Shih] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan, Taiwan; [Huang, Wen-Shih] Chang Gung Mem Hosp, Div Colon & Rectal Surg, Dept Surg, Chiayi, Taiwan; [Lin, Chien-Tsong] Natl Formosa Univ, Ctr Gen Educ, Huwei Township, Yunlin, Taiwan; [Lin, Chien-Tsong] Natl Chiayi Univ, Dept Wood Based Mat & Design, Chiayi, Taiwan; [Chen, Cheng-Nan; Chang, Hsin-I] Natl Chiayi Univ, Dept Biochem Sci & Technol, Chiayi, Taiwan; [Chang, Shun-Fu] Chang Gung Mem Hosp, Dept Med Res & Dev, Chiayi Branch, Chiayi, Taiwan; [Lee, Ko-Chao] Chang Gung Mem Hosp, Kaohsiung Med Ctr, Dept Colorectal Surg, Kaohsiung, Taiwan		Lee, KC (corresponding author), Chang Gung Mem Hosp, Dept Colorectal Surg, 123 Taipei Rd, Kaohsiung 833, Taiwan.	kmch4329@gmail.com		Chang, Shun-Fu/0000-0002-2276-7785	Ministry of Science and Technology, TaiwanMinistry of Science and Technology, Taiwan [MOST 105-2314-B-182A-132]; Chang Gung Memorial Hospital-Chiayi branch [CMRPG6E0332, CMRPG6G0301]	Ministry of Science and Technology, Taiwan, Grant number: MOST 105-2314-B-182A-132; Chang Gung Memorial Hospital-Chiayi branch, Grant numbers: CMRPG6E0332, CMRPG6G0301	Al Bandar MH, 2017, ONCOL REP, V37, P2553, DOI 10.3892/or.2017.5531; Banerjee S, 2009, CANCER RES, V69, P5575, DOI 10.1158/0008-5472.CAN-08-4235; Boteanu RM, 2017, J PROTEOMICS, V153, P21, DOI 10.1016/j.jprot.2016.11.006; Chen JL, 2017, CANCER CHEMOTH PHARM, V79, P369, DOI 10.1007/s00280-016-3225-1; Cheng H, 2017, ONCOL LETT, V14, P159, DOI 10.3892/ol.2017.6116; Choi YK, 2013, MOL CELLS, V36, P279, DOI 10.1007/s10059-013-0169-8; Daugan M, 2016, PHARMACOL RES, V113, P675, DOI 10.1016/j.phrs.2016.10.006; Giantonio BJ, 2007, J CLIN ONCOL, V25, P1539, DOI 10.1200/JCO.2006.09.6305; Hanna RK, 2012, GYNECOL ONCOL, V125, P458, DOI 10.1016/j.ygyno.2012.01.009; He WL, 2013, WORLD J SURG ONCOL, V11, DOI 10.1186/1477-7819-11-161; Hongo K, 2015, WORLD J SURG ONCOL, V13, DOI 10.1186/1477-7819-13-7; Hu T, 2016, WORLD J GASTROENTERO, V22, P6876, DOI 10.3748/wjg.v22.i30.6876; Huang J, 2012, CANCER RES, V72, P230, DOI 10.1158/0008-5472.CAN-11-2001; Huang WS, 2015, INT J MOL SCI, V16, P29370, DOI 10.3390/ijms161226174; Kang R, 2013, CLIN CANCER RES, V19, P4046, DOI 10.1158/1078-0432.CCR-13-0495; Kim HG, 2011, BRIT J PHARMACOL, V162, P1096, DOI 10.1111/j.1476-5381.2010.01101.x; Lee Jaeryun, 2017, Dev Reprod, V21, P139, DOI 10.12717/DR.2017.21.2.139; Li L, 2014, CLIN CANCER RES, V20, P2714, DOI 10.1158/1078-0432.CCR-13-2613; Liu WJ, 2015, CANCER BIOL THER, V16, P511, DOI 10.1080/15384047.2015.1017691; Luo QQ, 2012, BMC CANCER, V12, DOI 10.1186/1471-2407-12-517; Mao L, 2017, ONCOL LETT, V14, P647, DOI 10.3892/ol.2017.6209; Martinez-Balibrea E, 2015, MOL CANCER THER, V14, P1767, DOI 10.1158/1535-7163.MCT-14-0636; McQuade RM, 2017, CURR MED CHEM, V24, P1537, DOI 10.2174/0929867324666170111152436; Meng FQ, 2017, J DIABETES RES, V2017, DOI 10.1155/2017/5063239; Mohammad RM, 2015, SEMIN CANCER BIOL, V35, pS78, DOI 10.1016/j.semcancer.2015.03.001; Pancione M, 2017, CURR MED CHEM, V24, P1383, DOI 10.2174/0929867324666170227114356; Peng M, 2016, SCI REP-UK, V6, DOI 10.1038/srep28611; Pires IM, 2010, BRIT J PHARMACOL, V159, P1326, DOI 10.1111/j.1476-5381.2009.00607.x; Punt CJA, 2017, NAT REV CLIN ONCOL, V14, P235, DOI 10.1038/nrclinonc.2016.171; de Porras VR, 2016, SCI REP-UK, V6, DOI 10.1038/srep24675; Song J, 2016, ONCOTARGET, V7, P80803, DOI 10.18632/oncotarget.13096; Stros M, 2010, BBA-GENE REGUL MECH, V1799, P101, DOI 10.1016/j.bbagrm.2009.09.008; Sun Y, 2016, INT J ONCOL, V48, P225, DOI 10.3892/ijo.2015.3256; Sun ZN, 2017, ONCOL LETT, V13, P2377, DOI 10.3892/ol.2017.5722; Takada Y, 2005, J BIOL CHEM, V280, P17203, DOI 10.1074/jbc.M500077200; Tang D, 2010, ONCOGENE, V29, P5299, DOI 10.1038/onc.2010.261; Tang DF, 2017, MED SCI MONIT BASIC, V23, P141, DOI 10.12659/MSMBR.903910; Ueda M, 2014, ANTICANCER RES, V34, P5357; Volp K, 2006, GUT, V55, P234, DOI 10.1136/gut.2004.062729; Wang XB, 2015, INT J MOL SCI, V16, P22527, DOI 10.3390/ijms160922527; Wee P, 2017, CANCERS, V9, DOI 10.3390/cancers9050052; Wegiel B, 2008, INT J CANCER, V122, P1521, DOI 10.1002/ijc.23261; Wiegering A, 2017, NEOPLASIA, V19, P301, DOI 10.1016/j.neo.2017.01.007; Wu TY, 2016, ONCOTARGET, V7, P50417, DOI 10.18632/oncotarget.10413; Xia YF, 2014, CANCER IMMUNOL RES, V2, P823, DOI 10.1158/2326-6066.CIR-14-0112; Yardley DA, 2013, INT J BREAST CANCER, V2013, DOI 10.1155/2013/137414; Zahreddine H, 2013, FRONT PHARMACOL, V4, DOI 10.3389/fphar.2013.00028; Zhang BH, 2016, ONCOL REP, V35, P1807, DOI 10.3892/or.2015.4479; Zhang RG, 2015, TUMOR BIOL, V36, P8585, DOI 10.1007/s13277-015-3617-6; Zhang XL, 2016, ONCOTARGETS THER, V9, P4901, DOI 10.2147/OTT.S105512	50	8	9	1	12	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0730-2312	1097-4644		J CELL BIOCHEM	J. Cell. Biochem.	AUG	2018	119	8					6943	6952		10.1002/jcb.26898			10	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	GK9EG	WOS:000436542900061	29737584				2022-04-25	
J	Pourhanifeh, MH; Mehrzadi, S; Hosseinzadeh, A				Pourhanifeh, Mohammad Hossein; Mehrzadi, Saeed; Hosseinzadeh, Azam			Melatonin and regulation of miRNAs: novel targeted therapy for cancerous and noncancerous disease	EPIGENOMICS			English	Review						angiogenesis; apoptosis; cancer; chemotherapy; gene expression; inflammation; melatonin; metastasis; microRNA; oxidative stress	COLORECTAL-CANCER; OXIDATIVE STRESS; DRUG-RESISTANCE; GENE-EXPRESSION; NONCODING RNA; BREAST-CANCER; UP-REGULATION; ORAL-CANCER; CELL-LINES; AUTOPHAGY	miRNAs, small noncoding RNAs with crucial diagnostic and prognostic capabilities, play essential therapeutic roles in different human diseases. These biomarkers are involved in several biological mechanisms and are responsible for the regulation of multiple genes expressions in cells. miRNA-based therapy has shown a very bright future in the case of clinical interventions. Melatonin, the main product of the pineal gland, is a multifunctional neurohormone with numerous therapeutic potentials in human diseases. Melatonin is able to regulate miRNAs in different pathologies such as malignant and nonmalignant diseases, which can be considered as a novel kind of targeted therapy. Herein, this review discusses possible therapeutic utility of melatonin for the regulation of miRNAs in various pathological conditions.	[Pourhanifeh, Mohammad Hossein; Mehrzadi, Saeed; Hosseinzadeh, Azam] Iran Univ Med Sci, Razi Drug Res Ctr, Tehran, Iran		Hosseinzadeh, A (corresponding author), Iran Univ Med Sci, Razi Drug Res Ctr, Tehran, Iran.	hosseinzadeazam@gmail.com	Hosseinzadeh, Azam/AAN-6886-2021; Mehrzadi, Saeed/AAY-8389-2020	Hosseinzadeh, Azam/0000-0001-6379-5769; Mehrzadi, Saeed/0000-0001-6619-2330; Pourhanifeh, Mohammad Hossein/0000-0002-6752-2765			Ahmadloo N, 2013, J EGYPT NATL CANCER, V25, P21, DOI 10.1016/j.jnci.2012.11.001; Alghamdi BS, 2018, J NEUROSCI RES, V96, P1136, DOI 10.1002/jnr.24220; Ali T, 2019, ARCH BIOCHEM BIOPHYS, V661, P56, DOI 10.1016/j.abb.2018.11.007; Alves AM, 2018, J ORAL PATHOL MED, V47, P460, DOI 10.1111/jop.12643; Anderson G, 2019, BIOCHEM PHARMACOL, V168, P259, DOI 10.1016/j.bcp.2019.07.014; Anderson G, 2019, INT J TRYPTOPHAN RES, V12, DOI 10.1177/1178646919855942; Ang TL, 2014, SINGAP MED J, V55, P621, DOI 10.11622/smedj.2014174; Asghari MH, 2018, LIFE SCI, V196, P143, DOI 10.1016/j.lfs.2018.01.024; 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J	Ryoo, IG; Choi, BH; Ku, SK; Kwak, MK				Ryoo, In-geun; Choi, Bo-hyun; Ku, Sae-Kwang; Kwak, Mi-Kyoung			High CD44 expression mediates p62-associated NFE2L2/NRF2 activation in breast cancer stem cell-like cells: Implications for cancer stem cell resistance	REDOX BIOLOGY			English	Article						CD44; Cancer stem cell (CSC); NFE2L2/NRF2; Reactive oxygen species (ROS); Stress resistance; p62	TRANSCRIPTION FACTOR NRF2; COLORECTAL-CANCER; OXIDATIVE STRESS; IDENTIFICATION; AUTOPHAGY; INHIBITION; SYSTEM; REDOX; KEAP1; CHEMORESISTANCE	Cluster of differentiation 44 (CD44) is the most common cancer stem cell (CSC) marker and high CD44 expression has been associated with anticancer drug resistance, tumor recurrence, and metastasis. In this study, we aimed to investigate the molecular mechanism by which CD44 and nuclear factor erythroid 2-like 2 (NFE2L2; NRF2), a key regulator of antioxidant genes, are linked to CSC resistance using CD44(high) breast CSC-like cells. NRF2 expression was higher in CD44(high) cell populations isolated from doxorubicin-resistant MCF7 (ADR), as well as MCF7, MDA-MB231, and A549 cells, than in corresponding CD44(low) cells. High NRF2 expression in the CD44(high)CD24(low) CSC population (ADR44P) established from ADR cells depended on standard isoform of CD44. Silencing of CD44 or overexpression of CD44 resulted in the reduction or elevation of NRF2, respectively, and treatment with hyaluronic acid, a CD44 ligand, augmented NRF2 activation. As functional implications, NRF2 silencing rendered ADR44P cells to retain higher levels of reactive oxygen species and to be sensitive to anticancer drug toxicity. Moreover, NRF2-silenced ADR44P cells displayed tumor growth retardation and reduced colony/sphere formation and invasion capacity. In line with these, CD44 significantly colocalized with NRF2 in breast tumor clinical samples. The molecular mechanism of CD44-mediated NRF2 activation was found to involve high p62 expression. CD44 elevation led to an increase in p62, and inhibition of p62 resulted in NRF2 suppression in ADR44P. Collectively, our results showed that high CD44 led to p62-associated NRF2 activation in CD44(high) breast CSC-like cells. NRF2 activation contributed to the aggressive phenotype, tumor growth, and anticancer drug resistance of CD44(high) CSCs. Therefore, the CD44-NRF2 axis might be a promising therapeutic target for the control of stress resistance and survival of CD44(high) CSC population within breast tumors.	[Ryoo, In-geun; Kwak, Mi-Kyoung] Catholic Univ Korea, Integrated Res Inst Pharmaceut Sci, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea; [Choi, Bo-hyun; Kwak, Mi-Kyoung] Catholic Univ Korea, Dept Pharm, Grad Sch, Bucheon, Gyeonggi Do, South Korea; [Choi, Bo-hyun; Kwak, Mi-Kyoung] Catholic Univ Korea, PLUS Team Creat Leader Program Pharmac Based Futu, Grad Sch, Bucheon, Gyeonggi Do, South Korea; [Ku, Sae-Kwang] Daegu Haany Univ, Coll Korean Med, Gyongsan 712715, Gyeonsangbuk 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, Coll Pharm, 43 Jibong Ro, Bucheon 14662, Gyeonggi Do, South Korea.	mkwak@catholic.ac.kr			National Research Foundation of Korea (NRF) - Korea government (MSIP) [NRF-2015R1A2A1A10054384]; 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). This study was also supported by the BK21Plus grant of NRF funded by Korean government (22A20130012250).	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JUL	2018	17						246	258		10.1016/j.redox.2018.04.015			13	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	GW3JB	WOS:000446792900022	29729523	Green Published, gold			2022-04-25	
J	Patankar, JV; Becker, C				Patankar, Jay V.; Becker, Christoph			Cell death in the gut epithelium and implications for chronic inflammation	NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY			English	Review							DOMAIN-LIKE PROTEIN; APOPTOTIC CELLS; BOWEL-DISEASE; ULCERATIVE-COLITIS; SMALL-INTESTINE; GASDERMIN-D; STEM-CELLS; IN-VITRO; ENDOPLASMIC-RETICULUM; ACTIVATED MACROPHAGES	The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. As the transit-amplifying progenitors of the intestinal epithelium generate similar to 300 cells per crypt every day, regulated cell death and sloughing at the apical surface keeps the overall cell number in check. An aberrant increase in the rate of intestinal epithelial cell (IEC) death underlies instances of extensive epithelial erosion, which is characteristic of several intestinal diseases such as inflammatory bowel disease and infectious colitis. Emerging evidence points to a crucial role of necroptosis, autophagy and pyroptosis as important modes of programmed cell death in the intestine in addition to apoptosis. The mode of cell death affects tissue restitution responses and ultimately the long-term risks of intestinal fibrosis and colorectal cancer. A vicious cycle of intestinal barrier breach, misregulated cell death and subsequent inflammation is at the heart of chronic inflammatory and infectious gastrointestinal diseases. This Review discusses the underlying molecular and cellular underpinnings that control programmed cell death in IECs, which emerge during intestinal diseases. Translational aspects of cell death modulation for the development of novel therapeutic alternatives for inflammatory bowel diseases and colorectal cancer are also discussed.	[Patankar, Jay V.; Becker, Christoph] Friedrich Alexander Univ, Dept Med 1, Erlangen, Germany		Becker, C (corresponding author), Friedrich Alexander Univ, Dept Med 1, Erlangen, Germany.	christoph.becker@uk-erlangen.de	Becker, Christoph/L-2996-2016; Becker, Christoph/A-6694-2008	Becker, Christoph/0000-0002-1388-1041; Patankar, Jay/0000-0002-1884-7424	DFGGerman Research Foundation (DFG)European Commission [TRR241, SFB1181, FOR2438, BE3686/9]; Interdisciplinary Center for Clinical Research (IZKF) [J68, A76]	This work received funding from the DFG projects TRR241 (A03), SFB1181 (C05) and FOR2438 (TP05) and individual grant BE3686/9, as well as the Interdisciplinary Center for Clinical Research (IZKF; J68, A76).	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Rev. Gastroenterol. Hepatol.	SEP	2020	17	9					543	556		10.1038/s41575-020-0326-4		JUL 2020	14	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	NF2RW	WOS:000547227600001	32651553				2022-04-25	
J	Mogavero, A; Maiorana, MV; Zanutto, S; Varinelli, L; Bozzi, F; Belfiore, A; Volpi, CC; Gloghini, A; Pierotti, MA; Gariboldi, M				Mogavero, Angela; Maiorana, Maria Valeria; Zanutto, Susanna; Varinelli, Luca; Bozzi, Fabio; Belfiore, Antonino; Volpi, Chiara C.; Gloghini, Annunziata; Pierotti, Marco A.; Gariboldi, Manuela			Metformin transiently inhibits colorectal cancer cell proliferation as a result of either AMPK activation or increased ROS production	SCIENTIFIC REPORTS			English	Article							CYCLE ARREST; STEM-CELLS; MATRIX METALLOPROTEINASES; IN-VITRO; GROWTH; SURVIVAL; ROLES; DRUG; PHOSPHORYLATION; MECHANISMS	Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce cancer risk and improve the prognosis of certain malignancies. However, the mechanism underlying its anti-cancer effect is still unclear. We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin reduced cell proliferation and migration by inducing cell cycle arrest in the G0/G1 phase. This was accompanied by a sharp decrease in the expression of c-Myc and down-regulation of IGF1R. The anti-proliferative action of metformin was mediated by two different mechanisms: AMPK activation and increase in the production of reactive oxygen species, which suppressed the mTOR pathway and its downstream targets S6 and 4EBP1. A reduction in CD44 and LGR5 expression suggested that the drug had an effect on tumour cells with stem characteristics. However, a colony formation assay showed that metformin slowed the cells' ability to form colonies without arresting cell growth, as confirmed by absence of apoptosis, autophagy or senescence. Our finding that metformin only transiently arrests CRC cell growth suggests that efforts should be made to identify compounds that combined with the biguanide can act synergistically to induce cell death.	[Mogavero, Angela; Maiorana, Maria Valeria; Zanutto, Susanna; Varinelli, Luca; Gariboldi, Manuela] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Via G Amadeo 42, I-20133 Milan, Italy; [Mogavero, Angela; Maiorana, Maria Valeria; Zanutto, Susanna; Varinelli, Luca; Pierotti, Marco A.; Gariboldi, Manuela] Fdn Ist FIRC Oncol Mol, Mol Genet Canc, Via Adamello 16, I-20139 Milan, Italy; [Bozzi, Fabio; Belfiore, Antonino; Volpi, Chiara C.; Gloghini, Annunziata] Fdn IRCCS Ist Nazl Tumori, Dept Diagnost Pathol & Lab Med, Via G Venezian 1, I-20133 Milan, Italy		Gariboldi, M (corresponding author), Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Via G Amadeo 42, I-20133 Milan, Italy.; Gariboldi, M (corresponding author), Fdn Ist FIRC Oncol Mol, Mol Genet Canc, Via Adamello 16, I-20139 Milan, Italy.	manuela.gariboldi@istitutotumori.mi.it	zanutto, susanna/K-3431-2018; Gloghini, Annunziata/AAB-4809-2019; Zanutto, Susanna/AAC-7693-2022; Belfiore, Antonino AB/K-7657-2016; Gloghini, Annunziata/C-1992-2017; Pierotti, Marco Alessandro/AAC-4728-2022; Volpi, Chiara Costanza/C-2002-2017; Belfiore, Antonino/AAC-1284-2019; Gariboldi, Manuela/K-4744-2016; Bozzi, Fabio/H-6091-2017	zanutto, susanna/0000-0001-6115-8424; Gloghini, Annunziata/0000-0002-7226-1942; Zanutto, Susanna/0000-0001-6115-8424; Belfiore, Antonino AB/0000-0002-8011-6382; Gloghini, Annunziata/0000-0002-7226-1942; Pierotti, Marco Alessandro/0000-0002-7431-8332; Volpi, Chiara Costanza/0000-0002-8306-6851; Belfiore, Antonino/0000-0002-8011-6382; Varinelli, Luca/0000-0002-0273-5807; Gariboldi, Manuela/0000-0001-8406-165X; Bozzi, Fabio/0000-0003-0729-1288	AIRC (Associazione Italiana Ricerca Cancro)Fondazione AIRC per la ricerca sul cancro [14487]; Italian Ministry of Public HealthMinistry of Health, Italy	This research was supported in part by a grant [No. 14487] to MA Pierotti from AIRC (Associazione Italiana Ricerca Cancro), by the Italian Ministry of Public Health and by funds obtained through an Italian law that allows taxpayers to allocate 0.5 per cent share of their income tax contribution to a research institution. We thank the staff of the IFOM Imaging Facility and the staff of the IFOM Cell Culture Facility.	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J	Bouhidel, JO; Wang, P; Siu, KL; Li, H; Youn, JY; Cai, H				Bouhidel, Jalaleddinne Omar; Wang, Ping; Siu, Kin Lung; Li, Hong; Youn, Ji Youn; Cai, Hua			Netrin-1 improves post-injury cardiac function in vivo via DCC/NO-dependent preservation of mitochondrial integrity, while attenuating autophagy	BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE			English	Article						Netrin-1; Nitric oxide (NO); Ischemia reperfusion (I/R) injury; NADPH oxidase isoforms 4 (NOX4); Myocardial infarction (MI); Autophagy	NITRIC-OXIDE SYNTHASE; MYOCARDIAL-ISCHEMIA; PERMEABILITY TRANSITION; REPERFUSION INJURY; CA-2+-DEPENDENT PORE; HEART; INHIBITION; CARDIOPROTECTION; ANGIOGENESIS; DYSFUNCTION	Reperfusion injury of the heart is a severe complication of angioplasty treatment of acute myocardial ischemia, for which no therapeutics are currently available. The present study aimed to identify whether and how a novel protein, netrin-1, induces cardioprotection in vivo during ischemia/reperfusion (I/R) injury. Wild type (WT) C57BL6/j mice were subjected to a 30 min coronary occlusion followed by a 24 h reperfusion with vehicle (normal saline), netrin-1, UO126 (MEK1/2 inhibitor), PTIO (nitric oxide/NO scavenger), netrin-1/UO126 or netrin-l/PTIO intraventricularly. Some were injected of netrin-1 via tail vein. Netrin-1 at 5 mu g/kg induced a substantial reduction in infarct size (19.7 +/- 5.0% from 41.3 +/- 1.8% in the controls), and markedly improved cardiac function as measured by ejection fraction and fractional shortening from echocardiography. Experiments with mice deficient in netrin-1 receptor DCC (deleted in colorectal cancer, DCC+/-), or reperfusion with netrin-1/UO126 or netrin-1/PTIO, attenuated the protective effects of netrin-1, implicating intermediate roles of DCC, ERK1/2 and NO. Netrin-1 induced phosphorylation of ERK1/2 and eNOS was abolished in DCC+/- mice. Electron spin resonance (ESR) determination of NO production from isolated left ventricles demonstrated that netrin-1 improves NO bioavailability, which was attenuated by UO126 or in DCC+/- mice, suggesting upstream roles of DCC and ERK1/2 in NO production. Netrin-1 further reduced mitochondrial swelling and mitochondria] superoxide production, which was absent when co-treated with PTIO or UO126, or in DCC +/- mice, indicating critical roles of DCC, ERK1/2 and NO in preserving mitochondrial integrity. In a permanent coronary ligation model of myocardial infarction (MI) to assess post-MI remodeling, netrin-1 abolished the marked increase in autophagy. In summary, our data demonstrate robust cardioprotective effect of netrin-1 in vivo, as shown by reduced infarct size and improved cardiac function. Mechanistically, this protection is mediated by netrin-1 receptor DCC, and NO dependent preservation of mitochondria. This work clearly establishes a therapeutic potential of netrin-1 for acute treatment of MI, perhaps also for chronic post-MI remodeling. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases. (C) 2014 Elsevier B.V. All rights reserved.	[Bouhidel, Jalaleddinne Omar; Wang, Ping; Siu, Kin Lung; Li, Hong; Youn, Ji Youn; Cai, Hua] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol & Med, Div Mol Med & Cardiol,Cardiovasc Res Labs, Los Angeles, CA 90095 USA		Cai, H (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol & Med, Div Mol Med & Cardiol,Cardiovasc Res Labs, 650 Charles E Young Dr, Los Angeles, CA 90095 USA.	hcai@mednet.ucla.edu			National Institute of Health National Heart, Lung and Blood Institute (NHLBI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [HL077440, HL088975, HL108701, HL119968]; American Heart Association Established Investigator Award (EIA)American Heart Association [12EIA8990025]; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL108701, R01HL077440, R01HL119968, R01HL088975] Funding Source: NIH RePORTER	This study was supported by National Institute of Health National Heart, Lung and Blood Institute (NHLBI) Grants HL077440 (HC), HL088975 (HC), HL108701 (HC, DGH), HL119968 (HC), and an American Heart Association Established Investigator Award (EIA) 12EIA8990025 (HC).	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Biophys. Acta-Mol. Basis Dis.	FEB	2015	1852	2			SI		277	289		10.1016/j.bbadis.2014.06.005			13	Biochemistry & Molecular Biology; Biophysics; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics; Cell Biology	CA5QR	WOS:000348963400012	24928309	Green Accepted, Bronze			2022-04-25	
J	Otto, C; Hahlbrock, T; Eich, K; Karaaslan, F; Jurgens, C; Germer, CT; Wiegering, A; Kammerer, U				Otto, Christoph; Hahlbrock, Theresa; Eich, Kilian; Karaaslan, Ferdi; Juergens, Constantin; Germer, Christoph-Thomas; Wiegering, Armin; Kaemmerer, Ulrike			Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract	BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE			English	Article						FWGE; Benzoquinone; Cancer cells; Reactive oxygen species; Autophagy; Cytotoxicity; Cytostatic	POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; CANCER CELL-LINES; REACTIVE OXYGEN; COLORECTAL-CANCER; VITAMIN-C; APOPTOSIS; AVEMAR; GLYCOLYSIS; METABOLISM; REDUCTASE	Background: Fermented wheat germ extract (FWGE) sold under the trade name Avemar exhibits anticancer activity in vitro and in vivo. Its mechanisms of action are divided into antiproliferative and antimetabolic effects. Its influcence on cancer cell metabolism needs further investigation. One objective of this study, therefore, was to further elucidate the antimetabolic action of FWGE. The anticancer compound 2,6-dimethoxy-1,4-benzoquinone (DMBQ) is the major bioactive compound in FWGE and is probably responsible for its anticancer activity. The second objective of this study was to compare the antiproliferative properties in vitro of FWGE and the DMBQ compound. Methods: The IC50 values of FWGE were determined for nine human cancer cell lines after 24 h of culture. The DMBQ compound was used at a concentration of 24 mu mol/l, which is equal to the molar concentration of DMBQ in FWGE. Cell viability, cell cycle, cellular redox state, glucose consumption, lactic acid production, cellular ATP levels, and the NADH/NAD(+) ratio were measured. Results: The mean IC50 value of FWGE for the nine human cancer cell lines tested was 10 mg/ml. Both FWGE (10 mg/ml) and the DMBQ compound (24 mu mol/l) induced massive cell damage within 24 h after starting treatment, with changes in the cellular redox state secondary to formation of intracellular reactive oxygen species. Unlike the DMBQ compound, which was only cytotoxic, FWGE exhibited cytostatic and growth delay effects in addition to cytotoxicity. Both cytostatic and growth delay effects were linked to impaired glucose utilization which influenced the cell cycle, cellular ATP levels, and the NADH/NAD(+) ratio. The growth delay effect in response to FWGE treatment led to induction of autophagy. Conclusions: FWGE and the DMBQ compound both induced oxidative stress-promoted cytotoxicity. In addition, FWGE exhibited cytostatic and growth delay effects associated with impaired glucose utilization which led to autophagy, a possible previously unknown mechanism behind the influence of FWGE on cancer cell metabolism.	[Otto, Christoph; Hahlbrock, Theresa; Eich, Kilian; Karaaslan, Ferdi; Juergens, Constantin] Univ Hosp Wurzburg, Dept Gen Visceral Vasc & Pediat Surg, Expt Surg, Oberdurrbacher Str 6, D-97080 Wurzburg, Germany; [Hahlbrock, Theresa] Spital Bulach, Med Klin, Spitalstr 24, D-8180 Bulach, Germany; [Eich, Kilian] Missionsarztl Klin, Fachabteilung Urol, Salvatorstr 7, D-97074 Wurzburg, Germany; [Karaaslan, Ferdi] Krankenhaus Leopoldina Stadt Schweinfurt, Klin Allgemein Viszeral Gefass & Thoraxchirurg, Gustav Adolf Str 8, D-97422 Schweinfurt, Germany; [Otto, Christoph; Germer, Christoph-Thomas; Wiegering, Armin] Univ Hosp Wurzburg, Dept Gen Visceral Vasc & Pediat Surg, Oberdurrbacher Str 6, D-97080 Wurzburg, Germany; [Wiegering, Armin] Univ Wurzburg, Dept Biochem & Mol Biol, Theodor Boveri Inst, Bioctr, D-97070 Wurzburg, Germany; [Kaemmerer, Ulrike] Univ Wurzburg, Dept Obstet & Gynaecol, Josef Schneider Str 4, D-97070 Wurzburg, Germany		Otto, C (corresponding author), Univ Hosp Wurzburg, Dept Gen Visceral Vasc & Pediat Surg, Expt Surg, Oberdurrbacher Str 6, D-97080 Wurzburg, Germany.; Otto, C (corresponding author), Univ Hosp Wurzburg, Dept Gen Visceral Vasc & Pediat Surg, Oberdurrbacher Str 6, D-97080 Wurzburg, Germany.	Otto_c@ukw.de			Interdisciplinary Centre for Clinical Research (IZKF) of the University of Wurzburg [B-186, D-150]; University of Wurzburg	The study was supported by funds from the Interdisciplinary Centre for Clinical Research (IZKF) of the University of Wurzburg (B-186 to AW, and D-150 to CO). The publication was funded by the University of Wurzburg through the funding program "Open Access Publishing".	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Altern. Med.	JUN 1	2016	16								160	10.1186/s12906-016-1138-5			10	Integrative & Complementary Medicine	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine	DN4ZB	WOS:000377074600003	27245162	Green Published, gold			2022-04-25	
J	Lu, CC; Huang, BR; Liao, PJ; Yen, GC				Lu, Chi-Cheng; Huang, Bo-Ru; Liao, Pei-Jyuan; Yen, Gow-Chin			Ursolic acid triggers nonprogrammed death (necrosis) in human glioblastoma multiforme DBTRG-05MG cells through MPT pore opening and ATP decline	MOLECULAR NUTRITION & FOOD RESEARCH			English	Article						ATP depletion; Glioblastoma DBTRG-05MG cells; MPT pore opening; Necrosis; Ursolic acid	MITOCHONDRIAL PERMEABILITY TRANSITION; COLORECTAL-CANCER; INDUCE APOPTOSIS; DRUG-RESISTANCE; INHIBITS GROWTH; IN-VITRO; AUTOPHAGY; PATHWAY; ROS; TARGET	Scope: Ursolic acid, a natural pentacyclic triterpenic acid, possesses anticancer potential and diverse biological effects, but its correlation with glioblastoma multiforme cells and different modes of cell death is unclear. We studied the cellular actions of human glioblastoma multiforme DBTRG-05MG cells after ursolic acid treatment and explored cell-selective killing effect of necrotic death as a cell fate. Methods and results: Ursolic acid effectively reversed temozolomide resistance and reduced DBTRG-05MG cell viability. Surprisingly, ursolic acid failed to stimulate the apoptosis- and autophagy-related signaling networks. The necrotic death was characterized by annexin V/propidium iodide double-positive detection and release of high-mobility group protein B1 and lactate dehydrogenase. These ursolic acid elicited responses were accompanied by reactive oxygen species generation and glutathione depletion. Rapid mitochondrial dysfunction was paralleled by the preferential induction of necrosis, rather than apoptotic death. Mitochondrial permeability transition (MPT) is a phenomenon to provide the onset of mitochondrial depolarization during cellular necrosis. The opening of MPT pores that were mechanistically regulated by cyclophilin D, and adenosine triphosphate decline occurred in treated necrotic DBTRG-05MG cells. Cyclosporine A (an MPT pore inhibitor) prevented ursolic acid-provoked necrotic death and the acid-involved key regulators. Conclusion: Our study is the first to report that ursolic acid-modified mitochondrial function triggers defective death by necrosis in DBTRG-05MG cells rather than augmenting programmed death.	[Lu, Chi-Cheng; Huang, Bo-Ru; Liao, Pei-Jyuan; Yen, Gow-Chin] Natl Chung Hsing Univ, Dept Food Sci & Biotechnol, Taichung 40227, Taiwan; [Yen, Gow-Chin] Natl Chung Hsing Univ, Agr Biotechnol Ctr, Taichung 40227, Taiwan		Yen, GC (corresponding author), Natl Chung Hsing Univ, Dept Food Sci & Biotechnol, 250 Kuokuang Rd, Taichung 40227, Taiwan.	gcyen@nchu.edu.tw	Yen, Gow-Chin/B-7886-2009; Lu, Chi-Cheng/N-7770-2013	Lu, Chi-Cheng/0000-0003-3149-0914; Yen, Gow-Chin/0000-0001-9538-4219	National Science Council, TaiwanMinistry of Science and Technology, Taiwan [NSC99-2313-B-005-002-MY3]; Ministry of Education, Taiwan, under ATU planMinistry of Education, Taiwan	This research work was supported in part by the National Science Council, NSC99-2313-B-005-002-MY3, Taiwan, and by the Ministry of Education, Taiwan, under the ATU plan.	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Nutr. Food Res.	NOV	2014	58	11					2146	2156		10.1002/mnfr.201400051			11	Food Science & Technology	Science Citation Index Expanded (SCI-EXPANDED)	Food Science & Technology	AT8XK	WOS:000345212200005	25131308				2022-04-25	
J	Patel, KR; Andreadi, C; Britton, RG; Horner-Glister, E; Karmokar, A; Sale, S; Brown, VA; Brenner, DE; Singh, R; Steward, WP; Gescher, AJ; Brown, K				Patel, Ketan R.; Andreadi, Catherine; Britton, Robert G.; Horner-Glister, Emma; Karmokar, Ankur; Sale, Stewart; Brown, Victoria A.; Brenner, Dean E.; Singh, Rajinder; Steward, William P.; Gescher, Andreas J.; Brown, Karen			Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence	SCIENCE TRANSLATIONAL MEDICINE			English	Article							HEALTHY-VOLUNTEERS; IN-VIVO; CANCER; MECHANISMS; RESTRICTION; PHARMACOKINETICS; EXPRESSION; RESISTANCE; DISEASE	The phytochemical resveratrol has been shown to exert numerous health benefits in preclinical studies, but its rapid metabolism and resulting poor bioavailability may limit translation of these effects to humans. Resveratrol metabolites might contribute to in vivo activity through regeneration of the parent compound. We present quantitation of sulfate and glucuronide conjugates of resveratrol in human plasma and tissue after repeated ingestion of resveratrol by volunteers and cancer patients, respectively. Subsequent pharmacokinetic characterization of a mixture of resveratrol-3-O-sulfate and resveratrol-4'-O-sulfate in mice showed that these metabolites are absorbed orally but have low bioavailabilities of similar to 14 and 3%, respectively. Sulfate hydrolysis in vivo liberated free resveratrol, which accounted for similar to 2% of the total resveratrol species present in mouse plasma. Monosulfate metabolites were also converted to the parent in human colorectal cells. The extent of cellular uptake was dependent on specific membrane transporters and dictated antiproliferative activity. Sulfate metabolites induced autophagy and senescence in human cancer cells; these effects were abrogated by inclusion of a sulfatase inhibitor, which reduced intracellular resveratrol. Together, our findings suggest that resveratrol is delivered to target tissues in a stable sulfate-conjugated form and that the parent compound is gradually regenerated in selected cells and may give rise to the beneficial effects in vivo. At doses considered to be safe in humans, resveratrol generated via this route may be of greater importance than the unmetabolized form.	[Patel, Ketan R.; Andreadi, Catherine; Britton, Robert G.; Horner-Glister, Emma; Karmokar, Ankur; Sale, Stewart; Brown, Victoria A.; Singh, Rajinder; Steward, William P.; Gescher, Andreas J.; Brown, Karen] Univ Leicester, Dept Canc Studies & Mol Med, Leicester LE2 7LX, Leics, England; [Brenner, Dean E.] Univ Michigan, Sch Med, Dept Internal Med & Pharmacol, Ann Arbor, MI 48109 USA; [Brenner, Dean E.] Vet Affairs Med Ctr, Ann Arbor, MI 48109 USA		Brown, K (corresponding author), Univ Leicester, Dept Canc Studies & Mol Med, Leicester LE2 7LX, Leics, England.	kb20@le.ac.uk	Singh, Raj/A-5398-2011	Brown, Karen/0000-0002-5217-1501	Cancer Research UK programmeCancer Research UK [C325/A6691]; Cancer Research UK/UK Department of HealthCancer Research UK; U.S. National Cancer InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [NCI-N01-CN-25025]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MC_G0802524] Funding Source: UKRI; DIVISION OF CANCER PREVENTION AND CONTROLUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [N01CN025025] Funding Source: NIH RePORTER; Cancer Research UKCancer Research UK [13101] Funding Source: researchfish; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_G0802524] Funding Source: researchfish	Supported by a Cancer Research UK programme (C325/A6691) with assistance from the Leicester Experimental Cancer Medicine Centre (C325/A15575, funded by Cancer Research UK/UK Department of Health) and U.S. National Cancer Institute (NCI-N01-CN-25025).	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Transl. Med.	OCT 2	2013	5	205							205ra133	10.1126/scitranslmed.3005870			12	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	229MV	WOS:000325271300003	24089405	Green Submitted			2022-04-25	
J	Li, YZ; Ke, JZ; Peng, C; Wu, FG; Song, YK				Li, Yexuzi; Ke, Junzhong; Peng, Chen; Wu, Fugen; Song, Yukang			microRNA-300/NAMPT regulates inflammatory responses through activation of AMPK/mTOR signaling pathway in neonatal sepsis	BIOMEDICINE & PHARMACOTHERAPY			English	Article						Neonatal sepsis (NS); microRNA-300 (miR-300); Inflammation; Nicotinamide phosphoribosyltransferase (NAMPT); AMPK; Signaling	COLORECTAL-CANCER; NAMPT; CELLS; OVEREXPRESSION; SUPPRESSION; RESISTANCE; VISFATIN	Aim: Rapid and accurate diagnosis of neonatal sepsis (NS) is highly warranted because of high associated morbidity and mortality. The study aims to evaluate the effects of miR-300 on inflammatory responses in a septic neonate mouse model. Methods: A septic mouse model was established by intraperitoneal (i.p.) cecal slurry (CS) injection in order to validate the effect of miR-300 on the inflammatory response in endothelial cells. Bioinformatics tools and luciferase activity were employed to detect the target of miR-300. Serum inflammatory factors were determined by ELISA assay. RT-qPCR and western blot analysis were used to determine the gene expressions. Flow cytometry was employed to evaluate cell apoptosis. Results: Gain-and loss-of-function studies revealed that miR-300 overexpression augmented autophagy, inhibited cell apoptosis, enhanced cell cycle entry in endothelial cells, and decreased inflammatory response through the regulation of pro-and anti-apoptotic factors in endothelial cells. The effect of miR-300 on endothelial cells was upregulated after nicotinamide phosphoribosyltransferase (NAMPT) silencing and AMPK/mTOR signaling pathway activation, indicating that miR-300 influences sepsis via suppressing NAMPT and triggering the AMPK/mTOR signaling pathway. Conclusions: Our study provides evidence indicating that overexpressed miR-300 enhances autophagy by targeting NAMPT through activation of the AMPK/mTOR signaling pathway in septic mouse models, indicating it may serve as a potential therapeutic target for sepsis.	[Li, Yexuzi; Ke, Junzhong; Peng, Chen; Song, Yukang] First Peoples Hosp Wenling, Dept Med Intens Care Unit, Wenling 317500, Zhejiang, Peoples R China; [Wu, Fugen] First Peoples Hosp Wenling, Dept Neonatal Intens Care Unit, Wenling 317500, Zhejiang, Peoples R China		Wu, FG; Song, YK (corresponding author), 333 Chuanan Nan St, Taizhou 317500, Zhejiang, Peoples R China.	yexuzili@163.com; kejunzhongdoc@sina.com; linling_jiang@163.com; wufu_gen@163.com; garysongyk@163.com			Foundation of Zhejiang Provincial Medical and Health Science and Technology Project, Zhejiang Province, China [2017KY169]; Scientific Research Foundation of Taizhou Science and Technology Bureau, Taizhou, Zhejiang Province, China [1601KY45]; Scientific Research Foundation of Wenling Science and Technology Bureau, Wenling, Zhejiang Province, China [2012C31087]	This work was supported by the Foundation of Zhejiang Provincial Medical and Health Science and Technology Project, Zhejiang Province, China (No. 2017KY169), the Scientific Research Foundation of Taizhou Science and Technology Bureau, Taizhou, Zhejiang Province, China (1601KY45) and the Scientific Research Foundation of Wenling Science and Technology Bureau, Wenling, Zhejiang Province, China (No. 2012C31087).	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Pharmacother.	DEC	2018	108						271	279		10.1016/j.biopha.2018.08.064			9	Medicine, Research & Experimental; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine; Pharmacology & Pharmacy	HA2UZ	WOS:000450101800033	30223098	hybrid			2022-04-25	
J	Scuto, M; Salinaro, AT; Caligiuri, I; Ontario, ML; Greco, V; Sciuto, N; Crea, R; Calabrese, EJ; Rizzolio, F; Canzonieri, V; Calabrese, V				Scuto, Maria; Salinaro, Angela Trovato; Caligiuri, Isabella; Ontario, Maria Laura; Greco, Valentina; Sciuto, Nello; Crea, Roberto; Calabrese, Edward J.; Rizzolio, Flavio; Canzonieri, Vincenzo; Calabrese, Vittorio			Redox modulation of vitagenes via plant polyphenols and vitamin D: Novel insights for chemoprevention and therapeutic interventions based on organoid technology	MECHANISMS OF AGEING AND DEVELOPMENT			English	Article						Cancer; Plant polyphenols; Chemoprevention; Vitamin D; Vitagenes; Autophagy process; Organoids; Personalized therapy	HEME OXYGENASE-1 INDUCTION; MORINGA-OLEIFERA LEAVES; ABERRANT CRYPT FOCI; S-TRANSFERASE-PI; COLORECTAL-CANCER; OVARIAN-CANCER; OLIVE OIL; OXIDATIVE STRESS; SIGNALING PATHWAY; PROSTATE-CANCER	Polyphenols are chemopreventive through the induction of nuclear factor erythroid 2 related factor 2 (Nrf2)mediated proteins and anti-inflammatory pathways. These pathways, encoding cytoprotective vitagenes, include heat shock proteins, such as heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1), as well as glutathione redox system to protect against cancer initiation and progression. Phytochemicals exhibit biphasic dose responses on cancer cells, activating at low dose, signaling pathways resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol (HT) or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Here, the importance of vitagenes in redox stress response and autophagy mechanisms, as well as the potential use of dietary antioxidants in the prevention and treatment of multiple types of cancer are discussed. We also discuss the possible relationship between SARS-CoV-2, inflammation and cancer, exploiting innovative therapeutic approaches with HT-rich aqueous olive pulp extract (Hidrox (R)), a natural polyphenolic formulation, as well as the rationale of Vitamin D supplementation. Finally, we describe innovative approaches with organoids technology to study human carcinogenesis in preclinical models from basic cancer research to clinical practice, suggesting patient-derived organoids as an innovative tool to test drug toxicity and drive personalized therapy.	[Scuto, Maria; Salinaro, Angela Trovato; Ontario, Maria Laura; Greco, Valentina; Sciuto, Nello; Calabrese, Vittorio] Univ Catania, Dept Biomed & Biotechnol Sci, I-95124 Catania, Italy; [Scuto, Maria; Caligiuri, Isabella; Rizzolio, Flavio; Canzonieri, Vincenzo] IRCCS, Ctr Riferimento Oncol Aviano CRO, Pathol Unit, I-33081 Aviano, Italy; [Crea, Roberto] Oliphenol LLC, 26225 Eden Landing Rd,Suite C, Hayward, CA 94545 USA; [Calabrese, Edward J.] Univ Massachusetts, Dept Environm Hlth Sci, Morrill I,N344, Amherst, MA 01003 USA; [Rizzolio, Flavio] Ca Foscari Univ Venice, Dept Mol Sci & Nanosyst, I-30123 Venice, Italy; [Canzonieri, Vincenzo] Univ Trieste, Dept Med Surg & Hlth Sci, I-34127 Trieste, Italy		Calabrese, V (corresponding author), Univ Catania, Dept Biomed & Biotechnol Sci, I-95124 Catania, Italy.; Canzonieri, V (corresponding author), IRCCS, Ctr Riferimento Oncol Aviano CRO, Pathol Unit, I-33081 Aviano, Italy.; Canzonieri, V (corresponding author), Univ Trieste, Dept Med Surg & Hlth Sci, I-34127 Trieste, Italy.	mariaconcetta.scuto@unict.it; trovato@unict.it; Isabella.caligiuri@cro.it; Marialaura.ontario@ontariosrl.it; vgreco@unict.it; ssciuto@unict.it; robertocrea@oliphenol.com; edwardc@schoolph.umass.edu; Flavio.rizzolio@unive.it; vcanzonieri@cro.it; calabres@unict.it	Caligiuri, Isabella/J-9956-2016; Ontario, Maria Laura/AAC-7849-2022; Trovato Salinaro, Angela/AAC-1326-2022; Rizzolio, Flavio/K-2690-2018	Caligiuri, Isabella/0000-0002-4355-5597; Rizzolio, Flavio/0000-0002-3400-4363; TROVATO SALINARO, Angela/0000-0003-2377-858X; Greco, Valentina/0000-0002-6694-2151; Scuto, Maria/0000-0003-1019-5158	"Piano di incentivi per la Ricerca, Linea Intervento 2 PIACERI, 2020-2022", University of Cata-nia, Italy	This study was supported by grants from "Piano di incentivi per la Ricerca, Linea Intervento 2 PIACERI, 2020-2022", University of Cata-nia, Italy. We acknowledge helpful discussions with Sergio Modafferi, Thomas Hartung and Lena Smirnova, JHU) .	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Ageing Dev.	OCT	2021	199								111551	10.1016/j.mad.2021.111551		AUG 2021	25	Cell Biology; Geriatrics & Gerontology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Geriatrics & Gerontology	WC8TX	WOS:000704526000001	34358533				2022-04-25	
J	Han, D; Zhang, XJ; Zhang, JTT; Guo, XZ; Zheng, Y; Sui, SH; Zheng, JP				Han, Di; Zhang, Xuejuan; Zhang, Jietao; Guo, Xiaozi; Zheng, Yu; Sui, Shihua; Zheng, Jiaping			Oleanolic acid suppresses vascular smooth muscle cell proliferation by increasing lincRNA-p21 expression	ONCOLOGY LETTERS			English	Article						oleanolic acid; long non-coding RNA; vascular smooth muscle cell	INTERGENIC NONCODING RNA-P21; CANCER-CELLS; COLORECTAL-CANCER; PATHWAY; APOPTOSIS; AUTOPHAGY; KINASE	Arteriosclerosis poses a significant risk to human health and involves the thickening and hardening of the walls of arteries. Accumulated evidence demonstrates that aberrant proliferation of vascular smooth muscle cells (VSMCs) accounts for the onset and progression of arteriosclerosis. Suppression of their proliferation has been demonstrated to be an effective anti-arteriosclerosis strategy. Long non-coding RNAs (lncRNAs) have recently been observed to be implicated in the proliferation of VSMCs and arteriosclerosis. In this study, we observed that oleanolic acid (OA), a natural compound from plants, inhibited the proliferation of VSMCs. The expression of lincRNA-p21, an arteriosclerosis-associated lncRNA, was demonstrated to be elevated by OA treatment. Suppression of lincRNA-p21 rescued the effect of OA on the proliferation of VSMCs. Collectively, targeting lncRNA is a promising strategy for arteriosclerosis prevention and treatment, and OA ameliorates arteriosclerosis by increasing lncRNA levels.	[Han, Di; Zhang, Xuejuan; Zhang, Jietao; Guo, Xiaozi; Zheng, Yu] Qingdao Univ, Dept Gen Med, Affiliated Hosp, Qingdao 266031, Shandong, Peoples R China; [Sui, Shihua; Zheng, Jiaping] Peoples Hosp Rizhao, Dept Neurol, 126 Taian Rd, Rizhao 276800, Shandong, Peoples R China		Zheng, JP (corresponding author), Peoples Hosp Rizhao, Dept Neurol, 126 Taian Rd, Rizhao 276800, Shandong, Peoples R China.	jiapingzhengrz@126.com					Chaabane C, 2014, CURR OPIN LIPIDOL, V25, P374, DOI 10.1097/MOL.0000000000000113; Dimitrova N, 2014, MOL CELL, V54, P777, DOI 10.1016/j.molcel.2014.04.025; Feng J, 2011, J CELL BIOCHEM, V112, P1524, DOI 10.1002/jcb.23065; Gutschner T, 2012, RNA BIOL, V9, P703, DOI 10.4161/rna.20481; Hong D, 2014, PHARMAZIE, V69, P698, DOI 10.1691/ph.2014.4556; Liu J, 2014, J NUTR BIOCHEM, V25, P1154, DOI 10.1016/j.jnutbio.2014.06.006; Liu J, 2014, J AGR FOOD CHEM, V62, P5528, DOI 10.1021/jf500622p; Liu J, 2014, ASIAN PAC J CANCER P, V15, P4519, DOI 10.7314/APJCP.2014.15.11.4519; Liu J, 2014, ONCOL REP, V32, P567, DOI 10.3892/or.2014.3239; Liu J, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0091606; Qin XF, 2014, MOL CELL BIOCHEM, V390, P61, DOI 10.1007/s11010-013-1956-4; Rudijanto Achmad, 2007, Acta Med Indones, V39, P86; Spurlock CF, 2014, ARTHRITIS RHEUMATOL, V66, P2947, DOI 10.1002/art.38805; SUN AS, 1989, MUTAT RES, V219, P295, DOI 10.1016/0921-8734(89)90031-3; Wang GY, 2014, ONCOL REP, V31, P1839, DOI 10.3892/or.2014.3047; Wu GZ, 2014, CIRCULATION, V130, P1452, DOI 10.1161/CIRCULATIONAHA.114.011675; Yang F, 2014, MOL CELL, V53, P88, DOI 10.1016/j.molcel.2013.11.004; Yu LF, 2015, MOL MED REP, V12, P705, DOI 10.3892/mmr.2015.3383; Zhai HY, 2013, CLIN COLORECTAL CANC, V12, P261, DOI 10.1016/j.clcc.2013.06.003	19	7	8	0	3	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1792-1074	1792-1082		ONCOL LETT	Oncol. Lett.	NOV	2016	12	5					3519	3522		10.3892/ol.2016.5096			4	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	ED4RR	WOS:000388838900072	27900030	Green Published, gold			2022-04-25	
J	Bertrand, K				Bertrand, Kaeffer			Survival of Exfoliated Epithelial Cells: A Delicate Balance between Anoikis and Apoptosis	JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY			English	Review							GENE-EXPRESSION PROFILES; MOLECULAR-MECHANISMS; COLORECTAL-CANCER; CIRCADIAN-RHYTHM; BUCCAL MUCOSA; AUTOPHAGY; CLOCK; COLONOCYTES; TISSUE; STOOL	The recovery of exfoliated cells from biological fluids is a noninvasive technology which is in high demand in the field of translational research. Exfoliated epithelial cells can be isolated from several body fluids (i.e., breast milk, urines, and digestives fluids) as a cellular mixture (senescent, apoptotic, proliferative, or quiescent cells). The most intriguing are quiescent cells which can be used to derive primary cultures indicating that some phenotypes retain clonogenic potentials. Such exfoliated cells are believed to enter rapidly in anoikis after exfoliation. Anoikis can be considered as an autophagic state promoting epithelial cell survival after a timely loss of contact with extracellular matrix and cell neighbors. This paper presents current understanding of exfoliation along with the influence of methodology on the type of gastrointestinal epithelial cells isolated and, finally, speculates on the balance between anoikis and apoptosis to explain the survival of gastrointestinal epithelial cells in the environment.	UMR Phan 1280, F-44000 Nantes, France		Bertrand, K (corresponding author), UMR Phan 1280, Pl Alexis Ricordeau, F-44000 Nantes, France.	bertrand.kaeffer@univ-nantes.fr		Kaeffer, Bertrand/0000-0003-2459-5072	Departement Alimentation Humaine (Inra, France); Region Pays de la Loire, FranceRegion Pays de la Loire	The author is grateful for 2 financial supports: ANSSD-2008 from Departement Alimentation Humaine (Inra, France); PremaCol-2008 (Region Pays de la Loire, France).	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Biomed. Biotechnol.		2011									534139	10.1155/2011/534139			9	Biotechnology & Applied Microbiology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Research & Experimental Medicine	868EW	WOS:000298507500001	22131811	Green Published, gold			2022-04-25	
J	Su, M; Zhang, Z; Zhou, L; Han, C; Huang, CH; Nice, EC				Su, Miao; Zhang, Zhe; Zhou, Li; Han, Chao; Huang, Canhua; Nice, Edouard C.			Proteomics, Personalized Medicine and Cancer	CANCERS			English	Review						personalized; precision medicine; proteomics; cancer; biomarkers; microbiome; HUPO	SINGLE-CELL DATA; INTEGRATED PROTEOGENOMIC CHARACTERIZATION; COLORECTAL-CANCER; LUNG-CANCER; MASS-SPECTROMETRY; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; FUSOBACTERIUM-NUCLEATUM; PANCREATIC-CANCER; HELICOBACTER-PYLORI	Simple Summary Cancer, a major public health issue worldwide, is the second most common cause of death. Initiatives such as the Human Genome Project (HGP) and Human Proteome Project (HPP) have greatly advanced the understanding of human health and disease, including cancer, and are supporting the current trend towards personalized/precision medicine. In this review, we will overview recent technological achievements, the key hallmarks of cancer, and unmet clinical needs. We will specifically detail the importance of cancer biomarkers in diagnosis and treatment, the role of the microbiome in health and disease, the potential of emerging omics technologies and the goals of personalized/precision medicine. Finally, we will discuss future perspectives, both from the standpoint of perceived advances in treatment, but also from the hurdles that have to be overcome. As of 2020 the human genome and proteome are both at >90% completion based on high stringency analyses. This has been largely achieved by major technological advances over the last 20 years and has enlarged our understanding of human health and disease, including cancer, and is supporting the current trend towards personalized/precision medicine. This is due to improved screening, novel therapeutic approaches and an increased understanding of underlying cancer biology. However, cancer is a complex, heterogeneous disease modulated by genetic, molecular, cellular, tissue, population, environmental and socioeconomic factors, which evolve with time. In spite of recent advances in treatment that have resulted in improved patient outcomes, prognosis is still poor for many patients with certain cancers (e.g., mesothelioma, pancreatic and brain cancer) with a high death rate associated with late diagnosis. In this review we overview key hallmarks of cancer (e.g., autophagy, the role of redox signaling), current unmet clinical needs, the requirement for sensitive and specific biomarkers for early detection, surveillance, prognosis and drug monitoring, the role of the microbiome and the goals of personalized/precision medicine, discussing how emerging omics technologies can further inform on these areas. Exemplars from recent onco-proteogenomic-related publications will be given. Finally, we will address future perspectives, not only from the standpoint of perceived advances in treatment, but also from the hurdles that have to be overcome.	[Su, Miao; Zhang, Zhe; Zhou, Li; Han, Chao; Huang, Canhua] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China; [Su, Miao; Zhang, Zhe; Zhou, Li; Han, Chao; Huang, Canhua] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China; [Su, Miao; Zhang, Zhe; Zhou, Li; Han, Chao; Huang, Canhua] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China; [Su, Miao; Zhang, Zhe; Zhou, Li; Han, Chao; Huang, Canhua] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China; [Nice, Edouard C.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia		Huang, CH (corresponding author), Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.; Huang, CH (corresponding author), Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China.; Huang, CH (corresponding author), Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China.; Huang, CH (corresponding author), Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China.; Nice, EC (corresponding author), Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.	2019224065144@stu.scu.edu.cn; scuzz@stu.scu.edu.cn; 2015224060079@stu.scu.edu.cn; 2017141494205@stu.scu.edu.cn; hcanhua@scu.edu.cn; ed.nice@monash.edu		Nice, Edouard/0000-0001-5480-4715; Zhang, Zhe/0000-0001-7509-6965	Chinese NSFCNational Natural Science Foundation of China (NSFC) [81821002, 81790251]; National Key Research and Development Project of China [2020YFA0509400, 2020YFC2002705]; Guangdong Basic and Applied Basic Research Foundation [2019B030302012]; Sichuan Applied Basic Research Project [2020YJ0107]	This researchwas funded by the Chinese NSFC, grant number 81821002, and 81790251; National Key Research and Development Project of China, grant number 2020YFA0509400, and 2020YFC2002705; Guangdong Basic and Applied Basic Research Foundation, grant number 2019B030302012, and Sichuan Applied Basic Research Project, grant number (2020YJ0107).	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J	Zupa, A; Improta, G; Silvestri, A; Pin, E; Deng, JH; Aieta, M; Musto, P; Nitti, D; Mammano, E; Liotta, L; Belluco, C; Wulfkuhle, J; Petricoin, E				Zupa, Angela; Improta, Giuseppina; Silvestri, Alessandra; Pin, Elisa; Deng, Jianghong; Aieta, Michele; Musto, Pellegrino; Nitti, Donato; Mammano, Enzo; Liotta, Lance; Belluco, Claudio; Wulfkuhle, Julia; Petricoin, Emanuel, III			A Pilot Characterization of Human Lung NSCLC by Protein Pathway Activation Mapping	JOURNAL OF THORACIC ONCOLOGY			English	Article						Cell signaling; Protein pathway activation mapping; Reverse-phase protein microarrays; Non-small-cell lung cancer	GROWTH-FACTOR RECEPTOR; SMALL-CELL-LUNG; LASER-CAPTURE MICRODISSECTION; TYROSINE KINASE INHIBITORS; EXPRESSION PROFILES; SIGNALING ANALYSIS; COLORECTAL-CANCER; POOR-PROGNOSIS; MESSENGER-RNA; EGFR MUTATION	Background: An understanding of the activated protein signaling architecture in non-small-cell lung cancer (NSCLC) is of critical importance to the development of new therapeutic approaches and identification of predictive and prognostic biomarkers for patient stratification. Methods: We used reverse-phase protein microarrays to map the activated protein signaling networks of 47 NSCLC tumors, 28 of which were node negative, which were subjected to tumor cellular enrichment using laser capture microdissection. The phosphorylation/cleavage levels of 111 key signaling proteins and total levels of 17 proteins were measured for broadscale signaling analysis. Results: Pathway activation mapping of NSCLC revealed distinct subgroups composed of epidermal growth factor receptor (ERBB1), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ERBB4), v-akt murine thymoma viral oncogene homolog 1-mammalian target of rapamycin (AKT-mTOR), protein kinase, AMP-activated, alpha 2 catalytic subunit (AMPK), and autophagy-related signaling, along with transforming growth factor-beta-signaling protein 1 (SMAD), insulin-line growth factor receptor (IGFR), rearranged during transfection proto-oncogene (RET), and activated CDC42-associated kinase (ACK) activation. Investigation of epidermal growth factor receptor (EGFR)-driven signaling identified a unique cohort of tumors with low EGFR protein expression yet high relative levels of phosphorylated EGFR and high EGFR total protein with low relative levels of phosphorylation. Last, mapping analysis of patients with NSCLC with N0 disease revealed a pilot pathway activation signature composed of linked epidermal growth factor receptor family (HER)-AMPK-AKT-mTOR signaling network along with focal adhesion kinase-LIM domain kinase-1 (FAK-LIMK) and janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways that correlated with short-term survival and aggressive disease. Conclusions: Functional protein pathway activation mapping of NSCLC reveals distinct activation subgroups that are underpinned by important therapeutic targets and that patients with early-stage node negative disease and poor prognosis may be identified by activation of defined, biochemically linked protein signaling events. Such findings, if confirmed in larger study sets, could help select and stratify patients for personalized targeted therapies.	[Deng, Jianghong; Wulfkuhle, Julia; Petricoin, Emanuel, III] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA; [Silvestri, Alessandra; Pin, Elisa; Liotta, Lance; Belluco, Claudio] Natl Canc Inst, CRO IRCCS, Aviano, Italy; [Nitti, Donato; Mammano, Enzo] Univ Padua, Clin Chirurg 2, Padua, Italy		Petricoin, E (corresponding author), George Mason Univ, Ctr Appl Prote & Mol Med, 10900 Univ Blvd,MS 4E3, Manassas, VA 20110 USA.	epetrico@gmu.edu	aieta, michele/AAC-1978-2019; belluco, claudio/J-1339-2018	aieta, michele/0000-0001-9487-6238; PIN, ELISA/0000-0002-2158-2674; Silvestri, Alessandra/0000-0003-4891-1826; belluco, claudio/0000-0001-5972-9574; Musto, Pellegrino/0000-0003-3277-6594	U.S. law and George Mason University policy; Italian Istituto Superiore di Sanita; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R33CA157403] Funding Source: NIH RePORTER; 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) [R21AI099851, R21AI117425] 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) [R01AR068436] Funding Source: NIH RePORTER	J.W., L. L. and E. P. are inventors on U. S. government and/or University assigned patents and patent applications that cover aspects of the technologies discussed. As inventors, they are entitled to receive royalties as provided by U.S. law and George Mason University policy. J.W., L. L., and E. P. are consultants and shareholders of Theranostics Health, Inc. The authors declare no conflicts of interest.; The authors appreciate the generous support of Dr. Vikas Chandhoke and the College of Life Sciences at George Mason University. This work was partly supported by the Italian Istituto Superiore di Sanita within the framework Italy/USA cooperation agreement between the U.S. Department of Health and Human Services, George Mason University, and the Italian Ministry of Public Health.	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Thorac. Oncol.	DEC	2012	7	12					1755	1766		10.1097/JTO.0b013e3182725fc7			12	Oncology; Respiratory System	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Respiratory System	041GM	WOS:000311387700013	23154546	Green Accepted, Bronze			2022-04-25	
J	Sugito, N; Heishima, K; Ito, Y; Akao, Y				Sugito, Nobuhiko; Heishima, Kazuki; Ito, Yuko; Akao, Yukihiro			Synthetic MIR143-3p Suppresses Cell Growth in Rhabdomyosarcoma Cells by Interrupting RAS Pathways Including PAX3-FOXO1	CANCERS			English	Article						RMS; PAX3-FOXO1; MIR143-3p; KRAS; NRAS	MUSCLE-SPECIFIC MICRORNA; BLADDER-CANCER; OSTEOSARCOMA CELLS; TUMOR-SUPPRESSOR; IN-VITRO; FUSION; EXPRESSION; PAX3-FKHR; APOPTOSIS; MIR-143	Simple Summary Rhabdomyosarcoma (RMS) is a soft tissue sarcoma with embryonal (ERMS) and alveoral (ARMS) features, most frequently found in children. ARMS has the worse prognosis due to the formation of the chimeric PAX3-FOXO1 gene. New therapies are needed for the treatment of ARMS. The aim of this study is to evaluate the anticancer effect of chemically-modified MIR143-3p#12 (CM-MIR143#12) on RMS. The ectopic expression of CM-MIR143#12 induced a cell growth suppression by silencing not only KRAS, AKT, and ERK but also the PAX3-FOXO1 chimeric gene, and KRAS networks could control the expression of chimeric PAX3-FOXO1 in ARMS cells. Moreover, CM-MIR143#12 also silenced NRAS mutant in ERMS RD cells. CM-MIR143#12 can be a new nucleic acid medicine for the treatment of RMS by impairing the RAS networks including PAX3-FOXO1. Rhabdomyosarcoma (RMS) is a soft tissue sarcoma most frequently found in children. In RMS, there are two major subtypes, embryonal RMS (ERMS) and alveolar RMS (ARMS). ARMS has the worse prognosis of the two owing to the formation of the chimeric PAX3-FOXO1 gene. A novel therapeutic method is required for treating ARMS. In our previous study, we found that the ectopic expression of chemically modified MIR143-3p#12 (CM-MIR143#12), which is RNase-resistant and shows the highest anti-proliferation activity among the synthesized MIR143 derivatives that were tested, induces significant cell growth suppression by targeting KRAS, AKT, and ERK in colorectal cancer cells. The expression of MIR143-3p in RMS was dramatically downregulated compared with that of normal tissue. Ectopic expression of CM-MIR143#12 in RMS cells resulted in a significant growth inhibitory effect through the induction of apoptosis and autophagy. Interestingly, we found that CM-MIR143#12 also silenced the expression of chimeric PAX3-FOXO1 directly and, using siR-KRAS or siR-AKT, that KRAS networks regulated the expression of PAX3-FOXO1 in ARMS cells. In ERMS harboring NRAS mutation, CM-MIR143#12 silenced mutated NRAS. These findings indicate that CM-MIR143#12 efficiently perturbed the RAS signaling pathway, including the ARMS-specific KRAS/PAX3-FOXO1 networks.	[Sugito, Nobuhiko; Heishima, Kazuki; Akao, Yukihiro] Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, 1-1 Yanagido, Gifu 5011194, Japan; [Ito, Yuko] Osaka Med Coll, Div Life Sci, Dept Anat & Cell Biol, 2-7 Daigaku Machi, Takatsuki, Osaka 5698686, Japan		Akao, Y (corresponding author), Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, 1-1 Yanagido, Gifu 5011194, Japan.	nsugito@gifu-u.ac.jp; heishima@gifu-u.ac.jp; an1006@osaka-med.ac.jp; yakao@gifu-u.ac.jp	Heishima, Kazuki/J-6233-2019	Heishima, Kazuki/0000-0002-4629-8661; Sugito, Nobuhiko/0000-0003-1892-9005	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) [16cm0106202 h0001]	This work was supported by the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development (AMED; 16cm0106202 h0001 to Y.A.).	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J	Liu, CZ; Mottinelli, M; Nicholson, HE; McVeigh, BM; Wong, NK; McCurdy, CR; Bowen, WD				Liu, Cheri Z.; Mottinelli, Marco; Nicholson, Hilary E.; McVeigh, Bridget M.; Wong, Neelum K.; McCurdy, Christopher R.; Bowen, Wayne D.			Identification and characterization of MAM03055A: A novel bivalent sigma-2 receptor/TMEM97 ligand with cytotoxic activity	EUROPEAN JOURNAL OF PHARMACOLOGY			English	Article						TMEM97; Sigma-2 receptor; Progesterone receptor membrane component 1; Neuroblastoma; Cancer metabolism; Apoptosis	TUMOR-CELL DEATH; BINDING; DRUGS; AGONISTS; SN79	Sigma-2 receptor/transmembrane protein 97 (TMEM97) is upregulated in cancer cells compared to normal cells. Traditional sigma-2 receptor agonists induce apoptosis and autophagy, making them of interest in cancer therapy. Recently, we reported a novel metabolically stimulative function of the sigma-2 receptor, showing increased 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and stimulation of glycolytic hallmarks. 6-Substituted analogs of the canonical sigma-2 receptor antagonist, 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), produce both metabolically stimulative and cytotoxic effects. Here, we compare the activities of two related compounds: 6-amino-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (CM571), the 6-amino derivative of SN79, which binds with high affinity to both sigma-1 and sigma-2 receptors, and 1,3-bis(3-(4-(4-(4-fluorophenyl)piperazin-1-yl) butyl)-2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)thiourea (MAM03055A), a homo-bivalent dimer of CM571. MAM03055A resulted from the degradation of 3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)-6-isothiocyanatobenzo[d]oxazol-2(3H)-one (CM572), the cytotoxic 6-isothiocyanato SN79 derivative. MAM03055A exhibited high affinity and strong preference for sigma-2 receptors (sigma-1 K-i = 3371 nM; sigma-2 receptor K-i = 55.9 nM). Functionally, MAM03055A treatment potently induced cell death in SK-N-SH neuroblastoma, MDA-MB-231 breast, and both SW48 and SW480 colorectal cancer cell lines, causing proapoptotic BH3 interacting-domain death agonist (BID) cleavage in SK-N-SH cells. Conversely, CM571 induced metabolic stimulation. CM571 bound reversibly to both receptors, while MAM03055A bound pseudo-irreversibly to sigma 2 receptors and caused residual cytotoxic activity after acute exposure and removal of the compound from the media. Interestingly, MAM03055A induced a time-dependent loss of sigma-2 receptor/TMEM97 protein from cells, whereas monomer CM571 had no effect on receptor levels. These results suggest that monovalent and bivalent sigma-2 receptor ligands in this series interact differently with the receptor, thus resulting in divergent effects.	[Liu, Cheri Z.; Nicholson, Hilary E.; McVeigh, Bridget M.; Wong, Neelum K.; Bowen, Wayne D.] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA; [Mottinelli, Marco; McCurdy, Christopher R.] Univ Florida, Coll Pharm, Dept Med Chem, Gainesville, FL USA		Bowen, WD (corresponding author), 171 Meeting St,Box G-B389, Providence, RI USA.	wayne_bowen@brown.edu		Liu, Cheri/0000-0002-2394-750X; Nicholson, Hilary/0000-0002-3393-3013; Mottinelli, Marco/0000-0001-5725-0439; Mcveigh, Bridget/0000-0003-4200-6016; McCurdy, Christopher Robert/0000-0001-8695-2915	NIH NIGMSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [5T32GM077995]; Brown University Pharmacia Pre-doctoral Fellowship in Pharmacology; University of Florida College of Pharmacy start-up funds; State of Florida; Upjohn Professorship in Pharmacology, Brown University	This work was supported by NIH NIGMS 5T32GM077995 (CZL); Brown University Pharmacia Pre-doctoral Fellowship in Pharmacology (CZL); University of Florida College of Pharmacy start-up funds and the State of Florida (MM and CRM); and the Upjohn Professorship in Pharmacology, Brown University (WDB).	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J. Pharmacol.	SEP 5	2021	906								174263	10.1016/j.ejphar.2021.174263		JUL 2021	16	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	UJ8TH	WOS:000691551500006	34144027				2022-04-25	
J	Stenmark, H				Stenmark, Harald			How a lipid mediates tumour suppression. Delivered on 29 June 2010 at the 35th FEBS Congress in Gothenburg, Sweden	FEBS JOURNAL			English	Article						autophagy; cancer; cell division; cytokinesis; endocytosis; PI 3-kinase; tumour suppressor	PHOSPHATIDYLINOSITOL 3-KINASE COMPLEXES; MULTIVESICULAR-BODY; ESCRT-II; ENDOPLASMIC-RETICULUM; RAB5 EFFECTOR; SACCHAROMYCES-CEREVISIAE; AUTOPHAGOSOME FORMATION; COLORECTAL CANCERS; STRUCTURAL BASIS; MEMBRANE-FUSION	Phosphorylated derivatives of the membrane lipid phosphatidylinositol (PtdIns), known as phosphoinositides (PIs), regulate membrane-proximal cellular processes by recruiting specific protein effectors involved in cell signalling, membrane trafficking and cytoskeletal dynamics. Two PIs that are generated through the activities of distinct PI 3-kinases (PI3Ks) are of special interest in cancer research. PtdIns(3,4,5)P-3, generated by class I PI3Ks, functions as tumour promotor by recruiting effectors involved in cell survival, proliferation, growth and motility. Conversely, there is evidence that PtdIns3P, generated by class III PI3K, functions in tumour suppression. Three subunits of the class III PI3K complex (Beclin 1, UVRAG and BIF-1) have been independently identified as tumour suppressors in mice and humans, and their mechanism of action in this context has been proposed to entail activation of autophagy, a catabolic pathway that is considered to mediate tumour suppression by scavenging damaged organelles that would otherwise cause DNA instability through the production of reactive oxygen species. Recent studies have revealed two additional functions of PtdIns3P that might contribute to its tumour suppressor activity. The first involves endosomal sorting and lysosomal downregulation of mitogenic receptors. The second involves regulation of cytokinesis, which is the final stage of cell division. Further elucidation of the mechanisms of tumour suppression mediated by class III PI3K and PtdIns3P will identify novel Achilles' heels of the cell's defence against tumourigenesis and will be useful in the search for prognostic and diagnostic biomarkers in cancer.	[Stenmark, Harald] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Montebello, Norway; [Stenmark, Harald] Univ Oslo, Ctr Canc Biomed, Fac Med, N-0316 Oslo, Norway		Stenmark, H (corresponding author), Norwegian Radium Hosp, Inst Canc Res, N-0310 Oslo, Norway.	stenmark@ulrik.uio.no	Stenmark, Harald/B-8868-2008		Norwegian Cancer SocietyNorwegian Cancer Society; Research Council of NorwayResearch Council of Norway; South-Eastern Norway Regional Health Authority; European Research FoundationEuropean Science Foundation (ESF); European Research CouncilEuropean Research Council (ERC)European Commission	I thank my mentors Sjur Olsnes and Marino Zerial, and my excellent co-workers at the Institute for Cancer Research. Research in my laboratory is generously sponsored by the Norwegian Cancer Society, the Research Council of Norway, the South-Eastern Norway Regional Health Authority, the European Research Foundation, and by an Advanced Grant from the European Research Council.	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DEC	2010	277	23					4837	4848		10.1111/j.1742-4658.2010.07900.x			12	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	681NA	WOS:000284321400005	20977678	Green Published			2022-04-25	
J	Xu, JQ; Tang, N; Zhang, LF; Tan, C; Su, Y; George, DM; He, GX; Huang, TL				Xu, Jia-Qi; Tang, Ning; Zhang, Ling-Feng; Tan, Chen; Su, Yang; George, Daniel M.; He, Guang-Xu; Huang, Tian-Long			A bibliometric analysis of Wnt signaling pathway: from the top-100 cited articles to emerging trends	ANNALS OF TRANSLATIONAL MEDICINE			English	Article						Bibliometric analysis; top-100 articles; cell signaling; Wnt-beta-catenin; embryo development; cancer	CANONICAL WNT; COLORECTAL-CANCER; CELL APOPTOSIS; STEM-CELLS; CATENIN; AUTOPHAGY; DIFFERENTIATION; MECHANISMS; SURGERY; GROWTH	Background: Wnt signaling pathway plays a vital role in the regulation of development. An increasing number of articles about Wnt pathway components have been published. By analyzing these studies' characteristics and qualities, we aim to reveal the current research focus and emerging trends in Wnt signaling. Methods: The databases of Web of Science Core Collection, BIOSIS Citation Index, MEDLINE, etc. were utilized to identify articles on May 23rd, 2020. Wnt signaling pathway-related articles were identified, the 100 most cited articles and articles in the last decade were selected and calculated for citations without self-citation. The subsequent analysis included citation density (citations/article age), time-related flux, authorship, institution, journal, geographic distribution, and theme. Results: These articles were published mainly from 2000 to 2009 (62%). Citations per article ranged from 599 to 3,780 with a median number of 880 times. Most studies (66%) came from the United States. Nusse Roel and Clevers Hans (15 and 13 papers) have contributed significantly to the field. The most highlighted study themes were cancer (15%), embryo development (14%), and cytoplasm signal transduction (11%). From 2011 to 2020, interest in emerging subtopics, including osteogenesis, immune, apoptosis, autophagy, microRNA, and cancer stem cell, are rising. Conclusions: Cancer, embryo development, stem cell, and signal transduction process still play a major role in the field. With multiple emerging subtopics and investigation on an integrated view of the Wnt signal network, the association of Wnt with diseases was further revealed.	[Xu, Jia-Qi; Tang, Ning; Su, Yang; He, Guang-Xu; Huang, Tian-Long] Cent South Univ, Orthopaed Dept, Xiangya Hosp 2, Changsha, Peoples R China; [Xu, Jia-Qi; Zhang, Ling-Feng; Tan, Chen] Royal Adelaide Hosp, Adelaide, SA, Australia; [George, Daniel M.] Cent South Univ, Xiangya Sch Med, 139 Middle Renmin Rd, Changsha 410011, Peoples R China		Huang, TL (corresponding author), Cent South Univ, Xiangya Sch Med, 139 Middle Renmin Rd, Changsha 410011, Peoples R China.	tianlong.huang@csu.edu.cn		Zhang, Lingfeng/0000-0002-2216-5207	Hunan Provincial Innovation Foundation for Postgraduate [2020zzts885]; Innovation and Entrepreneurship Training Program for College Student [S2020105330605]; Hunan province Funds for Distinguished Young youth [2018JJ1046]; Youth program of national natural science foundation of China [81802207]	This work was supported by Hunan Provincial Innovation Foundation for Postgraduate (No.2020zzts885), the Innovation and Entrepreneurship Training Program for College Student (No. S2020105330605), Hunan province Funds for Distinguished Young youth: (grant number 2018JJ1046), and Youth program of national natural science foundation of China (grant number 81802207).	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TRANSL. MED.	JUL	2021	9	13							174	10.21037/atm-21-174			18	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	UN4WW	WOS:000694018300026	34422977	Green Published, gold			2022-04-25	
J	Romano, S; Di Giacinto, F; Primiano, A; Mazzini, A; Panzetta, C; Papi, M; Di Gaspare, A; Ortolani, M; Gervasoni, J; De Spirito, M; Nocca, G; Ciasca, G				Romano, Sabrina; Di Giacinto, Flavio; Primiano, Aniello; Mazzini, Alberto; Panzetta, Claudia; Papi, Massimiliano; Di Gaspare, Alessandra; Ortolani, Michele; Gervasoni, Jacopo; De Spirito, Marco; Nocca, Giuseppina; Ciasca, Gabriele			Fourier Transform Infrared Spectroscopy as a useful tool for the automated classification of cancer cell-derived exosomes obtained under different culture conditions	ANALYTICA CHIMICA ACTA			English	Article						Exosomes; Cancer cells; Infrared; Liquid biopsy; Personalized medicine	EXTRACELLULAR VESICLES; FTIR SPECTROSCOPY; HUMAN-SALIVA; TOLERANCE; SIGNATURE; AUTOPHAGY	Exosomes possess great potential as cancer biomarkers in personalized medicine due to their easy accessibility and capability of representing their parental cells. To boost the translational process of exosomes in diagnostics, the development of novel and effective strategies for their label-free and automated characterization is highly desirable. In this context, Fourier Transform Infrared Spectroscopy (FTIR) has great potential as it provides direct access to specific biomolecular bands that give compositional information on exosomes in terms of their protein, lipid and genetic content. Here, we used FTIR spectroscopy in the mid-Infrared (mid-IR) range to study exosomes released from human colorectal adenocarcinoma HT-29 cancer cells cultured in different media. To this purpose, cells were studied in well-fed condition of growth, with 10% of exosome-depleted FBS (EVd-FBS), and under serum starvation with 0.5% EVd-FBS. Our data show the presence of statistically significant differences in the shape of the Amide I and II bands in the two conditions. Based on these differences, we showed the possibility to automatically classify cancer cell-derived exosomes using Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA); we tested the effectiveness of the classifier with a crossvalidation approach, obtaining very high accuracy, precision, and recall. Aside from classification purposes, our FTIR data provide hints on the underlying cellular mechanisms responsible for the compositional differences in exosomes, suggesting a possible role of starvation-induced autophagy. (C) 2020 Elsevier B.V. All rights reserved.	[Romano, Sabrina; Di Giacinto, Flavio; Mazzini, Alberto; Panzetta, Claudia; Papi, Massimiliano; De Spirito, Marco; Ciasca, Gabriele] Univ Cattolica Sacro Cuore, Sez Fis, Dipartimento Neurosci, Rome, Italy; [Romano, Sabrina; Di Giacinto, Flavio; Primiano, Aniello; Papi, Massimiliano; Di Gaspare, Alessandra; Gervasoni, Jacopo; De Spirito, Marco; Ciasca, Gabriele] Fdn Policlin Univ A Gemelli IRCCS, Rome, Italy; [Primiano, Aniello; Gervasoni, Jacopo; Nocca, Giuseppina] Univ Cattolica Sacro Cuore, Dipartimento Sci Biotecnol Base Clin Intens & Per, Rome, Italy; [Di Gaspare, Alessandra] CNR, NEST, Ist Nanosci, Piazza San Silvestro 12, I-56127 Pisa, Italy; [Di Gaspare, Alessandra] Scuola Normale Super Pisa, Piazza San Silvestro 12, I-56127 Pisa, Italy; [Ortolani, Michele] Sapienza Univ Rome, Dipartimento Fis, Piazzale Aldo Moro 5, I-00185 Rome, Italy; [Ortolani, Michele] Ist Italiano Tecnol, Ctr Life Nanosci, Viale Regina Elena 291, I-00161 Rome, Italy		De Spirito, M; Ciasca, G (corresponding author), Univ Cattolica Sacro Cuore, Sez Fis, Dipartimento Neurosci, Rome, Italy.	marco.despirito@unicatt.it; gabriele.ciasca@unicatt.it	Ciasca, Gabriele/D-2447-2013; Primiano, Aniello/AAC-3548-2022; Papi, Massimiliano/AAC-3657-2022; Gervasoni, Jacopo/K-7251-2016; nocca, giuseppina/L-1659-2018	Papi, Massimiliano/0000-0002-0029-1309; Primiano, Aniello/0000-0001-9415-9175; Gervasoni, Jacopo/0000-0002-3600-392X; nocca, giuseppina/0000-0002-2799-4557; Di Giacinto, Flavio/0000-0002-6726-7768; Ciasca, Gabriele/0000-0002-3694-8229	Italian Ministry of HealthMinistry of Health, Italy [GR-2016-02363310]	The Italian Ministry of Health ("Progetto Giovani Ricercatori 2014e2015", Grant No. GR-2016-02363310) is gratefully acknowledged.	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Chim. Acta	DEC 15	2020	1140						219	227		10.1016/j.aca.2020.09.037			9	Chemistry, Analytical	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	OZ0YD	WOS:000594661300005	33218484				2022-04-25	
J	Hsieh, YY; Huang, TC; Lo, HL; Jhan, JY; Chen, ST; Yang, PM				Hsieh, Yao-Yu; Huang, Tsui-Chin; Lo, Hsiang-Ling; Jhan, Jyun-Yan; Chen, Shui-Tein; Yang, Pei-Ming			Systematic discovery of drug action mechanisms by an integrated chemical genomics approach: identification of functional disparities between azacytidine and decitabine	ONCOTARGET			English	Article						colorectal cancer; DNMT inhibitor; drug repurposing; polypharmacology; systems pharmacology	ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION SIGNATURES; CELL-CYCLE ARREST; RIBONUCLEOTIDE REDUCTASE; INHIBITORS AZACITIDINE; KINASE INHIBITOR; DNA METHYLATION; AURORA KINASE; 5-AZACYTIDINE; APOPTOSIS	Polypharmacology (the ability of a drug to affect more than one molecular target) is considered a basic property of many therapeutic small molecules. Herein, we used a chemical genomics approach to systematically analyze polypharmacology by integrating several analytical tools, including the LINCS (Library of Integrated Cellular Signatures), STITCH (Search Tool for Interactions of Chemicals), and WebGestalt (WEB-based GEne SeT AnaLysis Toolkit). We applied this approach to identify functional disparities between two cytidine nucleoside analogs: azacytidine (AZA) and decitabine (DAC). AZA and DAC are structurally and mechanistically similar DNA-hypomethylating agents. However, their metabolism and destinations in cells are distinct. Due to their differential incorporation into RNA or DNA, functional disparities between AZA and DAC are expected. Indeed, different cytotoxicities of AZA and DAC toward human colorectal cancer cell lines were observed, in which cells were more sensitive to AZA. Based on a polypharmacological analysis, we found that AZA transiently blocked protein synthesis and induced an acute apoptotic response that was antagonized by concurrently induced cytoprotective autophagy. In contrast, DAC caused cell cycle arrest at the G(2)/M phase associated with p53 induction. Therefore, our study discriminated functional disparities between AZA and DAC, and also demonstrated the value of this chemical genomics approach that can be applied to discover novel drug action mechanisms.	[Hsieh, Yao-Yu; Huang, Tsui-Chin; Lo, Hsiang-Ling; Jhan, Jyun-Yan; Chen, Shui-Tein; Yang, Pei-Ming] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan; [Hsieh, Yao-Yu; Huang, Tsui-Chin; Lo, Hsiang-Ling; Jhan, Jyun-Yan; Chen, Shui-Tein; Yang, Pei-Ming] Acad Sinica, Taipei 115, Taiwan; [Hsieh, Yao-Yu] Taipei Med Univ, Shuang Ho Hosp, Div Hematol & Oncol, Taipei, Taiwan; [Huang, Tsui-Chin; Lo, Hsiang-Ling; Jhan, Jyun-Yan; Yang, Pei-Ming] Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan; [Chen, Shui-Tein] Acad Sinica, Inst Biol Chem, Taipei, Taiwan		Yang, PM (corresponding author), Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan.; Yang, PM (corresponding author), Acad Sinica, Taipei 115, Taiwan.; Yang, PM (corresponding author), Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan.	yangpm@tmu.edu.tw	Yang, Pei-Ming/G-3763-2014	Yang, Pei-Ming/0000-0002-4004-2518	Taiwan's Ministry of Science and Technology [MOST103-2632-B-038-001, MOST104-2320-B-038-005]; Taipei Medical University-Shuang Ho Hospital [102TMU-SHH-04, 104TMU-SHH-03]; Research Team of Prevention and Therapy of Colorectal Cancer at Taipei Medical University [TMU-T104-01]; Ministry of Health and WelfareMinistry of Health, Labour and Welfare, Japan [MOHW103-TDU-B-212-113001, MOHW103-TDU-212-114006]; Comprehensive Cancer Center of Taipei Medical University - Health and welfare surcharge of tobacco products [MOHW103-TD-B-111-01, MOHW104-TDU-B-212-124-001, MOHW105-TDU-B-212-134001]	This work was supported by research grants from Taiwan's Ministry of Science and Technology (MOST103-2632-B-038-001 and MOST104-2320-B-038-005), Taipei Medical University-Shuang Ho Hospital (102TMU-SHH-04 and 104TMU-SHH-03), Research Team of Prevention and Therapy of Colorectal Cancer at Taipei Medical University (TMU-T104-01), Ministry of Health and Welfare (MOHW103-TDU-B-212-113001 and MOHW103-TDU-212-114006), and Comprehensive Cancer Center of Taipei Medical University (MOHW103-TD-B-111-01, MOHW104-TDU-B-212-124-001, and MOHW105-TDU-B-212-134001) funded by the Health and welfare surcharge of tobacco products. The authors would like to thank the Office of Research and Development (Taipei Medicial University, Taipei, Taiwan) for the help in English editing.	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J	Yang, Y; Gu, JJ; Li, XC; Xue, CL; Ba, L; Gao, Y; Zhou, JF; Bai, CM; Sun, Z; Zhao, RC				Yang, Ying; Gu, Junjie; Li, Xuechun; Xue, Chunling; Ba, Li; Gao, Yang; Zhou, Jianfeng; Bai, Chunmei; Sun, Zhao; Zhao, Robert Chunhua			HIF-1 alpha promotes the migration and invasion of cancer-associated fibroblasts by miR-210	AGING AND DISEASE			English	Article						cancer-associated fibroblasts; migration; invasion; colorectal cancer; HIF-1 alpha	MESENCHYMAL STEM-CELLS; DOWN-REGULATION; HYPOXIA; METASTASIS; AUTOPHAGY; PROLIFERATION	Metastasis is the major cause of death in colorectal cancer (CRC) patients. Inhibition of metastasis will prolong the survival of patients with CRC. Cancer cells bring their own soil, cancer-associated fibroblasts (CAFs), to metastasize together, promoting the survival and colonization of circulating cancer cells. However, the mechanism by which CAFs metastasize remains unclear. In this study, CAFs were derived from adipose mesenchymal stem cells (MSCs) after co-culture with CRC cell lines. Transwell assays showed that CAFs have stronger migration and invasion abilities than MSCs. In a nude mouse subcutaneous xenograft model, CAFs metastasized from the primary tumour to the lung and promoted the formation of CRC metastases. The expression of HIF-1 alpha was upregulated when MSCs differentiated into CAFs. Inhibition of HIF-1 alpha expression inhibited the migration and invasion of CAFs. Western blot and ChIP assays were used to identify the genes regulated by HIF-1 alpha. HIF-1 alpha regulated the migration and invasion of CAFs by upregulating miR-210 transcription. Bioinformatics analysis and luciferase reporter assays revealed that miR-210 specifically targeted the 3'UTR of VMP1 and regulated its expression. Downregulation of VMP1 enhanced the migration and invasion of CAFs. In vivo, inhibition of miR-210 expression in CAFs reduced the metastasis of CAFs and tumour cells. Therefore, the HIF-1 alpha/miR-210/VMP1 pathway might regulate the migration and invasion of CAFs in CRC. Inhibition of CAF metastasis might reduce CRC metastasis.	[Yang, Ying; Gu, Junjie; Gao, Yang; Zhou, Jianfeng; Bai, Chunmei; Sun, Zhao] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Med Oncol, Beijing 100730, Peoples R China; [Li, Xuechun; Xue, Chunling; Ba, Li; Zhao, Robert Chunhua] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Ctr Excellence Tissue Engn,Beijing Key Lab BZO381, Inst Basic Med Sci,Sch Basic Med,Peking Union Med, Beijing 100005, Peoples R China		Zhou, JF; Bai, CM; Sun, Z; Zhao, RC (corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Beijing, Peoples R China.	ZhouJF@pumch.cn; baichunmei1964@163.com; jessiesz@126.com; zhaochunhua@vip.163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [61435001]; CAMS Innovation Fund for Medical Sciences [2016-I2M-1-001]	We thank all the members involved in this study. This work was supported by grants from the National Natural Science Foundation of China (No. 61435001) and the CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-1-001).	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OCT	2021	12	7					1794	1807		10.14336/AD.2021.0315			14	Geriatrics & Gerontology	Science Citation Index Expanded (SCI-EXPANDED)	Geriatrics & Gerontology	WE3XT	WOS:000705563500020	34631221	Green Published, gold			2022-04-25	
J	Schulte, ML; Fu, A; Zhao, P; Li, J; Geng, L; Smith, ST; Kondo, J; Coffey, RJ; Johnson, MO; Rathmell, JC; Sharick, JT; Skala, MC; Smith, JA; Berlin, J; Washington, MK; Nickels, ML; Manning, HC				Schulte, Michael L.; Fu, Allie; Zhao, Ping; Li, Jun; Geng, Ling; Smith, Shannon T.; Kondo, Jumpei; Coffey, Robert J.; Johnson, Marc O.; Rathmell, Jeffrey C.; Sharick, Joe T.; Skala, Melissa C.; Smith, Jarrod A.; Berlin, Jordan; Washington, M. Kay; Nickels, Michael L.; Manning, H. Charles			Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models	NATURE MEDICINE			English	Article							BREAST-CANCER; SIGNALING PATHWAYS; COLORECTAL-CANCER; LUNG-CANCER; CELL-GROWTH; IN-VIVO; METABOLISM; INHIBITION; EXPRESSION; AUTOPHAGY	The unique metabolic demands of cancer cells underscore potentially fruitful opportunities for drug discovery in the era of precision medicine. However, therapeutic targeting of cancer metabolism has led to surprisingly few new drugs to date. The neutral amino acid glutamine serves as a key intermediate in numerous metabolic processes leveraged by cancer cells, including biosynthesis, cell signaling, and oxidative protection. Herein we report the preclinical development of V-9302, a competitive small molecule antagonist of transmembrane glutamine flux that selectively and potently targets the amino acid transporter ASCT2. Pharmacological blockade of ASCT2 with V-9302 resulted in attenuated cancer cell growth and proliferation, increased cell death, and increased oxidative stress, which collectively contributed to antitumor responses in vitro and in vivo. This is the first study, to our knowledge, to demonstrate the utility of a pharmacological inhibitor of glutamine transport in oncology, representing a new class of targeted therapy and laying a framework for paradigm-shifting therapies targeting cancer cell metabolism.	[Schulte, Michael L.; Fu, Allie; Zhao, Ping; Li, Jun; Geng, Ling; Smith, Shannon T.; Nickels, Michael L.; Manning, H. Charles] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Mol Probes, Nashville, TN 37235 USA; [Schulte, Michael L.; Nickels, Michael L.; Manning, H. Charles] Vanderbilt Univ, Med Ctr, Inst Imaging Sci, Nashville, TN 37235 USA; [Schulte, Michael L.; Nickels, Michael L.; Manning, H. Charles] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA; [Kondo, Jumpei; Coffey, Robert J.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA; [Coffey, Robert J.; Berlin, Jordan; Washington, M. Kay; Manning, H. Charles] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA; [Coffey, Robert J.] Tennessee Valley Healthcare Syst, Vet Hlth Adm, Nashville, TN USA; [Johnson, Marc O.; Rathmell, Jeffrey C.; Washington, M. Kay] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37235 USA; [Sharick, Joe T.; Skala, Melissa C.; Manning, H. Charles] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA; [Smith, Jarrod A.] Vanderbilt Univ, Vanderbilt Ctr Struct Biol, 221 Kirkland Hall, Nashville, TN 37235 USA; [Smith, Jarrod A.] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA; [Manning, H. Charles] Vanderbilt Univ, Med Ctr, Dept Neurosurg, Nashville, TN 37235 USA; [Manning, H. Charles] Vanderbilt Univ, Dept Chem, Nashville, TN 37235 USA; [Skala, Melissa C.] Univ Wisconsin, Dept Biomed Engn, Morgridge Inst Res, Madison, WI USA		Manning, HC (corresponding author), Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Mol Probes, Nashville, TN 37235 USA.; Manning, HC (corresponding author), Vanderbilt Univ, Med Ctr, Inst Imaging Sci, Nashville, TN 37235 USA.; Manning, HC (corresponding author), Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA.; Manning, HC (corresponding author), Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA.; Manning, HC (corresponding author), Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA.; Manning, HC (corresponding author), Vanderbilt Univ, Med Ctr, Dept Neurosurg, Nashville, TN 37235 USA.; Manning, HC (corresponding author), Vanderbilt Univ, Dept Chem, Nashville, TN 37235 USA.	henry.c.manning@vanderbilt.edu	Kondo, Jumpei/AAC-4336-2020	Coffey, Robert/0000-0002-2180-3844; Kondo, Jumpei/0000-0002-1350-0480	Vanderbilt Ingram Cancer Center (National Institutes of Health (NIH) National Cancer Institute (NCI)) [P30CA068485]; Center for Small Animal Imaging; Kleberg Foundation; Vanderbilt Trans-Institutional Program (TIPS) Award; Vanderbilt Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancer [NIH NCI P50CA095103]; NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R35CA197570]; Vanderbilt Digestive Disease Research Center (NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)) [P30DK058404]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R35CA197570, R01CA205101, R01CA185747, P50CA095103, R01CA046413, R01CA217987, P30CA068485, R01CA211082] Funding Source: NIH RePORTER; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL136664] 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) [P30DK058404, R01DK105550] 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) [T32GM007105] Funding Source: NIH RePORTER; OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [S10OD019963] Funding Source: NIH RePORTER	The authors acknowledge M. Tantawy for assistance with PET imaging, F. Revetta for histology expertise, and A. Rosenberg and A. Cohen for helpful discussions and editorial assistance. The authors wish to acknowledge research support from the Vanderbilt Ingram Cancer Center Support Grant (National Institutes of Health (NIH) National Cancer Institute (NCI) P30CA068485, H.C.M.), which supports the Vanderbilt-Ingram Cancer Center (VICC) Chemical Synthesis Core, Vanderbilt University Medical Center (VUMC) Radiochemistry Core, and Center for Small Animal Imaging; the Kleberg Foundation (H.C.M.); a Vanderbilt Trans-Institutional Program (TIPS) Award to the Vanderbilt Center for Molecular Probes (H.C.M.); the Vanderbilt Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancer (NIH NCI P50CA095103, R.J.C. and H.C.M.); an Outstanding Investigator Award from the NCI (R35CA197570, R.J.C.); and the Vanderbilt Digestive Disease Research Center (NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) P30DK058404, H.C.M.).	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Med.	FEB	2018	24	2					194	+		10.1038/nm.4464			13	Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine	FV1MQ	WOS:000424327200016	29334372	Green Accepted			2022-04-25	
J	Jin, YZ; Sun, HN; Liu, Y; Lee, DH; Kim, JS; Kim, SU; Jiao, BY; Han, YH; Jin, MH; Shen, GN; Lee, DS; Kwon, T; Xu, DY; Jin, Y				Jin, Yong-Zhe; Sun, Hu-Nan; Liu, Yue; Lee, Dong-Ho; Kim, Ji-Su; Kim, Sun-Uk; Jiao, Bing-Yang; Han, Ying-Hao; Jin, Mei-Hua; Shen, Gui-Nan; Lee, Dong-Seok; Kwon, Taeho; Xu, Dong-Yuan; Jin, Yu			Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway	IN VIVO			English	Article						Peroxiredoxin V; apoptosis; emodin; gastric cancer; ROS	EPITHELIAL-MESENCHYMAL TRANSITION; COLORECTAL-CANCER; OXIDATIVE STRESS; PATHOGENESIS; ANTIOXIDANT; PEROXIDASE; AUTOPHAGY; PROMOTES; BIOLOGY; BCL-2	Background/Aim: Peroxiredoxin (Prx) protein family is aberrantly expressed in various cancers including gastric cancer. Among the six family members, Prx V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS) and modulates cellular apoptosis. This study aimed at investigating the role of Prx V in apoptosis of gastric cancer cells. Materials and Methods: Stably constructed Prx V knockdown, over-expression and mock AGS cells (a human gastric adenocarcinoma cell line) were used to study the effect of Prx V on emodin-induced apoptosis by western blotting, cell viability, apoptosis and ROS detection assays. Results: Overexpression of Prx V significantly decreased emodin-induced cellular apoptosis and ROS levels compared to Mock and Prx V knockdown AGS cells. Also, overexpression of Prx V down-regulated the expression of proapoptotic proteins, Bad and cleaved PARP, and increased the expression of anti-apoptotic protein, Bcl2. Conclusion: Prx V suppresses AGS cell apoptosis via scavenging intracellular ROS and modulating apoptosis-related markers.	[Jin, Yong-Zhe; Xu, Dong-Yuan; Jin, Yu] Yanbian Univ, Sch Nursing, Yanji, Peoples R China; [Jin, Yong-Zhe; Xu, Dong-Yuan; Jin, Yu] Yanbian Univ, Coll Med, Gongyuan Rd 977, Yanji 133000, Peoples R China; [Sun, Hu-Nan; Liu, Yue; Jiao, Bing-Yang; Han, Ying-Hao; Jin, Mei-Hua; Shen, Gui-Nan] Heilongjiang Bayi Agr Univ, Coll Life Sci & Technol, Daqing, Peoples R China; [Lee, Dong-Ho; Kim, Ji-Su; Kwon, Taeho] KRIBB, Primate Resources Ctr, 351-33 Neongme Gil, Jeongeup Si 56216, Jeonbuk, South Korea; [Kim, Sun-Uk] Korea Res Inst Biosci & Biotechnol, Futurist Anim Resource & Res Ctr, Chungcheongbuk Do, South Korea; [Lee, Dong-Seok] Kyungpook Natl Univ, KNU Creat BioRes Grp Plus Project BK21, Sch Life Sci, Daegu, South Korea		Xu, DY; Jin, Y (corresponding author), Yanbian Univ, Coll Med, Gongyuan Rd 977, Yanji 133000, Peoples R China.; Kwon, T (corresponding author), KRIBB, Primate Resources Ctr, 351-33 Neongme Gil, Jeongeup Si 56216, Jeonbuk, South Korea.	kwon@kribb.re.kr; dyxu@ybu.edu.cn; jinyu@ybu.edu.cn			Innovative Research projects for postgraduates of Heilongjiang Bayi Agricultural University [YJSCX2018-Y60]; University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province [CXRC2017016]; National Research Foundation of Korea (NRF) - Ministry of Education [2017R1D1A1B03028188]; KRIBB Research Initiative Program [KGM5161914, KGM4251913];  [KRIBB-OGM5201922]	This research was supported by the Innovative Research projects for postgraduates of Heilongjiang Bayi Agricultural University (No: YJSCX2018-Y60) and University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (CXRC2017016). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1B03028188), KRIBB-OGM5201922. This study was supported by grants from the KRIBB Research Initiative Program (KGM5161914 and KGM4251913).	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J	Pol, J; Vacchelli, E; Aranda, F; Castoldi, F; Eggermont, A; Cremer, I; Sautes-Fridman, C; Fucikova, J; Galon, J; Spisek, R; Tartour, E; Zitvogel, L; Kroemer, G; Galluzzi, L				Pol, Jonathan; Vacchelli, Erika; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautes-Fridman, Catherine; Fucikova, Jitka; Galon, Jerome; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo			Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy	ONCOIMMUNOLOGY			English	Review						antigen-presenting cell; autophagy; damage-associated molecular pattern; dendritic cell; endoplasmic reticulum stress; type I interferon	METASTATIC COLORECTAL-CANCER; PHASE-II TRIAL; FIND-ME SIGNAL; CALRETICULIN EXPOSURE; PANCREATIC-CANCER; DENDRITIC CELL; MULTIPLE-MYELOMA; OVARIAN-CANCER; IMMUNE-SYSTEM; BREAST-CANCER	The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.	[Pol, Jonathan; Vacchelli, Erika; Castoldi, Francesca; Eggermont, Alexander; Zitvogel, Laurence; Galluzzi, Lorenzo] Gustave Roussy Canc Campus, Villejuif, France; [Pol, Jonathan; Vacchelli, Erika; Castoldi, Francesca; Cremer, Isabelle; Sautes-Fridman, Catherine; Galon, Jerome; Kroemer, Guido; Galluzzi, Lorenzo] INSERM, U1138, Paris, France; [Pol, Jonathan; Vacchelli, Erika; Castoldi, Francesca; Kroemer, Guido; Galluzzi, Lorenzo] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France; [Aranda, Fernando] Inst Invest Biomed August Pi i Sunyer IDIBAPS, Grp Immune Receptors Innate & Adapt Syst, Barcelona, Spain; [Castoldi, Francesca] Univ Paris 11, Fac Med, Le Kremlin Bicetre, France; [Castoldi, Francesca; Fucikova, Jitka; Spisek, Radek] Sotio Ac, Prague, Czech Republic; [Cremer, Isabelle; Sautes-Fridman, Catherine] Ctr Rech Cordeliers, Equipe 13, Paris, France; [Cremer, Isabelle; Sautes-Fridman, Catherine; Fucikova, Jitka] Univ Paris 06, Paris, France; [Fucikova, Jitka; Spisek, Radek] Charles Univ Prague, Fac Med 2, Dept Immunol, Prague, Czech Republic; [Fucikova, Jitka; Spisek, Radek] Charles Univ Prague, Univ Hosp Motol, Prague, Czech Republic; [Galon, Jerome] Ctr Rech Cordeliers, Lab Integrat Canc Immunol, Paris, France; [Tartour, Eric; Kroemer, Guido; Galluzzi, Lorenzo] Univ Paris 05, Sorbonne Paris Cite, Paris, France; [Tartour, Eric] INSERM, U970, Paris, France; [Tartour, Eric] Paris Cardiovasc Res Ctr PARCC, Paris, France; [Tartour, Eric] HEGP, AP HP, Serv Immunol Biol, Paris, France; [Zitvogel, Laurence] INSERM, U1015, CICBT507, Villejuif, France; [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France; [Kroemer, Guido] Gustave Roussy Canc Campus, Metab & Cell Biol Platforms, Villejuif, France		Kroemer, G (corresponding author), INSERM, U1138, Paris, France.	kroemer@orange.fr; deadoc@vodafone.it	Pol, Jonathan/R-6507-2016; Cremer, Isabelle/D-4278-2017; Galluzzi, Lorenzo/AAG-6432-2019; Aranda, Fernando/N-2112-2014; Galluzzi, Lorenzo/AAG-6294-2019; Kroemer, Guido/AAY-9859-2020; Vacchelli, Erika/E-5212-2018; KROEMER, Guido/B-4263-2013; Aranda, Fernando/N-9649-2019; Galluzzi, Lorenzo/AAH-3286-2021; Galon, Jerome/G-9838-2019; tartour, eric/O-7957-2017	Pol, Jonathan/0000-0002-8355-7562; Cremer, Isabelle/0000-0002-0963-1031; Aranda, Fernando/0000-0002-9364-474X; Vacchelli, Erika/0000-0001-8010-0594; KROEMER, Guido/0000-0002-9334-4405; Aranda, Fernando/0000-0002-9364-474X; Galon, Jerome/0000-0001-9635-1339; tartour, eric/0000-0002-7323-468X; sautes-fridman, catherine/0000-0003-1735-8722	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; AXA Chair for Longevity Research; 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)	Authors are 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; AXA Chair for Longevity Research; 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	Liu, KS; Jin, HT; Guo, YM; Liu, Y; Wan, Y; Zhao, P; Zhou, ZF; Wang, JH; Wang, ML; Zou, C; Wu, WQ; Cheng, ZQ; Dai, Y				Liu, Kaisheng; Jin, Hongtao; Guo, Yaomin; Liu, Ying; Wan, Yong; Zhao, Pan; Zhou, Zhifan; Wang, Jianhong; Wang, Maolin; Zou, Chang; Wu, Weiqing; Cheng, Zhiqiang; Dai, Yong			CFTR interacts with Hsp90 and regulates the phosphorylation of AKT and ERK1/2 in colorectal cancer cells	FEBS OPEN BIO			English	Article						AKT; cystic fibrosis transmembrane conductance regulator; extracellular signal-regulated kinase 1; 2; heat-shock protein 90; mitochondria	TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; CYCLE ARREST; APOPTOSIS; INHIBITOR; PROLIFERATION; DEGRADATION; EXPRESSION; AUTOPHAGY; SNX-2112	Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF cells and tissues exhibit various mitochondrial abnormalities. However, the underlying molecular mechanisms remain elusive. Here, we examined the mechanisms through which CFTR regulates Bcl-2 family proteins, which in turn regulate permeabilization of the mitochondrial outer membrane. Notably, inhibition of CFTR activated Bax and Bad, but inhibited Bcl-2. Moreover, degradation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and AKT increased significantly in CFTR-knockdown cells. Dysfunction of CFTR decreased heat-shock protein 90 (Hsp90) mRNA levels, and CFTR was found to interact with Hsp90. Inhibition of Hsp90 by SNX-2112 induced the degradation of phosphorylated AKT and ERK1/2 in Caco2 and HRT18 cells. These findings may help provide insights into the physiological role of CFTR in CF-related diseases.	[Liu, Kaisheng; Jin, Hongtao; Guo, Yaomin; Liu, Ying; Wan, Yong; Zhao, Pan; Zhou, Zhifan; Wang, Jianhong; Zou, Chang; Wu, Weiqing; Cheng, Zhiqiang; Dai, Yong] Jinan Univ, Clin Med Coll 2, Southern Univ Sci & Technol, Affiliated Hosp 1,Shenzhen Peoples Hosp, Shenzhen, Peoples R China; [Liu, Kaisheng] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Hong Kong, Peoples R China; [Wang, Maolin] Shenzhen Univ, Hlth Sci Ctr, Sch Med, Shenzhen, Peoples R China		Wu, WQ; Cheng, ZQ; Dai, Y (corresponding author), Jinan Univ, Affiliated Hosp 1, Southern Univ Sci & Technol, Clin Med Coll 2,Shenzhen Peoples Hosp, Shenzhen 518020, Guangdong, Peoples R China.	wweiqing007@sina.com; chengzhiqiang2004@aliyun.com; daiyong22@aliyun.com	Zou, Chang/AAS-3356-2021	Zou, Chang/0000-0002-2003-7834; Liu, Kaisheng/0000-0002-4755-0523; Dai, Yong/0000-0002-6840-9158	Science and Technology Foundation of Shenzhen [JCYJ20180301170047864]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81802749]; Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis	This work was supported by grants from the Science and Technology Foundation of Shenzhen (JCYJ20180301170047864) and the National Natural Science Foundation of China (No. 81802749). This work was also supported by the Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis.	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J	Li, WH; Zhang, L; Wu, YH				Li, W-H; Zhang, L.; Wu, Y-H			CDKN3 regulates cisplatin resistance to colorectal cancer through TIPE1	EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES			English	Article						CDKN3; TIPE1; Colorectal cancer (CRC); Cisplatin resistance	BIOMARKERS; AUTOPHAGY	OBJECTIVE: The aim of this study was to investigate the level of cyclin-dependent kinase inhibitor 3 (CDKN3) in colorectal cancer (CRC), to explore the underlying mechanism of CDKN3 in modulating cisplatin resistance and promoting the malignant progression of CRC. PATIENTS AND METHODS: 43 pairs of CRC tissues and para-cancerous tissues were collected from CRC patients. CDKN3 expression was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between CDKN3 expression and the prognosis of CRC patients was analyzed. Meanwhile, qRT-PCR was performed to verify CDKN3 level in CRC cell lines. Next, CDKN3 knockdown model was constructed in CRC cisplatin-resistant cell lines. The influence of CDKN3 on the biological function of CRC cells was analyzed by Cell Counting Kit-8 (CCK-8) and plate cloning assays. Furthermore, the mechanism of its regulation of TIPE1 affecting cisplatin resistance to CRC was explored. RESULTS: QRT-PCR results showed that CDKN3 level in CRC tissues was remarkably higher than that of the adjacent tissues (p<0.05). Compared with patients with low expression of CDKN3, the prognosis of patients with high expression of CDKN3 was significantly worse (p<0.05). Similarly, the proliferation and colony formation ability of cells in CDKN3 knockdown group remarkably decreased when compared with the sh-NC group (p<0.05). In addition, CDKN3 level was remarkably elevated in CRC patients with cisplatin resistance. In cisplatin-resistant cell lines (including HT28 and HCT-116), the knockdown of CDKN3 remarkably reduced cell viability (p<0.05). Furthermore, TIPE1 expression was remarkably downregulated in CRC tissues (p<0.05). A negative correlation was observed between the expressions of TIPE1 and CDKN3. Cell reverse experiment demonstrated that TIPE1 could reverse the promoting effect of CDKN3 on the malignant progression of CRC. All these findings suggested that there might exist a mutual regulation between CDKN3 and TIPE1. CONCLUSIONS: CDKN3 was highly expressed in CRC, which might be closely correlated with poor prognosis of CRC patients. In addition, CDKN3 regulated cisplatin resistance to CRC by modulating TIPE1, thereby promoting the proliferation of CRC.	[Li, W-H] North China Univ Sci & Technol, Dept Pharm, Affiliated Hosp, Tangshan, Peoples R China; [Zhang, L.] North China Univ Sci & Technol, Dept Neurol, Affiliated Hosp, Tangshan, Peoples R China; [Wu, Y-H] Kailuan Gen Hosp, Dept Pharm, Tangshan, Peoples R China		Li, WH (corresponding author), North China Univ Sci & Technol, Dept Pharm, Affiliated Hosp, Tangshan, Peoples R China.	Lwh_1919@163.com					Berumen J, 2014, EXPERT OPIN THER TAR, V18, P1149, DOI 10.1517/14728222.2014.941808; Chen P, 2019, CLIN TRANSL ONCOL, V21, P334, DOI 10.1007/s12094-018-1927-z; Chen QR, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0105393; Cress WD, 2017, INT J BIOCHEM CELL B, V91, P98, DOI 10.1016/j.biocel.2017.05.013; Dasari S, 2014, EUR J PHARMACOL, V740, P364, DOI 10.1016/j.ejphar.2014.07.025; Duan JC, 2018, J BUON, V23, P1402; Espina M, 2017, METALLOMICS, V9, P564, DOI 10.1039/c7mt00014f; HU WS, 2019, INTERN EMERG MED, V9, P1; Kostakis Ioannis, 2018, J BUON, V23, P84; Liao JK, 2018, BIOMED PHARMACOTHER, V97, P1341, DOI 10.1016/j.biopha.2017.11.024; Liu DF, 2018, INT J CANCER, V142, P1392, DOI 10.1002/ijc.31173; Liu TB, 2019, CANCER CELL INT, V19, DOI 10.1186/s12935-019-0827-9; Luan YY, 2019, J INFECT DIS, V220, P699, DOI 10.1093/infdis/jiz158; Luo H, 2016, DRUG DES DEV THER, V10, P1885; Mankaney G, 2019, CLEV CLIN J MED, V86, P385, DOI 10.3949/ccjm.86a.17125; Mastrokostas A, 2018, J BUON, V23, pS67; Pardieck IN, 2016, EXPERT REV GASTROENT, V10, P465, DOI 10.1586/17474124.2016.1122522; Rashtchizadeh N, 2019, BIOCHEM PHARMACOL, V163, P94, DOI 10.1016/j.bcp.2019.02.006; Sun CY, 2019, BIOMED PHARMACOTHER, V110, P518, DOI 10.1016/j.biopha.2018.12.010; Weinberg BA, 2017, ONCOLOGY-NY, V31, P381; Wu SX, 2019, ONCOL LETT, V17, P4667, DOI 10.3892/ol.2019.10076; Ye T, 2020, CARCINOGENESIS, V41, P25, DOI 10.1093/carcin/bgz079; Yiu AJ, 2016, ANTICANCER RES, V36, P1093; Yu Z, 2018, EUR REV MED PHARMACO, V22, P5867, DOI 10.26355/eurrev_201809_15913; Zhang F, 2017, ONCOTARGET, V8, P35460, DOI 10.18632/oncotarget.16727	25	2	2	2	7	VERDUCI PUBLISHER	ROME	VIA GREGORIO VII, ROME, 186-00165, ITALY	1128-3602			EUR REV MED PHARMACO	Eur. Rev. Med. Pharmacol. Sci.	APR	2020	24	7					3614	3623					10	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	LH4XH	WOS:000528789200028	32329836				2022-04-25	
J	Sain, A; Kandasamy, T; Naskar, D				Sain, Arindam; Kandasamy, Thirukumaran; Naskar, Debdut			In silico approach to target PI3K/Akt/mTOR axis by selected Olea europaea phenols in PIK3CA mutant colorectal cancer	JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS			English	Article; Early Access						Olive phenolic compounds; apigenin; pinoresinol; molecular docking; molecular dynamics simulation	OLIVE OIL; PROLIFERATION; OLEUROPEIN; APOPTOSIS; AUTOPHAGY; PATHWAY; INHIBITION; INVASION; COLITIS; CELLS	Worldwide disease burden of colorectal cancer (CRC) increasing alarmingly, but a suitable therapeutic strategy is not available yet. Abnormal activation of the PI3K/Akt/mTOR signalling because of mutation in the PIK3CA gene is a driving force behind CRC development. Therefore, this study aimed to comprehensively characterise the potential of phenolic compounds from Olea europaea against the PI3K/Akt/mTOR axis by using in silico methodologies. Molecular docking was utilised to study key interactions between phenolic compounds of O. europaea and target proteins PI3K, Akt, mTOR with reference to known inhibitor of target. Drug likeness and ADME/T properties of selected phenols were explored by online tools. Dynamic properties and binding free energy of target-ligand interactions were studied by molecular dynamic simulation and MM-PBSA method respectively. Molecular docking revealed apigenin, luteolin, pinoresinol, oleuropein, and oleuropein aglycone as the top five phenolic compounds which showed comparable/better binding affinity than the known inhibitor of the respective target protein. Drug likeness and ADME/T properties were employed to select the top three phenols namely, apigenin, luteolin, and pinoresinol which shown to bind stably to the catalytic cleft of target proteins as confirmed by molecular dynamics simulations. Therefore, Apigenin, luteolin, and pinoresinol have the potential to be used as the non-toxic alternative to synthetic chemical inhibitors generally used in CRC treatment as they can target PI3K/Akt/mTOR axis. Particularly, pinoresinol showed great potential as dual PI3K/mTOR inhibitor. However, this study needs to be complemented with future in vitro and in vivo studies to provide an alternative way of CRC treatment. Communicated by Ramaswamy H. Sarma	[Sain, Arindam; Naskar, Debdut] Maulana Abul Kalam Azad Univ Technol, Dept Biotechnol, Nadia 741249, W Bengal, India; [Kandasamy, Thirukumaran] Indian Inst Technol Guwahati, Dept Biosci & Bioengn, Gauhati, Assam, India		Naskar, D (corresponding author), Maulana Abul Kalam Azad Univ Technol, Dept Biotechnol, Nadia 741249, W Bengal, India.	debdut1984@gmail.com	Naskar, Debdut/AAY-8486-2021	, Thirukumaran/0000-0002-4533-9337; Naskar, Debdut/0000-0001-8243-2066	Department of Science and Technology, Govt. of India (DST)-Inspire faculty research grant [DST/INSPIRE/04/2017/000675]; Maulana Abul Kalam Azad University of Technology, West Bengal (MAKAUT); Council of Scientific and Industrial Research (CSIR), Govt. of IndiaCouncil of Scientific & Industrial Research (CSIR) - India	This work was supported by Department of Science and Technology, Govt. of India (DST)-Inspire faculty research grant (DST/INSPIRE/04/2017/000675) and Maulana Abul Kalam Azad University of Technology, West Bengal (MAKAUT, WB) research seed grant to D.N. A.S was supported by fellowship from Council of Scientific and Industrial Research (CSIR), Govt. of India.	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Biomol. Struct. Dyn.												10.1080/07391102.2021.1953603		JUL 2021	16	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	TN2AC	WOS:000676042400001	34296655				2022-04-25	
J	Nazeri, M; Mirzaie-asl, A; Saidijam, M; Moradi, M				Nazeri, Mehri; Mirzaie-asl, Asghar; Saidijam, Massoud; Moradi, Mohammadreza			Methanolic extract of Artemisia absinthium prompts apoptosis, enhancing expression of Bax/Bcl-2 ratio, cell cycle arrest, caspase-3 activation and mitochondrial membrane potential destruction in human colorectal cancer HCT-116 cells	MOLECULAR BIOLOGY REPORTS			English	Article						Artemisia absinthium; bcl-2-Associated X Protein; Caspase3 protein; Flow Cytometry; HCT116 cells	GENE-EXPRESSION; IN-VITRO; ASTERACEAE; INDUCTION; AUTOPHAGY; ANTITUMOR; ROOT; L.	The Artemisia absinthium (AA), belongs to the Asteraceae family, is used as a therapeutic agent in traditional medicine in Iran. It is a rich source of biology-active compounds. However, the molecular mechanism of AA contributing to cell proliferation and apoptosis is still unknown. This study aims to assess the anticancer activity of the methanolic extract of A. absinthium (MEAA) against human colorectal cancer HCT-116 cell line. The cytotoxic effects of MEAA on HCT-116 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. The expression levels of BAX and BCL-2 in HCT-116 cell line were examined by qRT-PCR. Annexin V/PI-flow cytometry technique was used to detect the cell cycle and apoptosis. MMP was predicted by Rhodamine 123 staining, and caspase 3 activity was analyzed by ELISA. Western blot method was performed to detect the expression level of BAX, Bcl-2 and Caspase-3 proteins. The MTT test revealed MEAA reduced the viability of HCT-116 cells. The mRNA and protein levels of BAX increased, but those of BCL-2 decreased in MEAA-treated cells. MEAA also prompted cell cycle arrest and induced apoptosis. After adding MEAA, the protein level and activity of caspase 3 and MMP destruction significantly increased. MEAA predominantly prompted apoptosis in HCT-116 cells by activating the mitochondrial pathway.	[Nazeri, Mehri; Mirzaie-asl, Asghar] Bu Ali Sina Univ, Fac Agr, Dept Biotechnol, Hamadan, Hamadan, Iran; [Saidijam, Massoud; Moradi, Mohammadreza] Hamadan Univ Med Sci, Res Ctr Mol Med, Hamadan, Iran		Mirzaie-asl, A (corresponding author), Bu Ali Sina Univ, Fac Agr, Dept Biotechnol, Hamadan, Hamadan, Iran.	a.mirzaie@basu.ac.ir			Bu-Ali Sina University, Hamedan, Iran	This original paper was supported by grants from Bu-Ali Sina University, Hamedan, Iran.	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Biol. Rep.	NOV	2020	47	11					8831	8840		10.1007/s11033-020-05933-2		NOV 2020	10	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	PB8WL	WOS:000585000700001	33141288				2022-04-25	
J	Gines, A; Bystrup, S; de Porras, VR; Guardia, C; Musulen, E; Martinez-Cardus, A; Manzano, JL; Layos, L; Abad, A; Martinez-Balibrea, E				Gines, Alba; Bystrup, Sara; Ruiz de Porras, Vicenc; Guardia, Cristina; Musulen, Eva; Martinez-Cardus, Anna; Luis Manzano, Jose; Layos, Laura; Abad, Albert; Martinez-Balibrea, Eva			PKM2 Subcellular Localization Is Involved in Oxaliplatin Resistance Acquisition in HT29 Human Colorectal Cancer Cell Lines	PLOS ONE			English	Article							PYRUVATE-KINASE M2; NUCLEAR TRANSLOCATION; MOLECULAR-MECHANISMS; GENE-TRANSCRIPTION; DEATH; IDENTIFICATION; METABOLISM; AUTOPHAGY; P53; DETERMINANTS	Chemoresistance is the main cause of treatment failure in advanced colorectal cancer (CRC). However, molecular mechanisms underlying this phenomenon remain to be elucidated. In a previous work we identified low levels of PKM2 as a putative oxaliplatin-resistance marker in HT29 CRC cell lines and also in patients. In order to assess how PKM2 influences oxaliplatin response in CRC cells, we silenced PKM2 using specific siRNAs in HT29, SW480 and HCT116 cells. MTT test demonstrated that PKM2 silencing induced resistance in HT29 and SW480 cells and sensitivity in HCT116 cells. Same experiments in isogenic HCT116 p53 null cells and double silencing of p53 and PKM2 in HT29 cells failed to show an influence of p53. By using trypan blue stain and FITC-Annexin V/PI tests we detected that PKM2 knockdown was associated with an increase in cell viability but not with a decrease in apoptosis activation in HT29 cells. Fluorescence microscopy revealed PKM2 nuclear translocation in response to oxaliplatin in HCT116 and HT29 cells but not in OXA-resistant HTOXAR3 cells. Finally, by using a qPCR Array we demonstrated that oxaliplatin and PKM2 silencing altered cell death gene expression patterns including those of BMF, which was significantly increased in HT29 cells in response to oxaliplatin, in a dose and time-dependent manner, but not in siPKM2-HT29 and HTOXAR3 cells. BMF gene silencing in HT29 cells lead to a decrease in oxaliplatin-induced cell death. In conclusion, our data report new non-glycolytic roles of PKM2 in response to genotoxic damage and proposes BMF as a possible target gene of PKM2 to be involved in oxaliplatin response and resistance in CRC cells.	[Gines, Alba; Bystrup, Sara; Ruiz de Porras, Vicenc; Guardia, Cristina; Musulen, Eva; Martinez-Cardus, Anna; Luis Manzano, Jose; Layos, Laura; Abad, Albert; Martinez-Balibrea, Eva] Germans Trias I Pujol Fdn IGTP, Hlth Sci Res Inst, Lab Mol Canc Biol, Translat Res Digest Tumours Grp, Badalona, Spain; [Musulen, Eva] Univ Hosp Germans Trias I Pujol, Human Pathol Dept, Badalona, Spain; [Luis Manzano, Jose; Layos, Laura; Abad, Albert; Martinez-Balibrea, Eva] Univ Hosp Germans Trias I Pujol, Catalan Inst Oncol ICO, Med Oncol Serv, Badalona, Spain		Martinez-Balibrea, E (corresponding author), Germans Trias I Pujol Fdn IGTP, Hlth Sci Res Inst, Lab Mol Canc Biol, Translat Res Digest Tumours Grp, Badalona, Spain.	embalibrea@iconcologia.net	Martinez, Anna/AAA-4939-2020; Musulen, Eva/AAI-9169-2020	Musulen, Eva/0000-0002-9667-6464; Martinez-Balibrea, Eva/0000-0002-4501-7100; Ruiz de Porras, Vicenc/0000-0002-4352-1784; Martinez Cardus, Anna/0000-0002-3937-8794; Guardia Valenzuela, Cristina/0000-0001-5176-1924; Bystrup, Sara/0000-0001-9029-1734	beca bianual de la Fundacion Olga Torres	This work was funded by beca bianual de la Fundacion Olga Torres 2008-2009 (http://www.fundacioolgatorres.org/beques_d-investigacio/) to EMB AGM AA AMC EM JLM.	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J	Pantelic, ND; Bozic, B; Zmejkovski, BB; Banjac, NR; Dojcinovic, B; Wessjohann, LA; Kaluderovic, GN				Pantelic, Nebojsa D.; Bozic, Bojan; Zmejkovski, Bojana B.; Banjac, Nebojsa R.; Dojcinovic, Biljana; Wessjohann, Ludger A.; Kaluderovic, Goran N.			In Vitro Evaluation of Antiproliferative Properties of Novel Organotin(IV) Carboxylate Compounds with Propanoic Acid Derivatives on a Panel of Human Cancer Cell Lines	MOLECULES			English	Article						triphenyltin(IV); breast cancer; cytotoxicity; apoptosis; ICP-MS	ANTITUMOR-ACTIVITY; METAL-COMPLEXES; GOLD(III) COMPLEXES; APOPTOSIS; AUTOPHAGY; CASPASE-3	The synthesis of novel triphenyltin(IV) compounds, Ph(3)SnLn (n = 1-3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), HL1, and the new propanoic acid derivatives 3-(4,5-bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, HL2, and 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)propanoic acid, HL3, has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC50 values ranging from 0.100 to 0.758 mu M. According to the CV assay (IC50 = 0.218 +/- 0.025 mu M), complex Ph(3)SnL1 demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound Ph(3)SnL1 on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that Ph(3)SnL1 induces caspase-independent apoptosis in MCF-7 cells.	[Pantelic, Nebojsa D.; Kaluderovic, Goran N.] Univ Appl Sci Merseburg, Dept Engn & Nat Sci, Eberhard Leibnitz Str 2, DE-06217 Merseburg, Germany; [Pantelic, Nebojsa D.; Banjac, Nebojsa R.] Univ Belgrade, Fac Agr, Dept Chem & Biochem, Nemanjina 6, Belgrade 11080, Serbia; [Pantelic, Nebojsa D.; Wessjohann, Ludger A.; Kaluderovic, Goran N.] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany; [Bozic, Bojan] Univ Belgrade, Inst Physiol & Biochem Ivan Djaja, Fac Biol, Studentski Trg 16, Belgrade 11000, Serbia; [Zmejkovski, Bojana B.; Dojcinovic, Biljana] Univ Belgrade, Inst Chem Technol & Met, Dept Chem, Studentski Trg 14, Belgrade 11000, Serbia		Pantelic, ND; Kaluderovic, GN (corresponding author), Univ Appl Sci Merseburg, Dept Engn & Nat Sci, Eberhard Leibnitz Str 2, DE-06217 Merseburg, Germany.; Pantelic, ND (corresponding author), Univ Belgrade, Fac Agr, Dept Chem & Biochem, Nemanjina 6, Belgrade 11080, Serbia.; Pantelic, ND; Kaluderovic, GN (corresponding author), Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany.	pantelic@agrif.bg.ac.rs; bbozic@bio.bg.ac.rs; bojana.zmejkovski@ihtm.bg.ac.rs; nbanjac@agrif.bg.ac.rs; bmatic@chem.bg.ac.rs; nbanjac@agrif.bg.ac.rs; goran.kaluderovic@hs-merseburg.de	Wessjohann, Ludger/AAZ-3838-2021; Kaluderovic, Goran/E-6310-2013	Kaluderovic, Goran/0000-0001-5168-1000; 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 [451-03-9/2021-14/200026, 451-03-9/202114/200116, 451-03-9/2021-14/200178]; German Academic Exchange Service (DAAD)Deutscher Akademischer Austausch Dienst (DAAD) [57448219]; National Scholarship for Postdoctoral Studies of the Republic of Serbia	This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Contract numbers: 451-03-9/2021-14/200026, 451-03-9/202114/200116 and 451-03-9/2021-14/200178; National Scholarship for Postdoctoral Studies of the Republic of Serbia (N. D. Panteli ' c); German Academic Exchange Service (DAAD) Grant number 57448219.	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J	Deng, YD; Zhang, XD; Yang, XS; Huang, ZL; Wei, X; Yang, XF; Liao, WZ				Deng, Yu-Di; Zhang, Xu-Dong; Yang, Xu-Shan; Huang, Zhen-Lie; Wei, Xi; Yang, Xing-Fen; Liao, Wen-Zhen			Subacute toxicity of mesoporous silica nanoparticles to the intestinal tract and the underlying mechanism	JOURNAL OF HAZARDOUS MATERIALS			English	Article						Mesoporous silica nanoparticles; Oral exposure; Subacute Toxicity; Intestinal flora; Metabolomics	COMMENSAL BACTERIA; OXIDATIVE STRESS; GUT MICROBIOTA; IN-VITRO; INFLAMMATION; GLUTAMINE; NANOTHERANOSTICS; PROLIFERATION; MITOCHONDRIA; HOMEOSTASIS	The biological safety of mesoporous silica nanoparticles (MSNs) has gradually attracted attention. However, few studies of their toxicity to the intestine and mechanism are available. In this study, their primary structures were characterized, and their subacute toxicity to mice was investigated. After 2 weeks of intragastric administration of MSNs, they significantly enhanced serum ALP, ALT, AST and TNF-alpha levels and caused infiltration of inflammatory cells in the spleen and intestines. MSNs induced intestinal oxidative stress and colonic epithelial cell apoptosis in mice. Intestinal epithelial cells exhibited mitochondrial ridge rupture and membrane potential decrease after MSN treatment. Additionally, MSNs increased ROS and NLRP3 levels and inhibited expression of the autophagy proteins LC3-II and Beclin1. MSNs significantly changed the intestinal flora diversity in mice, especially for harmful bacteria, leading to intestinal microecology imbalance. Meanwhile, MSNs influenced the expression of metabolites, which were involved in a range of metabolic pathways, including pyrimidine metabolism, central carbon metabolism in cancer, protein digestion and absorption, mineral absorption, ABC transport and purine metabolism. These results indicated that the subacute toxicity of mesoporous silicon was mainly caused by intestinal damage. Thus, our research provides additional evidence about the safe dosage of MSNs in the clinical and food industries.	[Deng, Yu-Di; Zhang, Xu-Dong; Yang, Xu-Shan; Wei, Xi; Liao, Wen-Zhen] Southern Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Guangdong Prov Key Lab Trop Dis Res, Guangzhou 510515, Peoples R China; [Huang, Zhen-Lie] Southern Med Univ, Sch Publ Hlth, Dept Toxicol, Guangdong Prov Key Lab Trop Dis Res, Guangzhou 510515, Peoples R China; [Yang, Xing-Fen] Southern Med Univ, Sch Publ Hlth, Food Safety & Hlth Res Ctr, Guangdong Prov Key Lab Trop Dis Res, Guangzhou 510515, Peoples R China		Liao, WZ (corresponding author), Southern Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Guangdong Prov Key Lab Trop Dis Res, Guangzhou 510515, Peoples R China.; Yang, XF (corresponding author), Southern Med Univ, Sch Publ Hlth, Food Safety & Hlth Res Ctr, Guangdong Prov Key Lab Trop Dis Res, Guangzhou 510515, Peoples R China.	xfyang@vip.163.com; wenzhenliao@163.com			Guangdong Key RD Program [2019B020210002]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81973013]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2018030310301, 2020A1515010594]; Guangdong Regular Institutions of Higher Learning Characteristic Innovation Projects [2018KTSCX030]	This research is partially supported by grants from Guangdong Key R&D Program (No. 2019B020210002), National Natural Science Foundation of China (No. 81973013), Natural Science Foundation of Guangdong Province (No. 2018030310301, 2020A1515010594), Guangdong Regular Institutions of Higher Learning Characteristic Innovation Projects (No. 2018KTSCX030).	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Hazard. Mater.	MAY 5	2021	409								124502	10.1016/j.jhazmat.2020.124502		FEB 2021	22	Engineering, Environmental; Environmental Sciences	Science Citation Index Expanded (SCI-EXPANDED)	Engineering; Environmental Sciences & Ecology	QM3GJ	WOS:000621669800006	33229260				2022-04-25	
J	Tato, I; Bartrons, R; Ventura, F; Rosa, JL				Tato, Irantzu; Bartrons, Ramon; Ventura, Francesc; Luis Rosa, Jose			Amino Acids Activate Mammalian Target of Rapamycin Complex 2 (mTORC2) via PI3K/Akt Signaling	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							P70 S6 KINASE; MUSCLE PROTEIN-SYNTHESIS; FOXO TRANSCRIPTION FACTORS; ISOLATED RAT HEPATOCYTES; CELL-SURVIVAL; LIFE-SPAN; PHOSPHOINOSITIDE 3-KINASE; INSULIN-RESISTANCE; COLORECTAL-CANCER; IN-VIVO	The activity of mammalian target of rapamycin (mTOR) complexes regulates essential cellular processes, such as growth, proliferation, or survival. Nutrients such as amino acids are important regulators of mTOR complex 1 (mTORC1) activation, thus affecting cell growth, protein synthesis, and autophagy. Here, we show that amino acids may also activate mTOR complex 2 (mTORC2). This activation is mediated by the activity of class I PI3K and of Akt. Amino acids induced a rapid phosphorylation of Akt at Thr-308 and Ser-473. Whereas both phosphorylations were dependent on the presence of mTOR, only Akt phosphorylation at Ser-473 was dependent on the presence of rictor, a specific component of mTORC2. Kinase assays confirmed mTORC2 activation by amino acids. This signaling was functional, as demonstrated by the phosphorylation of Akt substrate FOXO3a. Interestingly, using different starvation conditions, amino acids can selectively activate mTORC1 or mTORC2. These findings identify a new signaling pathway used by amino acids underscoring the crucial importance of these nutrients in cell metabolism and offering new mechanistic insights.	[Tato, Irantzu; Bartrons, Ramon; Ventura, Francesc; Luis Rosa, Jose] Univ Barcelona, Inst Invest Biomed Bellvitge IDIBELL, Dept Ciencies Fisiol 2, E-08907 Barcelona, Spain		Rosa, JL (corresponding author), Univ Barcelona, Inst Invest Biomed Bellvitge IDIBELL, Dept Ciencies Fisiol 2, Campus Bellvitge, E-08907 Barcelona, Spain.	joseluisrosa@ub.edu	Ventura, Francesc/K-9700-2014; Rosa, Jose Luis/K-6685-2014; Ventura, Francesc/ABG-2285-2020	Ventura, Francesc/0000-0001-9673-9405; Rosa, Jose Luis/0000-0002-6161-5688; Ventura, Francesc/0000-0001-9673-9405; Bartrons, Ramon/0000-0001-9349-5847	Ministerio de Educacion y Ciencia (MEC)Spanish GovernmentEuropean Commission [BFU2008-02084/BMC]; Instituto de Salud Carlos III Redes Tematicas de Investigacion Cooperativa en SaludInstituto de Salud Carlos III [RD06/0020]; Generalitat de CatalunyaGeneralitat de CatalunyaGeneral Electric [2009SGR1059]; Juan de la Cierva Program	This work was supported in part by Ministerio de Educacion y Ciencia (MEC) Grant BFU2008-02084/BMC, Instituto de Salud Carlos III Redes Tematicas de Investigacion Cooperativa en Salud Grant RD06/0020 and Generalitat de Catalunya Grant 2009SGR1059.; Supported by the Juan de la Cierva Program.	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Biol. Chem.	FEB 25	2011	286	8					6128	6142		10.1074/jbc.M110.166991			15	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	723AB	WOS:000287476400022	21131356	Green Published, hybrid			2022-04-25	
J	Bakke, D; Sun, J				Bakke, Danika; Sun, Jun			Ancient Nuclear Receptor VDR With New Functions: Microbiome and Inflammation	INFLAMMATORY BOWEL DISEASES			English	Review						immunity; infection; myeloid; nuclear receptor; Salmonella	VITAMIN-D-RECEPTOR; GENOME-WIDE ASSOCIATION; KAPPA-B ACTIVITY; CROHNS-DISEASE; GENE POLYMORPHISMS; COLORECTAL-CANCER; EPITHELIAL-CELLS; DENDRITIC CELLS; GUT MICROBIOME; KNOCKOUT MICE	The biological functions of 1 alpha,25-dihydroxyvitamin D-3 are regulated by nuclear receptor vitamin D receptor (VDR). The expression level of VDR is high in intestine. VDR is an essential regulator of intestinal cell proliferation, barrier function, and immunity. Vitamin D/VDR plays a protective role in inflammatory bowel diseases (IBDs), both ulcerative colitis and Crohn's disease. Emerging evidence demonstrates low VDR expression and dysfunction of vitamin D/VDR signaling in patients with IBD. Here, we summarize the progress made in vitamin D/VDR signaling in genetic regulation, immunity, and the microbiome in IBD. We cover the mechanisms of intestinal VDR in regulating inflammation through inhibiting the NF-kappa B pathway and activating autophagy. Recent studies suggest that the association of VDR single nucleotide polymorphisms with immune and intestinal pathology may be sex dependent. We emphasize the tissue specificity of VDR and its sex-and time-dependent effects. Furthermore, we discuss potential clinical application and future direction of vitamin D/VDR in preventing and treating IBD.	[Bakke, Danika; Sun, Jun] Univ Illinois, Dept Med, Div Gastroenterol & Hepatol, 840 S Wood St,Room 704 CSB,MC716, Chicago, IL 60612 USA		Sun, J (corresponding author), Univ Illinois, Dept Med, Div Gastroenterol & Hepatol, 840 S Wood St,Room 704 CSB,MC716, Chicago, IL 60612 USA.	junsun7@uic.edu			National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01 DK105118]; Department of DefenseUnited States Department of Defense [BC160450P1]; 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) [R01DK114126, R01DK105118] Funding Source: NIH RePORTER	Supported by: We would like to acknowledge the National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health grant R01 DK105118 and Department of Defense BC160450P1 to Jun Sun.	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Bowel Dis.	JUN	2018	24	6					1149	1154		10.1093/ibd/izy092			6	Gastroenterology & Hepatology	Science Citation Index Expanded (SCI-EXPANDED)	Gastroenterology & Hepatology	GG4WO	WOS:000432697200005	29718408	Green Published, Bronze, Green Accepted			2022-04-25	
J	Wen, PB; Xia, JF; Cao, XB; Chen, B; Tao, YP; Wu, LJ; Xu, A; Zhao, GP				Wen, Pengbo; Xia, Junfeng; Cao, Xianbin; Chen, Bin; Tao, Yinping; Wu, Lijun; Xu, An; Zhao, Guoping			dbCRSR: a manually curated database for regulation of cancer radiosensitivity	DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION			English	Article							COLORECTAL-CANCER; RADIOTHERAPY; CELLS; INHIBITOR; RADIORESISTANCE; STRATEGIES; AUTOPHAGY	Radiotherapy is used to treat approximately 50% of all cancer patients, with varying prognoses. Intrinsic radiosensitivity is an important factor underlying the radiotherapeutic efficacy of this precise treatment. During the past decades, great efforts have been made to improve radiotherapy treatment through multiple strategies. However, invaluable data remains buried in the extensive radiotherapy literature, making it difficult to obtain an overall view of the detailed mechanisms leading to radiosensitivity, thus limiting advances in radiotherapy. To address this issue, we collected data from the relevant literature contained in the PubMed database and developed a literature-based database that we term the cancer radiosensitivity regulation factors database (dbCRSR). dbCRSR is a manually curated catalogue of radiosensitivity, containing multiple radiosensitivity regulation factors (395 coding genes, 119 non-coding RNAs and 306 chemical compounds) with appropriate annotation. To illustrate the value of the data we collected, data mining was performed including functional annotation and network analysis. In summary, dbCRSR is the first literature-based database to focus on radiosensitivity and provides a resource to better understand the detailed mechanisms of radiosensitivity. We anticipate dbCRSR will be a useful resource to enrich our knowledge and to promote further study of radiosensitivity.	[Wen, Pengbo; Cao, Xianbin; Chen, Bin; Tao, Yinping; Wu, Lijun; Xu, An; Zhao, Guoping] Chinese Acad Sci, Anhui Prov Key Lab Environm Toxicol & Pollut Cont, Hefei Inst Phys Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei, Anhui, Peoples R China; [Wen, Pengbo] Univ Sci & Technol China, Hefei, Anhui, Peoples R China; [Xia, Junfeng] Anhui Univ, Inst Phys Sci & Informat Technol, Sch Comp Sci & Technol, Hefei, Anhui, Peoples R China		Xia, JF (corresponding author), Anhui Univ, Inst Phys Sci & Informat Technol, Sch Comp Sci & Technol, Hefei, Anhui, Peoples R China.	jfxia@ahu.edu.cn; gpz@ipp.ac.cn	Xia, Junfeng/S-2456-2019	Xia, Junfeng/0000-0003-3024-1705	CAS Pioneer Hundred Talents Program; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31601124, 61672037, 31470829]; Anhui Provincial Natural Science FoundationNatural Science Foundation of Anhui Province [1708085MC66]; Anhui Provincial Outstanding Young Talent Support Plan [gxyqZD2017005]; Young Wanjiang Scholar Program of Anhui Province, China	This work was supported by CAS Pioneer Hundred Talents Program (GZ), National Natural Science Foundation of China (31601124, 61672037 and 31470829), the Anhui Provincial Natural Science Foundation (1708085MC66), the Anhui Provincial Outstanding Young Talent Support Plan (gxyqZD2017005) and the Young Wanjiang Scholar Program of Anhui Province, China.	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J	Zhu, HH; Zhang, LJ; Xu, JM; Zhu, CH; Zhao, H; Zhu, YK; Lv, GQ				Zhu, Huanhuan; Zhang, Linjie; Xu, Jianmin; Zhu, Chunhua; Zhao, Hui; Zhu, Yongkang; Lv, Guoqiang			AntogomiR-451 protects human gastric epithelial cells from ethanol via activating AMPK signaling	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						AntogomiR-451; AMPK; Gastric epithelial cells; Ethanol; Oxidative stress	HELICOBACTER-PYLORI; COLORECTAL-CANCER; INDUCED APOPTOSIS; OXIDATIVE STRESS; PEPTIC-ULCER; KINASE AMPK; COMPOUND 13; GROWTH; AUTOPHAGY; PATHWAY	The prevention and treatment efficiency of ethanol-induced gastric epithelial injury are not satisfied. We have previously shown that AMP-activated protein kinase (AMPK) activation exerts a pro-survival function in human gastric epithelial cells (GECs). miroRNA-451 ("miR-451")'s inhibitor, antagomiR-451, can activate AMPK signaling. In the present study, we show that forced-expression of antagomiR-451 via a lentiviral vector depleted miR-451, leading to AMPK activation in established GES-1 cells and primary human GECs. AntagomiR-451 efficiently protected GES-1 cells and primary human GECs from ethanol-induced viability reduction and apoptosis. AMPK activation is required for antagomiR-451-induced GEC protection. AMPK alpha l knockdown (by targeted-shRNAs) or knockout (by CRISPR-Cas-9 KO plasmid) blocked antagomiR-451-induced AMPK activation, and GEC protection against ethanol. Further experimental results show that antagomiR-451 significantly attenuated ethanol-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage. Collectively, antagomiR-451 protects human GECs from ethanol via activating AMPK signaling. (C) 2018 Elsevier Inc. All rights reserved.	[Zhu, Huanhuan; Zhang, Linjie; Xu, Jianmin; Zhu, Chunhua; Zhao, Hui; Lv, Guoqiang] Nantong Univ, Wuxi Peoples Hosp 3, Dept Gastroenterol, 585 North Xingyuan Rd, Wuxi 214041, Jiangsu, Peoples R China; [Zhu, Yongkang] Nanjing Univ, TCM, Affiliated Hosp, Dept Gen Surg, 155 Hanzhong Rd, Nanjing 210000, Jiangsu, Peoples R China		Lv, GQ (corresponding author), Nantong Univ, Wuxi Peoples Hosp 3, Dept Gastroenterol, 585 North Xingyuan Rd, Wuxi 214041, Jiangsu, Peoples R China.; Zhu, YK (corresponding author), Nanjing Univ, TCM, Affiliated Hosp, Dept Gen Surg, 155 Hanzhong Rd, Nanjing 210000, Jiangsu, Peoples R China.	zhuykwuxiys@163.com; Ivguoqiangwuxivip@163.com			Wuxi Young Medical Talents of the program for developing health care through science and education	The authors thank the laboratory members. This study is supported by the Wuxi Young Medical Talents of the program for developing health care through science and education.	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J	Weng, YF; Lin, JX; Liu, H; Wu, H; Yan, ZM; Zhao, J				Weng, Yingfeng; Lin, Jixian; Liu, Hui; Wu, Hui; Yan, Zhimin; Zhao, Jing			AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation	ONCOTARGET			English	Article						OGDR; neuroprotection; Tanshinone IIA; AMP-activated protein kinase (AMPK); Ppm1e	IN-VITRO; OXIDATIVE STRESS; NEUROBLASTOMA-CELLS; ENERGY HOMEOSTASIS; COLORECTAL-CANCER; SIGNALING PATHWAY; KINASE; DEATH; AUTOPHAGY; APOPTOSIS	The current study tested the potential neuroprotective function of Tanshinone IIA (ThIIA) in neuronal cells with oxygen-glucose deprivation (ODG) and re-oxygenation (OGDR). In SH-SY5Y neuronal cells and primary murine cortical neurons, ThIIA pretreatment attenuated OGDR-induced viability reduction and apoptosis. Further, OGDR-induced mitochondrial depolarization, reactive oxygen species production, lipid peroxidation and DNA damages in neuronal cells were significantly attenuated by ThIIA. ThIIA activated AMP-activated protein kinase (AMPK) signaling, which was essential for neuroprotection against OGDR. AMPK alpha 1 knockdown or complete knockout in SH-SY5Y cells abolished ThIIA-induced AMPK activation and neuroprotection against OGDR. Further studies found that ThIIA up-regulated microRNA-135b to downregulate the AMPK phosphatase Ppm1e. Notably, knockdown of Ppm1e by targeted shRNA or forced microRNA-135b expression also activated AMPK and protected SH-SY5Y cells from OGDR. Together, AMPK activation by ThIIA protects neuronal cells from OGDR. microRNA-135b-mediated silence of Ppm1e could be the key mechanism of AMPK activation by ThIIA.	[Weng, Yingfeng; Lin, Jixian; Liu, Hui; Wu, Hui; Yan, Zhimin; Zhao, Jing] Fudan Univ, Zhongshan Hosp, Minhang Branch, Dept Neurol, Shanghai, Peoples R China		Yan, ZM; Zhao, J (corresponding author), Fudan Univ, Zhongshan Hosp, Minhang Branch, Dept Neurol, Shanghai, Peoples R China.	yanzhiminmh@163.com; zhaojinmhyy7@163.com	lin, jixian/Y-9573-2018	lin, jixian/0000-0002-8640-9995	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572232]; Central Hospital of Shanghai Minxing District young student research foundation [2016 MHLC04, 2017MHLC10]	This study was supported by the National Natural Science Foundation of China (81572232) and by the Central Hospital of Shanghai Minxing District young student research foundation (2016 MHLC04, 2017MHLC10).	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J	Liu, XL; Ardizzone, A; Sui, BL; Anzola, M; Ventosa, N; Liu, TH; Veciana, J; Belfield, KD				Liu, Xinglei; Ardizzone, Antonio; Sui, Binglin; Anzola, Mattia; Ventosa, Nora; Liu, Taihong; Veciana, Jaume; Belfield, Kevin D.			Fluorenyl-Loaded Quatsome Nanostructured Fluorescent Probes	ACS OMEGA			English	Article							TURN-ON SENSOR; 2-PHOTON ABSORPTION; IN-VIVO; DERIVATIVES; AUTOPHAGY; NANOPARTICLES	Delivery of hydrophobic materials in biological systems, for example, contrast agents or drugs, is an obdurate challenge, severely restricting the use of materials with otherwise advantageous properties. The synthesis and characterization of a highly stable and water-soluble nanovesicle, referred to as a quatsome (QS, vesicle prepared from cholesterol and amphiphilic quaternary amines), that allowed the nanostructuration of a nonwater soluble fluorene-based probe are reported. Photophysical properties of fluorenyl-quatsome nanovesicles were investigated via ultraviolet-visible absorption and fluorescence spectroscopy in various solvents. Colloidal stability and morphology of the nanostructured fluorescent probes were studied via cryogenic transmission electronic microscopy, revealing a "patchy" quatsome vascular morphology. As an example of the utility of these fluorescent nanoprobes, examination of cellular distribution was evaluated in HCT 116 (an epithelial colorectal carcinoma cell line) and COS-7 (an African green monkey kidney cell line) cell lines, demonstrating the selective localization of C-QS and M-QS vesicles in lysosomes with high Pearson's colocalization coefficient, where C-QS and M-QS refer to quatsomes prepared with hexadecyltrimethylammonium bromide or tetradecyldimethylbenzylammonium chloride, respectively. Further experiments demonstrated their use in time-dependent lysosomal tracking.	[Liu, Xinglei; Sui, Binglin; Liu, Taihong; Belfield, Kevin D.] New Jersey Inst Technol, Dept Chem & Environm Sci, Coll Sci & Liberal Arts, 323 Martin Luther King,Jr Blvd, Newark, NJ 07102 USA; [Ardizzone, Antonio; Anzola, Mattia; Ventosa, Nora; Veciana, Jaume] Inst Ciencia Mat Barcelona CSIC CIBER BBN, Campus Univ Bellaterra, Cerdanyola Del Valles 08193, Spain		Belfield, KD (corresponding author), New Jersey Inst Technol, Dept Chem & Environm Sci, Coll Sci & Liberal Arts, 323 Martin Luther King,Jr Blvd, Newark, NJ 07102 USA.; Ventosa, N; Veciana, J (corresponding author), Inst Ciencia Mat Barcelona CSIC CIBER BBN, Campus Univ Bellaterra, Cerdanyola Del Valles 08193, Spain.	ventosa@icmab.es; vecianaj@icmab.es; belfield@njit.edu	Ventosa, Nora/C-2170-2015; Belfield, Kevin D/D-4765-2009; Veciana, Jaume/A-2147-2008; Liu, Xinglei/AAS-9515-2021; Liu, Taihong/Y-9421-2019	Ventosa, Nora/0000-0002-8008-4974; Belfield, Kevin D/0000-0002-7339-2813; Veciana, Jaume/0000-0003-1023-9923; Liu, Taihong/0000-0002-9600-1045	DGI, Spain [BE-WELL CTQ2013-40480-R, Mother MAT 2016-80826-R]; AGAUR, Generalitat de CatalunyaAgencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR)Generalitat de Catalunya [2014-SGR-17]; Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN); Spanish Ministry of Economy and Competitiveness, through the "Severo Ochoa" Programme for Centres of Excellence in R&D through FIP Flowers project [SEV-2015-0496]; People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7 under REA grant [607721]; National Science FoundationNational Science Foundation (NSF) [CBET-1517273]	This work was supported by the DGI, Spain, "Grants BE-WELL CTQ2013-40480-R" and "Mother MAT 2016-80826-R", by AGAUR, Generalitat de Catalunya, "Grant 2014-SGR-17", the Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), and the Spanish Ministry of Economy and Competitiveness, through the "Severo Ochoa" Programme for Centres of Excellence in R&D (SEV-2015-0496) through FIP Flowers project. Characterizations of nanovesicles were made at the ICTS "NANBIOSIS", more specifically by the U6 unit of CIBER-BBN. The research leading to these results received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013 under REA grant agreement no. 607721 (Nano2-Fun) A.A. is enrolled in the Materials Science Ph.D. program of UAB. K.D.B. and X.L. acknowledge support from the National Science Foundation (CBET-1517273).	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J	Zhang, D; Yan, PG; Han, TT; Cheng, XY; Li, JN				Zhang, Di; Yan, Pengguang; Han, Taotao; Cheng, Xiaoyun; Li, Jingnan			Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis	PEERJ			English	Article						Ulcerative colitis; Colitis associated dysplasia; Ulcerative colitis associated colorectal cancer; Weighted gene co-expression network analysis	INFLAMMATORY-BOWEL-DISEASE; BREAST-CANCER CELLS; COLORECTAL-CANCER; EXPRESSION; PROTEIN; PROLIFERATION; SUPPRESSES; ACTIVATION; APOPTOSIS; AUTOPHAGY	Background. Ulcerative colitis-associated colorectal cancer (UC-CRC) is a life-threatening complication of ulcerative colitis (UC). The mechanisms underlying UC-CRC remain to be elucidated. The purpose of this study was to explore the key genes and biological processes contributing to colitis-associated dysplasia (CAD) or carcinogenesis in UC via database mining, thus offering opportunities for early prediction and intervention of UC-CRC. Methods. Microarray datasets (GSE47908 and GSE87466) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between groups of GSE47908 were identified using the "limma'' R package. Weighted gene co-expression network analysis (WGCNA) based on DEGs between the CAD and control groups was conducted subsequently. Functional enrichment analysis was performed, and hub genes of selected modules were identified using the "clusterProfiler'' R package. Single-gene gene set enrichment analysis (GSEA) was conducted to predict significant biological processes and pathways associated with the specified gene. Results. Six functional modules were identified based on 4929 DEGs. Green and blue modules were selected because of their consistent correlation with UC and CAD, and the highest correlation coefficient with the progress of UC-associated carcinogenesis. Functional enrichment analysis revealed that genes of these two modules were significantly enriched in biological processes, including mitochondrial dysfunction, cell-cell junction, and immune responses. However, GSEA based on differential expression analysis between sporadic colorectal cancer (CRC) and normal controls from The Cancer Genome Atlas (TCGA) indicated that mitochondrial dysfunction may not be the major carcinogenic mechanism underlying sporadic CRC. Thirteen hub genes (SLC25A3, ACO2, AIFM1, ATP5A1, DLD, TFE3, UQCRC1, ADIPOR2, SLC35D1, TOR1AIP1, PRR5L, ATOX1, and DTX3) were identified. Their expression trends were validated in UC patients of GSE87466, and their potential carcinogenic effects in UC were supported by their known functions and other relevant studies reported in the literature. Single-gene GSEA indicated that biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to angiogenesis and immune response were positively correlated with the upregulation of TFE3, whereas those related to mitochondrial function and energy metabolism were negatively correlated with the upregulation of TFE3. Conclusions. Using WGCNA, this study found two gene modules that were significantly correlated with CAD, of which 13 hub genes were identified as the potential key genes. The critical biological processes in which the genes of these two modules were significantly enriched include mitochondrial dysfunction, cell-cell junction, and immune responses. TFE3, a transcription factor related to mitochondrial function and cancers, may play a central role in UC-associated carcinogenesis.	[Zhang, Di; Yan, Pengguang; Han, Taotao; Cheng, Xiaoyun; Li, Jingnan] Chinese Acad Med Sci, Dept Gastroenterol, Peking Union Med Coll Hosp, Peking Union Med Coll, Beijing, Peoples R China; [Zhang, Di; Yan, Pengguang; Han, Taotao; Cheng, Xiaoyun; Li, Jingnan] Chinese Acad Med Sci, Key Lab Gut Microbiota Translat Med Res, Beijing, Peoples R China		Li, JN (corresponding author), Chinese Acad Med Sci, Dept Gastroenterol, Peking Union Med Coll Hosp, Peking Union Med Coll, Beijing, Peoples R China.; Li, JN (corresponding author), Chinese Acad Med Sci, Key Lab Gut Microbiota Translat Med Res, Beijing, Peoples R China.	puincjnl@126.com			Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine [CAMS-2016-I2M-1-007]	This work was supported by the Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-2016-I2M-1-007). 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	Liu, JH; Li, JJ; Chen, G; Cai, XY; Huang, YB; Li, CJ; Gan, XN; Wei, DM; Dang, YW; Luo, DZ				Liu, Jianghua; Li, Jianjun; Chen, Gang; Cai, Xiaoyong; Huang, Yubin; Li, Chunjun; Gan, Xiaoning; Wei, Danming; Dang, Yiwu; Luo, Dianzhong			Association of microRNA-23b-3p down-regulation with progression and survival in pancreatic duct adenocarcinoma and its prospective function via bioinformatics analysis	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY			English	Article						Pancreatic duct adenocarcinoma (PDAC); MiR-23b-3p; disease specific survival (DSS); prognosis; real time RT-qPCR	PROGNOSTIC-SIGNIFICANCE; COLORECTAL-CANCER; CELLS; EXPRESSION; STATISTICS; AUTOPHAGY; THERAPY; TARGETS; MIR-23B; GROWTH	Background: MicroRNAs (miRNAs) have been reported in various human malignancies, which play important roles in tumorigenesis and progression, acting as oncogenes or tumor suppressors. However, the role of miR-23b-3p in pancreatic duct adenocarcinoma (PDAC) is to be elucidated. The goal of this study was to explore the association of miR-23b-3p expression with clinic features in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and survival in PDAC patients and to investigate the prospective function of miR-23b-3p via bioinformatics analysis. Methods: The expression of miR-23b-3p was detected in 57 PDAC and 25 adjacent normal pancreatic tissues (ANT), also in five PDAC cell lines and an immortal pancreatic epithelium cell line HPDE6c-7 by qRT-PCR. The relationship between miR-23b-3p level and clinicopathological parameters including survival of PDAC patients was analyzed with Spearman correlation, Kaplan-Meier method and Cox proportional hazards mode, respectively. In addition, the validated target genes of miR-23b-3p gathered from DIANA-TarBase v7.0 and miRTarBase 6.0 were assessed with Gene Ontology (GO) and KEGG pathway enrichment analyses. Results: The relative level of miR-23b3p was significantly lower in PDAC compared to ANT (P=0.0053). Remarkably lesser expression of miR-23b-3p was also found in capan-1, aspc1 and panc-1 PDAC cells, compared with HPDE6c-7 cell line, respectively (all P<0.05). Furthermore, miR-23b-3p expression level was significantly correlated with tumor size (r=0.341, P=0.001), depth of invasion (r=0.264 P=0.048) and tumor stage (r=0.281, P=0.034). Kaplan-Meier analysis displayed that patients with lower miR-23b-3p expression presented a poorer disease specific survival (DSS) (P=0.036). Additionally, multivariate analysis revealed that down-expression of miR-23b-3p, as well as the histological grade and tumor stage, was an independent predictor of DSS of PDAC. A total of 173 validated targets were collected and they had enriched GO terms in different pathways. KEGG enrichment analysis revealed that the validated targets of miR-23b3p were significantly enriched in some well-known oncogenic pathways of malignancies, including the pathway of "Pancreatic cancer" with the genes of E2F1, RAF1, JAK1, RB1, BCL2L1, CHUK and RAD51. Conclusion: MiR-23b-3p might become as a potential indicator related to progress and prognosis via targeting various key pathways in PDAC.	[Liu, Jianghua; Chen, Gang; Li, Chunjun; Gan, Xiaoning; Wei, Danming; Dang, Yiwu; Luo, Dianzhong] Guangxi Med Univ, Affiliated Hosp 1, Dept Pathol, 6 Shuangyong Rd, Nanning 530021, Guangxi Zhuang, Peoples R China; [Liu, Jianghua] Guangxi Med Univ, Affiliated Hosp 1, Dept Emergency, Nanning, Guangxi Zhuang, Peoples R China; [Li, Jianjun; Cai, Xiaoyong; Huang, Yubin] Guangxi Med Univ, Affiliated Hosp 1, Dept Gen Surg, Western Branch, Nanning, Guangxi Zhuang, Peoples R China		Dang, YW; Luo, DZ (corresponding author), Guangxi Med Univ, Affiliated Hosp 1, Dept Pathol, 6 Shuangyong Rd, Nanning 530021, Guangxi Zhuang, Peoples R China.	dangyiwu@126.com; 13878802796@163.com			Fund of Guangxi National Science Foundation [2014GXNS-FBA118167]; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC 81560448]	The study was supported by the Fund of Guangxi National Science Foundation (2014GXNS-FBA118167) and Natural Science Foundation of China (NSFC 81560448). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	Brunetti O, 2015, ONCOTARGET, V6, P23323, DOI 10.18632/oncotarget.4492; Cekaite L, 2016, ONCOTARGET, V7, P6476, DOI 10.18632/oncotarget.6390; Chen WQ, 2016, CA-CANCER J CLIN, V66, P115, DOI 10.3322/caac.21338; Chou CH, 2016, NUCLEIC ACIDS RES, V44, pD239, DOI 10.1093/nar/gkv1258; Conroy T, 2016, EUR J CANCER, V57, P10, DOI 10.1016/j.ejca.2015.12.026; Frixa T, 2015, CANCERS, V7, P2466, DOI 10.3390/cancers7040904; Gharibi A, 2016, ACTA HISTOCHEM, V118, P305, DOI 10.1016/j.acthis.2016.01.009; Ibrahim AM, 2016, WORLD J GASTROENTERO, V22, P748, DOI 10.3748/wjg.v22.i2.748; Ishteiwy RA, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0052106; Jin LJ, 2013, CANCER RES, V73, P2884, DOI 10.1158/0008-5472.CAN-12-2162; Kimura Hitomi, 2004, Nucleic Acids Symp Ser (Oxf), P213; Kowalewska M, 2013, TUMOR BIOL, V34, P2153, DOI 10.1007/s13277-013-0748-5; Krska Zdenek, 2015, Prague Med Rep, V116, P253, DOI 10.14712/23362936.2015.65; Le TD, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0145386; Lee YJ, 2015, DRUG DEVELOP RES, V76, P389, DOI 10.1002/ddr.21278; Li BL, 2013, CELL PHYSIOL BIOCHEM, V32, P1729, DOI 10.1159/000356607; Liu JH, 2014, ASIAN PAC J CANCER P, V15, P2971, DOI 10.7314/APJCP.2014.15.7.2971; Majid S, 2012, CANCER RES, V72, P6435, DOI 10.1158/0008-5472.CAN-12-2181; O'Connell RM, 2010, NAT REV IMMUNOL, V10, P111, DOI 10.1038/nri2708; Ostenfeld MS, 2014, CANCER RES, V74, P5758, DOI 10.1158/0008-5472.CAN-13-3512; Qu JJ, 2015, INT J CLIN EXP MED, V8, P17110; Qureshi A, 2011, ASIAN PAC J CANCER P, V12, P953; Salvi A, 2009, FEBS J, V276, P2966, DOI 10.1111/j.1742-4658.2009.07014.x; Siegel RL, 2016, CA-CANCER J CLIN, V66, P7, DOI 10.3322/caac.21332; Slaby O, 2013, NUTR CANCER, V65, P247, DOI 10.1080/01635581.2013.756530; Sun LH, 2015, J GENET GENOMICS, V42, P563, DOI 10.1016/j.jgg.2015.07.003; Tian L, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0075885; Vlachos IS, 2015, NUCLEIC ACIDS RES, V43, pD153, DOI 10.1093/nar/gku1215; Wang KC, 2010, P NATL ACAD SCI USA, V107, P3234, DOI 10.1073/pnas.0914825107; Wang P, 2013, AUTOPHAGY, V9, P2171, DOI 10.4161/auto.26463; Wang P, 2013, GASTROENTEROLOGY, V145, P1133, DOI 10.1053/j.gastro.2013.07.048; Yuan B, 2011, FEBS LETT, V585, P927, DOI 10.1016/j.febslet.2011.02.031; Zaman MS, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0050203; Zhang HS, 2011, NAT COMMUN, V2, DOI 10.1038/ncomms1555; Zheng J, 2012, ALLERGY, V67, P362, DOI 10.1111/j.1398-9995.2011.02776.x	35	0	0	0	5	E-CENTURY PUBLISHING CORP	MADISON	40 WHITE OAKS LN, MADISON, WI 53711 USA	1936-2625			INT J CLIN EXP PATHO	Int. J. Clin. Exp. Pathol.		2016	9	7					6645	6658					14	Oncology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pathology	DT8GY	WOS:000381729200004					2022-04-25	
J	Chern, YJ; Wong, JCT; Cheng, GSW; Yu, A; Yin, YL; Schaeffer, DF; Kennecke, HF; Morin, G; Tai, IT				Chern, Yi-Jye; Wong, John C. T.; Cheng, Grace S. W.; Yu, Angel; Yin, Yaling; Schaeffer, David F.; Kennecke, Hagen F.; Morin, Gregg; Tai, Isabella T.			The interaction between SPARC and GRP78 interferes with ER stress signaling and potentiates apoptosis via PERK/eIF2 alpha and IRE1 alpha/XBP-1 in colorectal cancer	CELL DEATH & DISEASE			English	Article							UNFOLDED PROTEIN RESPONSE; EXPRESSION; CELLS; RICH; SENSITIVITY; METABOLISM; RESISTANCE; AUTOPHAGY; MIGRATION; TARGET	Therapy-refractory disease is one of the main contributors of treatment failure in cancer. In colorectal cancer (CRC), SPARC can function as a sensitizer to conventional chemotherapy by enhancing apoptosis by interfering with the activity of Bcl-2. Here, we examine a novel mechanism by which SPARC further potentiates apoptosis via its modulation of the unfolded protein response (UPR). Using mass spectrometry to identify SPARC-associated proteins, GRP78 was identified as a protein partner for SPARC in CRC. In vitro studies conducted to assess the signaling events resulting from this interaction, included induction of ER stress with tunicamycin, 5-fluorouracil (5-FU), and irinotecan (CPT-11). We found that the interaction between GRP78 and SPARC increased during exposure to 5-FU, CPT-11, and tunicamycin, resulting in an attenuation of GRP78's inhibition of apoptosis. In addition, we also show that SPARC can sensitize CRC cells to PERK/eIF2 alpha and IRE1 alpha/XBP-1 UPR signaling by interfering with ER stress following binding to GRP78, which leads to ER stress-associated cell death in CRC cells. In line with these findings, a lower expression of GRP78 relative to SPARC in CRC is associated with a lower IC50 for 5-FU in either sensitive or therapy-refractory CRC cells. Interestingly, this observation correlates with tissue microarray analysis of 143 human CRC, where low GRP78 to SPARC expression level was prognostic of higher survival rate (P= 0.01) in individuals with CRC. This study demonstrates that modulation of UPR signaling by SPARC promotes ER stress-associated death and potentiates apoptosis. This may be an effective strategy that can be combined with current treatment options to improve therapeutic efficacy in CRC.	[Chern, Yi-Jye; Wong, John C. T.; Yu, Angel; Tai, Isabella T.] Univ British Columbia, Dept Med, Div Gastroenterol, Vancouver, BC, Canada; [Chern, Yi-Jye; Wong, John C. T.; Cheng, Grace S. W.; Yu, Angel; Morin, Gregg; Tai, Isabella T.] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC, Canada; [Cheng, Grace S. W.; Morin, Gregg] British Columbia Canc Agcy, Dept Med Genet, Vancouver, BC, Canada; [Yin, Yaling] British Columbia Canc Agcy, Canc Surveillance & Outcomes, Vancouver, BC, Canada; [Yin, Yaling; Kennecke, Hagen F.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC, Canada; [Schaeffer, David F.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada		Tai, IT (corresponding author), Univ British Columbia, Dept Med, Div Gastroenterol, Vancouver, BC, Canada.; Tai, IT (corresponding author), British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.	itai@bcgsc.ca	Morin, Gregg B/E-9123-2012; Chern, Yi-Jye/AAE-9283-2022; Tai, Isabella T/E-8035-2012	Morin, Gregg B/0000-0001-8949-4374; Chern, Yi-Jye/0000-0003-3533-5735	Canadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR) [MOP-82881]; CIHRCanadian Institutes of Health Research (CIHR) [MSH-95344]	This work was supported by Canadian Institutes of Health Research (CIHR) research grant#MOP-82881; CIHR New Investigator salary award to Isabella T. Tai (MSH-95344). The authors would like to thank Dr. Hla Win Piazza for her technical assistance in this study.	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JUN 26	2019	10								504	10.1038/s41419-019-1687-x			14	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	IF2YV	WOS:000472947600003	31243264	gold, Green Published			2022-04-25	
J	Li, MY; Zhang, SH; Qiu, Y; He, Y; Chen, BL; Mao, R; Cui, Y; Zeng, ZR; Chen, MH				Li, Manying; Zhang, Shenghong; Qiu, Yun; He, Yao; Chen, Baili; Mao, Ren; Cui, Yi; Zeng, Zhirong; Chen, Minhu			Upregulation of miR-665 promotes apoptosis and colitis in inflammatory bowel disease by repressing the endoplasmic reticulum stress components XBP1 and ORMDL3	CELL DEATH & DISEASE			English	Article							UNFOLDED PROTEIN RESPONSE; ER STRESS; HEPATOCELLULAR-CARCINOMA; ULCERATIVE-COLITIS; EXPRESSION; CANCER; AUTOPHAGY; IMMUNITY; CELLS; RISK	MicroRNAs are critical post-transcriptional regulators of gene expression and key mediators of pathophysiology of inflammatory bowel disease (IBD). This study is aimed to study the role of miR-665 in the progression of IBD. Real-time PCR analysis was used to determine miR-665 expression in 89 freshly isolated IBD samples and dextran sulfate sodium (DSS)-induced colonic mucosal tissues. The role of miR-665 in inducing apoptosis and colitis were examined by Annexin V, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, colony formation in vitro and DSS-induced colitis mice model in vivo. Moreover, luciferase reporter assay, western blot analysis and microribonucleoprotein immunoprecipitation were performed to determine that miR-665 directly repressed XBP1 (X-box-binding protein-1) and ORMDL3 expression. Herein, our results revealed that miR-665 was markedly upregulated in active colitis. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-665 promoted apoptosis under different inflammatory stimuli. Importantly, delivery of miR-665 mimic promoted, while injection of antagomiR-665 markedly impaired DSS-induced colitis in vivo. Mechanistically, we demonstrated that miR-665 induced apoptosis by inhibiting XBP1 and ORMDL3. Taken together, our findings reveal a new regulatory mechanism for ER stress signaling and suggest that miR-665 might be a potential target in IBD therapy.	[Li, Manying; Zhang, Shenghong; Qiu, Yun; He, Yao; Chen, Baili; Mao, Ren; Cui, Yi; Zeng, Zhirong; Chen, Minhu] Sun Yat Sen Univ, First Affiliated Hosp, Div Gastroenterol, 58,Zhongshan Rd 2, Guangzhou 510080, Peoples R China		Zhang, SH (corresponding author), Sun Yat Sen Univ, First Affiliated Hosp, Div Gastroenterol, 58,Zhongshan Rd 2, Guangzhou 510080, Peoples R China.	shenghongzhang@163.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81670498, 81470821, 81630018]; Pearl River S&T Nova Program of Guangzhou [201610010126]; Guangdong Science and Technology [2014A020212128, 2016A020214006]; Fundamental Research Funds for Sun Yat-sen University [15ykpy12]	This project was supported by grants from the National Natural Science Foundation of China (nos 81670498, 81470821 and 81630018), the Pearl River S&T Nova Program of Guangzhou (no. 201610010126), Guangdong Science and Technology (nos 2014A020212128 and 2016A020214006) and the Fundamental Research Funds for Sun Yat-sen University (no. 15ykpy12).	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MAR	2017	8								e2699	10.1038/cddis.2017.76			8	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	EP5VM	WOS:000397447100023	28333149	gold, Green Published			2022-04-25	
J	Qian, XL; Pan, YH; Huang, QY; Shi, YB; Huang, QY; Hu, ZZ; Xiong, LX				Qian, Xian-Ling; Pan, Yi-Hang; Huang, Qi-Yuan; Shi, Yu-Bo; Huang, Qing-Yun; Hu, Zhen-Zhen; Xiong, Li-Xia			Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment	ONCOTARGETS AND THERAPY			English	Review						breast cancer; caveolin-1; migration; metastasis; prognosis; invasion	ANTIBODY-DRUG CONJUGATE; STEM-CELLS; MESENCHYMAL TRANSITION; COLORECTAL-CANCER; DOWN-REGULATION; LIPID RAFTS; TRANSCRIPTIONAL REGULATION; PROGNOSTIC BIOMARKER; DOCOSAHEXAENOIC ACID; ANTITUMOR-ACTIVITY	Human breast cancer is one of the most frequent cancer diseases and causes of death among female population worldwide. It appears at a high incidence and has a high malignancy, mortality, recurrence rate and poor prognosis. Caveolin-1 (Cav1) is the main component of caveolae and participates in various biological events. More and more experimental studies have shown that Cav1 plays a critical role in the progression of breast cancer including cell proliferation, apoptosis, autophagy, invasion, migration and breast cancer metastasis. Besides, Cav1 has been found to be involved in chemotherapeutics and radiotherapy resistance, which are still the principal problems encountered in clinical breast cancer treatment. In addition, stromal Cav1 may be a potential indicator for breast cancer patients' prognosis. In the current review, we cover the state-of-the-art study, development and progress on Cav1 and breast cancer, altogether describing the role of Cav1 in breast cancer progression and application in clinical treatment, in the hope of providing a basis for further research and promoting CAV1 gene as a potential target to diagnose and treat aggressive breast cancers.	[Qian, Xian-Ling; Pan, Yi-Hang; Huang, Qi-Yuan; Shi, Yu-Bo; Huang, Qing-Yun; Hu, Zhen-Zhen; Xiong, Li-Xia] Nanchang Univ, Dept Pathophysiol, Basic Med Coll, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China; [Qian, Xian-Ling; Pan, Yi-Hang] Nanchang Univ, Clin Med Coll 1, Nanchang 330006, Jiangxi, Peoples R China; [Huang, Qi-Yuan] Nanchang Univ, Clin Med Coll 2, Nanchang 330006, Jiangxi, Peoples R China; [Hu, Zhen-Zhen; Xiong, Li-Xia] Jiangxi Prov Key Lab Tumor Pathogenesis & Mol Pat, Nanchang, Jiangxi, Peoples R China		Hu, ZZ; Xiong, LX (corresponding author), Nanchang Univ, Dept Pathophysiol, Basic Med Coll, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China.	huzhenzhen@ncu.edu.cn; xionglixia@ncu.edu.cn	Qian, Xianling/V-6981-2019	Qian, Xianling/0000-0001-5366-4976; Xiong, Lixia/0000-0003-3769-2496	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31860317]	LXX received a grant from the National Natural Science Foundation of China (No 31860317). The authors report no other conflicts of interest in this work.	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Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Oncology	HN3GI	WOS:000460071400001	30881011	Green Published, gold			2022-04-25	
J	Zhang, LP; Zhang, Q; Lv, LX; Zhu, JH; Ting, C; Wu, YT				Zhang, Liping; Zhang, Qiang; Lv, Lingxia; Zhu, Jianhua; Ting, Chen; Wu, Yutao			LncRNA SNHG1 regulates vascular endothelial cell proliferation and angiogenesis via miR-196a	JOURNAL OF MOLECULAR HISTOLOGY			English	Article						Atherosclerosis; SNHG1; Inflammatory cytokines; HUVECs	INFLAMMATORY CYTOKINES; COLORECTAL-CANCER; NONCODING RNAS; ATHEROSCLEROSIS; APOPTOSIS; MIGRATION; DISEASE; MAPK; INHIBITION; INVASION	Inflammatory cytokines are important protagonists in the formation of atherosclerotic plaques, triggering effects throughout the atherosclerotic vessels due to the destruction in proliferation, migration and angiogenesis of endothelial cells. In this study, we found SNHG1 is upregulated in TNF-alpha-treated HUVECs. We silenced SNHG1 and found it inhibited vascular endothelial cell proliferation and angiogenesis. In the other hand, exogenetic overexpression of SNHG1 promotes proliferation, migration and angiogenesis. Then we demonstrated that SNHG1 may interact directly with miR-196a to act as a miR-196a sponge. Further, MAPK6 were predicted to be the target of miR-196a. So we blocked miR-196a, which increased expression level of MAPK6, enhanced cell proliferation, migration and angiogenesis. These data indicated that SNHG1/miR-196a/MAPK6 axis may take a part in autophagy regulation in TNF-alpha-treated HUVECs. The subsequent rescue experiments come to the results ascertained the specificity of SNHG1/miR-196a/MAPK6 axis in regulating MAPK6. Overall, our findings demonstrate a novel mechanism by which SNHG1 overexpression protects the function of HUVECs, which may delay the progression of AS. SNHG1/miR-196a/MAPK6 axis may be of therapeutic significance in AS.	[Zhang, Liping; Zhang, Qiang; Lv, Lingxia; Zhu, Jianhua; Ting, Chen; Wu, Yutao] Zhejiang Univ, Affiliated Hosp 1, Dept Cardiol, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China		Wu, YT (corresponding author), Zhejiang Univ, Affiliated Hosp 1, Dept Cardiol, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China.	vfdgijgjn@sina.com			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81700238, 81670397, 91539103]; Zhejiang Medical Science and Technology Project [2019KY376, 2018KY071]	This work was supported by the National Natural Science Foundation of China Grants (81700238, 81670397, 91539103), and the Zhejiang Medical Science and Technology Project (2019KY376, 2018KY071).	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Mol. Histol.	APR	2020	51	2					117	124		10.1007/s10735-020-09862-z		APR 2020	8	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	LE2JF	WOS:000526249700001	32297149				2022-04-25	
J	Maiese, K				Maiese, Kenneth			FoxO Proteins in the Nervous System	ANALYTICAL CELLULAR PATHOLOGY			English	Review							FORKHEAD TRANSCRIPTION FACTORS; COLORECTAL-CANCER CELLS; OXIDATIVE-STRESS; BETA-CATENIN; SIGNALING PATHWAY; STEM-CELLS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CEREBRAL-ISCHEMIA; AMYLOID TOXICITY	Acute as well as chronic disorders of the nervous system lead to significant morbidity and mortality for millions of individuals globally. Given the ability to govern stem cell proliferation and differentiated cell survival, mammalian forkhead transcription factors of the forkhead box class O (FoxO) are increasingly being identified as potential targets for disorders of the nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and auditory neuronal disease. FoxO proteins are present throughout the body, but they are selectively expressed in the nervous system and have diverse biological functions. The forkhead O class transcription factors interface with an array of signal transduction pathways that include protein kinase B (Akt), serum-and glucocorticoid-inducible protein kinase (SgK), I kappa B kinase (IKK), silentmating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), growth factors, and Wnt signaling that can determine the activity and integrity of FoxO proteins. Ultimately, there exists a complex interplay between FoxO proteins and their signal transduction pathways that can significantly impact programmed cell death pathways of apoptosis and autophagy as well as the development of clinical strategies for the treatment of neurodegenerative disorders.	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	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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Cell. Pathol.		2015	2015								569392	10.1155/2015/569392			15	Oncology; Cell Biology; Pathology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Cell Biology; Pathology	CL2MQ	WOS:000356778700001	26171319	gold, Green Submitted, Green Published			2022-04-25	
J	Velloso, FJ; Trombetta-Lima, M; Anschau, V; Sogayar, MC; Correa, RG				Velloso, Fernando J.; Trombetta-Lima, Marina; Anschau, Valesca; Sogayar, Mari C.; Correa, Ricardo G.			NOD-like receptors: major players (and targets) in the interface between innate immunity and cancer	BIOSCIENCE REPORTS			English	Review							NF-KAPPA-B; APOPTOSIS INHIBITORY PROTEIN; CENTRAL-NERVOUS-SYSTEM; NLRP3 INFLAMMASOME; PROSTATE-CANCER; COLORECTAL-CANCER; NUCLEOTIDE-BINDING; HOST-DEFENSE; BACTERIAL PEPTIDOGLYCAN; PATHOGEN-RECOGNITION	Innate immunity comprises several inflammation-related modulatory pathways which receive signals from an array of membrane-bound and cytoplasmic pattern recognition receptors (PRRs). The NLRs (NACHT (NAIP (neuronal apoptosis inhibitor protein), C2TA (MHC class 2 transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TP1 (telomerase-associated protein) and Leucine-Rich Repeat (LRR) domain containing proteins) relate to a large family of cytosolic innate receptors, involved in detection of intracellular pathogens and endogenous byproducts of tissue injury. These receptors may recognize pathogen-associated molecular patterns (PAMPs) and/or danger-associated molecular patterns (DAMPs), activating host responses against pathogen infection and cellular stress. NLR-driven downstream signals trigger a number of signaling circuitries, which may either initiate the formation of inflammasomes and/or activate nuclear factor kappa B (NF-kappa B), stress kinases, interferon response factors (IRFs), inflammatory caspases and autophagy. Disruption of those signals may lead to a number of pro-inflammatory conditions, eventually promoting the onset of human malignancies. In this review, we describe the structures and functions of the most well-defined NLR proteins and highlight their association and biological impact on a diverse number of cancers.	[Velloso, Fernando J.] Rutgers New Jersey Med Sch Newark, Dept Pharmacol Physiol & Neurosci, Newark, NJ 07103 USA; [Velloso, Fernando J.; Trombetta-Lima, Marina; Sogayar, Mari C.] Univ Sao Paulo, Cell & Mol Therapy Ctr NUCEL, Sch Med, Internal Med Dept, Sao Paulo, SP, Brazil; [Anschau, Valesca] Univ Valencia, Inst Integrat Syst Biol I2SysBio, CSIC, Valencia 46980, Spain; [Sogayar, Mari C.] Univ Sao Paulo, Chem Inst, Biochem Dept, Sao Paulo, Brazil; [Correa, Ricardo G.] Sanford Burnham Prebys Med Discovery Inst, NCI Designated Canc Ctr, La Jolla, CA 92037 USA		Velloso, FJ (corresponding author), Rutgers New Jersey Med Sch Newark, Dept Pharmacol Physiol & Neurosci, Newark, NJ 07103 USA.; Velloso, FJ (corresponding author), Univ Sao Paulo, Cell & Mol Therapy Ctr NUCEL, Sch Med, Internal Med Dept, Sao Paulo, SP, Brazil.; Correa, RG (corresponding author), Sanford Burnham Prebys Med Discovery Inst, NCI Designated Canc Ctr, La Jolla, CA 92037 USA.	fernando.velloso@rutgers.edu; rcorrea@sbpdiscovery.org	Correa, Ricardo G/G-7613-2012; Anschau, Valesca/Z-6231-2019; Velloso, Fernando/AAA-5262-2020; Anschau, Ph. D, Valesca/ABH-3426-2021; Lima, Marina Trombetta/P-1757-2015	Correa, Ricardo G/0000-0001-6940-7034; Anschau, Valesca/0000-0002-9681-7204; Velloso, Fernando/0000-0002-5582-2912; Lima, Marina Trombetta/0000-0002-3687-6210	CAPES (Federal Agency for Superior Education and Training) research funding agency [88887.091759/2015-00]; FAPESP (Sao Paulo State Foundation for Research)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/05311-2]; CNPq (National Research Council)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [148684/2013-0, 457201/2013-2]; BNDES (Brazilian National Bank for Economic and Social Development) [09.2.1066.1]; FINEP (Project Financing Agency) [01.06.0664.00, 01.08.0622.00]; MCTI (Science, Technology and Innovation Ministry); MS-DECIT (Science and Technology Department of the Health Ministry); 'Science without Borders' Program (CAPES, Brazil) [88887.091759/2015-00]	This work was supported by CAPES (Federal Agency for Superior Education and Training) research funding agency [grant number 88887.091759/2015-00 (to F.J.V.)]; FAPESP (Sao Paulo State Foundation for Research) [grant number 2016/05311-2 (to M.C.S.)]; CNPq (National Research Council) [grant number 148684/2013-0; 457201/2013-2 (to M.C.S.)]; BNDES (Brazilian National Bank for Economic and Social Development) [grant number 09.2.1066.1 (to M.C.S.)]; FINEP (Project Financing Agency) [grant number 01.06.0664.00; 01.08.0622.00 (to M.C.S.)]; MCTI (Science, Technology and Innovation Ministry) (to M.C.S.); MS-DECIT (Science and Technology Department of the Health Ministry) (to M.C.S.); and a Special Visiting Researcher (PVE) grant from the 'Science without Borders' Program (CAPES, Brazil) [grant number 88887.091759/2015-00 (to R.G.C.)].	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2016, METHOD MOL BIOL, V1417, P1, DOI DOI 10.1007/978-1-4939-3566-6.1; 2009, J BIOL CHEM, V284, P1276, DOI DOI 10.1074/JBC.M806084200	219	50	53	2	17	PORTLAND PRESS LTD	LONDON	CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND	0144-8463	1573-4935		BIOSCIENCE REP	Biosci. Rep.	APR 30	2019	39		4						BSR20181709	10.1042/BSR20181709			21	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	HW3RC	WOS:000466609400022	30837326	Green Submitted, gold, Green Published			2022-04-25	
J	Jung, O; Lee, J; Lee, YJ; Yun, JM; Son, YJ; Cho, JY; Ryou, C; Lee, SY				Jung, Okkeun; Lee, Jongsung; Lee, Yu Jin; Yun, Jung-Mi; Son, Young-Jin; Cho, Jae Youl; Ryou, Chongsuk; Lee, Sang Yeol			Timosaponin AIII inhibits migration and invasion of A549 human non-small-cell lung cancer cells via attenuations of MMP-2 and MMP-9 by inhibitions of ERK1/2, Src/FAK and beta-catenin signaling pathways	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS			English	Article						Timosaponin AIII; ERK1/2; Src; FAK; Metastasis; Matrix metalloproteinases; Human non-small-cell lung cancer	ANEMARRHENA-ASPHODELOIDES; SUPPRESSES MIGRATION; METASTASIS; APOPTOSIS; MEMORY; BUNGE; MYC	Timosaponin AIII (TAIII) is a type of steroidal saponins isolated from Anemarrhena asphodeloides. It was known to improve learning and memory deficits through anti-inflammatory effects. TAIII was also reported to induce autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells and inhibit the growth of human colorectal cancer cells, thus regarded as a potential candidate for anti-cancer agent. In this study, we verified apoptosis-inducing and cell-cycle-arresting effects of TAIII in A549 human non-small-cell lung cancer (NSCLC) cells. Then, we report that TAIII suppresses migration and invasion of A549 human NSCLC cells. We propose that two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, which are well known to be involved in cancer-metastasis, are attenuated by the treatment of TAIII. TAIII exerts its suppressive effects on MMP-2 and MMP-9 via inhibitions of ERK1/2, Src/FAK and beta-catenin signalings which are closely related with the regulations of MMP-2 and MMP-9. (C) 2016 Elsevier Ltd. All rights reserved.	[Jung, Okkeun; Lee, Yu Jin; Lee, Sang Yeol] Gachon Univ, Dept Life Sci, San 65, Songnam 461701, Gyeonggi, South Korea; [Lee, Jongsung; Cho, Jae Youl] Sungkyunkwan Univ, Dept Genet Engn, Suwon 440746, Gyeonggi, South Korea; [Yun, Jung-Mi] Chonnam Natl Univ, Dept Food & Nutr, Gwangju, South Korea; [Son, Young-Jin] Sunchon Natl Univ, Dept Pharm, Sunchon 530742, Jeonnam, South Korea; [Ryou, Chongsuk] Hanyang Univ, Coll Pharm, Dept Pharm, Ansan 426791, Gyeonggi Do, South Korea; [Ryou, Chongsuk] Hanyang Univ, Inst Pharmaceut Sci & Technol, Ansan 426791, Gyeonggi Do, South Korea		Lee, SY (corresponding author), Gachon Univ, Dept Life Sci, San 65, Songnam 461701, Gyeonggi, South Korea.	leesaye@gachon.ac.kr			Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2015R1D1A1A09058494]	This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A1A09058494).	Dang CV, 2012, CELL, V149, P22, DOI 10.1016/j.cell.2012.03.003; Dufour A, 2008, J CELL PHYSIOL, V217, P643, DOI 10.1002/jcp.21535; HAMAGUCHI M, 1995, ONCOGENE, V10, P1037; Huang C, 2004, J CELL SCI, V117, P4619, DOI 10.1242/jcs.01481; Ji X., 2010, CHIN TRADIT HERB DRU, V41, P12; Kang YJ, 2011, J NAT PROD, V74, P701, DOI 10.1021/np1007735; Kim JH, 2015, CHEM-BIOL INTERACT, V242, P25, DOI 10.1016/j.cbi.2015.08.014; King FW, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0007283; Ku MJ, 2013, BIOORG MED CHEM LETT, V23, P5609, DOI 10.1016/j.bmcl.2013.08.043; Ku MJ, 2015, MOL CELL BIOCHEM, V402, P243, DOI 10.1007/s11010-015-2331-4; Lee B, 2009, PHARMACOL BIOCHEM BE, V93, P121, DOI 10.1016/j.pbb.2009.04.021; [李素燕 LI SuYan], 2006, [军事医学科学院院刊, Bulletin of the Academy of Military Medical Sciences], V30, P340; Li TJ, 2007, NEUROSCI LETT, V421, P147, DOI 10.1016/j.neulet.2007.04.082; Matsuzaki S, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0061690; NIWA A, 1988, YAKUGAKU ZASSHI, V108, P555, DOI 10.1248/yakushi1947.108.6_555; Ryu BJ, 2014, MOL CELL BIOCHEM, V389, P69, DOI 10.1007/s11010-013-1928-8; Sy LK, 2008, CANCER RES, V68, P10229, DOI 10.1158/0008-5472.CAN-08-1983; Takeda Y, 2001, J GASTROENTEROL, V36, P79, DOI 10.1007/s005350170135; Wang N, 2013, BBA-MOL CELL RES, V1833, P2890, DOI 10.1016/j.bbamcr.2013.07.018; Wang YL, 2014, J ETHNOPHARMACOL, V153, P42, DOI 10.1016/j.jep.2014.02.013; Westermarck J, 1999, FASEB J, V13, P781, DOI 10.1096/fasebj.13.8.781; Wolfer A, 2011, CANCER RES, V71, P2034, DOI 10.1158/0008-5472.CAN-10-3776	22	44	51	3	22	PERGAMON-ELSEVIER SCIENCE LTD	OXFORD	THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND	0960-894X	1464-3405		BIOORG MED CHEM LETT	Bioorg. Med. Chem. Lett.	AUG 15	2016	26	16					3963	3967		10.1016/j.bmcl.2016.07.004			5	Chemistry, Medicinal; Chemistry, Organic	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy; Chemistry	DS2FB	WOS:000380574400024	27422337				2022-04-25	
J	Nagasawa, I; Kunimasa, K; Tsukahara, S; Tomida, A				Nagasawa, Ikuko; Kunimasa, Kazuhiro; Tsukahara, Satomi; Tomida, Akihiro			BRAF-mutated cells activate GCN2-mediated integrated stress response as a cytoprotective mechanism in response to vemurafenib	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS			English	Article						Vemurafenib; BRAF; Integrated stress response; GCN2; ATF4	UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; MELANOMA-CELLS; BRAF(V600E) INHIBITION; GENE-EXPRESSION; KINASE; RESISTANCE; AUTOPHAGY; CANCER; GCN2	In BRAF-mutated melanoma cells, the BRAF inhibitor, vemurafenib, induces phosphorylation of eukaryotic initiation factor 2 alpha (eIF2 alpha) and subsequent induction of activating transcription factor 4 (ATF4), the central regulation node of the integrated stress response (ISR). While the ISR supports cellular adaptation to various stresses, the role of vemurafenib-triggered ISR has not been fully characterized. Here, we showed that in response to vemurafenib, BRAF-mutated melanoma and colorectal cancer cells rapidly induced the ISR as a cytoprotective mechanism through activation of general control non-derepressible 2 (GCN2), an eIF2 alpha kinase sensing amino acid levels. The vemurafenib-triggered ISR, an event independent of downstream MEK inhibition, was specifically prevented by silencing GCN2, but not other eIF2 alpha kinases, including protein kinase-like endoplasmic reticulum kinase, which transmits endoplasmic reticulum (ER) stress. Consistently, the ER stress gatekeeper, GRP78, was not induced by vemurafenib. Interestingly, ATF4 silencing by siRNA rendered BRAF-mutated melanoma cells sensitive to vemurafenib. Thus, the GCN2-mediated ISR can promote cellular adaptation to vemurafenib-induced stress, providing an insight into the development of drug resistance. (C) 2016 Elsevier Inc. All rights reserved.	[Nagasawa, Ikuko; Kunimasa, Kazuhiro; Tsukahara, Satomi; Tomida, Akihiro] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Koto Ku, 3-8-31 Ariake, Tokyo 1358550, Japan; [Nagasawa, Ikuko; Tomida, Akihiro] Meiji Pharmaceut Univ, 2-522-1 Noshio, Tokyo 2048588, Japan		Tomida, A (corresponding author), Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Koto Ku, 3-8-31 Ariake, Tokyo 1358550, Japan.	akihiro.tomida@jfcr.or.jp			JSPS KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [25290061, 16H04717]	This work was supported in part by JSPS KAKENHI Grant Numbers 25290061 and 16H04717. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.	B'chir W, 2013, NUCLEIC ACIDS RES, V41, P7683, DOI 10.1093/nar/gkt563; Baenke F, 2016, MOL ONCOL, V10, P73, DOI 10.1016/j.molonc.2015.08.003; Beck D, 2013, SCI SIGNAL, V6, DOI 10.1126/scisignal.2003057; Berlanga JJ, 1999, EUR J BIOCHEM, V265, P754, DOI 10.1046/j.1432-1327.1999.00780.x; Chen JJ, 2007, BLOOD, V109, P2693, DOI 10.1182/blood-2006-08-041830; Clarke HJ, 2014, CANCER CELL, V25, P563, DOI 10.1016/j.ccr.2014.03.015; Davies H, 2002, NATURE, V417, P949, DOI 10.1038/nature00766; Flaherty KT, 2012, NAT REV CANCER, V12, P349, DOI 10.1038/nrc3218; Flaherty KT, 2010, NEW ENGL J MED, V363, P809, DOI 10.1056/NEJMoa1002011; Haq R, 2013, CANCER CELL, V23, P302, DOI 10.1016/j.ccr.2013.02.003; Harding HP, 2000, MOL CELL, V5, P897, DOI 10.1016/S1097-2765(00)80330-5; Harding HP, 2003, MOL CELL, V11, P619, DOI 10.1016/S1097-2765(03)00105-9; Hernandez-Davies JE, 2015, J TRANSL MED, V13, DOI 10.1186/s12967-015-0581-2; Hetz C, 2013, NAT REV DRUG DISCOV, V12, P703, DOI 10.1038/nrd3976; Kawaguchi K, 2016, ONCOTARGET, V7, P71737, DOI 10.18632/oncotarget.12328; Kilberg MS, 2009, TRENDS ENDOCRIN MET, V20, P436, DOI 10.1016/j.tem.2009.05.008; Lito P, 2013, NAT MED, V19, P1401, DOI 10.1038/nm.3392; Lu PD, 2004, J CELL BIOL, V167, P27, DOI 10.1083/jcb.200408003; Ma XH, 2014, J CLIN INVEST, V124, P1406, DOI 10.1172/JCI70454; Ma YJ, 2004, NAT REV CANCER, V4, P966, DOI 10.1038/nrc1505; Nakamura T, 2010, CELL, V140, P338, DOI 10.1016/j.cell.2010.01.001; Padyana AK, 2005, J BIOL CHEM, V280, P29289, DOI 10.1074/jbc.M504096200; Romano PR, 1998, MOL CELL BIOL, V18, P2282, DOI 10.1128/MCB.18.4.2282; Rzymski T, 2010, ONCOGENE, V29, P4424, DOI 10.1038/onc.2010.191; Saito S, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0045845; Saito S, 2009, CANCER RES, V69, P4225, DOI 10.1158/0008-5472.CAN-08-2689; Sueda T, 2016, SCI REP-UK, V6, DOI 10.1038/srep18949; Sun C, 2014, NATURE, V508, P118, DOI 10.1038/nature13121; Tsai J, 2008, P NATL ACAD SCI USA, V105, P3041, DOI 10.1073/pnas.0711741105; Tsukumo Y, 2015, BIOCHEM BIOPH RES CO, V462, P383, DOI 10.1016/j.bbrc.2015.04.144; Vattem KM, 2004, P NATL ACAD SCI USA, V101, P11269, DOI 10.1073/pnas.0400541101; Ye JB, 2010, EMBO J, V29, P2082, DOI 10.1038/emboj.2010.81	32	11	11	0	2	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 22	2017	482	4					1491	1497		10.1016/j.bbrc.2016.12.062			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	EK1XB	WOS:000393720000149	27965097				2022-04-25	
J	Bitorina, AV; Oligschlaeger, Y; Ding, LL; Yadati, T; Westheim, A; Houben, T; Vaes, RDW; Damink, SWMO; Theys, J; Shiri-Sverdlov, R				Bitorina, Albert V.; Oligschlaeger, Yvonne; Ding, Lingling; Yadati, Tulasi; Westheim, Annemarie; Houben, Tom; Vaes, Rianne D. W.; Damink, Steven W. M. Olde; Theys, Jan; Shiri-Sverdlov, Ronit			OxLDL as an Inducer of a Metabolic Shift in Cancer Cells	JOURNAL OF CANCER			English	Article						Pancreatic cancer cells; oxLDL; metabolic switch; HIF-1 alpha; autophagy	LOW-DENSITY-LIPOPROTEIN; OXIDIZED LDL; NONALCOHOLIC STEATOHEPATITIS; CARDIOVASCULAR-DISEASE; COLORECTAL-CANCER; OXIDATIVE STRESS; RISK; AUTOPHAGY; HYPOXIA; PROLIFERATION	Recent evidence established a link between disturbed lipid metabolism and increased risk for cancer. One of the most prominent features related to disturbed lipid metabolism is an increased production of oxidized low-density-lipoproteins (oxLDL), which results from elevated oxidative stress. OxLDL is known to have detrimental effects on healthy cells and plays a primary role in diseases related to the metabolic syndrome. Nevertheless, so far, the exact role of oxLDL in cancer cell metabolism is not yet known. To examine changes in metabolic profile induced by oxLDL, pancreatic KLM-1 cells were treated with oxLDL in a concentration- (25 or 50 mu g/ml) and/or time-dependent (4 hr or 8 hr) manner and the impact of oxLDL on oxygen consumption rates (OCR) as well as extracellular acidification rates (ECAR) was analyzed using Seahorse technology. Subsequently, to establish the link between oxLDL and glycolysis, stabilization of the master regulator hypoxia-inducible factor 1-alpha (HIF-1 alpha) was measured by means of Western blot. Furthermore, autophagic responses were assessed by measuring protein levels of the autophagosomal marker LC3B-II. Finally, the therapeutic potential of natural anti-oxLDL IgM antibodies in reversing these effects was tested. Incubation of KLM-1 cells with oxLDL shifted the energy balance towards a more glycolytic phenotype, which is an important hallmark of cancer cells. These data were supported by measurement of increased oxLDL-mediated HIF-1 alpha stabilization. In line, oxLDL incubation also increased the levels of LC3B-II, suggesting an elevated autophagic response. Importantly, antibodies against oxLDL were able to reverse these oxLDL-mediated metabolic effects. Our data provides a novel proof-of-concept that oxLDL induces a shift in energy balance. These data not only support a role for oxLDL in the progression of cancer but also suggest the possibility of targeting oxLDL as a therapeutic option in cancer.	[Bitorina, Albert V.; Oligschlaeger, Yvonne; Yadati, Tulasi; Houben, Tom; Shiri-Sverdlov, Ronit] Maastricht Univ, Sch Nutr & Translat Res Metab NUTRIM, Dept Mol Genet, Maastricht, Netherlands; [Vaes, Rianne D. W.; Damink, Steven W. M. Olde] Maastricht Univ, Sch Nutr & Translat Res Metab NUTRIM, Dept Surg, Maastricht, Netherlands; [Westheim, Annemarie; Theys, Jan] Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Precis Med, Med Ctr, Maastricht, Netherlands		Shiri-Sverdlov, R (corresponding author), Maastricht Univ, Sch Nutr & Translat Res Metab NUTRIM, Dept Mol Genet, Maastricht, Netherlands.; Theys, J (corresponding author), Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Precis Med, Med Ctr, Maastricht, Netherlands.	jan.theys@maastrichtuniversity.nl; r.sverdlov@maastrichtuniversity.nl	Theys, Jan/AAI-9211-2021; Houben, Tom/T-1083-2017; Shiri-Sverdlov, Ronit/E-5571-2017	Theys, Jan/0000-0002-9718-8251; Houben, Tom/0000-0002-0441-3166; Shiri-Sverdlov, Ronit/0000-0002-6736-7814; Olde Damink, Steven/0000-0002-5202-9345	CVON IN-CONTROL grant [CVON2012-03]; Dutch Organisation for Scientific Research (NWO)Netherlands Organization for Scientific Research (NWO) [016.126.327]; ASPASIA [015.008.043]; TKI-LSH [40-41200-98-9306]; Dutch Cancer Society (KWF)KWF Kankerbestrijding [10820]; VCK [Swu16.0057-VT]	This research was supported by the CVON IN-CONTROL grant (CVON2012-03), the Dutch Organisation for Scientific Research (NWO; Vidi grant no. 016.126.327), ASPASIA (grant no. 015.008.043), TKI-LSH (grant no. 40-41200-98-9306), Dutch Cancer Society (KWF grant no. 10820) and VCK (grant no. Swu16.0057-VT). The funding bodies had no role in the preparation of this manuscript or the decision to publish.	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Cancer		2021	12	19					5817	5824		10.7150/jca.56307			8	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	UE2KC	WOS:000687721900012	34475995	gold, Green Published			2022-04-25	
J	Nkwe, DO; Lotshwao, B; Rantong, G; Matshwele, J; Kwape, TE; Masisi, K; Gaobotse, G; Hefferon, K; Makhzoum, A				Nkwe, David O.; Lotshwao, Bonolo; Rantong, Gaolathe; Matshwele, James; Kwape, Tebogo E.; Masisi, Kabo; Gaobotse, Goabaone; Hefferon, Kathleen; Makhzoum, Abdullah			Anticancer Mechanisms of Bioactive Compounds from Solanaceae: An Update	CANCERS			English	Review						Solanaceae; cancer; anticancer/antitumour; apoptosis; cell cycle; transcription; autophagy; signalling	CELL-CYCLE ARREST; C-MYB; METABOLITES INHIBIT; MAD2-CDC20 COMPLEX; COLORECTAL-CANCER; VEGF-A; APOPTOSIS; BREAST; GROWTH; EXPRESSION	Simple Summary The Solanaceae plant family has been a good source of natural compounds that can treat several diseases, including cancer. However, the site and mechanism of action of these compounds in cells has not been entirely clear. With ongoing developments in biological science research, it has become possible to study and identify some of the cellular targets. In this review, we assess publications from the last five years and identify research articles that explain how some of these compounds may work against cancer. These studies show that a number of different components or pathways in cells are targeted by these compounds to inhibit cell proliferation. Interestingly, some compounds have multiple targets and may be effective against different types of cancer. This knowledge may allow scientists to design new and more effective anticancer drugs. Plants continue to provide unlimited pharmacologically active compounds that can treat various illnesses, including cancer. The Solanaceae family, besides providing economically important food plants, such as potatoes and tomatoes, has been exploited extensively in folk medicine, as it provides an array of bioactive compounds. Many studies have demonstrated the anticancer potency of some of the compounds, but the corresponding molecular targets are not well defined. However, advances in molecular cell biology and in silico modelling have made it possible to dissect some of the underlying mechanisms. By reviewing the literature over the last five years, we provide an update on anticancer mechanisms associated with phytochemicals isolated from species in the Solanaceae plant family. These mechanisms are conveniently grouped into cell cycle arrest, transcription regulation, modulation of autophagy, inhibition of signalling pathways, suppression of metabolic enzymes, and membrane disruption. The majority of the bioactive compounds exert their antiproliferative effects by inhibiting diverse signalling pathways, as well as arresting the cell cycle. Furthermore, some of the phytochemicals are effective against more than one cancer type. Therefore, understanding these mechanisms provides paths for future formulation of novel anticancer drugs, as well as highlighting potential areas of research.	[Nkwe, David O.; Lotshwao, Bonolo; Rantong, Gaolathe; Kwape, Tebogo E.; Masisi, Kabo; Gaobotse, Goabaone; Makhzoum, Abdullah] Botswana Int Univ Sci & Technol, Dept Biol Sci & Biotechnol, Palapye, Botswana; [Matshwele, James] Botswana Int Univ Sci & Technol, Dept Chem & Forens Sci, Palapye, Botswana; [Matshwele, James] Botho Univ, Dept Appl Sci, Gaborone, Botswana; [Hefferon, Kathleen] Univ Toronto, Dept Cell & Syst Biol, Virol Lab, Toronto, ON M5S 3B2, Canada		Nkwe, DO; Makhzoum, A (corresponding author), Botswana Int Univ Sci & Technol, Dept Biol Sci & Biotechnol, Palapye, Botswana.	nkwed@biust.ac.bw; bonolo.lotshwao@studentmail.biust.ac.bw; rantongg@biust.ac.bw; james.matshwele@studentmail.biust.ac.bw; kwapet@biust.ac.bw; masisik@biust.ac.bw; gaobotseg@biust.ac.bw; kathleen.hefferon@alumni.utoronto.ca; makhzouma@biust.ac.bw		Nkwe, David/0000-0001-6673-5980; Hefferon, Kathleen/0000-0003-3550-0366; Gaobotse, Goabaone/0000-0003-2174-2823			Akhtar N, 2020, BIOMEDICINES, V8, DOI 10.3390/biomedicines8090333; 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J	Zhang, H; Hu, CAA; Kovacs-Nolan, J; Mine, Y				Zhang, Hua; Hu, Chien-An A.; Kovacs-Nolan, Jennifer; Mine, Yoshinori			Bioactive dietary peptides and amino acids in inflammatory bowel disease	AMINO ACIDS			English	Article						Apoptosis; Autophagy; Dietary peptides; Amino acids; Inflammatory bowel disease; CasR	NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; EGG-YOLK PHOSVITIN; OXIDATIVE STRESS; CROHNS-DISEASE; EXTRACELLULAR CALCIUM; ANTIOXIDATIVE PROPERTIES; CA2+-SENSING RECEPTOR; SIGNAL-TRANSDUCTION; GENE-EXPRESSION	Inflammatory bowel disease (IBD), most commonly ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammation of the gastrointestinal tract. Patients affected with IBD experience symptoms including abdominal pain, persistent diarrhea, rectal bleeding, and weight loss. There is no cure for IBD; thus treatments typically focus on preventing complications, inducing and maintaining remission, and improving quality of life. During IBD, dysregulation of the intestinal immune system leads to increased production of pro-inflammatory cytokines, such as TNF-alpha and IL-6, and recruitment of activated immune cells to the intestine, causing tissue damage and perpetuating the inflammatory response. Recent biological therapies targeting specific inflammatory cytokines or pathways, in particular TNF-alpha, have shown promise, but not all patients respond to treatment, and some individuals become intolerant to treatment over time. Dietary peptides and amino acids (AAs) have been shown to modulate intestinal immune functions and influence inflammatory responses, and may be useful as alternative or ancillary treatments in IBD. This review focuses on dietary interventions for IBD treatment, in particular the role of dietary peptides and AAs in reducing inflammation, oxidative stress, and apoptosis in the gut, as well as recent advances in the cellular mechanisms responsible for their anti-inflammatory activity.	[Zhang, Hua; Kovacs-Nolan, Jennifer; Mine, Yoshinori] Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada; [Hu, Chien-An A.] Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA		Mine, Y (corresponding author), Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada.	ymine@uoguelph.ca	Zhang, hua/AAF-9354-2019				Adibi SA, 1997, GASTROENTEROLOGY, V113, P332, DOI 10.1016/S0016-5085(97)70112-4; Aggarwal BB, 2003, NAT REV IMMUNOL, V3, P745, DOI 10.1038/nri1184; Ajibade AA, 2012, IMMUNITY, V36, P43, DOI 10.1016/j.immuni.2011.12.010; Bailey M, 2006, VET RES, V37, P443, DOI 10.1051/vetres:2006013; Bassaganya-Riera J, 2006, CLIN NUTR, V25, P454, DOI 10.1016/j.clnu.2005.12.008; Baud V, 2001, TRENDS CELL BIOL, V11, P372, DOI 10.1016/S0962-8924(01)02064-5; Baumgart DC, 2007, LANCET, V369, P1641, DOI 10.1016/S0140-6736(07)60751-X; Beutheu S, 2013, CLIN NUTR, V32, P863, DOI 10.1016/j.clnu.2013.01.014; Borm M, 2004, DRUG DISCOV TODAY, V1, P437; Bouwmeester T, 2004, NAT CELL BIOL, V6, P97, DOI 10.1038/ncb1086; 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J	Yang, X; Zhao, HJ; Wang, Y; Liu, JJ; Guo, MH; Fei, DX; Mu, MY; Xing, MW				Yang, Xin; Zhao, Hongjing; Wang, Yu; Liu, Juanjuan; Guo, Menghao; Fei, Dongxue; Mu, Mengyao; Xing, Mingwei			The Activation of Heat-Shock Protein After Copper(II) and/or Arsenic(III)-Induced Imbalance of Homeostasis, Inflammatory Response in Chicken Rectum	BIOLOGICAL TRACE ELEMENT RESEARCH			English	Article						Arsenic; Copper; Rectum; Elemental disorder; Oxidative stress; Heat-shock proteins	NF-KAPPA-B; INDUCED OXIDATIVE STRESS; ARSENIC EXPOSURE; NITRIC-OXIDE; APOPTOSIS; AUTOPHAGY; CADMIUM; TISSUES; ACCUMULATION; INDUCTION	Arsenic and copper, two toxic pollutants, are powerful inducers of oxidative stress. Exposure to copper and arsenic can cause intestinal injury in cockerel. This study was carried out to investigate the effects of these two pollutants on the gastrointestinal tract of cockerels. Experimental results showed that the activity of antioxidant enzymes (catalase and glutathione peroxidase) was inhibited and the ionic balance was destroyed after exposure to copper sulfate (300 mg/kg) and/or arsenic trioxide (30 mg/kg). However, the expression of pro-inflammatory cytokines (nuclear factor kappa-B, cyclooxygenase-2, tumor necrosis factor-alpha, and prostaglandin E2 synthases) increased markedly. Damages to the biofilm structure and inflammatory cell infiltration were simultaneously observed during histological examination. Heat-shock proteins were also expressed in large quantities after exposure to the poisons. Collectively, exposure to arsenite and/or Cu2+ can cause rectal damage in cockerels, inducing inflammation and an imbalance in immune system responses. Sometimes, exposure to both pollutants can produce even more toxic effects. Heat-shock proteins can protect the tissue from the exotoxins but the specific mechanisms require exploration. After oral ingestion of toxins, the rectum can still be damaged, necessitating attention to the safety of poultry breeding, human food safety, and environmental protection.	[Yang, Xin; Zhao, Hongjing; Wang, Yu; Liu, Juanjuan; Guo, Menghao; Fei, Dongxue; Mu, Mengyao; Xing, Mingwei] Northeast Forestry Univ, Coll Wildlife & Protected Area, Harbin 150040, Heilongjiang, Peoples R China		Xing, MW (corresponding author), Northeast Forestry Univ, Coll Wildlife & Protected Area, Harbin 150040, Heilongjiang, Peoples R China.	xingmingwei@nefu.edu.cn		Xing, Mingwei/0000-0003-1636-897X			Ahmad S, 2000, ARCH BIOCHEM BIOPHYS, V382, P195, DOI 10.1006/abbi.2000.2023; Al-Waeli A, 2012, BRIT POULTRY SCI, V53, P817, DOI 10.1080/00071668.2012.751523; Bisceglie F, 2016, METALLOMICS, V8, P1255, DOI 10.1039/c6mt00170j; Bonizzi G, 2004, TRENDS IMMUNOL, V25, P280, DOI 10.1016/j.it.2004.03.008; Brahman KD, 2014, CHEMOSPHERE, V100, P182, DOI 10.1016/j.chemosphere.2013.11.035; Pereira TCB, 2016, J APPL TOXICOL, V36, P876, DOI 10.1002/jat.3303; Burger J, 2013, ENVIRON RES, V122, P11, DOI 10.1016/j.envres.2013.01.003; Cakic M, 2013, EXPERT OPIN DRUG DIS, V8, P1253, DOI 10.1517/17460441.2013.825245; 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J	Abbruzzese, C; Matteoni, S; Persico, M; Ascione, B; Schenone, S; Musumeci, F; Amato, R; Perrotti, N; Matarrese, P; Paggi, MG				Abbruzzese, Claudia; Matteoni, Silvia; Persico, Michele; Ascione, Barbara; Schenone, Silvia; Musumeci, Francesca; Amato, Rosario; Perrotti, Nicola; Matarrese, Paola; Paggi, Marco G.			The small molecule SI113 hinders epithelial-to-mesenchymal transition and subverts cytoskeletal organization in human cancer cells	JOURNAL OF CELLULAR PHYSIOLOGY			English	Article						activity-based protein profiling (ABPP); cytoskeleton; epithelial-to-mesenchymal transition; kinase inhibitors; SI113	IN-VITRO; SGK1; ACTIVATION; DISCOVERY; PROTEINS; GROWTH; FAK	The small molecule SI113 is an inhibitor of the kinase activity of SGK1, a key biological regulator acting on the PI3K/mTOR signal transduction pathway. Several studies demonstrate that this compound is able to strongly restrain cancer growth in vitro and in vivo, alone or in associative antineoplastic treatments, being able to elicit an autophagic response, either cytotoxic or cytoprotective. To elucidate more exhaustively the molecular mechanisms targeted by SI113, we performed activity-based protein profiling (ABPP) proteomic analysis using a kinase enrichment procedure. This technique allowed the identification via mass spectrometry of novel targets of this compound, most of them involved in functions concerning cell motility and cytoskeletal architecture. Using a glioblastoma multiforme, hepatocarcinoma and colorectal carcinoma cell line, we recognized an inhibitory effect of SI113 on cell migration, invading, and epithelial-to-mesenchymal transition. In addition, these cancer cells, when exposed to this compound, showed a remarkable subversion of the cytoskeletal architecture characterized by F-actin destabilization, phospho-FAK delocalization, and tubulin depolimerization. These results were definitely concordant in attributing to SI113 a key role in hindering cancer cell malignancy and, due to its negligible in vivo toxicity, can sustain performing a Phase I clinical trial to employ this drug in associative cancer therapy.	[Abbruzzese, Claudia; Matteoni, Silvia; Persico, Michele; Paggi, Marco G.] IRCCS Regina Elena Natl Canc Inst, Prote Unit, Div Cellular Networks & Mol Therapeut Targets, Rome, Italy; [Ascione, Barbara; Matarrese, Paola] Ist Super Sanita, Oncol Unit, Ctr Gender Specif Med, Viale Regina Elena 299, I-00162 Rome, Italy; [Schenone, Silvia; Musumeci, Francesca] Univ Genoa, Dept Pharm, Genoa, Italy; [Amato, Rosario; Perrotti, Nicola] Magna Graecia Univ Catanzaro, Dept Sci Salute, Catanzaro, Italy		Matarrese, P (corresponding author), Ist Super Sanita, Oncol Unit, Ctr Gender Specif Med, Viale Regina Elena 299, I-00162 Rome, Italy.; Paggi, MG (corresponding author), IRCCS Regina Elena Natl Canc Inst, Via Elio Chianesi 53, I-00144 Rome, Italy.	paola.matarrese@iss.it; marco.paggi@ifo.gov.it	Matteoni, Silvia/U-7578-2017; Abbruzzese, Claudia/U-7576-2017	Matteoni, Silvia/0000-0001-6926-6593; Abbruzzese, Claudia/0000-0003-3301-9421; Persico, Michele/0000-0001-9030-3707; MUSUMECI, Francesca Michela/0000-0002-7228-0086; matarrese, paola/0000-0001-5477-3752	Associazione Italiana per la Ricerca sul CancroFondazione AIRC per la ricerca sul cancro [IG 16971, IG 18526]; Peretti Foundation; Arcobaleno ONLUS; Italian Association for Cancer ResearchFondazione AIRC per la ricerca sul cancro; Ricerca Corrente IRE	Associazione Italiana per la Ricerca sul Cancro, Grant/Award Numbers: IG 16971, IG 18526; Peretti Foundation; Arcobaleno ONLUS; Ricerca Corrente IRE; The Italian Association for Cancer Research	Abbruzzese C, 2017, ONCOTARGET, V8, P110743, DOI 10.18632/oncotarget.22500; Abbruzzese C, 2012, J EXP CLIN CANC RES, V31, DOI 10.1186/1756-9966-31-4; Amato R, 2013, ONCOGENE, V32, P4572, DOI 10.1038/onc.2012.470; Amato R, 2009, J MOL MED, V87, P1221, DOI 10.1007/s00109-009-0525-5; Andres-Mateos E, 2013, EMBO MOL MED, V5, P80, DOI 10.1002/emmm.201201443; Barglow KT, 2007, NAT METHODS, V4, P822, DOI 10.1038/NMETH1092; Berman HM, 2000, NUCLEIC ACIDS RES, V28, P235, DOI 10.1093/nar/28.1.235; BRATTAIN MG, 1981, CANCER RES, V41, P1751; Castel P, 2016, CANCER CELL, V30, P229, DOI 10.1016/j.ccell.2016.06.004; Conza D, 2017, J CELL PHYSIOL, V232, P3735, DOI 10.1002/jcp.25850; D'Antona L, 2015, CELL PHYSIOL BIOCHEM, V35, P2006, DOI 10.1159/000374008; Dattilo V, 2017, SCI REP-UK, V7, DOI 10.1038/srep45361; DeBerardinis RJ, 2008, CELL METAB, V7, P11, DOI 10.1016/j.cmet.2007.10.002; Dogterom M, 2019, NAT REV MOL CELL BIO, V20, P38, DOI 10.1038/s41580-018-0067-1; KNOWLES BB, 1980, SCIENCE, V209, P497, DOI 10.1126/science.6248960; Kuo JC, 2013, J CELL MOL MED, V17, P704, DOI 10.1111/jcmm.12054; Lang F, 2013, EXPERT OPIN INV DRUG, V22, P701, DOI 10.1517/13543784.2013.778971; Leonetti C, 2008, CLIN CANCER RES, V14, P7284, DOI 10.1158/1078-0432.CCR-08-0941; Liang CC, 2007, NAT PROTOC, V2, P329, DOI 10.1038/nprot.2007.30; Liu WW, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0743-1; Liu YZ, 2014, PROTEOMICS, V14, P399, DOI 10.1002/pmic.201300261; MALORNI W, 1994, CELL BIOL TOXICOL, V10, P207, DOI 10.1007/BF00756761; Matarrese P, 2016, ONCOTARGET, V7, P50972, DOI 10.18632/oncotarget.8646; Matarrese P, 2014, AUTOPHAGY, V10, P750, DOI 10.4161/auto.27959; Matarrese P, 2010, MOL CANCER, V9, DOI 10.1186/1476-4598-9-207; Matteoni S, 2019, J EXP CLIN CANC RES, V38, DOI 10.1186/s13046-019-1212-1; Nagano Makoto, 2012, Int J Cell Biol, V2012, P310616, DOI 10.1155/2012/310616; Ortuso F, 2014, J CHEM INF MODEL, V54, P1828, DOI 10.1021/ci500235f; Riemann D, 2005, BIOCHEM BIOPH RES CO, V331, P1408, DOI 10.1016/j.bbrc.2005.04.061; Roberts DJ, 2015, CELL DEATH DIFFER, V22, P248, DOI 10.1038/cdd.2014.173; Schaller MD, 2010, J CELL SCI, V123, P1007, DOI 10.1242/jcs.045112; Spagnuolo R, 2018, INFLAMM BOWEL DIS, V24, P1967, DOI 10.1093/ibd/izy158; Stehbens SJ, 2014, NAT CELL BIOL, V16, P558, DOI 10.1038/ncb2975; Sulzmaier FJ, 2014, NAT REV CANCER, V14, P598, DOI 10.1038/nrc3792; Talarico C, 2016, ONCOTARGET, V7, DOI 10.18632/oncotarget.7520; Talarico C, 2015, ONCOTARGET, V6, P37520, DOI 10.18632/oncotarget.5527; Xiao YS, 2013, ANAL CHEM, V85, P3198, DOI 10.1021/ac303383c	37	7	7	0	34	WILEY	HOBOKEN	111 RIVER ST, HOBOKEN 07030-5774, NJ USA	0021-9541	1097-4652		J CELL PHYSIOL	J. Cell. Physiol.	DEC	2019	234	12					22529	22542		10.1002/jcp.28816			14	Cell Biology; Physiology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Physiology	IV6KF	WOS:000484376600093	31099037				2022-04-25	
J	Yao, QH; Zhang, XC; Fu, T; Gu, JZ; Wang, L; Wang, Y; Lai, YB; Wang, YQ; Guo, Y				Yao, Qing-Hua; Zhang, Xiao-Chen; Fu, Ting; Gu, Jian-Zhong; Wang, Lu; Wang, Yun; Lai, Yue-Biao; Wang, Yu-Qi; Guo, Yong			.-3 polyunsaturated fatty acids inhibit the proliferation of the lung adenocarcinoma cell line A549 in vitro	MOLECULAR MEDICINE REPORTS			English	Article						-3 polyunsaturated fatty acids; eicosapentaenoic acid; docosahexaenoic acid; lung cancer	NORMAL COLONIC-MUCOSA; BREAST-CANCER CELLS; FISH-OIL; INCREASES APOPTOSIS; PROSTATE-CANCER; OMEGA-3; OMEGA-3-FATTY-ACIDS; MICE; CONSUMPTION; GROWTH	-3 polyunsaturated fatty acids (n-3 PUFA), in particular the marine-derived forms eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been demonstrated to affect cancer cell replication, the cell cycle and cell death. Epidemiological studies have also suggested diets rich in n-3 PUFA were inversely correlated with the development of cancer. In the present study, we explored the effects of DHA and EPA on the proliferation activity and apoptosis of the human lung adenocarcinoma cell line A549. A methyl thiazolyl tetrazolium (MTT) assay was used to detect cell proliferation, apoptosis was detected by flow cytometry and morphological analysis was determined by fluorescence microscopy and transmission electron microscopy. A549 cells were treated with different doses of DHA (40, 45, 50 and 55 g/ml) or EPA (45, 50, 55 and 60 g/ml) for 24, 48 and 72 h. The results demonstrated that DHA and EPA significantly suppressed the proliferation of A549 cells and induced apoptosis of A549 cells in a dose- and time-dependent manner. The apoptotic phenomenon was also confirmed by fluorescence microscopy and transmission electron microscopy. Furthermore, compared with the control, the formation of autophagosomes was clearly enhanced in DHA- or EPA-treated cells. In conclusion, DHA and EPA inhibited the proliferation of A549 cells and induced cell apoptosis and autophagy, which may provide new safe and effective options for the treatment of lung cancer in the future.	[Yao, Qing-Hua; Gu, Jian-Zhong; Guo, Yong] Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Oncol, Hangzhou 310006, Zhejiang, Peoples R China; [Zhang, Xiao-Chen] Zhejiang Univ, Dept Oncol, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China; [Fu, Ting; Wang, Lu; Wang, Yun; Lai, Yue-Biao; Wang, Yu-Qi] Zhejiang Chinese Med Univ, Dept Tradit Chinese Med, Hangzhou 310053, Zhejiang, Peoples R China		Guo, Y (corresponding author), Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Oncol, 54 Youdian Rd, Hangzhou 310006, Zhejiang, Peoples R China.	guoyong1047@163.com			Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [64212006]	This study was supported by a grant from the Zhejiang Provincial Natural Science Foundation of China (Grant no. 64212006). We would like to thank the Zhejiang Provincial Key Laboratory of Gastroenterology for providing the experimental facilities, instruments and guidance.	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Med. Rep.	FEB	2014	9	2					401	406		10.3892/mmr.2013.1829			6	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	AC7FU	WOS:000332694100003	24276408	Bronze			2022-04-25	
J	Zhao, LL; Wang, XB; Yu, Y; Deng, L; Chen, L; Peng, XP; Jiao, CC; Gao, GL; Tan, X; Pan, WJ; Ge, X; Wang, P				Zhao, Linlin; Wang, Xinbo; Yu, Yue; Deng, Lu; Chen, Lei; Peng, Xiaoping; Jiao, Chenchen; Gao, Guoli; Tan, Xiao; Pan, Weijuan; Ge, Xin; Wang, Ping			OTUB1 protein suppresses mTOR complex 1 (mTORC1) activity by deubiquitinating the mTORC1 inhibitor DEPTOR	JOURNAL OF BIOLOGICAL CHEMISTRY			English	Article							BETA-TRCP; CELL-PROLIFERATION; SIGNALING PATHWAYS; COLORECTAL-CANCER; UBIQUITIN CODE; POOR-PROGNOSIS; ER-ALPHA; ENZYMES; DEGRADATION; GROWTH	Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates various environmental signals to regulate cell growth and metabolism. DEPTOR, also termed DEPDC6, is an endogenous inhibitor of mTORC1 and mTORC2 activities. The abundance of DEPTOR centrally orchestrates the mTOR signaling network. However, the mechanisms by which DEPTOR stability is regulated are still elusive. Here, we report that OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) specifically deubiquitinates DEPTOR in a deubiquitination assay. We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and there by stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity-independent non-canonical mechanism. The interaction between OTUB1 and DEPTOR was enhanced when the cells were treated with amino acids. Moreover, OTUB1 suppressed amino acid-induced activation of mTORC1 in a DEPTOR-dependent manner and thereby ultimately controlled cellular autophagy, cell proliferation, and size. Our findings reveal a mechanism that stabilizes the mTORC1 inhibitor DEPTOR via OTUB1's deubiquitinase activity. Our insights may inform research into various mTOR activity-related diseases, such as cancer, and may contribute to the identification of new diagnostic markers and therapeutic strategies for cancer treatments.	[Zhao, Linlin; Wang, Xinbo; Yu, Yue; Pan, Weijuan] East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China; [Zhao, Linlin; Wang, Xinbo; Yu, Yue; Pan, Weijuan] East China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China; [Deng, Lu; Chen, Lei; Peng, Xiaoping; Jiao, Chenchen; Tan, Xiao; Wang, Ping] Tongji Univ, Sch Life Sci & Technol, Sch Med, Dept Cent Lab,Shanghai Peoples Hosp 10, Shanghai 200092, Peoples R China; [Ge, Xin] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Clin Lab Med, Shanghai 200072, Peoples R China; [Gao, Guoli] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China		Wang, P (corresponding author), Tongji Univ, Sch Life Sci & Technol, Sch Med, Dept Cent Lab,Shanghai Peoples Hosp 10, Shanghai 200092, Peoples R China.; Ge, X (corresponding author), Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Clin Lab Med, Shanghai 200072, Peoples R China.	xin.ge@tongji.edu.cn; wangp@tongji.edu.cn			National Key Research and Development Program of China [2016YFC0902102]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81625019, 91440104, 91519322, 81402417]; Science Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [16JC1404500]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [1501219106, 1500219121, 1500219133]	This work was supported by National Key Research and Development Program of China Grant 2016YFC0902102; National Natural Science Foundation of China Grants 81625019, 91440104, 91519322, and 81402417; Science Technology Commission of Shanghai Municipality Grant 16JC1404500; and Fundamental Research Funds for the Central Universities Grants 1501219106, 1500219121, and 1500219133. The authors declare that they have no conflicts of interest with the contents of this article.	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Biol. Chem.	MAR 30	2018	293	13					4883	4892		10.1074/jbc.M117.809533			10	Biochemistry & Molecular Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology	GB1YT	WOS:000428848300027	29382726	Green Published, hybrid			2022-04-25	
J	Zhang, M; Wang, R; Tian, J; Song, MQ; Zhao, R; Liu, KD; Zhu, F; Shim, JH; Dong, ZG; Lee, MH				Zhang, Man; Wang, Rui; Tian, Jie; Song, Mengqiu; Zhao, Ran; Liu, Kangdong; Zhu, Feng; Shim, Jung-Hyun; Dong, Zigang; Lee, Mee-Hyun			Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE			English	Article						LIMK1; luteolin; non&#8208; small cell lung cancer	COLORECTAL-CANCER; SIGNALING PATHWAYS; CELL-MIGRATION; APOPTOSIS; KINASE; MODELS; XENOGRAFTS; ACTIVATION	Lung cancer is the leading cause of cancer-related deaths. LIM domain kinase (LIMK) 1 is a member of serine/threonine kinase family and highly expressed in various cancers. Luteolin, a polyphenolic plant flavonoid, has been reported to suppress tumour proliferation through inducing apoptosis and autophagy via MAPK activation in glioma. However, the mechanism of luteolin on suppressing lung cancer growth is still unclear. We found that luteolin targeted LIMK1 from the in silico screening and significantly inhibited the LIMK1 kinase activity, which was confirmed with pull-down binding assay and computational docking models. Treatment with luteolin inhibited lung cancer cells anchorage-independent colony growth and induced apoptosis and cell cycle arrest at G1 phase. Luteolin also decreased the expression of cyclin D1 and increased the levels of cleaved caspase-3 by down-regulating LIMK1 signalling related targets, including p-LIMK and p-cofilin. Furthermore, luteolin suppressed the lung cancer patient-derived xenograft tumour growth by decreasing Ki-67, p-LIMK and p-cofilin expression in vivo. Taken together, these results provide insight into the mechanism that underlies the anticancer effects of luteolin on lung cancer, which involved in down-regulation of LIMK1 and its interaction with cofilin. It also provides valuable evidence for translation towards lung cancer clinical trials with luteolin.	[Zhang, Man; Wang, Rui; Tian, Jie; Song, Mengqiu; Zhao, Ran; Liu, Kangdong; Dong, Zigang; Lee, Mee-Hyun] China US Henan Hormel Canc Inst, 127 Dongming Rd, Zhengzhou 450008, Henan, Peoples R China; [Song, Mengqiu; Zhao, Ran; Liu, Kangdong; Dong, Zigang; Lee, Mee-Hyun] Zhengzhou Univ, Sch Basic Med Sci, Dept Pathophysiol, Zhengzhou 450001, Henan, Peoples R China; [Zhu, Feng] Guilin Med Univ, Canc Res Inst, Affiliated Hosp, Guilin, Peoples R China; [Shim, Jung-Hyun] Mokpo Natl Univ, Dept Pharm, Coll Pharm, Muan, South Korea; [Lee, Mee-Hyun] Dongshin Univ, Coll Korean Med, Naju, South Korea; [Zhang, Man] Zhengzhou Univ, Henan Prov Key Lab Childrens Genet & Metab Dis, Childrens Hosp, Zhengzhou 450018, Henan, Peoples R China		Lee, MH (corresponding author), China US Henan Hormel Canc Inst, 127 Dongming Rd, Zhengzhou 450008, Henan, Peoples R China.; Dong, ZG (corresponding author), Zhengzhou Univ, Sch Basic Med Sci, Dept Pathophysiol, Zhengzhou 450001, Henan, Peoples R China.	zgdong@hci-cn.org; mhyun_lee@hanmail.net		Lee, Mee-Hyun/0000-0002-1216-0218	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC81972839]	This work was supported by grant funding from the National Natural Science Foundation of China NSFC81972839, China.	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Cell. Mol. Med.	JUN	2021	25	12					5560	5571		10.1111/jcmm.16568		MAY 2021	12	Cell Biology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Research & Experimental Medicine	SN7XS	WOS:000649700700001	33982869	Green Published, gold			2022-04-25	
J	Hu, XJ; Li, XJ; Yin, M; Li, P; Huang, P; Wang, LH; Jiang, YG; Wang, H; Chen, N; Fan, CH; Song, HY				Hu, Xingjie; Li, Xiaojiao; Yin, Min; Li, Ping; Huang, Ping; Wang, Lihua; Jiang, Yiguo; Wang, Hui; Chen, Nan; Fan, Chunhai; Song, Haiyun			Nanodiamonds Mediate Oral Delivery of Proteins for Stem Cell Activation and Intestinal Remodeling in Drosophila	ACS APPLIED MATERIALS & INTERFACES			English	Article						nanodiamonds; protein delivery; oral delivery; stem cells microenvironment; intestinal remodeling	WALLED CARBON NANOTUBES; FLUORESCENT NANODIAMONDS; DNA NANOSTRUCTURES; DRUG-DELIVERY; NANOPARTICLES; CANCER; PATHWAY; AUTOPHAGY; OXIDE; BIOCOMPATIBILITY	Introduction of exogenous biomacromolecules into living systems is of great interest in genome editing, cancer immunotherapy, and stem cell reprogramming. Whereas current strategies generally depend on nucleic acids transfection, direct delivery of functional proteins that provides enhanced specificity, increased safety, and fast and temporal regulation is highly desirable. Nevertheless, intracellular delivery of intact and bioactive proteins, especially in vivo, remains poorly explored. In this study, we developed a nanodiamonds (NDs)-based protein delivery system in cultured cells and in Drosophila that showed high adsorption, high efficiency, and effective cytosolic release of fully functional proteins. Through live-cell imaging, we observed a novel phenomenon wherein a substantial amount of internalized NDsprotein complex rejected fusion with the early endosome, thereby evading protein degradation in the lysosome. More significantly, we demonstrated that dietary NDsRNase induced apoptosis in enterocytes, stimulating regenerative divisions in intestinal stem cells and increasing the number of stem cells and precursor cells in Drosophila intestine. As stem cells are poorly accessible by exogenous agents in vivo, NDs-mediated oral delivery of proteins provides a new approach to modulate the stem cell microenvironment for intestinal remodeling, which has important implications for colorectal cancer therapy and regenerative medicine.	[Hu, Xingjie; Yin, Min; Wang, Lihua; Chen, Nan; Fan, Chunhai] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Appl Phys, Div Phys Biol, Shanghai 201800, Peoples R China; [Hu, Xingjie; Yin, Min; Wang, Lihua; Chen, Nan; Fan, Chunhai] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Appl Phys,CAS Key Lab Interfacial P, Bioimaging Ctr,Shanghai Synchrotron Radiat Facil, Shanghai 201800, Peoples R China; [Li, Xiaojiao; Li, Ping; Huang, Ping; Wang, Hui; Song, Haiyun] Univ Chinese Acad Sci, Chinese Acad Sci, Key Lab Food Safety Res, Inst Nutr Sci,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; [Li, Xiaojiao; Li, Ping; Huang, Ping; Wang, Hui; Song, Haiyun] Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing 100021, Peoples R China; [Jiang, Yiguo] Guangzhou Med Univ, Sch Publ Hlth, Guangzhou 511436, Guangdong, Peoples R China		Chen, N; Fan, CH (corresponding author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Appl Phys, Div Phys Biol, Shanghai 201800, Peoples R China.; Chen, N; Fan, CH (corresponding author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Appl Phys,CAS Key Lab Interfacial P, Bioimaging Ctr,Shanghai Synchrotron Radiat Facil, Shanghai 201800, Peoples R China.; Song, HY (corresponding author), Univ Chinese Acad Sci, Chinese Acad Sci, Key Lab Food Safety Res, Inst Nutr Sci,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.; Song, HY (corresponding author), Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing 100021, Peoples R China.	chennan@sinap.ac.cn; fchh@sinap.ac.cn; hysong@sibs.ac.cn	Fan, Chunhai/A-7569-2011	Fan, Chunhai/0000-0002-7171-7338; Song, Haiyun/0000-0001-8146-5552; Li, Xiaojiao/0000-0002-0662-2850	National Basic Research Program of ChinaNational Basic Research Program of China [2016YFA0201200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31371493, 31571498, 31470970, 31322039, U1332119]; Youth Innovation Promotion Association from Chinese Academy of Sciences [2015211]; Key Research Program of Frontier Sciences, CAS [QYZDJ-SSW-SLH019]	We would like to dedicate this article to Prof. Qing Huang. This study was supported by the National Basic Research Program of China (2016YFA0201200), National Natural Science Foundation of China (31371493, 31571498, 31470970, 31322039 and U1332119), the Youth Innovation Promotion Association from Chinese Academy of Sciences (2015211), and the Key Research Program of Frontier Sciences, CAS (QYZDJ-SSW-SLH019).	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Mater. Interfaces	JUN 7	2017	9	22					18575	18583		10.1021/acsami.7b04788			9	Nanoscience & Nanotechnology; Materials Science, Multidisciplinary	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics; Materials Science	EX3MO	WOS:000403136400022	28509532				2022-04-25	
J	Kalas, W; Swiderek, E; Rapak, A; Kopij, M; Rak, J; Strzadala, L				Kalas, Wojciech; Swiderek, Ewelna; Rapak, Andrzej; Kopij, Magdalena; Rak, Janusz; Strzadala, Leon			H-ras Up-regulates Expression of BNIP3	ANTICANCER RESEARCH			English	Article						Ras; BNIP3; CD47; cancer; programmed cell death; 4N1K	PROTEIN-KINASE-A; DEATH GENE BNIP3; CELL-DEATH; VENTRICULAR MYOCYTES; CANCER-CELLS; COLORECTAL-CANCER; PANCREATIC-CANCER; INDUCED APOPTOSIS; IN-SITU; KAPPA-B	Background: Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3) is a key regulator of cell death/autophagy and can act as an effector of a necrosis-like, atypical death program. It was implicated in execution of cell death induced by cluster of differentiation 47 (CD47). Despite the postulated role of BNIP3 in the regulation of survival of cancer cells, the influence of oncogenic transformation on BNIP3 expression is unclear. Materials and Methods: The influence of oncogenic transformation on expression of BNIP3 was studied using H-ras-transformed cells. The consequences of BNIP3 expression for sensitivity to CD47-mediated cell death were assessed using tetrazolium salt-based assay. Results: Here, the enforced and endogenous expression of Ras coincided with the up-regulation of BNIP3 across a wide spectrum of cancer cells, providing the first experimental evidence that BNIP3 is a regulatory target of H-Ras. This indicated that merely the introduction of a single oncogene may result in the up-regulation of BNIP3. The consequences of CD47 ligation strongly depended on the BNIP3 presence, which in turn correlated with Ras expression. Interestingly, the indirect effect of that phenomenon was the selective sensitivity of Ras-transformed cells to CD47-mediated cell death.	[Kalas, Wojciech] Polish Acad Sci, Ludwik Hirszfeld Inst Immunol & Expt Therapy, Dept Expt Oncol, PL-53114 Wroclaw, Poland; [Rak, Janusz] McGill Univ, Montreal Childrens Hosp, Res Inst, Montreal, PQ H3H 1P3, Canada		Kalas, W (corresponding author), Polish Acad Sci, Ludwik Hirszfeld Inst Immunol & Expt Therapy, Dept Expt Oncol, PL-53114 Wroclaw, Poland.	kalas@iitd.pan.wroc.pl	Kałas, Wojciech/AAB-4469-2019; Rapak, Andrzej/ABE-6262-2021	Kałas, Wojciech/0000-0003-2656-5192; Rapak, Andrzej/0000-0003-4897-0287; Strzadala, Leon/0000-0002-7323-2254	Polish State Committee for Scientific ResearchPolish State Committee for Scientific Research [N301 104 31/3087, 1243/B/P01/2007/33]; Canadian Cancer Society Research InstituteCanadian Cancer Society (CCS)	This work was supported by grant no. N301 104 31/3087 and 1243/B/P01/2007/33 from the Polish State Committee for Scientific Research and a grant from the Canadian Cancer Society Research Institute to JR, who also holds the Jack Cole Chair in Pediatric Hematology/Oncology.	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SEP	2011	31	9					2869	2875					7	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	800KG	WOS:000293357700024	21868531				2022-04-25	
J	Cao, P; Chen, YY; Chen, Y; Su, WH; Zhan, N; Dong, WG				Cao, Pan; Chen, Yongyu; Chen, Yan; Su, Wenhao; Zhan, Na; Dong, Weiguo			Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn's Disease Development via the Upregulation of CARD3 Expression	FRONTIERS IN PHARMACOLOGY			English	Article						Fusobacterium nucleatum; intestinal mucosal barrier; endoplasmic reticulum stress; Crohn's disease; gene regulation	COLORECTAL-CANCER; CARCINOGENESIS; MICROBIOTA; AUTOPHAGY; CELLS	There is increasing evidence that members of the gut microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with Crohn's disease (CD), but the specific mechanism by which F. nucleatum promotes CD development is unclear. Here, we first examined the abundance of F. nucleatum and its effects on CD disease activity and explored whether F. nucleatum aggravated intestinal inflammation and promoted intestinal mucosal barrier damage in vitro and in vivo. Our data showed that F. nucleatum was enriched in 41.21% of CD tissues from patients and was correlated with the clinical course, clinical activity, and refractory behavior of CD (P < 0.05). In addition, we found that F. nucleatum infection is involved in activating the endoplasmic reticulum stress (ERS) pathway during CD development to promote intestinal mucosal barrier destruction. Mechanistically, F. nucleatum targeted caspase activation and recruitment domain 3 (CARD3) to activate the ERS pathway and promote F. nucleatum-mediated mucosal barrier damage in vivo and in vitro. Thus, F. nucleatum coordinates a molecular network involving CARD3 and ERS to control the CD process. Measuring and targeting F. nucleatum and its associated pathways will provide valuable insight into the prevention and treatment of CD.	[Cao, Pan; Chen, Yongyu; Chen, Yan; Su, Wenhao; Zhan, Na; Dong, Weiguo] Wuhan Univ, Dept Gastroenterol, Renmin Hosp, Wuhan, Peoples R China; [Cao, Pan; Chen, Yongyu; Chen, Yan; Su, Wenhao; Zhan, Na; Dong, Weiguo] Wuhan Univ, Key Lab Hubei Prov Digest Syst Dis, Renmin Hosp, Wuhan, Peoples R China; [Su, Wenhao; Zhan, Na] Wuhan Univ, Cent Lab, Renmin Hosp, Wuhan, Peoples R China		Dong, WG (corresponding author), Wuhan Univ, Dept Gastroenterol, Renmin Hosp, Wuhan, Peoples R China.; Dong, WG (corresponding author), Wuhan Univ, Key Lab Hubei Prov Digest Syst Dis, Renmin Hosp, Wuhan, Peoples R China.	dongweiguo@whu.edu.cn			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, and No. 81572426) and the Guiding Foundation of Renmin Hospital of Wuhan University (No. RMYD2018Z01).	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Pharmacol.	FEB 21	2020	11								106	10.3389/fphar.2020.00106			13	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	KZ7QY	WOS:000523455200001	32153411	Green Published, gold			2022-04-25	
J	Koehler, BC; Scherr, AL; Lorenz, S; Elssner, C; Kautz, N; Welte, S; Jaeger, D; Urbanik, T; Schulze-Bergkamen, H				Koehler, Bruno Christian; Scherr, Anna-Lena; Lorenz, Stephan; Elssner, Christin; Kautz, Nicole; Welte, Stefan; Jaeger, Dirk; Urbanik, Toni; Schulze-Bergkamen, Henning			Pan-Bcl-2 Inhibitor Obatoclax Delays Cell Cycle Progression and Blocks Migration of Colorectal Cancer Cells	PLOS ONE			English	Article							ACUTE LYMPHOBLASTIC-LEUKEMIA; BH3 MIMETICS; E-CADHERIN; PHASE-I; APOPTOSIS; AUTOPHAGY; GX15-070; EXPRESSION; MCL-1; RESISTANCE	Despite the fact that new treatment regimes have improved overall survival of patients challenged by colorectal cancer (CRC), prognosis in the metastatic situation is still restricted. The Bcl-2 family of proteins has been identified as promising anti cancer drug target. Even though small molecules targeting Bcl-2 proteins are in clinical trials, little is known regarding their effects on CRC. The aim of this study was to preclinically investigate the value of ABT-737 and Obatoclax as anticancer drugs for CRC treatment. The effects of the BH3-mimetics ABT-737 and Obatoclax on CRC cells were assessed using viability and apoptosis assays. Wound healing migration and boyden chamber invasion assays were applied. 3-dimensional cell cultures were used for long term assessment of invasion and proliferation. Clinically relevant concentrations of pan-Bcl-2 inhibitor Obatoclax did not induce cell death. In contrast, the BH3-mimetic ABT-737 induced apoptosis in a dose dependent manner. Obatoclax caused a cell line specific slowdown of CRC cell growth. Furthermore, Obatoclax, but not ABT-737, recovered E-Cadherin expression and led to impaired migration and invasion of CRC cells. The proliferative capacity and invasiveness of CRC cells was strikingly inhibited by low dose Obatoclax in long term 3-dimensional cell cultures. Obatoclax, but not ABT-737, caused a G1-phase arrest accompanied by a downregulation of Cyclin D1 and upregulation of p27 and p21. Overexpression of Mcl-1, Bcl-xL or Bcl-2 reversed the inhibitory effect of Obatoclax on migration but failed to restore the proliferative capacity of Obatoclax-treated CRC cells. The data presented indicate broad and multifaceted antitumor effects of the pan-Bcl-2 inhibitor Obatoclax on CRC cells. In contrast to ABT-737, Obatoclax inhibited migration, invasion and proliferation in sublethal doses. In summary, this study recommends pan-Bcl-2 inhibition as a promising approach for clinical trials in CRC.	[Koehler, Bruno Christian; Scherr, Anna-Lena; Lorenz, Stephan; Elssner, Christin; Kautz, Nicole; Welte, Stefan; Jaeger, Dirk; Urbanik, Toni; Schulze-Bergkamen, Henning] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Dept Med Oncol, Heidelberg, Germany		Koehler, BC (corresponding author), Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Dept Med Oncol, Heidelberg, Germany.	Bruno.koehler@nct-heidelberg.de			Medical Faculty of the University of Heidelberg, Germany; German Research Foundation (Deutsche Forschungsgemeinschaft)German Research Foundation (DFG) [DFG SCHU 1443/4-1]	This study was supported by a Postdoctoral-Fellowship granted to BCK from the Medical Faculty of the University of Heidelberg, Germany (http://www.medizinische-fakultaet-hd.uni-heidelberg.de), and grants to HSB from the German Research Foundation (Deutsche Forschungsgemeinschaft, http://www.dfg.de/, DFG SCHU 1443/4-1). 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	Wu, YN; Wu, PC; Yang, LX; Ratinac, KR; Thordarson, P; Jahn, KA; Chen, DH; Shieh, DB; Braet, F				Wu, Ya-Na; Wu, Ping-Ching; Yang, Li-Xing; Ratinac, Kyle R.; Thordarson, Pall; Jahn, Kristina A.; Chen, Dong-Hwang; Shieh, Dar-Bin; Braet, Filip			The anticancer properties of iron core-gold shell nanoparticles in colorectal cancer cells	INTERNATIONAL JOURNAL OF NANOMEDICINE			English	Article						cancer therapy; Fe; gold-coated iron; nanoparticles; differential cytotoxicity	FE-AT-AU; OXIDE NANOPARTICLES; MAGNETITE NANOPARTICLES; BIOMEDICAL APPLICATIONS; CARBON NANOTUBES; ORAL-CANCER; IN-VIVO; APOPTOSIS; TRICHLOROETHYLENE; HYPERTHERMIA	Previously, iron core-gold shell nanoparticles (Fe@Au) have been shown to possess cancer-preferential cytotoxicity in oral and colorectal cancer (CRC) cells. However, CRC cell lines are less sensitive to Fe@Au treatment when compared with oral cancer cell lines. In this research, Fe@Au are found to decrease the cell viability of CRC cell lines, including Caco-2, HT-29, and SW480, through growth inhibition rather than the induction of cell death. The cytotoxicity induced by Fe@Au in CRC cells uses different subcellular pathways to the mitochondria-mediated autophagy found in Fe@Au-treated oral cancer cells, OECM1. Interestingly, the Caco-2 cell line shows a similar response to OECM1 cells and is thus more sensitive to Fe@Au treatment than the other CRC cell lines studied. We have investigated the underlying cell resistance mechanisms of Fe@Au-treated CRC cells. The resistance of CRC cells to Fe@Au does not result from the total amount of Fe@Au internalized. Instead, the different amounts of Fe and Au internalized appear to determine the different response to treatment with Fe-only nanoparticles in Fe@Au-resistant CRC cells compared with the Fe@Au-sensitive OECM1 cells. The only moderately cytotoxic effect of Fe@Au nanoparticles on CRC cells, when compared to the highly sensitive OECM1 cells, appears to arise from the CRC cells' relative insensitivity to Fe, as is demonstrated by our Fe-only treatments. This is a surprising outcome, given that Fe has thus far been considered to be the "active" component of Fe@Au nanoparticles. Instead, we have found that the Au coatings, previously considered only as a passivating coating to protect the Fe cores from oxidation, significantly enhance the cytotoxicity of Fe@Au in certain CRC cells. Therefore, we conclude that both the Fe and Au in these core-shell nanoparticles are essential for the anticancer properties observed in CRC cells.	[Wu, Ya-Na; Wu, Ping-Ching; Yang, Li-Xing; Shieh, Dar-Bin] Natl Cheng Kung Univ Hosp, Coll Med, Inst Oral Med, Tainan 701, Taiwan; [Wu, Ya-Na; Wu, Ping-Ching; Yang, Li-Xing; Shieh, Dar-Bin] Natl Cheng Kung Univ Hosp, Coll Med, Dept Stomatol, Tainan 701, Taiwan; [Ratinac, Kyle R.; Jahn, Kristina A.; Braet, Filip] Univ Sydney, Australian Ctr Microscopy & Microanal, Sydney, NSW 2006, Australia; [Chen, Dong-Hwang] Natl Cheng Kung Univ, Dept Chem Engn, Tainan, Taiwan; [Thordarson, Pall] Univ New S Wales, Sch Chem, Sydney, NSW, Australia; [Shieh, Dar-Bin] Natl Cheng Kung Univ, Ctr Micro Nano Sci & Technol, Tainan 70101, Taiwan; [Shieh, Dar-Bin] Natl Cheng Kung Univ, Adv Optoelect Technol Ctr, Tainan 70101, Taiwan; [Braet, Filip] Univ Sydney, Sch Med Sci, Discipline Anat & Histol, Bosch Inst, Sydney, NSW 2006, Australia		Wu, YN (corresponding author), Natl Cheng Kung Univ Hosp, Coll Med, Inst Oral Med, Tainan 701, Taiwan.	yana.wu@gmail.com	Braet, F/AAB-3660-2022; Thordarson, Pall/A-2138-2015; Wu, Ya-Na/AGX-5385-2022; Chen, Dong-Hwang/B-7299-2011; Braet, F/V-7003-2019	Thordarson, Pall/0000-0002-1200-8814; Braet, F/0000-0002-5222-0895; Ratinac, Kyle/0000-0001-6492-9490; Yang, Li-Xing/0000-0002-3723-4391	Taiwan National Science CouncilMinistry of Science and Technology, Taiwan [101-2120-M-006-008-, 101-2314-B-006-048-MY3, 101-2320-B-006-004]; Taiwan Department of Health [DOH101-TD-PB-111-NSC004, DOH102-TD-PB-111-TM017]; Australian Research CouncilAustralian Research Council [DP0985059]; Cancer Institute NSW [08/RFG/1-29]	DBS is indebted to Taiwan National Science Council (grant number 101-2120-M-006-008-, 101-2314-B-006-048-MY3) and the Taiwan Department of Health (grant number DOH101-TD-PB-111-NSC004, DOH102-TD-PB-111-TM017). PCW thanks Taiwan National Science Council for grant support (101-2320-B-006-004). We also thank the Australian Research Council for a Discovery Project Grant (DP0985059) to PT and FB, as well as the Cancer Institute NSW (08/RFG/1-29) for supporting our work. We acknowledge the facilities as well as scientific and technical assistance from staff at the Australian Microscopy and Microanalysis Research Facility at the Australian Centre for Microscopy and Microanalysis, the University of Sydney. All animal studies and human primary cell cultures were performed in accordance with the University of Cheng-Kung Internal Review Board for Ethics and Human Research (ethical approval No 97218).	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J. Nanomed.		2013	8						3321	3331		10.2147/IJN.S47742			11	Nanoscience & Nanotechnology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Science & Technology - Other Topics; Pharmacology & Pharmacy	209DK	WOS:000323734200001	24039416	Green Published, gold, Green Submitted			2022-04-25	
J	Olejniczak-Keder, A; Szarynska, M; Wronska, A; Siedlecka-Kroplewska, K; Kmiec, Z				Olejniczak-Keder, Agata; Szarynska, Magdalena; Wronska, Agata; Siedlecka-Kroplewska, Kamila; Kmiec, Zbigniew			Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines	INTERNATIONAL JOURNAL OF ONCOLOGY			English	Article						colorectal cancer cell lines; spherical cultures; cancer stem like cells; 5-fluorouracil; anti-epidermal growth factor receptor antibody; aspirin	GROWTH-FACTOR-RECEPTOR; STEM-CELLS; CYCLOOXYGENASE-2 EXPRESSION; BREAST-CANCER; ASPIRIN; RESISTANCE; CETUXIMAB; CD95; CHEMOTHERAPY; RECURRENCE	The aim of this study was to examine the effects of 5-fluorouracil (5-FU), anti-epidermal growth factor receptor (EGFR) antibody and aspirin (ASA) on the characteristics of two CRC cell lines, HCT116 and HT29, maintained in a spherical culture system. We observed that the morphology of both the HCT116 and HT29 cell-derived spheres was significantly impaired and the size of the colonospheres was markedly reduced following treatment with the aforementioned three drugs. In contrast to adherent cultures, the spherical cultures were more resistant to the tested drugs, as was reflected by their capacity to re-create the colonospheres when sustained in serum-free medium. Flow cytometric analysis of the drug-treated HCT116 cell-derived spheres revealed changes in the fraction of cells expressing markers of cancer stem cells (CSCs), whereas the CSC phenotype of HT29 cell-derived colonospheres was affected to a lesser extent. All reagents enhanced the percentage of non-viable cells in the colonospheres despite the diminished fraction of active caspase-3-positive cells following treatment of the HT29 cell-derived spheres with anti-EGFR antibody. Increased autophagy, assessed by acridine orange staining, was noted following the incubation of the HT29-colonospheres with ASA and 5-FU in comparison to the control. Notably, the percentage of cyclooxygenase (COX)-2-positive cells was not affected by ASA, although its activity was markedly elevated in the colonospheres incubated with anti-EGFR antibody. On the whole, the findings of this study indicate that all the tested drugs were involved in different cellular processes, which suggests that they should be considered for the combined therapeutic treatment of CRC, particularly for targeting the population of CSC-like cells. Thus, cancer cell-derived spheres may be used as a preferable model for in vitro anticancer drug testing.	[Olejniczak-Keder, Agata; Szarynska, Magdalena; Wronska, Agata; Siedlecka-Kroplewska, Kamila; Kmiec, Zbigniew] Med Univ Gdansk, Dept Histol, 1 Debinki St, PL-80211 Gdansk, Poland		Olejniczak-Keder, A (corresponding author), Med Univ Gdansk, Dept Histol, 1 Debinki St, PL-80211 Gdansk, Poland.	agata.olejniczak-keder@gumed.edu.pl	Olejniczak-Kęder, Agata/AAO-7667-2020; Szarynska, Magdalena/N-5871-2018	Olejniczak-Kęder, Agata/0000-0001-5201-9254; Siedlecka-Kroplewska, Kamila/0000-0002-6313-0799; Szarynska, Magdalena/0000-0002-9976-5833	Polish Ministry of Science and Higher EducationMinistry of Science and Higher Education, Poland [MN 01-0232/08/280]	This study was supported by the grant from the Polish Ministry of Science and Higher Education no. MN 01-0232/08/280.	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Yan KS, 2012, P NATL ACAD SCI USA, V109, P466, DOI 10.1073/pnas.1118857109; Ye XQ, 2011, INT J CANCER, V129, P820, DOI 10.1002/ijc.25944	89	8	8	0	7	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1019-6439	1791-2423		INT J ONCOL	Int. J. Oncol.	JUL	2019	55	1					223	242		10.3892/ijo.2019.4809			20	Oncology	Science Citation Index Expanded (SCI-EXPANDED)	Oncology	IK4LE	WOS:000476557600019	31180528	Bronze			2022-04-25	
J	Narsale, AA; Carson, JA				Narsale, Aditi A.; Carson, James A.			Role of interleukin-6 in cachexia: therapeutic implications	CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE			English	Review						cancer cachexia; gut; IL-6 therapies; liver; skeletal muscle	SKELETAL-MUSCLE; CANCER CACHEXIA; COLORECTAL-CANCER; IL-6; TOCILIZUMAB; PATHWAY; SUPPRESSION; TURNOVER; ANTIBODY; SYSTEM	Purpose of review Interleukin-6 (IL-6) has emerged as a cytokine involved in cachexia progression with some cancers. This review will present the recent breakthroughs in animal models and humans related to targeting IL-6 as a cancer cachexia therapy. Recent findings IL-6 can target adipose, skeletal muscle, gut, and liver tissue, which can all affect cachectic patient recovery. IL-6 trans-signaling through the soluble IL-6R has the potential to amplify IL-6 signaling in the cachectic patient. In the skeletal muscle, chronic IL-6 exposure induces proteasome and autophagy protein degradation pathways that lead to wasting. IL-6 is also indirectly associated with AMP-activated kinase (AMPK) and nuclear factor kappa B (NF-kappa B) activation. Several mouse cancer models have clearly demonstrated that blocking IL-6 and associated signaling can attenuate cachexia progression. Additionally, pharmaceuticals targeting IL-6 and associated signaling can relieve some cachectic symptoms in cancer patients. Research with cachectic mice has demonstrated that exercise and nutraceutical administration can interact with chronic IL-6 signaling during cachexia progression. Summary IL-6 remains a promising therapeutic strategy for attenuating cachexia progression with many types of cancer. However, improvement of this treatment will require a better understanding of the indirect and direct effects of IL-6 as well as its tissue-specific actions in the cancer patient.	[Narsale, Aditi A.; Carson, James A.] Univ S Carolina, Dept Exercise Sci, Integrat Muscle Biol Lab, Columbia, SC 29208 USA; [Narsale, Aditi A.; Carson, James A.] Univ S Carolina, Dept Exercise Sci, Div Appl Physiol, Columbia, SC 29208 USA; [Carson, James A.] Univ S Carolina, Ctr Colon Canc Res, Columbia, SC 29208 USA		Carson, JA (corresponding author), Univ S Carolina, Publ Hlth Res Ctr, Dept Exercise Sci, Room 405,921 Assembly St, Columbia, SC 29208 USA.	carsonj@mailbox.sc.edu	Carson, James/Q-5693-2019; Narsale, Aditi/U-4643-2019	Carson, James/0000-0003-3733-8796; Narsale, Aditi/0000-0002-1421-5104	NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [RO1CA121249]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R01CA121249] Funding Source: NIH RePORTER	J.A.C. is currently being funded by the NCI grant RO1CA121249.	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Opin Support Palliat. Car.	DEC	2014	8	4					321	327		10.1097/SPC.0000000000000091			7	Health Care Sciences & Services	Science Citation Index Expanded (SCI-EXPANDED)	Health Care Sciences & Services	AT2CA	WOS:000344737500002	25319274	Green Accepted			2022-04-25	
J	Lin, Z; Hegarty, JP; Cappel, JA; Yu, W; Chen, X; Faber, P; Wang, Y; Kelly, AA; Poritz, LS; Peterson, BZ; Schreiber, S; Fan, JB; Koltun, WA				Lin, Z.; Hegarty, J. P.; Cappel, J. A.; Yu, W.; Chen, X.; Faber, P.; Wang, Y.; Kelly, A. A.; Poritz, L. S.; Peterson, B. Z.; Schreiber, S.; Fan, J-B; Koltun, W. A.			Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease	CLINICAL GENETICS			English	Article						Crohn's disease; DNA methylation; inflammatory bowel disease; intestinal tissue; ulcerative colitis	GENOME-WIDE ASSOCIATION; ULCERATIVE-COLITIS; SUSCEPTIBILITY LOCI; COLORECTAL-CANCER; CROHN-DISEASE; GENE; HYPERMETHYLATION; EPIGENETICS; AUTOPHAGY; DEFINES	Overwhelming evidence supports the theory that inflammatory bowel disease (IBD) is caused by a complex interplay between genetic predispositions of multiple genes, combined with an abnormal interaction with environmental factors. It is becoming apparent that epigenetic factors can have a significant contribution in the pathogenesis of disease. Changes in the methylation state of IBD-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We have explored the role of DNA methylation in IBD pathogenesis. DNA methylation profiles (1505 CpG sites of 807 genes) of matched diseased (n = 26) and non-diseased (n = 26) intestinal tissues from 26 patients with IBD [Crohn's disease (CD) n = 9, ulcerative colitis (UC) n = 17] were profiled using the GoldenGate (TM) methylation assay. After an initial identification of a panel of 50 differentially methylated CpG sites from a training set (14 non-diseased and 14 diseased tissues) and subsequent validation with a testing set (12 non-diseased and 12 diseased tissues), we identified seven CpG sites that are differentially methylated in intestinal tissues of IBD patients. We have also identified changes in DNA methylation associated with the two major IBD subtypes, CD and UC. This study reports IBD-associated changes in DNA methylation in intestinal tissue, which may be disease subtype-specific.	[Lin, Z.; Hegarty, J. P.; Cappel, J. A.; Yu, W.; Wang, Y.; Kelly, A. A.; Poritz, L. S.; Koltun, W. A.] Penn State Univ, Dept Surg, Coll Med, Hershey, PA 17033 USA; [Chen, X.] Vanderbilt Univ, Dept Biostat, Nashville, TN USA; [Faber, P.] Cleveland Clin, Inst Mol Med, Cleveland, OH 44106 USA; [Poritz, L. S.; Peterson, B. Z.] Penn State Univ, Dept Cell & Mol Physiol, Coll Med, Hershey, PA 17033 USA; [Schreiber, S.] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany; [Fan, J-B] Illumina Inc, San Diego, CA USA		Lin, Z (corresponding author), Penn State Univ, Dept Surg, Coll Med, 500 Univ Dr,H 137, Hershey, PA 17033 USA.	zlin@hmc.psu.edu; wkoltun@hmc.psu.edu	yu, wei/B-5859-2011		Philadelphia Health Care Trust, Philadelphia, PA; Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, PA	This study was supported by a grant from the Philadelphia Health Care Trust, Philadelphia, PA (W. A. K.) and a feasibility research grant from the Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, PA (Z. L.).	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Genet.	JUL	2011	80	1					59	67		10.1111/j.1399-0004.2010.01546.x			9	Genetics & Heredity	Science Citation Index Expanded (SCI-EXPANDED)	Genetics & Heredity	774QW	WOS:000291402200009	20950376				2022-04-25	
J	Bernatsky, S; Ramsey-Goldman, R; Urowitz, MB; Hanly, JG; Gordon, C; Petri, MA; Ginzler, EM; Wallace, DJ; Bae, SC; Romero-Diaz, J; Dooley, MA; Peschken, CA; Isenberg, DA; Rahman, A; Manzi, S; Jacobsen, S; Lim, SS; van Vollenhoven, R; Nived, O; Kamen, DL; Aranow, C; Ruiz-Irastorza, G; Sanchez-Guerrero, J; Gladman, DD; Fortin, PR; Alarcon, GS; Merrill, JT; Kalunian, KC; Ramos-Casals, M; Steinsson, K; Zoma, A; Askanase, A; Khamashta, MA; Bruce, I; Inanc, M; Clarke, AE				Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Urowitz, Murray B.; Hanly, John G.; Gordon, Caroline; Petri, Michelle A.; Ginzler, Ellen M.; Wallace, Daniel J.; Bae, Sang-Cheol; Romero-Diaz, Juanita; Dooley, Mary Anne; Peschken, Christine A.; Isenberg, David A.; Rahman, Anisur; Manzi, Susan; Jacobsen, Soren; Lim, S. Sam; van Vollenhoven, Ronald; Nived, Ola; Kamen, Diane L.; Aranow, Cynthia; Ruiz-Irastorza, Guillermo; Sanchez-Guerrero, Jorge; Gladman, Dafna D.; Fortin, Paul R.; Alarcon, Graciela S.; Merrill, Joan T.; Kalunian, Kenneth C.; Ramos-Casals, Manuel; Steinsson, Kristjan; Zoma, Asad; Askanase, Anca; Khamashta, Munther A.; Bruce, Ian; Inanc, Murat; Clarke, Ann E.			Cancer Risk in a Large Inception Systemic Lupus Erythematosus Cohort: Effects of Demographic Characteristics, Smoking, and Medications	ARTHRITIS CARE & RESEARCH			English	Article							DISEASE-ACTIVITY; MALIGNANCY; HYDROXYCHLOROQUINE; AUTOPHAGY	Objective To assess cancer risk factors in incident systemic lupus erythematosus (SLE). Methods Clinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (overall risk and most common cancers) included demographic characteristics and time-dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and the adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 score. Results Among 1,668 patients (average 9 years follow-up), 65 cancers occurred: 15 breast, 10 nonmelanoma skin, 7 lung, 6 hematologic, 6 prostate, 5 melanoma, 3 cervical, 3 renal, 2 each gastric, head and neck, and thyroid, and 1 each rectal, sarcoma, thymoma, and uterine cancers. Half of the cancers (including all lung cancers) occurred in past/current smokers, versus one-third of patients without cancer. Multivariate analyses indicated that overall cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively associated and antimalarial drugs were negatively associated. Antimalarial drugs and higher disease activity were also negatively associated with nonmelanoma skin cancer risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with nonmelanoma skin cancer risk. Conclusion Smoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and nonmelanoma skin cancer. Antimalarials were negatively associated with breast cancer and nonmelanoma skin cancer risk. SLE activity was associated positively with hematologic cancer and negatively with nonmelanoma skin cancer. Since the absolute number of cancers was small, additional follow-up will help consolidate these findings.	[Bernatsky, Sasha] McGill Univ, Montreal, PQ, Canada; [Ramsey-Goldman, Rosalind] Northwestern Univ, Chicago, IL 60611 USA; [Ramsey-Goldman, Rosalind] Feinberg Sch Med, Chicago, IL 60611 USA; [Urowitz, Murray B.; Sanchez-Guerrero, Jorge; Gladman, Dafna D.] Toronto Western Hosp, Toronto, ON, Canada; [Urowitz, Murray B.; Sanchez-Guerrero, Jorge; Gladman, Dafna D.] Univ Toronto, Toronto, ON, Canada; [Hanly, John G.] Queen Elizabeth II Hlth Sci, Halifax, NS, Canada; [Hanly, John G.] Dalhousie Univ, Halifax, NS, Canada; [Gordon, Caroline] Univ Birmingham, Coll Med & Dent Sci, Birmingham, W Midlands, England; [Petri, Michelle A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA; [Ginzler, Ellen M.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA; [Wallace, Daniel J.] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai, Los Angeles, CA 90095 USA; [Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, Seoul, South Korea; [Romero-Diaz, Juanita] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico; [Dooley, Mary Anne] Univ N Carolina, Chapel Hill, NC 27515 USA; [Peschken, Christine A.] Univ Manitoba, Winnipeg, MB, Canada; [Isenberg, David A.] UCL, London, England; [Manzi, Susan] Allegheny Hlth Network, Pittsburgh, PA USA; [Jacobsen, Soren] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark; [Lim, S. Sam] Emory Univ, Atlanta, GA 30322 USA; [van Vollenhoven, Ronald] Univ Amsterdam, Med Ctr, Amsterdam, Netherlands; [Nived, Ola] Lund Univ, Lund, Sweden; [Kamen, Diane L.] Med Univ South Carolina, Charleston, SC 29425 USA; [Aranow, Cynthia] Feinstein Inst Med Res, Manhasset, NY USA; [Ruiz-Irastorza, Guillermo] Univ Basque Country, Hosp Univ Cruces, Baracaldo, Spain; [Fortin, Paul R.] Univ Laval, CHU Quebec, Quebec City, PQ, Canada; [Alarcon, Graciela S.] Univ Alabama Birmingham, Birmingham, AL USA; [Merrill, Joan T.] Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA; [Kalunian, Kenneth C.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA; [Ramos-Casals, Manuel] Hosp Clin Barcelona, Barcelona, Spain; [Steinsson, Kristjan] Fossvogur Landspitali Univ Hosp, Reykjavik, Iceland; [Zoma, Asad] Hairmyres Hosp, E Kilbride, Lanark, Scotland; [Askanase, Anca] Columbia Univ, Coll Phys & Surg, New York, NY USA; [Khamashta, Munther A.] Kings Coll London, St Thomas Hosp, Sch Med, London, England; [Bruce, Ian] Univ Manchester, Manchester, Lancs, England; [Bruce, Ian] Manchester Univ NHS Fdn Trust, NIHR Manchester Musculoskeletal Biomed Res Ctr, Manchester, Lancs, England; [Bruce, Ian] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England; [Inanc, Murat] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey; [Clarke, Ann E.] Univ Calgary, Cumming Sch Med, Calgary, AB, Canada		Bernatsky, S (corresponding author), Div Clin Epidemiol, 5252 Boul Maisonneuve Ouest,3F-51, Montreal, PQ H4A 3S5, Canada.	Sasha.bernatsky@mcgill.ca	van Vollenhoven, Ronald/ABE-1244-2021	Gordon, Caroline/0000-0002-1244-6443; Bernatsky, Sasha/0000-0002-9515-2802; Kalunian, Kenneth/0000-0003-0261-3102; Urowitz, Murray B./0000-0001-7506-9166; Jacobsen, Soren/0000-0002-5654-4993	Montreal General Hospital Lupus Clinic; Singer Family Fund for Lupus Research; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [5UL1-TR-001422-02, 8UL1-TR-000150, UL-1RR-025741, K24-AR-02318, P60-AR-064464, P60-AR-48098, RR-00046]; Lupus UK; West Birmingham Hospitals NHS Trust; National Institute for Health Research/Wellcome Trust Birmingham Clinical Research Facility [AR-69572]; Republic of Korea [NRF-2017M3A9B4050335]; National Institute for Health Research University College London Hospitals Biomedical Research CentreGeneral Electric; Danish Rheumatism Association [A3865]; Novo Nordisk FoundationNovo Nordisk FoundationNovocure Limited [A05990]; Centers for Disease Control and PreventionUnited States Department of Health & Human ServicesCenters for Disease Control & Prevention - USA [U01DP005119]; Department of Education, Universities, and Research of the Basque Government; Arthritis Research UKVersus Arthritis; NIHR Manchester Biomedical Centre; NIHR/Wellcome Trust Manchester Clinical Research Facility; Arthritis Society Chair in Rheumatic Diseases at the University of Calgary	Dr. Bernatsky's work was supported by the Montreal General Hospital Lupus Clinic, which is supported by the Singer Family Fund for Lupus Research. Dr. Ramsey-Goldman's work was supported by the NIH (5UL1-TR-001422-02, formerly 8UL1-TR-000150 and UL-1RR-025741, K24-AR-02318, and P60-AR-064464, formerly P60-AR-48098). Dr. Gordon's work was supported by Lupus UK, Sandwell, and West Birmingham Hospitals NHS Trust and the National Institute for Health Research/Wellcome Trust Birmingham Clinical Research Facility. Dr. Petri's work was supported by the Hopkins Lupus Cohort (NIH AR-69572). Dr. Bae's work was supported by the Republic of Korea (NRF-2017M3A9B4050335). Dr. Dooley's work was supported by the NIH (RR-00046). Dr. Isenberg's and Dr. Rahman's work was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Dr. Jacobsen's work was supported by the Danish Rheumatism Association (A3865) and the Novo Nordisk Foundation (A05990). Dr. Lim's work was supported by the Centers for Disease Control and Prevention (U01DP005119). Dr. Ruiz-Irastorza's work was supported by the Department of Education, Universities, and Research of the Basque Government. Dr. Fortin holds a Tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Universite Laval. Dr. Bruce is a National Institute for Health Research (NIHR) Senior Investigator and is supported by Arthritis Research UK, the NIHR Manchester Biomedical Centre and the NIHR/Wellcome Trust Manchester Clinical Research Facility. Dr. Clarke holds The Arthritis Society Chair in Rheumatic Diseases at the University of Calgary.	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J	Kulka, LAM; Fangmann, PV; Panfilova, D; Olzscha, H				Kulka, Linda Anna Michelle; Fangmann, Pia-Victoria; Panfilova, Diana; Olzscha, Heidi			Impact of HDAC Inhibitors on Protein Quality Control Systems: Consequences for Precision Medicine in Malignant Disease	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY			English	Review						autophagy; bromodomain-containing protein; epigenetic drug; histone deacetylase inhibitor; molecular chaperone; precision medicine; protein quality control; ubiquitin proteasome system	HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; CELL LUNG-CANCER; SYNERGISTIC ANTITUMOR-ACTIVITY; ORAL PANOBINOSTAT LBH589; MESSENGER-RNA EXPRESSION; HUMAN COLORECTAL-CANCER; HIGH-DOSE DEXAMETHASONE; PHASE-I TRIAL; MULTIPLE-MYELOMA	Lysine acetylation is one of the major posttranslational modifications (PTM) in human cells and thus needs to be tightly regulated by the writers of this process, the histone acetyl transferases (HAT), and the erasers, the histone deacetylases (HDAC). Acetylation plays a crucial role in cell signaling, cell cycle control and in epigenetic regulation of gene expression. Bromodomain (BRD)-containing proteins are readers of the acetylation mark, enabling them to transduce the modification signal. HDAC inhibitors (HDACi) have been proven to be efficient in hematologic malignancies with four of them being approved by the FDA. However, the mechanisms by which HDACi exert their cytotoxicity are only partly resolved. It is likely that HDACi alter the acetylation pattern of cytoplasmic proteins, contributing to their anti-cancer potential. Recently, it has been demonstrated that various protein quality control (PQC) systems are involved in recognizing the altered acetylation pattern upon HDACi treatment. In particular, molecular chaperones, the ubiquitin proteasome system (UPS) and autophagy are able to sense the structurally changed proteins, providing additional targets. Recent clinical studies of novel HDACi have proven that proteins of the UPS may serve as biomarkers for stratifying patient groups under HDACi regimes. In addition, members of the PQC systems have been shown to modify the epigenetic readout of HDACi treated cells and alter proteostasis in the nucleus, thus contributing to changing gene expression profiles. Bromodomain (BRD)-containing proteins seem to play a potent role in transducing the signaling process initiating apoptosis, and many clinical trials are under way to test BRD inhibitors. Finally, it has been demonstrated that HDACi treatment leads to protein misfolding and aggregation, which may explain the effect of panobinostat, the latest FDA approved HDACi, in combination with the proteasome inhibitor bortezomib in multiple myeloma. Therefore, proteins of these PQC systems provide valuable targets for precision medicine in cancer. In this review, we give an overview of the impact of HDACi treatment on PQC systems and their implications for malignant disease. We exemplify the development of novel HDACi and how affected proteins belonging to PQC can be used to determine molecular signatures and utilized in precision medicine.	[Kulka, Linda Anna Michelle; Fangmann, Pia-Victoria; Panfilova, Diana; Olzscha, Heidi] Martin Luther Univ Halle Wittenberg, Inst Physiol Chem, Fac Med, Halle, Saale, Germany		Olzscha, H (corresponding author), Martin Luther Univ Halle Wittenberg, Inst Physiol Chem, Fac Med, Halle, Saale, Germany.	Heidi.Olzscha@medizin.uni-halle.de	Olzscha, Heidi/AAU-1296-2020	Olzscha, Heidi/0000-0002-1929-1384	DFGGerman Research Foundation (DFG)European Commission [RTK 2155, FKZ PK28]	LK and HO were supported by the DFG, RTK 2155 (ProMoAge) and P-VF by theWilhelm Roux Program HaPKoM (FKZ PK28).	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Cell. Dev. Biol.	JUN 3	2020	8								425	10.3389/fcell.2020.00425			28	Cell Biology; Developmental Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology; Developmental Biology	MC3JI	WOS:000543187200001	32582706	Green Published, gold			2022-04-25	
J	Hofer, SJ; Davinelli, S; Bergmann, M; Scapagnini, G; Madeo, F				Hofer, Sebastian J.; Davinelli, Sergio; Bergmann, Martina; Scapagnini, Giovanni; Madeo, Frank			Caloric Restriction Mimetics in Nutrition and Clinical Trials	FRONTIERS IN NUTRITION			English	Review						caloric restriction mimetics; nutrition; spermidine; clinical trials; polyphenols; polyamines; healthy diet	FOOD-FREQUENCY QUESTIONNAIRE; CAMBOGIA HYDROXYCITRIC ACID; CARDIOVASCULAR RISK-FACTORS; TYPE-2 DIABETES-MELLITUS; DIETARY POLYAMINE INTAKE; COLORECTAL-CANCER RISK; C-REACTIVE PROTEIN; ELEGANS LIFE-SPAN; GARCINIA-CAMBOGIA; RESVERATROL SUPPLEMENTATION	The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD(+) precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.	[Hofer, Sebastian J.; Bergmann, Martina; Madeo, Frank] Karl Franzens Univ Graz, Inst Mol Biosci, NAWI Graz, Graz, Austria; [Hofer, Sebastian J.; Madeo, Frank] BioTechMed Graz, Graz, Austria; [Hofer, Sebastian J.; Madeo, Frank] Karl Franzens Univ Graz, Field Excellence BioHlth, Graz, Austria; [Davinelli, Sergio; Scapagnini, Giovanni] Univ Molise, Dept Med & Hlth Sci V Tiberio, Campobasso, Italy		Hofer, SJ (corresponding author), Karl Franzens Univ Graz, Inst Mol Biosci, NAWI Graz, Graz, Austria.; Hofer, SJ (corresponding author), BioTechMed Graz, Graz, Austria.; Hofer, SJ (corresponding author), Karl Franzens Univ Graz, Field Excellence BioHlth, Graz, Austria.	sebastian.hofer@uni-graz.at	Davinelli, Sergio/U-1545-2017	Davinelli, Sergio/0000-0003-2578-7199; Madeo, Frank/0000-0002-5070-1329; Hofer, Sebastian/0000-0002-0756-0014	Austrian Science Fund FWFAustrian Science Fund (FWF) [F3007, F3012, W1226, P29203, P29262, P27893, P31727]; Austrian Federal Ministry of Education, Science and Research; University of Graz; flysleep(BMWFW) [80.109/0001-WF/V/3b/2015]; Field of Excellence BioHealth; NAWI Graz; BioTechMed-Graz flagship project EPIAge	FM was grateful to the Austrian Science Fund FWF (SFB LIPOTOX F3007 and F3012, DK-MCD W1226, as well as Grant Nos. P29203, P29262, P27893, and P31727) and the Austrian Federal Ministry of Education, Science and Research, as well as the University of Graz for grants Unkonventionelle Forschung-InterFast and Fast4Health, as well as flysleep(BMWFW-80.109/ 0001-WF/V/3b/2015). We acknowledge the support of the Field of Excellence BioHealth, of NAWI Graz and the BioTechMed-Graz flagship project EPIAge.	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Nutr.	SEP 6	2021	8								717343	10.3389/fnut.2021.717343			20	Nutrition & Dietetics	Science Citation Index Expanded (SCI-EXPANDED)	Nutrition & Dietetics	UT2LJ	WOS:000697952300001	34552954	Green Published, gold			2022-04-25	
J	Luo, H; Vong, CT; Chen, HB; Gao, Y; Lyu, P; Qiu, L; Zhao, MM; Liu, Q; Cheng, ZH; Zou, J; Yao, PF; Gao, CF; Wei, JC; Ung, COL; Wang, SP; Zhong, ZF; Wang, YT				Luo, Hua; Vong, Chi Teng; Chen, Hanbin; Gao, Yan; Lyu, Peng; Qiu, Ling; Zhao, Mingming; Liu, Qiao; Cheng, Zehua; Zou, Jian; Yao, Peifen; Gao, Caifang; Wei, Jinchao; Ung, Carolina Oi Lam; Wang, Shengpeng; Zhong, Zhangfeng; Wang, Yitao			Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine	CHINESE MEDICINE			English	Review						Cancer; Chinese herbal medicine; Natural products; Bioactive compounds; Traditional Chinese medicine	CELL-CYCLE ARREST; NF-KAPPA-B; BREAST-CANCER CELLS; ENDOPLASMIC-RETICULUM STRESS; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN COLORECTAL-CANCER; HUMAN BLADDER-CANCER; ORIDONIN-INDUCED APOPTOSIS; HUMAN PANCREATIC-CANCER; MULTIPLE-MYELOMA CELLS	Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including anti-proliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, beta-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.	[Luo, Hua; Vong, Chi Teng; Chen, Hanbin; Gao, Yan; Lyu, Peng; Qiu, Ling; Zhao, Mingming; Liu, Qiao; Cheng, Zehua; Zou, Jian; Yao, Peifen; Gao, Caifang; Wei, Jinchao; Ung, Carolina Oi Lam; Wang, Shengpeng; Zhong, Zhangfeng; Wang, Yitao] Univ Macau, State Key Lab Qual Res Chinese Med, Inst Chinese Med Sci, Macau, Peoples R China		Zhong, ZF; Wang, YT (corresponding author), Univ Macau, State Key Lab Qual Res Chinese Med, Inst Chinese Med Sci, Macau, Peoples R China.	zfzhong@aliyun.com; ytwang@um.edu.mo	Huan, Zhao/AAU-8477-2021; Ung, Carolina Oi Lam/AAR-2672-2020	Jinchao, Wei/0000-0002-9777-4867; Ung, Carolina Oi Lam/0000-0003-1915-5099; Vong, Chi Teng/0000-0002-4032-657X	Macao Science and Technology Development Fund [FDCT 071/2017/A2]; Research Committee of the University of Macau [CPG2019-00006-ICMS]	This work was financially supported by the Macao Science and Technology Development Fund (FDCT 071/2017/A2), and the Research Committee of the University of Macau (CPG2019-00006-ICMS).	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Zuo AR, 2018, CHIN MED-UK, V13, DOI 10.1186/s13020-018-0206-9; Zuo W, 2014, INT J MOL SCI, V15, P14298, DOI 10.3390/ijms150814298	988	127	131	99	206	BMC	LONDON	CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND	1749-8546			CHIN MED-UK	Chin. Med.	NOV 6	2019	14	1							48	10.1186/s13020-019-0270-9			58	Integrative & Complementary Medicine; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Integrative & Complementary Medicine; Pharmacology & Pharmacy	JL6FK	WOS:000495625600001	31719837	Green Published, gold	Y	N	2022-04-25	
J	Yamaguchi, N; Suzuki, Y; Mahbub, MH; Takahashi, H; Hase, R; Ishimaru, Y; Sunagawa, H; Watanabe, R; Eishi, Y; Tanabe, T				Yamaguchi, Natsu; Suzuki, Yoshimi; Mahbub, M. H.; Takahashi, Hidekazu; Hase, Ryosuke; Ishimaru, Yasutaka; Sunagawa, Hiroshi; Watanabe, Rie; Eishi, Yoshinobu; Tanabe, Tsuyoshi			The different roles of innate immune receptors in inflammation and carcinogenesis between races	ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE			English	Review						TLR; NOD; Crohn's disease; Sarcoidosis	JAPANESE PATIENTS; CROHNS-DISEASE; NOD2/CARD15 VARIANTS; 3020INSC MUTATION; HOST RECOGNITION; CARD15 MUTATIONS; GENE; NOD1; TRANSPLANTATION; POLYMORPHISMS	Innate immune factors exert widespread effects on cytokine secretion, cell survival, autophagy, and apoptosis. Nucleotide-binding and oligomerization domain-like receptors (NLRs) are members of the innate immune system in the cytosol that sense pathogens, endogenous danger molecules such as uric acid, and pollutants. Nucleotidebinding oligomerization domain-containing protein 1 and 2 (NOD1 and NOD2) are components of NLR family, and ligands of these factors are gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and muramyl dipeptide (MDP), respectively. Upon recognition of ligands, NOD1 and NOD2 induce the production of inflammatory cytokines and transcription factors including interleukin-6 (IL-6) and nuclear factor-kappa B (NF-kappa B). We examined the function of NOD1 and NOD2 in innate immunity, with a focus on their differing roles in disease pathogenesis between Japanese and Caucasian populations. Susceptibility to several immune-related diseases, including Crohn's disease, colorectal and breast cancers, and graft-versus-host-disease (GVHD) showed a correlation with genetic variants of NOD2 in Caucasian, but not in Japanese, populations. This difference may be primarily due to the fact that three major NOD2 SNPs (R702W, G908R, L1007insC) prevalent in Caucasians are rare or absent in Japanese populations. Because NLR has diverse effects on immune function, it is possible that many as yet uncharacterized immune-related diseases will also show different susceptibilities between races due to the different ratio of genetic variants in innate immune genes.	[Yamaguchi, Natsu; Mahbub, M. H.; Takahashi, Hidekazu; Hase, Ryosuke; Ishimaru, Yasutaka; Sunagawa, Hiroshi; Watanabe, Rie; Tanabe, Tsuyoshi] Yamaguchi Univ, Grad Sch Med, Depnt Publ Hlth & Prevent Med, 1-1-1 Minami Kogushi, Ube, Yamaguchi 7558505, Japan; [Suzuki, Yoshimi; Eishi, Yoshinobu] Tokyo Med & Dent Univ, Grad Sch, Dept Human Pathol, Tokyo, Japan; [Suzuki, Yoshimi; Eishi, Yoshinobu] Tokyo Med & Dent Univ, Fac Med, Tokyo, Japan		Tanabe, T (corresponding author), Yamaguchi Univ, Grad Sch Med, Depnt Publ Hlth & Prevent Med, 1-1-1 Minami Kogushi, Ube, Yamaguchi 7558505, Japan.	tanabe@yamaguchi-u.ac.jp					Akahoshi M, 2008, TISSUE ANTIGENS, V71, P564, DOI 10.1111/j.1399-0039.2008.01043.x; Bonen DK, 2003, GASTROENTEROLOGY, V124, P140, DOI 10.1053/gast.2003.50019; Chamaillard M, 2003, NAT IMMUNOL, V4, P702, DOI 10.1038/ni945; Croucher PJP, 2003, EUR J HUM GENET, V11, P6, DOI 10.1038/sj.ejhg.5200897; Dostert C, 2008, SCIENCE, V320, P674, DOI 10.1126/science.1156995; Granell M, 2006, HAEMATOLOGICA, V91, P1372; Holler E, 2006, BLOOD, V107, P4189, DOI 10.1182/blood-2005-09-3741; Holler E, 2004, BLOOD, V104, P889, DOI 10.1182/blood-2003-10-3543; Inohara N, 2003, J BIOL CHEM, V278, P5509, DOI 10.1074/jbc.C200673200; Inohara N, 2000, J BIOL CHEM, V275, P27823; Inohara N, 2005, ANNU REV BIOCHEM, V74, P355, DOI 10.1146/annurev.biochem.74.082803.133347; Inohara N, 2001, J BIOL CHEM, V276, P2551, DOI 10.1074/jbc.M009728200; Ishige I, 1999, LANCET, V354, P120, DOI 10.1016/S0140-6736(98)12310-3; JABS DA, 1985, AM J MED, V78, P801, DOI 10.1016/0002-9343(85)90286-4; Karin M, 2006, CELL, V124, P823, DOI 10.1016/j.cell.2006.02.016; Kawai T, 2006, NAT IMMUNOL, V7, P131, DOI 10.1038/ni1303; Kobayashi KS, 2005, SCIENCE, V307, P731, DOI 10.1126/science.1104911; Kurzawski G, 2004, CANCER RES, V64, P1604, DOI 10.1158/0008-5472.CAN-03-3791; Lener MR, 2006, BREAST CANCER RES TR, V95, P141, DOI 10.1007/s10549-005-9057-z; Leong RWL, 2003, ALIMENT PHARM THER, V17, P1465, DOI 10.1046/j.1365-2036.2003.01607.x; Masumoto J, 2006, J EXP MED, V203, P203, DOI 10.1084/jem.20051229; Miceli-Richard C, 2001, NAT GENET, V29, P19, DOI 10.1038/ng720; Ogino K, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0092710; Oh H, 2005, BLOOD, V105, P1408, DOI 10.1182/blood-2004-06-2385; Okafuji I, 2009, ARTHRITIS RHEUM-US, V60, P242, DOI 10.1002/art.24134; Rosenstiel P, 2006, CELL MICROBIOL, V8, P1188, DOI 10.1111/j.1462-5822.2006.00701.x; Schurmann M, 2003, EUR RESPIR J, V22, P748, DOI 10.1183/09031936.03.00040602; Sioud M, 2009, J LEUKOCYTE BIOL, V85, P939, DOI 10.1189/jlb.1008650; Sugimura M, 2003, CLIN GENET, V63, P160, DOI 10.1046/j.0009-9163.2002.00174.x; Tanabe T, 2004, EMBO J, V23, P1587, DOI 10.1038/sj.emboj.7600175; Tanabe T, 2006, BBA-MOL BASIS DIS, V1762, P794, DOI 10.1016/j.bbadis.2006.07.006; Tanabe T, 2011, INT J HEMATOL, V93, P771, DOI 10.1007/s12185-011-0860-5; van Beelen AJ, 2007, IMMUNITY, V27, P660, DOI 10.1016/j.immuni.2007.08.013; Yamazaki K, 2002, J HUM GENET, V47, P469, DOI 10.1007/s100380200067	34	7	7	0	4	SPRINGER	NEW YORK	ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES	1342-078X	1347-4715		ENVIRON HEALTH PREV	Environ. Health Prev.		2017	22	1							70	10.1186/s12199-017-0678-8			5	Public, Environmental & Occupational Health	Science Citation Index Expanded (SCI-EXPANDED); Social Science Citation Index (SSCI)	Public, Environmental & Occupational Health	FL5QA	WOS:000414299400005	29165176	Green Published, gold			2022-04-25	
J	Ray, M; Rai, N; Jana, K; Ghatak, S; Basu, A; Mustafi, SB; Raha, S				Ray, Mahan; Rai, Neha; Jana, Kuladip; Ghatak, Supratim; Basu, Arnab; Mustafi, Soumyajit Banerjee; Raha, Sanghamitra			Beta catenin is degraded by both caspase-3 and proteasomal activity during resveratrol-induced apoptosis in He. La cells in a GSK3 beta-independent manner	INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS			English	Article						Resveratrol; HeLa; Apoptosis; beta-Catenin; Caspase-3; GSK3 beta; Proteasomal degradation	COLORECTAL-CANCER CELLS; DEPENDENT DEGRADATION; PROTEIN; INHIBITION; GSK-3-BETA; AUTOPHAGY; PATHWAY; AKT	Increased activity of beta-catenin, an important transcriptional activator for survival and proliferation-associated genes has been linked with many cancers. We examined whether beta-catenin is a target of resveratrol and whether its degradation contributes to the pro-apoptotic effects of resveratrol. HeLa cells were exposed to 60 mu M resveratrol for 48 h. Apoptosis was confirmed by measurement of annexin V externalization, caspase-3 activation and DNA fragmentation. Induction of apoptosis was observed as early as 12 h, when both caspase-3 activation and PARP (poly ADP ribose polymerase) cleavage occurred. Nuclear beta-catenin levels remained unchanged for 48 h during resveratrol exposure. However, extranuclear cell lysate beta-catenin underwent a decrease at a late stage of apoptosis namely at 36-48 h. Alterations in the phosphorylation status of Akt/GSK3 beta were not observed during resveratrol-induced apoptosis. Furthermore, inhibition of GSK3 beta activity which is largely responsible for beta-catenin degradation failed to influence beta-catenin stability. However, inhibition of caspase-3 activity prevented the decline in beta-catenin levels at 36-48 h of resveratrol exposure. Lactacystin, a proteosomal inhibitor also prevented the degradation of beta-catenin by resveratrol. In conclusion, resveratrol induced apoptosis in He La cells in an Akt/GSK3 beta-independent manner and down-regulated beta-catenin levels during apoptosis through action of caspase-3 and proteasomal degradation, independent of GSK3 beta-mediated phosphorylation.	[Ray, Mahan; Rai, Neha; Jana, Kuladip; Ghatak, Supratim; Mustafi, Soumyajit Banerjee; Raha, Sanghamitra] Saha Inst Nucl Phys, Crystallog & Mol Biol Div, Kolkata 700064, India; [Basu, Arnab] Saha Inst Nucl Phys, Div Chem Sci, Kolkata 700064, India; [Raha, Sanghamitra] VisvaBharati, Integrated Sci Educ & Res Ctr, Santini Ketan 731235, W Bengal, India; [Raha, Sanghamitra] VisvaBharati, Dept Biotechnol, Santini Ketan 731235, W Bengal, India		Raha, S (corresponding author), Saha Inst Nucl Phys, Crystallog & Mol Biol Div, 1-AF Bidhannagar, Kolkata 700064, India.	sanghamitra.raha@visva-bharati.ac.in			CBAUNP project of Saha Institute of Nuclear Physics	We thank Mr. Sushanta Debnath for his excellent support with microscopy. We also thank Ms. Fatema Calcuttawala, who did a project in the lab, for her help during the initial period of the project. This study was funded by the CBAUNP project of Saha Institute of Nuclear Physics and the experimental work was done in the Crystallography & Molecular Biology Division of Saha Institute of Nuclear Physics.	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Biochem. Biophys.	FEB	2015	52	1					7	13					7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	CI5WH	WOS:000354830000001	26040106				2022-04-25	
J	Iuchi, K; Ema, M; Suzuki, M; Yokoyama, C; Hisatomi, H				Iuchi, Katsuya; Ema, Mika; Suzuki, Moe; Yokoyama, Chikako; Hisatomi, Hisashi			Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells	MOLECULAR MEDICINE REPORTS			English	Article						polyunsaturated fatty acids; non-enzymatic oxidation; cell death; apoptosis; lipotoxicity	OMEGA-3-FATTY-ACID OXIDATION-PRODUCTS; BREAST-CANCER; LIPID-PEROXIDATION; PPAR-GAMMA; GENERATION; EXPRESSION; AUTOPHAGY; FAMILY	Polyunsaturated fatty acids are oxidized by non-enzymatic or enzymatic reactions. The oxidized products are multifunctional. In this study, we investigated how oxidized fatty acids inhibit cell proliferation in cultured cells. We used polyunsaturated and saturated fatty acids, docosahexaenoic acid (DHA; 22:6), eicosapentaenoic acid (EPA; 20:5), linoleic acid (LA; 18:2), and palmitic acid (16:0). Oxidized fatty acids were produced by autoxidation of fatty acids for 2 days in the presence of a gas mixture (20% O-2 and 80% N-2). We found that oxidized polyunsaturated fatty acids (OxDHA, OxEPA and OxLA) inhibited cell proliferation much more effectively compared with un-oxidized fatty acids (DHA, EPA and LA, respectively) in THP-1 (a human monocytic leukemia cell line) and DLD-1 (a human colorectal cancer cell line) cells. In particular, OxDHA markedly inhibited cell proliferation. DHA has the largest number of double bonds and is most susceptible to oxidation among the fatty acids. OxDHA has the largest number of highly active oxidized products. Therefore, the oxidative levels of fatty acids are associated with the anti-proliferative activity. Moreover, caspase-3/7 was activated in the cells treated with OxDHA, but not in those treated with DHA. A pan-caspase inhibitor (zVAD-fmk) reduced the cell death induced by OxDHA. These results indicated that oxidized products from polyunsaturated fatty acids induced apoptosis in cultured cells. Collectively, the switch between cell survival and cell death may be regulated by the activity and/or number of oxidized products from polyunsaturated fatty acids.	[Iuchi, Katsuya; Ema, Mika; Suzuki, Moe; Hisatomi, Hisashi] Seikei Univ, Dept Mat & Life Sci, Fac Sci & Technol, 3-3-1 Kichijojikitamachi, Tokyo 1808633, Japan; [Yokoyama, Chikako] Yamagata Univ, Dept Biochem Engn, Grad Sch Sci & Engn, Yonezawa, Yamagata 9928510, Japan		Iuchi, K (corresponding author), Seikei Univ, Dept Mat & Life Sci, Fac Sci & Technol, 3-3-1 Kichijojikitamachi, Tokyo 1808633, Japan.	iuchi@st.seikei.ac.jp	Iuchi, Katsuya/F-3317-2015	Iuchi, Katsuya/0000-0003-0625-6018	Seikei University (Tokyo, Japan); Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15K16524, 18K11001]	Financial support for this research was provided by Grants-in-Aid for Scientific Research of Seikei University (Tokyo, Japan; grant no. 2017) and Scientific Research from the Japan Society for the Promotion of Science (grant nos. 15K16524 and 18K11001 to KI).	Abdelmagid SA, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0116195; Bochkov VN, 2010, ANTIOXID REDOX SIGN, V12, P1009, DOI 10.1089/ars.2009.2597; Calder PC, 2005, BIOCHEM SOC T, V33, P423, DOI 10.1042/BST0330423; Chen R, 2007, J BIOL CHEM, V282, P24842, DOI 10.1074/jbc.M702865200; Clay CE, 2002, J LIPID RES, V43, P1818, DOI 10.1194/jlr.M200224-JLR200; D'Eliseo D, 2016, J CLIN MED, V5, DOI 10.3390/jcm5020015; Dwarakanath RS, 2004, J MOL CELL CARDIOL, V36, P585, DOI 10.1016/j.yjmcc.2004.02.007; Eguchi Y, 1997, CANCER RES, V57, P1835; ESTERBAUER H, 1991, FREE RADICAL BIO MED, V11, P81, DOI 10.1016/0891-5849(91)90192-6; Gao B, 2016, CELL DEATH DIS, V7, DOI 10.1038/cddis.2016.144; Haeiwa H, 2014, MOL CELL BIOCHEM, V386, P73, DOI 10.1007/s11010-013-1846-9; Hill BG, 2008, BIOCHEM J, V410, P525, DOI 10.1042/BJ20071063; Iuchi K, 2016, SCI REP-UK, V6, DOI 10.1038/srep18971; Kang KS, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0010296; Lim SY, 2004, J BIOL CHEM, V279, P46263, DOI 10.1074/jbc.M406555200; Liu XB, 2008, J CLIN BIOCHEM NUTR, V43, P26, DOI 10.3164/jcbn.2008040; Majkova Z, 2011, TOXICOL APPL PHARM, V251, P41, DOI 10.1016/j.taap.2010.11.013; Mansara PP, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0136542; Martinez B, 2005, J LIPID RES, V46, P736, DOI 10.1194/jlr.M400392-JLR200; Meilhac O, 2000, J LIPID RES, V41, P1205; Miller YI, 2017, TRENDS ENDOCRIN MET, V28, P143, DOI 10.1016/j.tem.2016.11.002; Milne GL, 2011, CHEM REV, V111, P5973, DOI 10.1021/cr200160h; Mu YM, 2001, ENDOCRINOLOGY, V142, P3590, DOI 10.1210/en.142.8.3590; Murray M, 2014, BRIT J PHARMACOL, V171, P2051, DOI 10.1111/bph.12417; Niki E, 2014, BBA-GEN SUBJECTS, V1840, P809, DOI 10.1016/j.bbagen.2013.03.020; Notarnicola M, 2017, INT J MOL SCI, V18, DOI 10.3390/ijms18030485; Notarnicola M, 2011, LIPIDS HEALTH DIS, V10, DOI 10.1186/1476-511X-10-10; Nourooz-Zadeh J, 1998, BIOCHEM BIOPH RES CO, V242, P338, DOI 10.1006/bbrc.1997.7883; Parisi LR, 2018, ACS CHEM BIOL, V13, P506, DOI 10.1021/acschembio.7b01082; Perluigi M, 2012, ANTIOXID REDOX SIGN, V17, P1590, DOI 10.1089/ars.2011.4406; Pizato N, 2018, SCI REP-UK, V8, DOI 10.1038/s41598-018-20422-0; Schley PD, 2005, BREAST CANCER RES TR, V92, P187, DOI 10.1007/s10549-005-2415-z; Shimizu S, 2000, P NATL ACAD SCI USA, V97, P577, DOI 10.1073/pnas.97.2.577; Timucin AC, 2017, FREE RADICAL BIO MED, V111, P209, DOI 10.1016/j.freeradbiomed.2016.11.010; Tsujimoto Y, 2003, J CELL PHYSIOL, V195, P158, DOI 10.1002/jcp.10254; Usatyuk PV, 2012, MICROVASC RES, V83, P45, DOI 10.1016/j.mvr.2011.04.012; Wang LM, 2009, J LIPID RES, V50, P204, DOI 10.1194/jlr.M700505-JLR200; Wang WC, 2014, PROSTAG OTH LIPID M, V113, P13, DOI 10.1016/j.prostaglandins.2014.07.002; Xie Y, 2016, CELL DEATH DIFFER, V23, P369, DOI 10.1038/cdd.2015.158; Yadav UCS, 2013, OXID MED CELL LONGEV, V2013, DOI 10.1155/2013/690545; Yee LD, 2005, J NUTR, V135, P983, DOI 10.1093/jn/135.5.983; Yeh A, 2015, TOXICOL IN VITRO, V29, P672, DOI 10.1016/j.tiv.2015.01.015; Yin YQ, 2017, LIPIDS HEALTH DIS, V16, DOI 10.1186/s12944-017-0474-x; Yotsumoto S, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-15668-z; Yun EJ, 2016, ONCOTARGET, V7, P49961, DOI 10.18632/oncotarget.10266; Zajdel A, 2013, ACTA POL PHARM, V70, P365; Zhang Y, 2012, LIPIDS HEALTH DIS, V11, DOI 10.1186/1476-511X-11-1	47	14	14	1	5	SPANDIDOS PUBL LTD	ATHENS	POB 18179, ATHENS, 116 10, GREECE	1791-2997	1791-3004		MOL MED REP	Mol. Med. Rep.	APR	2019	19	4					2767	2773		10.3892/mmr.2019.9940			7	Oncology; Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Research & Experimental Medicine	HQ7YD	WOS:000462639100033	30720142	Green Submitted, Green Published, hybrid			2022-04-25	
J	Phosri, S; Jangpromma, N; Chang, LC; Tan, GT; Wongwiwatthananukit, S; Maijaroen, S; Anwised, P; Payoungkiattikun, W; Klaynongsruang, S				Phosri, Santi; Jangpromma, Nisachon; Chang, Leng Chee; Tan, Ghee T.; Wongwiwatthananukit, Supakit; Maijaroen, Surachai; Anwised, Preeyanan; Payoungkiattikun, Wisarut; Klaynongsruang, Sompong			Siamese Crocodile White Blood Cell Extract Inhibits Cell Proliferation and Promotes Autophagy in Multiple Cancer Cell Lines	JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY			English	Article						Antitumor; breast cancer; colorectal cancer; Crocodylus siamensis; lung cancer; prostate cancer	ANTIBACTERIAL ACTIVITY; ANTICANCER ACTIVITY; ANTIMICROBIAL PEPTIDES; CYCLE ARREST; IN-VITRO; APOPTOSIS; ANTIOXIDANT; EXPRESSION; MIGRATION; TOXICITY	Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and 200 mu g/ml cWBC exhibits a strong cytotoxic effect against all investigated cell lines (IC50 70.34-101.0 mu g/ml), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the S-G(2)/M transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.	[Phosri, Santi] Burapha Univ, Off Educ, Fac Engn, Chon Buri 20131, Thailand; [Phosri, Santi; Jangpromma, Nisachon; Maijaroen, Surachai; Anwised, Preeyanan; Payoungkiattikun, Wisarut; Klaynongsruang, Sompong] Khon Kaen Univ, Prot & Prote Res Ctr Commercial & Ind Purposes Pr, Fac Sci, Khon Kaen 40002, Thailand; [Jangpromma, Nisachon] Khon Kaen Univ, Fac Sci, Off Dean, Khon Kaen 40002, Thailand; [Chang, Leng Chee; Tan, Ghee T.] Univ Hawaii, Coll Pharm, Dept Pharmaceut Sci, Hilo, HI 96720 USA; [Wongwiwatthananukit, Supakit] Univ Hawaii, Dept Pharm Practice, Coll Pharm, Hilo, HI 96720 USA; [Maijaroen, Surachai; Klaynongsruang, Sompong] Khon Kaen Univ, Dept Biochem, Fac Sci, Khon Kaen 40002, Thailand		Klaynongsruang, S (corresponding author), Khon Kaen Univ, Prot & Prote Res Ctr Commercial & Ind Purposes Pr, Fac Sci, Khon Kaen 40002, Thailand.; Klaynongsruang, S (corresponding author), Khon Kaen Univ, Dept Biochem, Fac Sci, Khon Kaen 40002, Thailand.	somkly@kku.ac.th	Jangpromma, Nisachon/AFR-0011-2022	Jangpromma, Nisachon/0000-0002-2071-2406; Klaynongsruang, Sompong/0000-0003-2872-1291	Protein and Proteomics Research Center for Commercial and Industrial Purposes (ProCCI), Faculty of Science, Khon Kaen University	This present research was supported by the Protein and Proteomics Research Center for Commercial and Industrial Purposes (ProCCI), Faculty of Science, Khon Kaen University. We would like to thank the Department of Pharmaceutical Sciences, College of Pharmacy, University of Hawaii at Hilo, USA, for providing laboratory facilities and equipment to perform the anticancer assays. Our special thanks to Sriracha Moda Co. Ltd., Chonburi, Thailand, for providing the crocodile blood samples, as well as the Research Instrument Center, Khon Kaen University, for granting access to and support on the flow cytometer.	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Microbiol. Biotechnol.	JUN	2018	28	6					1007	1021		10.4014/jmb.1712.12002			15	Biotechnology & Applied Microbiology; Microbiology	Science Citation Index Expanded (SCI-EXPANDED)	Biotechnology & Applied Microbiology; Microbiology	GL3AC	WOS:000436997500018	29847866	Bronze			2022-04-25	
J	Okuda, Y; Shimura, T; Iwasaki, H; Katano, T; Kitagawa, M; Nishigaki, R; Fukusada, S; Natsume, M; Tanaka, M; Nishie, H; Ozeki, K; Yamada, T; Kataoka, H				Okuda, Yusuke; Shimura, Takaya; Iwasaki, Hiroyasu; Katano, Takahito; Kitagawa, Mika; Nishigaki, Ruriko; Fukusada, Shigeki; Natsume, Makoto; Tanaka, Mamoru; Nishie, Hirotada; Ozeki, Keiji; Yamada, Tamaki; Kataoka, Hiromi			Serum Exosomal Dicer Is a Useful Biomarker for Early Detection of Differentiated Gastric Adenocarcinoma	DIGESTION			English	Article						Biomarker; Dicer; Exosome; Gastric cancer; Serum	FECAL OCCULT BLOOD; MICRORNA BIOGENESIS; CANCER EXOSOMES; PROLIFERATION; AUTOPHAGY	Background and Aim: A recent basic study identified that Dicer is contained in exosomes derived from cancer cells and plays crucial roles in microRNA maturation and cancer development. Based on this novel basic concept, we analyzed the usefulness of serum exosomal Dicer as a diagnostic biomarker for gastrointestinal cancers. Methods: Enrolled participants (691) were categorized into 3 groups: gastric cancer (GC) cohort, 183 patients (90 healthy controls (HCs) and 93 GC patients); esophageal cancer (EC) cohort, 115 patients (90 HCs and 25 EC patients); and colorectal cancer (CRC) cohort, 188 patients (92 HCs and 96 CRC patients) after age- and sex matching using the propensity score. The quality of isolated serum exosomes was validated with an electron microscope, particle size analyzer, and exosome marker, CD63. Results: Serum exosomal Dicer was significantly higher in the GC group than in the HC group (p = 0.004), whereas no significant differences were found in both EC and CRC cohorts. Serum exosomal Dicer was significantly higher in only differentiated gastric adenocarcinoma and not in the undifferentiated type. Moreover, serum exosomal Dicer showed no significant differences regardless of Helicobacter pylori (H. pylori) status. The biomarker panel combining serum exosomal Dicer with H. pylori status distinguished between HC and differentiated GC patients with an area under the curve (AUC) of 0.762. As for early-stage diagnosis, this combination distinguished between HC and stage I differentiated GC with an AUC = 0.758. Conclusions: Serum exosomal Dicer is a potential noninvasive diagnostic biomarker for early detection of differentiated gastric adenocarcinoma.	[Okuda, Yusuke; Shimura, Takaya; Iwasaki, Hiroyasu; Katano, Takahito; Kitagawa, Mika; Nishigaki, Ruriko; Fukusada, Shigeki; Natsume, Makoto; Tanaka, Mamoru; Nishie, Hirotada; Ozeki, Keiji; Kataoka, Hiromi] Nagoya City Univ, Grad Sch Med Sci, Dept Gastroenterol & Metab, Nagoya, Aichi, Japan; [Yamada, Tamaki] Okazaki Publ Hlth Ctr, Okazaki, Aichi, Japan		Shimura, T (corresponding author), Nagoya City Univ, Grad Sch Med Sci, Dept Gastroenterol & Metab, Mizuho Ku, 1 Kawasumi, Nagoya, Aichi 4678601, Japan.	tshimura@med.nagoya-cu.ac.jp		Okuda, Yusuke/0000-0003-1390-0609; Shimura, Takaya/0000-0002-6048-0021	Suzuken Memorial Foundation	This study was supported, in part, by Suzuken Memorial Foundation (to T.S.).	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J	Shao, M; Chang, C; Liu, ZH; Chen, K; Zhou, YM; Zheng, GH; Huang, ZJ; Xu, HX; Xu, PH; Lu, B				Shao, Mei; Chang, Cong; Liu, Zuhao; Chen, Kai; Zhou, Yimin; Zheng, Guohua; Huang, Zhijun; Xu, Haixing; Xu, Peihu; Lu, Bo			Polydopamine coated hollow mesoporous silica nanoparticles as pH-sensitive nanocarriers for overcoming multidrug resistance	COLLOIDS AND SURFACES B-BIOINTERFACES			English	Article						Polydopamine; Hollow mesoporous silica nanoparticles; Multidrug resistance; Stimuli response; Drug delivery system	DRUG-DELIVERY SYSTEM; CO-DELIVERY; INSPIRED POLYDOPAMINE; PHOTOTHERMAL THERAPY; IN-VITRO; QUERCETIN; RELEASE; DOXORUBICIN; AUTOPHAGY; PLATFORM	A nanocarrier system of methoxypolyethylene glycol amine (mPEG-NH2) functionalized polydopamine (PDA) coated hollow mesoporous silica nanoparticles (HMSNs-PDA-PEG) was developed with pH-responsive, which combined doxorubicin hydrochloride (DOX) and quercetin (QUR) to reverse multidrug resistance (MDR) and improved anticancer effects on taxol (TAX) and DOX double resistant human colorectal cancer cell line HCT-8 (HCT-8/TAX cells). Well-dispersed nanoparticles (HMSNs-PDA-PEG) were prepared with a dimension of around 170 nm. The surface morphology and chemical properties of HMSNs-PDA-PEG were also successfully characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) method, Fourier transform infrared spectroscopy (FT-IR) and dynamic light scattering (DLS). Drug release experiments results indicated that DOX and QUR (QD) loaded nanoparticles (HMSNs-PDA-PEG@QD) had similar release kinetic profiles of each drug, which all exhibited highly sensitive to pH value due to the surface PDA coating. Additionally, the HCT-8 cells or HCT-8/TAX cells were employed to assess the cellular uptake and cytotoxicity of various drug-free or drug-loaded HMSNs samples. Meanwhile, a series of biological evaluations demonstrated that the HMSNs-PDA-PEG@QD exhibited remarkable ability to overcome MDR compared with free DOX and HMSNs-PDA-PEG@DOX. Taken together, these results revealed that HMSNs-PDA-PEG@QD was suitable as a prospective and efficient drug delivery nanosystem for overcoming multidrug resistance.	[Shao, Mei; Chen, Kai; Zhou, Yimin; Huang, Zhijun; Xu, Haixing; Xu, Peihu; Lu, Bo] Wuhan Univ Technol, Sch Chem Chem Engn & Life Sci, Wuhan 430070, Hubei, Peoples R China; [Chang, Cong; Liu, Zuhao; Zheng, Guohua] Hubei Univ Chinese Med, Coll Pharm, Wuhan, Hubei, Peoples R China		Lu, B (corresponding author), Wuhan Univ Technol, Sch Chem Chem Engn & Life Sci, Wuhan 430070, Hubei, Peoples R China.	lvb@whut.edu.cn			National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [51773162, 21204071]; Open Fund Project of Hubei TCM Standardization Engineering and Technology Center [ZDSYS201802]	This work was financially supported by the National Natural Science Foundation of China (51773162, 21204071) and the Open Fund Project of Hubei TCM Standardization Engineering and Technology Center (ZDSYS201802).	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B-Biointerfaces	NOV 1	2019	183								110427	10.1016/j.colsurfb.2019.110427			8	Biophysics; Chemistry, Physical; Materials Science, Biomaterials	Science Citation Index Expanded (SCI-EXPANDED)	Biophysics; Chemistry; Materials Science	JJ3GD	WOS:000494048600032	31408782				2022-04-25	
J	Elgenaidi, IS; Spiers, JP				Elgenaidi, Ismail Suliman; Spiers, James Paul			Hypoxia modulates protein phosphatase 2A through HIF-1 alpha dependent and independent mechanisms in human aortic smooth muscle cells and ventricular cardiomyocytes	BRITISH JOURNAL OF PHARMACOLOGY			English	Article							SERINE/THREONINE PHOSPHATASES; REGULATORY SUBUNITS; COLORECTAL-CANCER; CATALYTIC SUBUNIT; CONCISE GUIDE; PP2A; EXPRESSION; INHIBITION; PHOSPHORYLATION; AUTOPHAGY	Background and Purpose Although protein phosphatases regulate multiple cellular functions, their modulation under hypoxia remains unclear. We investigated expression of the protein phosphatase system under normoxic/hypoxic conditions and the mechanism by which hypoxia alters protein phosphatase 2A (PP2A) activity. Experimental Approach Human cardiovascular cells were cultured in cell type specific media under normoxic or hypoxic conditions (1% O-2). Effects on mRNA expression, phosphatase activity, post-translational modification, and involvement of hypoxia inducible factor 1 alpha (HIF-1 alpha) were assessed using RT-PCR, immunoblotting, an activity assay, and siRNA silencing. Key Results All components of the protein phosphatase system studied were expressed in each cell line. Hypoxia attenuated mRNA expression of the transcripts in a cell line- and time-dependent manner. In human aortic smooth muscle cells (HASMC) and AC16 cells, hypoxia decreased PP2Ac activity and mRNA expression without altering PP2Ac abundance. Hypoxia increased demethylated PP2Ac (DPP2Ac) and phosphatase methylesterase 1 (PME-1) abundance but decreased leucine carboxyl methyltransferase 1 (LCMT-1) abundance. HIF-1 alpha siRNA prevented the hypoxia-mediated decrease in phosphatase activity and expression of the catalytic subunit of protein phosphatase 2A (PPP2CA), independently of altering pPP2Ac, DPP2Ac, LCMT-1, or PME-1 abundance. Conclusion and Implications Cardiovascular cells express multiple components of the PP2A system. In HASMC and AC16 cells, hypoxia inhibits PP2A activity through HIF-1 alpha-dependent and -independent mechanisms, with the latter being consistent with altered PP2A holoenzyme assembly. This indicates a complex inhibitory effect of hypoxia on the PP2A system, and highlights PP2A as a therapeutic target for diseases associated with dysregulated protein phosphorylation.	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J. Pharmacol.	JUN	2019	176	11					1745	1763		10.1111/bph.14648			19	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	HY1FZ	WOS:000467862800010	30825189	Green Published, Bronze			2022-04-25	
J	Singh, D; Khan, MA; Siddique, HR				Singh, Deepti; Khan, Mohammad A.; Siddique, Hifzur R.			Apigenin, A Plant Flavone Playing Noble Roles in Cancer Prevention Via Modulation of Key Cell Signaling Networks	RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY			English	Review						Apigenin; bioavailability; cancer; cell signaling; chemoresistance; patents; prevention; therapy	HUMAN PROSTATE-CANCER; CYCLE ARREST; COLORECTAL-CANCER; INDUCED APOPTOSIS; IN-VITRO; INHIBITS PROLIFERATION; ANTITUMOR-ACTIVITY; MOLECULAR TARGETS; AUTOPHAGY; MIGRATION	Background: Cancer is a global health problem and the continuous rise in incidence and mortality due to cancer carries a real economic burden to all countries. Accumulation of genetic mutation, exposure of environmental carcinogens and food habits due to change in lifestyles arc the key reasons for cancer. Targeting cancer cells, we need a multitargeting molecule with low/no toxicity. Objective: To review the current update of the research status of chemopreventive/therapeutic molecule, Apigenin. Methods: Compare the results of the published articles and granted patents on this compound. We also discuss the pros and cons of the present research and future direction. Results: Cancer cells have characteristic alterations and dysregulation of various cell signaling pathways that control cell homeostasis, proliferation, motility, and survival in normal cells. Natural tlavonoids are the compounds well known for their anti-inflammatory, anti-oxidant, and anti-cancerous properties. Apigenin, along with several other physiological effects, has a very low intrinsic toxicity and striking effects on the proliferation of cancer cells. Interestingly, this multitargeting molecule is getting wide acceptance among researchers. It is evident from the recent patents filed in this compound. At present, three patents have been granted only on the anticancer properties of apigenin. Conclusion: This mini-review will explain the present research status of apigenin and will further shine some light on how apigenin performs its anti-cancerous actions by interfering with the key cell-signaling pathways.	[Singh, Deepti; Khan, Mohammad A.; Siddique, Hifzur R.] Aligarh Muslim Univ, Sect Genet, Mol Canc Genet & Translat Res Lab, Dept Zool, Aligarh 202002, Uttar Pradesh, India		Siddique, HR (corresponding author), Aligarh Muslim Univ, Sect Genet, Mol Canc Genet & Translat Res Lab, Dept Zool, Aligarh 202002, Uttar Pradesh, India.	hifzur.zo@amu.ac.in	Khan, Anish/X-6117-2019; Khan, Anish/H-6033-2012; Siddique, Hifzur R/H-4049-2019	Khan, Anish/0000-0002-3806-5956; Khan, Anish/0000-0002-3806-5956; Siddique, Hifzur R/0000-0001-8736-0487; KHAN, MOHAMMAD AFSAR/0000-0002-6326-1000; SINGH, DEEPTI/0000-0002-4271-2351	University Grant Commissions, India [F.30377/2017]; DST-SERB, India [EMR/2017/001758]	University Grant Commissions, India: Grant no. F.30377/2017(BSR) DST-SERB, India: Grant no. EMR/2017/001758.	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Drug Discov.		2019	14	4					298	311		10.2174/1574892814666191026095728			14	Oncology; Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Oncology; Pharmacology & Pharmacy	KA1YR	WOS:000505595500002	31746310				2022-04-25	
J	Wu, YD; Liu, F; Luo, SY; Yin, XH; He, DQ; Liu, JG; Yue, ZH; Song, JK				Wu, Yadong; Liu, Feng; Luo, Siyang; Yin, Xinhai; He, Dengqi; Liu, Jianguo; Yue, Zhaohui; Song, Jukun			Co-expression of key gene modules and pathways of human breast cancer cell lines	BIOSCIENCE REPORTS			English	Article							REDUCTASE 3 CBR3; PROGNOSTIC MARKERS; EXPRESSION; REGULATOR; SDR21C2	Breast cancer (BC) is the most common leading cause of cancer-related death in women worldwide. Gene expression profiling analysis for human BCs has been studied previously. However, co-expression analysis for BC cell lines is still devoid to date. The aim of the study was to identify key pathways and hub genes that may serve as a biomarker for BC and uncover potential molecular mechanism using weighted correlation network analysis. We analyzed microarray data of BC cell lines (GSE 48213) listed in the Gene Expression Omnibus database. Gene co-expression networks were used to construct and explore the biological function in hub modules using the weighted correlation network analysis algorithm method. Meanwhile, Gene ontology and KEGG pathway analysis were performed using Cytoscape plug-in ClueGo. The network of the key module was also constructed using Cytoscape. A total of 5000 genes were selected, 28 modules of co-expressed genes were identified from the gene co-expression network, one of which was found to be significantly associated with a subtype of BC lines. Functional enrichment analysis revealed that the brown module was mainly involved in the pathway of the autophagy, spliceosome, and mitophagy, the black module was mainly enriched in the pathway of colorectal cancer and pancreatic cancer, and genes in midnightblue module played critical roles in ribosome and regulation of lipolysis in adipocytes pathway. Three hub genes CBR3, SF3B6, and RHPN1 may play an important role in the development and malignancy of the disease. The findings of the present study could improve our understanding of the molecular pathogenesis of breast cancer.	[Wu, Yadong; Luo, Siyang; Yin, Xinhai; Yue, Zhaohui; Song, Jukun] Guizhou Prov Peoples Hosp, Dept Oral & Maxillofacial Surg, Guiyang, Guizhou, Peoples R China; [Liu, Feng] Guizhou Prov Peoples Hosp, Dept Ultrason, Guiyang, Guizhou, Peoples R China; [He, Dengqi] Lanzphou Univ, Hosp 1, Dept Stomatol, Lanzhou, Gansu, Peoples R China; [Liu, Jianguo] Zunyi Med Univ, Stomatol Hosp, Special Key Lab Oral Dis Res, Zunyi, Guizhou, Peoples R China		Yue, ZH; Song, JK (corresponding author), Guizhou Prov Peoples Hosp, Dept Oral & Maxillofacial Surg, Guiyang, Guizhou, Peoples R China.	458085768@qq.com; songjukun@163.com		jukun, song/0000-0003-2542-9340	Guizhou Science and Technology Cooperation Project [Qiankehe LH character [2017] 1110]	The work was supported by the Guizhou Science and Technology Cooperation Project (Qiankehe LH character [2017] 1110).	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Rep.	JUL 19	2019	39		7						BSR20181925	10.1042/BSR20181925			18	Biochemistry & Molecular Biology; Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Cell Biology	IK3FK	WOS:000476474700001	31285391	Green Published, gold, Green Submitted			2022-04-25	
J	Zimmermann, L; Moldzio, R; Vazdar, K; Krewenka, C; Pohl, EE				Zimmermann, Lars; Moldzio, Rudolf; Vazdar, Katarina; Krewenka, Christopher; Pohl, Elena E.			Nutrient deprivation in neuroblastoma cells alters 4-hydroxynonenal-induced stress response	ONCOTARGET			English	Article						cancer cell metabolism; mitochondrial membrane potential; starvation; oxononenal; beta-oxidation	LIPID-PEROXIDATION PRODUCT; SMOOTH-MUSCLE-CELLS; OXIDATIVE STRESS; CANCER-CELLS; MITOCHONDRIAL DYSFUNCTION; COLORECTAL-CANCER; APOPTOSIS; METABOLISM; GLUTAMINE; AUTOPHAGY	4-hydroxy-2-nonenal (HNE), a toxic lipid peroxidation product, is associated with oxidative damage in cells and involved in various diseases including the initiation and progression of cancer. Cancer cells have a high, adaptable metabolism with a shift from oxidative phosphorylation to glycolysis and rely on high levels of glucose and glutamine as essential nutrients for cell growth. Here we investigated whether the toxic effects of HNE on the mitochondrial membrane potential (MMP) of cancer cells depends on their metabolic state by deprivation of glucose and/or glutamine. The addition of 16 mu M HNE to N18TG2 neuroblastoma cells incubated in glucose medium led to a severe reduction of MMP, which was similar to the MMP of cells fed with both glucose and glutamine. In contrast, HNE addition to cells starved in glutamine medium increased their MMP slightly for a prolonged time period and this was accompanied by increased cellular survival. We found that beta-oxidation of HNE did not cause the increased MMP, since the aldehyde dehydrogenase was distinctly more active in cells with glucose medium. However, after blocking fatty acid beta-oxidation in cells starved in glutamine medium with etomoxir, which inhibits carnitine palmitoyltransferase 1, HNE addition induced a strong reduction of MMP similar to cells in glucose medium. Surprisingly, the effect of more toxic 4-oxo-2-nonenal was less pronounced. Our results suggest that in contrast to cells fed with glucose, glutamine-fed cancer cells are capable of beta-oxidizing fatty acids to maintain their MMP to combat the toxic effects of HNE.	[Zimmermann, Lars; Pohl, Elena E.] Univ Vet Med, Dept Biomed Sci, Inst Physiol Pathophysiol & Biophys, Vienna, Austria; [Moldzio, Rudolf; Krewenka, Christopher] Univ Vet Med, Inst Med Biochem, Dept Biomed Sci, Vienna, Austria; [Vazdar, Katarina] Rudjer Boskovic Inst, Div Organ Chem & Biochem, Zagreb, Croatia		Zimmermann, L; Pohl, EE (corresponding author), Univ Vet Med, Dept Biomed Sci, Inst Physiol Pathophysiol & Biophys, Vienna, Austria.	lars.zimmermann@vetmeduni.ac.at; elena.pohl@vetmeduni.ac.at	Pohl, Elena E./A-4025-2009	Pohl, Elena E./0000-0002-0604-5950	Austrian Research Fund (FWF)Austrian Science Fund (FWF) [P25123]; Croatian Science Foundation [UIP-2014-09-6090]; Austrian Science Fund (FWF)Austrian Science Fund (FWF) [P 25123] Funding Source: researchfish	This work was supported by the Austrian Research Fund (FWF, P25123 to E.P.) and Croatian Science Foundation (UIP-2014-09-6090 to KV).	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J	Gong, XL; Sun, RB; Gao, ZW; Han, WL; Liu, YW; Zhao, L; Jing, LL; Yao, XQ; Sun, XG				Gong, Xianling; Sun, Ruibo; Gao, Zhuowei; Han, Weili; Liu, Yawei; Zhao, Liang; Jing, Linlin; Yao, Xueqing; Sun, Xuegang			Tubeimoside 1 Acts as a Chemotherapeutic Synergist via Stimulating Macropinocytosis	FRONTIERS IN PHARMACOLOGY			English	Article						tubeimoside 1; chemotherapeutic synergist; macropinocytosis; methuosis; endocytosis	NONAPOPTOTIC-CELL-DEATH; CANCER-CELLS; PROGRAMMED NECROSIS; AUTOPHAGY; MIGRATION; COMPLEX; HYPERSTIMULATION; PHOSPHORYLATION; INFLAMMATION; INHIBITION	Macropinocytosis is a highly conserved endocytic process which characterizes the engulfment of extracellular fluid and its contents into cells via large, heterogeneous vacuoles known as macropinosomes. Tubeimoside-1 (TBM1) is a low toxic triterpenoid saponin extracted from a traditional Chinese herb Bolbostemma paniculatum (Maxim.). TBM1 stimulates a quick accumulation of numerous phase-lucent cytoplasmic vacuoles in multiple colorectal cancer (CRC) cell lines. These vacuoles can be termed as macropinosomes that efficiently engulf lucifer yellow. These vesicles are not overlaps with endocytic organelle tracers, such as ERTracker, LysoTracker and mitoTracker. These vacuoles induced by TBM1 partially incorporate into lysosomes. Transmission electron microscope indicates membrane ruffling to form lamellipodia. Protrusions collapse onto and then fuse back with the plasma membrane to generate these large endocytic vacuoles. Notably, TBM1 efficiently trafficks dextrans into heterotopic xenografts in vivo, thus provide consolidated evidence that the vacuolization can be mainly defined as macropinocytosis. TBM1 downregulates cell viability and increases PI-positive, but not highlighted Hoechst 33342-positive cells. TBM1 induced cell death can be ascribed as methuosis by hyperstimulation of macropinocytosis which can be compromised by amiloride derivative 5-(Nethyl-N-isopropyl). Light chain 3 II is recruited to these vesicles to stimulate macropinocytosis. The cell death and vacuoles can be significantly neutralized by chloroquine, but can not be the inhibited by 3-methyladenine. TBM1 can coordinate with 5-FU to exert toxicity reducing and efficacy enhancing effects in vivo by increasing the uptake of the latter without hepatic injury. In conclusion, TBM1 effectively induces in vitro and in vivo macropinocytosis which can traffick small molecules into CRC cells. It is an attractive drug transporter and can be harnessed as a chemotherapeutic synergist with translational potential.	[Gong, Xianling; Sun, Ruibo; Gao, Zhuowei; Yao, Xueqing; Sun, Xuegang] Southern Med Univ, Sch Tradit Chinese Med, State Adm Tradit Chinese Med, Key Lab Mol Biol, Guangzhou, Guangdong, Peoples R China; [Gong, Xianling] Guangdong Med Univ, Sch Pharm, Dongguan, Peoples R China; [Gao, Zhuowei] Southern Med Univ, Shunde Hosp, Foshan, Peoples R China; [Han, Weili] Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China; [Liu, Yawei] Southern Med Univ, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China; [Zhao, Liang] Southern Med Univ, Sch Basic Med Sci, Guangzhou, Guangdong, Peoples R China; [Jing, Linlin] Southern Med Univ, Tradit Chinese Med Integrated Hosp, Guangzhou, Guangdong, Peoples R China		Sun, XG (corresponding author), Southern Med Univ, Sch Tradit Chinese Med, State Adm Tradit Chinese Med, Key Lab Mol Biol, Guangzhou, Guangdong, Peoples R China.	sxg_smu@126.com	Zhao, Liang/T-9147-2019		National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81573848, 81774172]; Guangdong Natural Science FoundationNational Natural Science Foundation of Guangdong Province [2014A030313323, 2017A030313903]; Combined Science Technology Project of Guangdong Provincial Department of Science and Technology [2014A020221011]; Guangdong Provincial Academy of Traditional Chinese Medicine [2014A020221011]; Planned Science Technology Project of Guangzhou [201607010146]; Guangdong Province Bureau of Traditional Chinese Medicine Scientific Research Project [20151024, 20161161]	This work was supported by the National Science Foundation of China (81573848 and 81774172), Guangdong Natural Science Foundation (2014A030313323 and 2017A030313903), Combined Science Technology Project of Guangdong Provincial Department of Science and Technology and Guangdong Provincial Academy of Traditional Chinese Medicine (2014A020221011), Planned Science Technology Project of Guangzhou (201607010146), and Guangdong Province Bureau of Traditional Chinese Medicine Scientific Research Project (Nos. 20151024 and 20161161).	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Pharmacol.	SEP 26	2018	9								1044	10.3389/fphar.2018.01044			10	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	GU9EB	WOS:000445646400001	30319403	gold, Green Published			2022-04-25	
J	Zhu, XH; Li, SQ; Huang, C; Huang, GC; Xu, J				Zhu, Xiaohua; Li, Shuiqi; Huang, Chen; Huang, Gongcheng; Xu, Jing			LncRNA CRNDE inhibits cardiomyocytes apoptosis by YAP1 in myocardial ischaemia/reperfusion injury	AUTOIMMUNITY			English	Article						Myocardial ischaemia; reperfusion injury; lncRNA CRNDE; YAP1; cardiomyocytes apoptosis	NONCODING RNA CRNDE; HIPPO PATHWAY; PROLIFERATION; PROTECTS; EXPRESSION; AUTOPHAGY; CANCER; CELLS; HEART	Background Cardiomyocytes apoptosis is the basic pathological process of myocardial ischaemia/reperfusion (MI/R) injury, so inhibiting apoptosis of cardiomyocytes can effectively improve MI/R injury. Long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) can inhibit cell apoptosis, but its specific role in MI/R injury has not been studied. The aim of this study is to explore the specific effect of lncRNA CRNDE on cardiomyocytes apoptosis. Methods MI/R model in vivo and hypoxia/re-oxygenation (H/R) model in vitro were constructed. Apoptotic levels were assessed by TUNEL staining assay. QRT-PCR was used to validate lncRNA CRNDE level in myocardial tissues and HL-1 cells. The protein expressions of YAP1, Bcl-2 and cleaved caspase-3 were detected by western blot analysis. Flow cytometry was used to determine the apoptosis rate of cardiomyocytes. RIP assay was used to detect the interaction between lncRNA CRNDE and YAP1. Results The extent of cardiomyocytes apoptosis was significantly increased, and the levels of lncRNA CRNDE, YAP1 and Bcl-2 were down-regulated, while cleaved caspase-3 expression was up-regulated in MI/R mice and H/R-treated HL-1 cells. The expressions of YAP1 and Bcl-2 were decreased, while the expression of cleaved caspase-3 was increased after the knockdown of lncRNA CRNDE. Furthermore, lncRNA CRNDE could bind to YAP1 and regulated the protein level of YAP1 by ubiquitination and proteasomal degradation pathway. After transfection of Si-YAP1 in the H/R-treated HL-1 cells transfected with pc-DNA CRNDE, the protein level of Bcl-2 was decreased, while cleaved caspase-3 expression and the apoptosis rate were increased. Conclusion Our study suggested that lncRNA CRNDE could regulate YAP1 level by ubiquitination and proteasomal degradation pathway, thus inhibiting cardiomyocytes apoptosis in MI/R injury.	[Zhu, Xiaohua; Huang, Chen; Huang, Gongcheng; Xu, Jing] Zhengzhou Univ, Dept Cardiovasc Surg, Affiliated Hosp 1, 1 East Jianshe Rd, Zhengzhou 450052, Peoples R China; [Li, Shuiqi] Zhengzhou Univ, Dept Dermatol, Affiliated Hosp 1, Zhengzhou, Peoples R China		Xu, J (corresponding author), Zhengzhou Univ, Dept Cardiovasc Surg, Affiliated Hosp 1, 1 East Jianshe Rd, Zhengzhou 450052, Peoples R China.	xujing00111@sina.com					Ding J, 2017, CELL DEATH DIS, V8, DOI 10.1038/cddis.2017.328; Ebadollahi SH, 2021, CELL J, V22, P532, DOI 10.22074/cellj.2021.6902; Ellis BC, 2014, BBA-MOL CELL RES, V1843, P372, DOI 10.1016/j.bbamcr.2013.10.016; Ellis Blake C., 2012, Frontiers in Genetics, V3, P270, DOI 10.3389/fgene.2012.00270; Fan YF, 2019, MED SCI MONITOR, V25, P2745, DOI 10.12659/MSM.913420; Fu V, 2017, CURR OPIN CELL BIOL, V49, P99, DOI 10.1016/j.ceb.2017.12.012; Fujita T, 2009, BMC CANCER, V9, DOI 10.1186/1471-2407-9-87; Gao D, 2017, J CELL BIOCHEM, V118, P3341, DOI 10.1002/jcb.25987; Graham Lloyd D, 2011, Genes Cancer, V2, P829, DOI 10.1177/1947601911431081; Hausenloy DJ, 2017, EUR HEART J, V38, P935, DOI 10.1093/eurheartj/ehw145; Heallen T, 2011, SCIENCE, V332, P458, DOI 10.1126/science.1199010; Huang JM, 2013, ONCOGENE, V32, P2220, DOI 10.1038/onc.2012.231; Jiang BM, 2013, CARDIOVASC RES, V99, P92, DOI 10.1093/cvr/cvt085; Jing XZ, 2018, INT J MOL MED, V42, P1526, DOI 10.3892/ijmm.2018.3734; Kaminskyy VO, 2014, ANTIOXID REDOX SIGN, V21, P86, DOI 10.1089/ars.2013.5746; Khan K, 2019, EXP BIOL MED, V244, P802, DOI 10.1177/1535370219851243; Liu PD, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0168767; Meng YB, 2017, ONCOL RES, V25, P1207, DOI 10.3727/096504017X14886679715637; Miskinyte S, 2011, AM J HUM GENET, V88, P718, DOI 10.1016/j.ajhg.2011.04.017; Peng G., 2018, CELL PROLIFERAT, V51; Quan CJ, 2018, J CELL COMMUN SIGNAL, V12, P549, DOI 10.1007/s12079-017-0406-6; Roman Madeline G, 2020, Aging Pathobiol Ther, V2, P20, DOI 10.31491/apt.2020.03.009; Ruan XF, 2017, EXP THER MED, V14, P3523, DOI 10.3892/etm.2017.4964; Setsuie R, 2007, NEUROCHEM INT, V51, P105, DOI 10.1016/j.neuint.2007.05.007; Song HX, 2017, BBA-MOL BASIS DIS, V1863, P1893, DOI 10.1016/j.bbadis.2016.11.015; Wang J, 2017, J DENT RES, V96, P1229, DOI 10.1177/0022034517719886; Wang JS, 2006, CELL MOL IMMUNOL, V3, P255; Wang J, 2018, NAT REV CARDIOL, V15, P672, DOI 10.1038/s41569-018-0063-3; Xiao Yang, 2016, Curr Treat Options Cardiovasc Med, V18, P38, DOI 10.1007/s11936-016-0461-y; Xue JY, 2019, BASIC RES CARDIOL, V114, DOI 10.1007/s00395-019-0748-8; Yang F, 2019, EXP CELL RES, V382, DOI 10.1016/j.yexcr.2019.06.029; Yang J, 2021, J CELL PHYSIOL, V236, P157, DOI 10.1002/jcp.29831; Yingchun H., 2016, W CHINA MED J, V31, P06; Zhai ME, 2017, J PINEAL RES, V63, DOI 10.1111/jpi.12419; Zheng JY, 2019, LIFE SCI, V219, P129, DOI 10.1016/j.lfs.2019.01.014; Zhu Y, 2020, LIFE SCI, V255, DOI 10.1016/j.lfs.2020.117849	36	0	0	2	4	TAYLOR & FRANCIS LTD	ABINGDON	2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND	0891-6934	1607-842X		AUTOIMMUNITY	Autoimmunity	MAY 19	2021	54	4					204	212		10.1080/08916934.2021.1913580		MAY 2021	9	Immunology	Science Citation Index Expanded (SCI-EXPANDED)	Immunology	SO3QK	WOS:000650632500001	33988471				2022-04-25	
J	Slaihim, MM; Al-Suede, FSR; Khairuddean, M; Ahamed, MBK; Majid, AMSA				Slaihim, Mukhlif Mohsin; Al-Suede, Fouad Saleih R.; Khairuddean, Melati; Ahamed, Mohamed B. Khadeer; Majid, Amin Malik Shah Abdul			Synthesis, characterisation of new derivatives with mono ring system of 1,2,4-triazole scaffold and their anticancer activities	JOURNAL OF MOLECULAR STRUCTURE			English	Article						Pyridinium salt; Piperidinium salt; Anticancer activity; MTT assay; Anti-proliferation; 1,2,4-Triazole		In the present study, two important starting materials and 18 new 1,2,4-triazole compounds with mono ring system have been synthesized and characterized. The mono system showed 16 compounds of a Schiff base moiety attached to the triazole ring which was prepared from the corresponding starting material 5(A-B) or piperidinium salt system 6(A-B). All these compounds were characterized using Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy and carbon hydrogen nitrogen (CHN) elemental analysis. The compounds were selected for in vitro anticancer study to test the therapeutic cytotoxic potential against cancer cells. The MIT test was conducted against human breast (MCF-7) and colorectal (HCT-116) cancer cells. Among all the compounds tested, 7A-i demonstrated more pronounced in vitro anticancer effect against MCF-7 and HCT-116 cells with IC50 of 38 and 19.2 mu M, respectively, comparable to that of the standard reference drugs, tamoxifen and 5-fluorouracil, respectively. Compound 7A-vi showed a considerable cytotoxic effect with IC50 53 and 41.2 mu M against MCF-7 and HCT-116 cells, respectively. Compounds 7A-ii, 7A-iii and 7A-v exhibited moderate cytotoxicity with IC50 68, 91 and 85 mu M, respectively against MCF-7 cells and also 59.3, 81.7 and 137.1 mu M against HCT-116 cells, respectively. However, all other compounds tested in this study showed poor cytotoxicity against both the cell lines. Cellular morphological analysis revealed that the cytotoxicity induced by the compounds could probably due to autophagy. It can be concluded that 1,2,4-triazole derivatives can be promising therapeutic agents. Further studies will be done to investigate the antitumor efficacy of the 1,2,4-triazole derivatives using suitable preclinical models. (C) 2019 Elsevier B.V. All rights reserved.	[Slaihim, Mukhlif Mohsin] Samarra Univ, Appl Sci Fac, Samarra, Iraq; [Al-Suede, Fouad Saleih R.; Ahamed, Mohamed B. Khadeer] EMAN Biodiscoveries Sdn Bhd, A1-4,Lot 5,Persiaran 2-1,Kedah Halal Pk, Sungai Petani 08000, Kedah, Malaysia; [Khairuddean, Melati] Univ Sains Malaysia, Sch Chem Sci, George Town 11800, Malaysia; [Majid, Amin Malik Shah Abdul] Univ Sains Malaysia, Sch Pharmaceut Sci, George Town 11800, Malaysia; [Majid, Amin Malik Shah Abdul] Australian Natl Univ, John Curtin Sch Med Res, ACRF Dept Canc Biol & Therapeut, Acton, Australia; [Majid, Amin Malik Shah Abdul] Eman Res Ltd, Acton, Australia		Khairuddean, M (corresponding author), Univ Sains Malaysia, Sch Chem Sci, George Town 11800, Malaysia.	melati@usm.my	Alsuede, Fouad Saleih Resq/AAE-6203-2021; Basheer, Mohamed Khadeer Ahamed/P-1681-2014; Khairuddean, Melati/B-2622-2018	Basheer, Mohamed Khadeer Ahamed/0000-0001-9616-1770; M. Slaihim, Mukhlif/0000-0002-6801-4148; Khairuddean, Melati/0000-0001-7280-302X; Al-Suede, fouad/0000-0003-1816-6722	 [1001/PKIMIA/811332]	The authors would like to thank the Universiti Sains Malaysia in providing the lab facilities and the finical support under a research grant (1001/PKIMIA/811332).	Abdel-Rahman R. 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H., 2016, EPIDEMIOLOGY HLTH, V38; Rajesh K.S., 2012, J CANC RES UPDATES, V1, P129; Riss T., 2003, CELL NOTES, P6, DOI [10.1200/JCO.2011.36.1360, DOI 10.1200/JCO.2011.36.1360]; Siddiqui N, 2011, J PHARM BIOALLIED SC, V3, P194, DOI 10.4103/0975-7406.80765; Skrzydlewska E, 2005, WORLD J GASTROENTERO, V11, P403, DOI 10.3748/wjg.v11.i3.403; Sliwka L, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0155772; Song MX, 2018, J ENZYM INHIB MED CH, V33, P453, DOI 10.1080/14756366.2017.1423068; Swamy D. K., 2010, J CHEM CHEM PHARM RE, V2, P411; Sztanke K, 2008, EUR J MED CHEM, V43, P404, DOI 10.1016/j.ejmech.2007.03.033; Unver Y, 2016, J ENZYM INHIB MED CH, V31, P89, DOI 10.1080/14756366.2016.1206088	35	11	11	2	11	ELSEVIER	AMSTERDAM	RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS	0022-2860	1872-8014		J MOL STRUCT	J. Mol. Struct.	NOV 15	2019	1196						78	87		10.1016/j.molstruc.2019.06.066			10	Chemistry, Physical	Science Citation Index Expanded (SCI-EXPANDED)	Chemistry	JA6DB	WOS:000487930600008					2022-04-25	
J	Si, LL; Fu, JN; Liu, WW; Hayashi, T; Nie, YH; Mizuno, K; Hattori, S; Fujisaki, H; Onodera, S; Ikejima, T				Si, Lingling; Fu, Jianing; Liu, Weiwei; Hayashi, Toshihiko; Nie, Yuheng; Mizuno, Kazunori; Hattori, Shunji; Fujisaki, Hitomi; Onodera, Satoshi; Ikejima, Takashi			Silibinin inhibits migration and invasion of breast cancer MDA-MB-231 cells through induction of mitochondrial fusion	MOLECULAR AND CELLULAR BIOCHEMISTRY			English	Article						Silibinin; Mitochondrial fusion; ROS; Migration and invasion; Inflammation; MDA-MB-231 cells	EPITHELIAL-MESENCHYMAL TRANSITION; NF-KAPPA-B; COLORECTAL-CANCER; ROS; APOPTOSIS; FISSION; LPS; DNA; MICROENVIRONMENT; PROLIFERATION	Human triple negative breast cancer cells, MDA-MB-231, show typical epithelial to mesenchymal transition associated with cancer progression. Mitochondria play a major role in cancer progression, including metastasis. Changes in mitochondrial architecture affect cellular migration, autophagy and apoptosis. Silibinin is reported to have anti-breast cancer effect. We here report that silibinin at lower concentrations (30-90 mu M) inhibits epithelial to mesenchymal transition (EMT) of MDA-MB-231, by increasing the expression of epithelial marker, E-cadherin, and decreasing the expression of mesenchymal markers, N-cadherin and vimentin. Besides, silibinin inhibition of cell migration is associated with reduction in the protein expression of matrix metalloproteinases 2 and 9 (MMP2 and MMP9) and paxillin. In addition, silibinin treatment increases mitochondrial fusion through down-regulating the expression of mitochondrial fission-associated protein dynamin-related protein 1 (DRP1) and up-regulating the expression of mitochondrial fusion-associated proteins, optic atrophy 1, mitofusin 1 and mitofusin 2. Silibinin perturbed mitochondrial biogenesis via down-regulating the levels of mitochondrial biogenesis regulators including mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor gamma coactivator (PGC1) and nuclear respiratory factor (NRF2). Moreover, DRP1 knockdown or silibinin inhibited cell migration, and MFN1&2 knockdown restored it. Mitochondrial fusion contributes to silibinin's negative effect on cell migration. Silibinin decreased reactive oxygen species (ROS) generation, leading to inhibition of the NLRP3 inflammasome activation. In addition, knockdown of mitofusin 1&2 (MFN 1&2) relieved silibinin-induced inhibition of NLRP3 inflammasome activation. Repression of ROS contributes to the inhibition of the expression of NLRP3, caspase-1 and IL-beta proteins as well as of cell migration. Taken together, our study provides evidence that silibinin impairs mitochondrial dynamics and biogenesis, resulting in reduced migration and invasion of the MDA-MB-231 breast cancer cells.	[Si, Lingling; Fu, Jianing; Liu, Weiwei; Hayashi, Toshihiko; Nie, Yuheng; Ikejima, Takashi] Shenyang Pharmaceut Univ, Wuya Coll Innovat, Shenyang 110016, Liaoning, Peoples R China; [Hayashi, Toshihiko] Kogakuin Univ, Sch Adv Engn, Dept Chem & Life Sci, 2665-1 Nakanomachi, Hachioji, Tokyo 1920015, Japan; [Mizuno, Kazunori; Hattori, Shunji; Fujisaki, Hitomi] Nippi Res Inst Biomatrix, Toride, Ibaraki 3020017, Japan; [Onodera, Satoshi] Med Res Inst Curing Mibyo, 1-6-28 Narusedai, Machida, Tokyo 1940042, Japan; [Ikejima, Takashi] Shenyang Pharmaceut Univ, Key Lab Computat Chem Based Nat Antitumor Drug Re, Shenyang 110016, Liaoning, Peoples R China		Ikejima, T (corresponding author), Shenyang Pharmaceut Univ, Wuya Coll Innovat, Shenyang 110016, Liaoning, Peoples R China.; Ikejima, T (corresponding author), Shenyang Pharmaceut Univ, Key Lab Computat Chem Based Nat Antitumor Drug Re, Shenyang 110016, Liaoning, Peoples R China.	ikejimat@vip.sina.com	Mizuno, Kazunori/AAY-7613-2021	Mizuno, Kazunori/0000-0003-3354-6264; Ikejima, Takashi/0000-0001-8202-9429	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81703528]	This research was supported by National Natural Science Foundation of China (No. 81703528).	Arumugam A, 2016, TUMOR BIOL, V37, P6527, DOI 10.1007/s13277-015-4468-x; Bahat A, 2018, NAT COMMUN, V9, DOI 10.1038/s41467-018-07519-w; Bordon Y, 2018, NAT REV IMMUNOL, V18, P539, DOI 10.1038/s41577-018-0049-8; Byun HJ, 2017, ONCOL REP, V37, P3270, DOI 10.3892/or.2017.5588; Caino MC, 2015, P NATL ACAD SCI USA, V112, P8638, DOI 10.1073/pnas.1500722112; Campello S, 2006, J EXP MED, V203, P2879, DOI 10.1084/jem.20061877; Chio IIC, 2017, TRENDS MOL MED, V23, P411, DOI 10.1016/j.molmed.2017.03.004; Cohen EN, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0132710; Dong X, 2017, NEUROSCI LETT, V636, P127, DOI 10.1016/j.neulet.2016.10.054; El Hasasna H, 2016, SCI REP-UK, V6, DOI 10.1038/srep21144; Fonseca TB, 2019, NATURE, V570, pE34, DOI 10.1038/s41586-019-1296-y; Gao Q, 2012, CANCER RES, V72, P3546, DOI 10.1158/0008-5472.CAN-11-4032; Ham J, 2018, J CELL PHYSIOL, V233, P1638, DOI 10.1002/jcp.26069; Han XJ, 2015, INT J ONCOL, V46, P691, DOI 10.3892/ijo.2014.2781; Jiang K, 2015, ONCOL REP, V33, P2711, DOI 10.3892/or.2015.3915; Jin X, 2019, CLIN TRANSL ONCOL, V21, P1207, DOI 10.1007/s12094-019-02042-w; Kalemci S, 2015, EXP THER MED, V10, P503, DOI 10.3892/etm.2015.2542; Kim KW, 2009, NEUROCHEM RES, V34, P1479, DOI 10.1007/s11064-009-9935-6; Kim TH, 2014, J PHARMACOL EXP THER, V349, P268, DOI 10.1124/jpet.113.207563; Kolgiri V, 2017, BRAZ J INFECT DIS, V21, P35, DOI 10.1016/j.bjid.2016.09.007; Lee H, 2016, BIOCHEM SOC T, V44, P1725, DOI 10.1042/BST20160129; Lee JY, 2014, J CELL SCI, V127, P4954, DOI 10.1242/jcs.157321; Li HJ, 2017, CELL PHYSIOL BIOCHEM, V44, P2073, DOI 10.1159/000485946; Li H, 2018, EXCLI J, V17, P302, DOI 10.17179/excli2017-1018; Li X, 2019, MED SCI MONITOR, V25, P711, DOI 10.12659/MSM.912218; Liu BB, 2011, FREE RADICAL RES, V45, P835, DOI 10.3109/10715762.2011.580343; Liu XX, 2017, BIOMED PHARMACOTHER, V92, P429, DOI 10.1016/j.biopha.2017.05.102; Lood C, 2016, NAT MED, V22, P146, DOI 10.1038/nm.4027; Lugus JJ, 2011, J MOL CELL CARDIOL, V51, P885, DOI 10.1016/j.yjmcc.2011.07.023; Mao WJ, 2016, LASER MED SCI, V31, P1697, DOI 10.1007/s10103-016-2040-6; Masso-Welch P, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20010085; Qiu Y, 2018, ONCOL REP, V39, P138, DOI 10.3892/or.2017.6081; Seol MA, 2017, ONCOTARGET, V8, P40190, DOI 10.18632/oncotarget.15360; Shimada K, 2012, IMMUNITY, V36, P401, DOI 10.1016/j.immuni.2012.01.009; Si LL, 2019, ARCH BIOCHEM BIOPHYS, V671, P42, DOI 10.1016/j.abb.2019.05.009; Song XY, 2016, NEUROCHEM RES, V41, P1662, DOI 10.1007/s11064-016-1881-5; Wang ZW, 2010, CURR STEM CELL RES T, V5, P74, DOI 10.2174/157488810790442813; West AP, 2017, NAT REV IMMUNOL, V17, P363, DOI 10.1038/nri.2017.21; Wu YZ, 2014, CANCER LETT, V345, P164, DOI 10.1016/j.canlet.2013.08.014; Ye K, 2018, J CELL BIOCHEM, V119, P1922, DOI 10.1002/jcb.26353; Zhang HL, 2017, CARDIOVASC RES, V113, P160, DOI 10.1093/cvr/cvw212; Zhang JS, 2019, ONCOL REP, V41, P3292, DOI 10.3892/or.2019.7131; Zhao J, 2013, ONCOGENE, V32, P4814, DOI 10.1038/onc.2012.494; Zhong ZY, 2018, NATURE, V560, P198, DOI 10.1038/s41586-018-0372-z; Zhou Q, 2015, VASC PHARMACOL, V72, P163, DOI 10.1016/j.vph.2015.05.007	45	21	21	3	14	SPRINGER	DORDRECHT	VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS	0300-8177	1573-4919		MOL CELL BIOCHEM	Mol. Cell. Biochem.	JAN	2020	463	1-2					189	201		10.1007/s11010-019-03640-6		OCT 2019	13	Cell Biology	Science Citation Index Expanded (SCI-EXPANDED)	Cell Biology	KI4DF	WOS:000489917600001	31612353				2022-04-25	
J	Wang, JQ; Zhang, YB; Liu, X; Wang, JZ; Li, B; Liu, YK; Wang, JS				Wang, Jiquan; Zhang, Yingbing; Liu, Xu; Wang, Jizhao; Li, Bin; Liu, Yongkang; Wang, Jiansheng			Alantolactone enhances gemcitabine sensitivity of lung cancer cells through the reactive oxygen species-mediated endoplasmic reticulum stress and Akt/GSK3 beta pathway	INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE			English	Article						lung cancer cells; apoptosis; cell cycle arrest; endoplasmic reticulum stress; Akt; glycogen synthase kinase 3 beta; alantolactone; gemcitabine resistance	ER STRESS; DEPENDENT APOPTOSIS; GALLBLADDER CANCER; ANTITUMOR-ACTIVITY; SIGNALING PATHWAY; BREAST-CANCER; ROS; INDUCTION; AUTOPHAGY; CURCUMIN	Lung cancer is one of the leading causes of cancer-associated mortality in China and globally. Gemcitabine (GEM), as a first-line therapeutic drug, has been used to treat lung cancer, but GEM resistance poses a major limitation on the efficacy of GEM chemotherapy. Alantolactone (ALT), a sesquiterpene lactone compound isolated from Inula helenium, has been identified to exert anticancer activity in various types of cancer, including breast, pancreatic, lung squamous and colorectal cancer. However, the underlying mechanisms of the anticancer activity of ALT in lung cancer remain to be fully elucidated. The present study aimed to determine whether ALT enhances the anticancer efficacy of GEM in lung cancer cells and investigated the underlying mechanisms. The cell viability was assessed with a Cell Counting Kit-8 assay. The cell cycle, apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression of cell cycle-associated and apoptosis-associated proteins were determined by western blot analysis. The results demonstrated that ALT inhibited cell growth and induced S-phase arrest and cell apoptosis in A549 and NCI-H520 cells. Furthermore, ALT increased the level of ROS, inhibited the Akt/glycogen synthase kinase (GSK)3 beta pathway and induced endoplasmic reticulum (ER) stress in A549 and NCI-H520 cells. Additionally, ALT treatment sensitized lung cancer cells to GEM. Analysis of the molecular mechanisms further revealed that ALT enhanced the anticancer effects of GEM via ROS-mediated activation of the Akt/GSK3 beta and ER stress pathways. In conclusion, combined treatment with ALT and GEM may have potential as a clinical strategy for lung cancer treatment.	[Wang, Jiquan; Zhang, Yingbing] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Radiat Oncol, Xian 710061, Shaanxi, Peoples R China; [Liu, Xu; Wang, Jizhao; Wang, Jiansheng] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China; [Li, Bin; Liu, Yongkang] Northwest Univ, Key Lab Resource Biol & Biotechnol Western China, Xian 710069, Shaanxi, Peoples R China		Wang, JS (corresponding author), Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Thorac Surg, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China.	wangjsh@mail.xjtu.edu.cn			Shaanxi Provincial Education Department [16JK1761]; National Key Research and Development Program [2016YFC0905001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81471710]	This study was supported by grants from the Scientific Research Program Funded by Shaanxi Provincial Education Department (program no. 16JK1761), the National Key Research and Development Program (grant. no. 2016YFC0905001) and the National Natural Science Foundation of China (grant. no. 81471710).	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J. Mol. Med.	SEP	2019	44	3					1026	1038		10.3892/ijmm.2019.4268			13	Medicine, Research & Experimental	Science Citation Index Expanded (SCI-EXPANDED)	Research & Experimental Medicine	IN5ZZ	WOS:000478757000023	31524219	Green Published, Green Submitted, hybrid			2022-04-25	
J	Alnuqaydan, AM; Rah, B				Alnuqaydan, Abdullah M.; Rah, Bilal			Comparative assessment of biological activities of different parts of halophytic plant Tamarix articulata (T. articulata) growing in Saudi Arabia	SAUDI JOURNAL OF BIOLOGICAL SCIENCES			English	Article						Tamarix articulata; Antioxidant activity; Antimicrobial activity; Antiproliferative activity; Cancer cell	ANTIMICROBIAL ACTIVITIES; MEDICINAL-PLANTS; ANTIOXIDANT; EXTRACTS; L.; WITHAFERIN; APOPTOSIS; AUTOPHAGY	Owing to extremely high salinity and harsh environmental conditions, T. articulata is one of the most abundant wild plants growing in the deserts of Saudi Arabia. Such plants may contain novel compounds to display promising biological activities. Here, in this study, we evaluate the biological activities of methanolic extracts of fresh leaves, dry leaves, stem, and roots of T. articulata. The antioxidant activity was determined by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and total phenolic and flavonoid content were determined using standard colorimetric methods. Whereas antimicrobial and ant-proliferative activities were determined by standard well-diffusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods, respectively. Our results demonstrate that all methanolic extracts of T. articulata showed antioxidant activity, however, the methanolic extract of dry leaves exhibits promising antioxidant effect with IC50 value 49.08 +/- 1.98, which was strongly supported by total phenolic (409.92 +/- 6.03 mg GAE/g DW) and flavonoid (177.71 mg QE/g DW) content. Although, antimicrobial activity was also exhibited by all the methanolic extracts, however, methanolic extract of dry leaves exhibits promising antimicrobial activity in Gram-positive bacteria Staphylococcus epidemidis. Furthermore, MTT assay revealed that all methanolic extracts exhibit antiproliferative activity in MCF-7 (breast cancer) and RKO (colorectal cancer) cells with IC50 values ranges from 219 +/- 5.112 mg/ml to 253 +/- 5.231 mg/ml and 220 +/- 4.330 mu g/ml to 325 +/- 6.213 mu g/ml, respectively. However, the most promising antiproliferative effect was displayed by methanolic extract of dry leaves with IC50 values 219 +/- 5.112 mu g/ml and 220 +/- 4.330 mu g/ml, respectively. In summary, these findings provide evidence that T. articulata has promising biological activities and can be used for many pharmaceutical activities in the future. (C) 2020 Published by Elsevier B.V. on behalf of King Saud University.	[Alnuqaydan, Abdullah M.; Rah, Bilal] Qassim Univ, Coll Appl Med Sci, Dept Med Biotechnol, GPO POB 6666, Buraydah 51452, Saudi Arabia		Alnuqaydan, AM; Rah, B (corresponding author), Qassim Univ, Coll Appl Med Sci, Dept Med Biotechnol, GPO POB 6666, Buraydah 51452, Saudi Arabia.	ami.alnuqaydan@qu.edu.sa; b.rah@qu.edu.sa					Ahmad I, 2001, J ETHNOPHARMACOL, V74, P113, DOI 10.1016/S0378-8741(00)00335-4; Alara OR, 2019, J KING SAUD UNIV SCI, V31, P495, DOI 10.1016/j.jksus.2017.05.018; Alnuqaydan AM, 2020, AM J CANCER RES, V10, P799; Alnuqaydan AM, 2019, CURR PHARM BIOTECHNO, V20, P285, DOI 10.2174/1389201020666190318120103; Bag A, 2012, MICROBIOL RES, V167, P352, DOI 10.1016/j.micres.2012.02.005; BRAND-WILLIAMS W, 1995, FOOD SCI TECHNOL-LEB, V28, P25; Chanda D, 2012, EUR J PHARM SCI, V47, P988, DOI 10.1016/j.ejps.2012.08.013; de Fatima Angelo, 2014, Recent Pat Biotechnol, V8, P76, DOI 10.2174/1872208307666131220163108; de Oliveira AC, 2009, FOOD CHEM, V115, P469, DOI 10.1016/j.foodchem.2008.12.045; Eberle L., 2018, TRENDS PHYTOCHEM RES, V2, P37; Ghasemzadeh A, 2011, J MED PLANTS RES, V5, P6697, DOI 10.5897/JMPR11.1404; Hebi Morad, 2019, Cardiovascular & Hematological Agents in Medicinal Chemistry, V16, P94, DOI 10.2174/1871525717666181211143858; Hebi M, 2017, J INTEGR MED-JIM, V15, P476, DOI 10.1016/S2095-4964(17)60361-3; Hebi M, 2017, BIOMED PHARMACOTHER, V87, P230, DOI 10.1016/j.biopha.2016.12.111; Hogberg LD, 2010, TRENDS PHARMACOL SCI, V31, P509, DOI 10.1016/j.tips.2010.08.002; Iwara I., 2014, PHARM PHARM, V2014; Jeong JH, 2010, J KOREAN SOC APPL BI, V53, P33, DOI 10.3839/jksabc.2010.006; Kasote DM, 2015, INT J BIOL SCI, V11, P982, DOI 10.7150/ijbs.12096; Ksouri R, 2009, FOOD CHEM TOXICOL, V47, P2083, DOI 10.1016/j.fct.2009.05.040; Kumar MSY, 2013, FOOD CHEM, V141, P3443, DOI 10.1016/j.foodchem.2013.06.057; Kumaran A, 2006, FOOD CHEM, V97, P109, DOI 10.1016/j.foodchem.2005.03.032; Menshawi El., 2013, INT J PHARM PHARM SC, V5, P178; Mubashir K, 2017, BMC COMPLEM ALTERN M, V17, DOI 10.1186/s12906-017-1593-7; Nascimento GGF, 2000, BRAZ J MICROBIOL, V31, P247; Patridge E, 2016, DRUG DISCOV TODAY, V21, P204, DOI 10.1016/j.drudis.2015.01.009; Patwardhan B, 2005, J ETHNOPHARMACOL, V100, P50, DOI 10.1016/j.jep.2005.06.006; Rah B, 2015, AUTOPHAGY, V11, P314, DOI 10.1080/15548627.2015.1017182; Rah B, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0044039; Rahmani AH, 2014, INT J CLIN EXP MED, V7, P483; Ramesh N, 2002, J ETHNOPHARMACOL, V79, P129, DOI 10.1016/S0378-8741(01)00352-X; Samy RP, 1999, J ETHNOPHARMACOL, V66, P235, DOI 10.1016/S0378-8741(99)00038-0; Shakeel-u-Rehman, 2015, J MED CHEM, V58, P3432, DOI 10.1021/jm501942m; Sher H, 2010, J MED PLANTS RES, V4, P1853; Tabet A., 2018, J ADV PHARM ED RES, V8; Tatsimo Simplice Joel Ndendoung, 2012, BMC Res Notes, V5, P158, DOI 10.1186/1756-0500-5-158; Wannes WA, 2010, FOOD CHEM TOXICOL, V48, P1362, DOI 10.1016/j.fct.2010.03.002; Zilla MK, 2014, CHEM-BIOL INTERACT, V224, P100, DOI 10.1016/j.cbi.2014.09.022	37	3	3	0	1	ELSEVIER	AMSTERDAM	RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS	1319-562X	2213-7106		SAUDI J BIOL SCI	Saudi J. Biol. Sci.	OCT	2020	27	10					2586	2592		10.1016/j.sjbs.2020.05.028			7	Biology	Science Citation Index Expanded (SCI-EXPANDED)	Life Sciences & Biomedicine - Other Topics	NQ4UB	WOS:000570858800013	32994715	Green Published, gold			2022-04-25	
J	Juszczak, GR; Stankiewicz, AM				Juszczak, Grzegorz R.; Stankiewicz, Adrian M.			Glucocorticoids, genes and brain function	PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY			English	Article						Gene; Brain; Glucocorticoids; Cortisol; Corticosterone; Dexamethasone	EPIDERMAL-GROWTH-FACTOR; NF-KAPPA-B; CELL-CYCLE PROGRESSION; PYRUVATE-DEHYDROGENASE KINASE; CEREBRAL GLUCOSE-UTILIZATION; CHAIN AMINOTRANSFERASE PROTEINS; COLORECTAL-CANCER PROLIFERATION; STRESS-INDUCED GLUCOCORTICOIDS; MONO-ADP-RIBOSYLTRANSFERASE; AKT/MTOR SIGNALING PATHWAY	The identification of key genes in transcriptomic data constitutes a huge challenge. Our review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain. Replicable transcriptomic data were combined with biochemical and physiological data to create an integrated view of the effects induced by GCs. The most frequently reported genes were Errfi1 and Ddit4. Their up-regulation was associated with the altered transcription of genes regulating growth factor and mTORC1 signaling (Gab1, Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1, Cdkn1a and Cables1). The GC-induced reprogramming of cell function involves changes in the mRNA level of genes responsible for the regulation of transcription (Klf9, Bcl6, Klf15, Tle3, Cxxc5, Litaf, Tle4, Jun, Sox4, Sox2, Sox9, Irf1, Sall2, Nfkbia and Id1) and the selective degradation of mRNA (Tob2). Other genes are involved in the regulation of metabolism (Gpd1, Aldoc and Pdk4), actin cytoskeleton (Myh2, Nedd9, Mical2, Rhou, Arl4d, Osbpl3, Arhgef3, Sdc4, Rdx, Wipf3, Chst1 and Hepacam), autophagy (Eva1a and Plekhf1), vesicular transport (Rhob, Ehd3, Vps37b and Scamp2), gap junctions (Gjb6), immune response (Tiparp, Mertk, Lyve1 and Il6r), signaling mediated by thyroid hormones (Thra and Sult1a1), calcium (Calm2), adrenaline/noradrenaline (Adcy9 and Adra1d), neuropeptide Y (Npy1r) and histamine (Hdc). GCs also affected genes involved in the synthesis of polyamines (Azin1) and taurine (Cdo1). The actions of GCs are restrained by feedback mechanisms depending on the transcription of Sgk1, Fkbp5 and Nr3c1. A side effect induced by GCs is increased production of reactive oxygen species. Available data show that the brain's response to GCs is part of an emergency mode characterized by inactivation of non-core activities, restrained inflammation, restriction of investments (growth), improved efficiency of energy production and the removal of unnecessary or malfunctioning cellular components to conserve energy and maintain nutrient supply during the stress response.	[Juszczak, Grzegorz R.] Inst Genet & Anim Breeding, Dept Anim Behav, Ul Postepu 36A, PL-05552 Jastrzebiec, Magdalenka, Poland; [Stankiewicz, Adrian M.] Inst Genet & Anim Breeding, Dept Mol Biol, Ul Postepu 36A, PL-05552 Jastrzebiec, Magdalenka, Poland		Juszczak, GR (corresponding author), Inst Genet & Anim Breeding, Dept Anim Behav, Ul Postepu 36A, PL-05552 Jastrzebiec, Magdalenka, Poland.	g.juszczak@ighz.pl	Stankiewicz, Adrian/AAD-1363-2021; Juszczak, Grzegorz R/A-1339-2008	Stankiewicz, Adrian/0000-0002-2719-6205; Juszczak, Grzegorz/0000-0002-0976-6905	Polish Ministry of Science and Higher EducationMinistry of Science and Higher Education, Poland [N N311 604938]; KNOW (Leading National Research Centre) Scientific Consortium "Healthy Animal - Safe Food" (decision of Ministry of Science and Higher Education) [05-1/KNOW2/2015]	The authors declare no conflicts of interest. This work was supported by the Polish Ministry of Science and Higher Education (grant number N N311 604938) and KNOW (Leading National Research Centre) Scientific Consortium "Healthy Animal - Safe Food" (decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015"). The editorial assistance of Ewa Pajak is highly appreciated. All authors have approved the final article.	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Neuro-Psychopharmacol. Biol. Psychiatry	MAR 2	2018	82						136	168		10.1016/j.pnpbp.2017.11.020			33	Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry	Science Citation Index Expanded (SCI-EXPANDED)	Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry	FV6OT	WOS:000424701600014	29180230				2022-04-25	
J	Salla, M; Aguayo-Ortiz, R; Danmaliki, GI; Zare, A; Said, A; Moore, J; Pandya, V; Manaloor, R; Fong, S; Blankstein, AR; Gibson, SB; Garcia, LR; Meier, P; Bhullar, KS; Hubbard, BP; Fiteh, Y; Vliagoftis, H; Goping, IS; Brocks, D; Hwang, P; Velazquez-Martinez, CA; Baksh, S				Salla, Mohamed; Aguayo-Ortiz, Rodrigo; Danmaliki, Gaddafi I.; Zare, Alaa; Said, Ahmed; Moore, Jack; Pandya, Vrajeshkumar; Manaloor, Robin; Fong, Sunny; Blankstein, Anna R.; Gibson, Spencer B.; Garcia, Laura Ramos; Meier, Pascal; Bhullar, Khushwant S.; Hubbard, Basil P.; Fiteh, Yahya; Vliagoftis, Harissios; Goping, Ing Swie; Brocks, Dion; Hwang, Peter; Velazquez-Martinez, Carlos A.; Baksh, Shairaz			Identification and Characterization of Novel Receptor-Interacting Serine/Threonine-Protein Kinase 2 Inhibitors Using Structural Similarity Analysis	JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS			English	Article							INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; COLORECTAL-CANCER; DISCOVERY; COLITIS; DESIGN; SYSTEM; POTENT; CELLS	Receptor-interacting protein kinase 2 (RIP2 or RICK, herein referred to as RIPK2) is linked to the pathogen pathway that activates nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and autophagic activation. Using molecular modeling (docking) and chemoinformatics analyses, we used the RIPK2/ponatinib crystal structure and searched in chemical databases for small molecules exerting binding interactions similar to those exerted by ponatinib. The identified RIPK2 inhibitors potently inhibited the proliferation of cancer cells by. > 70% and also inhibited NFkB activity. More importantly, in vivo inhibition of intestinal and lung inflammation rodent models suggests effectiveness to resolve inflammation with low toxicity to the animals. Thus, our identified RIPK2 inhibitor may offer possible therapeutic control of inflammation in diseases such as inflammatory bowel disease, asthma, cystic fibrosis, primary sclerosing cholangitis, and pancreatitis.	[Salla, Mohamed; Danmaliki, Gaddafi I.; Said, Ahmed; Moore, Jack; Pandya, Vrajeshkumar; Goping, Ing Swie; Hwang, Peter; Baksh, Shairaz] Univ Alberta, Dept Biochem, Edmonton, AB, Canada; [Zare, Alaa; Manaloor, Robin; Fong, Sunny; Baksh, Shairaz] Univ Alberta, Dept Pediat, Edmonton, AB, Canada; [Bhullar, Khushwant S.; Hubbard, Basil P.] Univ Alberta, Dept Pharmacol, Edmonton, AB, Canada; [Baksh, Shairaz] Univ Alberta, Dept Oncol, Edmonton, AB, Canada; [Fiteh, Yahya; Vliagoftis, Harissios; Hwang, Peter] Univ Alberta, Dept Med, Edmonton, AB, Canada; [Aguayo-Ortiz, Rodrigo; Brocks, Dion; Velazquez-Martinez, Carlos A.] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB, Canada; [Aguayo-Ortiz, Rodrigo] Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City, DF, Mexico; [Blankstein, Anna R.; Gibson, Spencer B.] Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB, Canada; [Blankstein, Anna R.; Gibson, Spencer B.] Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada; [Garcia, Laura Ramos; Meier, Pascal] Chester Beatty Labs, Breakthrough Breast Canc Res Ctr, London, England; [Baksh, Shairaz] Canc Res Inst Northern Alberta, Edmonton, AB, Canada; [Baksh, Shairaz] Women & Childrens Hlth Res Inst, Edmonton, AB, Canada		Baksh, S (corresponding author), Univ Alberta, Div Hematol Oncol, Fac Med & Dent, Dept Pediat,Ctr Pharm & Hlth Res,Katz Grp 020E 3, 113 St 87 Ave, Edmonton, AB T6G 2E1, Canada.	sbaksh@ualberta.ca	Velazquez-Martinez, Carlos A/G-3595-2012; Salla, Mohamed/ABA-5843-2021	Gaddafi Ibrahim, Danmaliki/0000-0003-1688-0711; Meier, Pascal/0000-0003-2760-6523; Hubbard, Basil/0000-0003-4353-9674; Salla, Mohamed/0000-0003-4744-0954; Aguayo-Ortiz, Rodrigo/0000-0001-9455-5397	Alberta Innovates - Health Solutions CRIO; Alberta Heritage Foundation for Medical ResearchAlberta Heritage Foundation for Medical ResearchGeneral Electric; Department of Pediatrics/Stollery Children's Hospital-WCHRI Hair Massacure Donation Fund; CONACyT (Mexico)Consejo Nacional de Ciencia y Tecnologia (CONACyT) [510728/288862]; division of Hematology/Oncology/Palliative Care/Epidemiology; Alberta Innovates [201600099] Funding Source: researchfish	The research in this study was supported by grants from Alberta Innovates - Health Solutions CRIO, Alberta Heritage Foundation for Medical Research, from the division of Hematology/Oncology/Palliative Care/Epidemiology under Dr. David Eisenstat for funds to partially support this project and from the Department of Pediatrics/Stollery Children's Hospital-WCHRI Hair Massacure Donation Fund. Aguayo-Ortiz is very grateful to CONACyT (Mexico) for the fellowship granted (No. 510728/288862).	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Pharmacol. Exp. Ther.	MAY 1	2018	365	2					354	367		10.1124/jpet.117.247163			14	Pharmacology & Pharmacy	Science Citation Index Expanded (SCI-EXPANDED)	Pharmacology & Pharmacy	GC1OY	WOS:000429552700016	29555876	hybrid			2022-04-25	
J	Malik, P; Chaudhry, N; Mittal, R; Mukherjee, TK				Malik, Parth; Chaudhry, Narender; Mittal, Rashmi; Mukherjee, Tapan K.			Role of receptor for advanced glycation end products in the complication and progression of various types of cancers	BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS			English	Review						RAGE; Cancer; Ligands; Inflammation; Cancer therapy	CELL-SURFACE RECEPTOR; DIABETIC-RETINOPATHY; COLORECTAL-CANCER; NITRIC-OXIDE; IN-VITRO; RAGE; EXPRESSION; AMINOGUANIDINE; LYSOZYME; PROLIFERATION	Background: Receptor for advanced glycation end-products popularly known as RAGE is a cell surface immunoglobulin class of molecule, binds with multiple ligands and therefore considered as a multi-ligand receptor. Use of RAGE deficient mice (RAGE(-/-)) as well as established mouse models pertaining to inflammation-associated carcinogenesis such as that of chemically induced carcinogenesis and colitis associated cancer provides a direct genetic evidence for a likelihood novel role of RAGE in cancer, with respect to its ability to lead cancer cell proliferation and survival. Besides inflammation, interaction of RAGE with its various ligands enhances oxidative stress both in cancerous and noncancerous cells which further complicates the progression of cancers. Scope of review: Till date, no single review article has discussed the mechanism of RAGE dependent complication of cancers, particularly the role of RAGE in cancer cell proliferation, angiogenesis, survival and anti-apoptosis needs to be discussed. Major conclusion: RAGE enhances the number of cancer cells by activating the cell cycle proteins (e.g., cyclin D1), anti-apoptotic proteins (e.g., BCl2), prosurvival (AKT) and autophagic proteins. Role of RAGE has also been detected in formation of new blood vessels (angiogenesis) in the cancer cells and activation of myeloid derived suppressor cells (MDSCs). General significance: This review article describes the role of RAGE in the complication of various types of cancers and the possible usefulness of RAGE dependent therapy to confront cancers in a stronger magnitude. (C) 2015 Elsevier B.V. All rights reserved.	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Biophys. Acta-Gen. Subj.	SEP	2015	1850	9					1898	1904		10.1016/j.bbagen.2015.05.020			7	Biochemistry & Molecular Biology; Biophysics	Science Citation Index Expanded (SCI-EXPANDED)	Biochemistry & Molecular Biology; Biophysics	CO5BF	WOS:000359173900028	26028296				2022-04-25	
