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Pancreatic Neoplasms: HELP
Articles by Min Wang
Based on 36 articles published since 2010
(Why 36 articles?)
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Between 2010 and 2020, Min Wang wrote the following 36 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Article PINK1/Parkin-Mediated Mitophagy Regulation by Reactive Oxygen Species Alleviates Rocaglamide A-Induced Apoptosis in Pancreatic Cancer Cells. 2019

Zhao, Chunle / He, Ruizhi / Shen, Ming / Zhu, Feng / Wang, Min / Liu, Yuhui / Chen, Hua / Li, Xu / Qin, Renyi. ·Laboratory of Biliary-Pancreatic Surgery, Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ·Front Pharmacol · Pubmed #31551778.

ABSTRACT: Pancreatic cancer (PC) is one of the most lethal diseases, and effective treatment of PC patients remains an enormous challenge. Rocaglamide A (Roc-A), a bioactive molecule extracted from the plant

2 Article TFEB-driven autophagy potentiates TGF-β induced migration in pancreatic cancer cells. 2019

He, Ruizhi / Wang, Min / Zhao, Chunle / Shen, Ming / Yu, Yahong / He, Li / Zhao, Yan / Chen, Hua / Shi, Xiuhui / Zhou, Min / Pan, Shutao / Liu, Yuhui / Guo, Xingjun / Li, Xu / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Wuhan, 430030, China. · Department of Trauma Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Wuhan, 430030, China. 2013tj0574@hust.edu.cn. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Wuhan, 430030, China. ryqin@tjh.tjmu.edu.cn. ·J Exp Clin Cancer Res · Pubmed #31387632.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma is one of the most aggressive cancers, with a 5-year survival rate of less than 8%. The complicated tumor microenvironment, particularly TGF-β, provides possible convenience for the progression of PC cells. TGF-β regulates critical cellular processes, including autophagy. However, the mechanism and effects of TGF-β-mediated autophagy are still poorly understood. METHODS: Bioinformatics analysis, western blot, transmission electron microscopy and confocal microscopy were used to identify that TFEB is the key factors in TGF-β-induced autophagy. The biological effects of TFEB-driven autophagy were investigated in vitro using transwell and wound healing assays and in vivo using liver metastasis and LSL-KrasG12D/Pdx1-Cre mice models. Luciferase assays and motif analysis were used to assess regulation of RAB5A gene promoter activity by TGF-β-induced TFEB. TFEB levels were measured by real-time PCR, western blot and immunohistochemical staining in clinical pancreatic ductal adenocarcinoma tissues. RESULTS: We demonstrated that TGF-β induces TFEB expression via the canonical smad pathway in Smad4-positive PC cells and facilitates TFEB-mediated autophagic activation. TFEB-driven autophagy caused by TGF-β regulates RAB5A-dependent endocytosis of Itgα5 and promotes progression of PC cells. We further showed that enhanced TFEB expression and its direct target RAB5A both predict poor prognosis in PC patients. CONCLUSIONS: Our findings reveal TFEB-driven autophagy is required for TGF-β induced migration and metastasis of PC cells by promoting endocytosis of Itgα5β1 and focal adhesion disassembly through the TGF-β-TFEB-RAB5A axis. Our results highlight the potential utility of suppressing TFEB-driven autophagy to block PC metastasis.

3 Article Danthron suppresses autophagy and sensitizes pancreatic cancer cells to doxorubicin. 2019

Chen, Hua / Zhao, Chunle / He, Ruizhi / Zhou, Min / Liu, Yuhui / Guo, Xingjun / Wang, Min / Zhu, Feng / Qin, Renyi / Li, Xu. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: xjguo@tjh.tjmu.edu.cn. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: ryqin@tjh.tjmu.edu.cn. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: 2013tj0574@hust.edu.cn. ·Toxicol In Vitro · Pubmed #30389604.

ABSTRACT: In contrast to the steady increase in survival observed for most cancer types, advances have been slow for pancreatic cancers. Current chemotherapy has limited benefits for patients with pancreatic cancer. Therefore, there is an urgent need for effective pancreatic cancer treatment strategies. At present, targeting the autophagic pathway is regarded as a promising new strategy for cancer treatment. Danthron (1,8-dihydroxyanthrquinone), a component from Rheum palmatum L. (polygonaceae), has several biological activities. However, the inhibition of autophagy by danthron has never been recognized, previously.Here we find that danthron may prevent autophagy, inhibit proliferation and induce apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells and inhibition of autophagy by chloroquine or silencing autophagy protein 5 (Atg5) may chemosensitize pancreatic cancer cell lines to doxorubicin. Similarly, inhibition of autophagy by danthron also enhances toxicity of doxorubicin to pancreatic cancer cells. These results indicate that danthron has an anticancer effect and can sensitize the chemotherapeutic effect of doxorubicin on pancreatic cancer cells. These findings also suggest that inhibition of autophagy may be an effective way to promote the chemotherapy of pancreatic cancer.

4 Article The use of magnetic resonance elastography in differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma: A preliminary study. 2018

Shi, Yu / Cang, Lizhuo / Zhang, Xianyi / Cai, Xiaoli / Wang, Xiaoqi / Ji, Ruoyun / Wang, Min / Hong, Yang. ·Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, PR China. · Philips Healthcare, Beijing, PR China. · Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, PR China. Electronic address: hongy@sj-hospital.org. ·Eur J Radiol · Pubmed #30396645.

ABSTRACT: PURPOSE: To assess the value of magnetic resonance elastography (MRE) in patients with autoimmune pancreatitis (AIP) and in the differentiation of AIP from pancreatic ductal adenocarcinoma (PDAC). METHOD AND MATERIALS: This prospective study included 14 AIP patients, 26 PDAC patients, and 14 healthy volunteers. All participants underwent pancreatic MRE (40-Hz; 3 T scanner) at enrollment, and 7 AIP patients underwent a second MRE after initiation of steroid therapy. Pancreatic stiffness values were obtained by MRE and a new logistic regression model (the calculated Rad score) was used to combine pancreatic stiffness and the distribution and shape of high-stiffness areas for differentiation of AIP and PDAC. The area under the curve (AUC) was calculated for all parameters using receiver operating characteristic (ROC) analysis. RESULTS: Pancreatic stiffness was significantly higher (2.67 kPa [interquartile range, 2.24-3.56 kPa]) in AIP than in healthy pancreas (1.24 kPa [1.18-1.24 kPa]) and significantly lower in AIP than in PDAC (3.78 kPa [3.22-5.11 kPa]; both P < 0.05). Diffuse (n = 4 vs 1; P = 0.043) and multiple (n = 3 vs 0; P = 0.037) lesions were more common in AIP, while solitary (n = 25 vs 7; P = 0.001) and nodular lesions (n = 18 vs 2; P =  0.002) were more frequent in PDAC. Rad scores outperformed individual imaging parameters in distinguishing AIP from PDAC (AUC, 0.948 vs 0.607 to 0.782; all P < 0.05), with 84.6% specificity and 92.9% sensitivity. Pancreatic stiffness in AIP decreased significantly, from 2.66 kPa [2.29 to 3.05 kPa] to 1.55 kPa [1.43 to 1.67 kPa] (P = 0.016), during treatment. CONCLUSIONS: MRE shows promise as a quantitative imaging method for differentiating AIP from PDAC and for monitoring the treatment response in AIP.

5 Article Combined inhibition of autophagy and Nrf2 signaling augments bortezomib-induced apoptosis by increasing ROS production and ER stress in pancreatic cancer cells. 2018

Li, Xu / Liang, Meng / Jiang, Jianxin / He, Ruizhi / Wang, Min / Guo, Xingjun / Shen, Ming / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. · Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei, China. · Department of Hepatic-Biliary-Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, China. ·Int J Biol Sci · Pubmed #30123077.

ABSTRACT: Pancreatic cancer (PC) is highly resistant to current therapies; thus, there is an urgent need to develop new treatment strategies. The proteasome is crucially important for proteostasis, which is involved in cell proliferation and survival, making it an attractive therapeutic target in cancer. However, recent studies have indicated that bortezomib, a highly selective proteasome inhibitor, has limited effects in solid tumors including PC. Thus, more mechanistic insights into chemo-sensitization strategies for bortezomib are urgently needed. Herein, we demonstrate that bortezomib induced apoptosis and autophagy via a mechanism involving endoplasmic reticulum (ER) stress in PC cells. Additionally, bortezomib treatment led to increased levels of intracellular reactive oxygen species (ROS), which play critical roles in bortezomib-induced ER stress and apoptosis. Moreover, autophagy functions as a compensatory mechanism to eliminate bortezomib-induced ROS and resists ER stress-mediated apoptosis. Additionally, the Nrf2-mediated antioxidative response, which works against with bortezomib-induced autophagy, also protected cells against bortezomib-induced ROS production. Finally, the dual inhibition of autophagy and Nrf2 signaling cooperatively enhanced bortezomib-induced apoptosis by elevating ROS levels and ER stress. Together, these data demonstrate that activation of autophagy and the Nrf2 antioxidant system, which lowers intracellular ROS, are mechanistically how PC cells overcome bortezomib treatment. In summary, combining proteasome inhibitors with drugs targeting autophagy and Nrf2 signaling could be a promising therapeutic approach for PC treatment.

6 Article Alantolactone induces apoptosis and improves chemosensitivity of pancreatic cancer cells by impairment of autophagy-lysosome pathway via targeting TFEB. 2018

He, Ruizhi / Shi, Xiuhui / Zhou, Min / Zhao, Yan / Pan, Shutao / Zhao, Chunle / Guo, Xingjun / Wang, Min / Li, Xu / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: kuai_1985@hotmail.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: ryqin@tjh.tjmu.edu.cn. ·Toxicol Appl Pharmacol · Pubmed #30086361.

ABSTRACT: The lysosome is emerging as a central regulator of the autophagic process, which plays a critical role in tumor growth and chemoresistance. Alantolactone, which is a natural compound produced by Inula helenium, has been shown to induce apoptosis in numerous cancer types. However, the mechanism by which alantolactone regulates apoptosis is still poorly understood. In this work, we observed that alantolactone caused the accumulation of autophagosomes due to impaired autophagic degradation and substantially inhibited the activity and expression of CTSB/CTSD proteins that when depleted caused lysosomal dysfunction. Furthermore, we found that alantolactone inhibited the proliferation of pancreatic cancer cells in vitro and in vivo and enhanced the chemosensitivity of pancreatic cancer cells to oxaliplatin. In addition, a reduction in TFEB levels was a critical event in the apoptosis and cell death caused by alantolactone. Our data demonstrated that alantolactone, which impaired autophagic degradation, was a pharmacological inhibitor of autophagy in pancreatic cancer cells and markedly enhanced the chemosensitivity of pancreatic cancer cells to oxaliplatin.

7 Article Loss of Linc01060 induces pancreatic cancer progression through vinculin-mediated focal adhesion turnover. 2018

Shi, Xiuhui / Guo, Xingjun / Li, Xu / Wang, Min / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Electronic address: 2013tj0574@hust.edu.cn. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Electronic address: minwang@tjh.tjmu.edu.cn. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Electronic address: ryqin@tjh.tjmu.edu.cn. ·Cancer Lett · Pubmed #29913236.

ABSTRACT: There is currently limited knowledge regarding the involvement of long non-coding RNAs (lncRNAs) in cancer development. We aimed to identify lncRNAs with important roles in pancreatic cancer progression. We screened for lncRNAs that were differentially expressed in pancreatic cancer tissues. Among 349 differentially expressed lncRNAs, Linc01060 showed the lowest expression in pancreatic cancer tissues compared with normal pancreatic tissues. Lower Linc01060 expression in pancreatic cancer tissues was significantly associated with a poor prognosis. Linc01060 inhibited pancreatic cancer proliferation and invasion in vitro and in vivo. Vinculin overexpression inhibited Linc01060KD-mediated increases in FAK and paxillin phosphorylation, whereas vinculin knockdown reversed the Linc01060-mediated repression of FAK and inactivation of focal adhesion turnover. Vinculin knockdown also accelerated pancreatic cancer cell proliferation by upregulating ERK activity. In biological function analyses, vinculin overexpression abrogated Linc01060-mediated repression of pancreatic cancer cell proliferation and invasion, whereas vinculin counteracted the Linc01060-mediated repression of PC cell proliferation and invasion. These data demonstrate that Linc01060 plays a key role in suppressing pancreatic cancer progression by regulating vinculin expression. These findings suggest that the Linc01060-vinculin-focal adhesion axis is a therapeutic target for pancreatic cancer treatment.

8 Article A Five-microRNA Signature for Survival Prognosis in Pancreatic Adenocarcinoma based on TCGA Data. 2018

Shi, Xiu-Hui / Li, Xu / Zhang, Hang / He, Rui-Zhi / Zhao, Yan / Zhou, Min / Pan, Shu-Tao / Zhao, Chun-Le / Feng, Ye-Chen / Wang, Min / Guo, Xing-Jun / Qin, Ren-Yi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. xjguo@tjh.tjmu.edu.cn. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ryqin@tjh.tjmu.edu.cn. ·Sci Rep · Pubmed #29769534.

ABSTRACT: Novel biomarkers for pancreatic adenocarcinoma are urgently needed because of its poor prognosis. Here, by using The Cancer Genome Atlas (TCGA) RNA-seq data, we evaluated the prognostic values of the differentially expressed miRNAs and constructed a five-miRNA signature that could effectively predict patient overall survival (OS). The Kaplan-Meier overall survival curves of two groups based on the five miRNAs were notably different, showing overall survival in 10.2% and 47.8% at five years for patients in high-risk and low-risk groups, respectively. The ROC curve analysis achieved AUC of 0.775, showing good sensitivity and specificity of the five-miRNA signature model in predicting pancreatic adenocarcinoma patient survival risk. The functional enrichment analysis suggested that the target genes of the miRNA signature may be involved in various pathways related to cancer, including PI3K-Akt, TGF-β, and pluripotent stem cell signaling pathways. Finally, we analyzed expression of the five specific miRNAs in the miRNA signature, and validated the reliability of the results in 20 newly diagnosed pancreatic adenocarcinoma patients using qRT-PCR. The expression results of qRT-PCR were consistent with the TCGA results. Taken together, these findings suggested that the five-miRNA signature (hsa-miR-203, hsa-miR-424, hsa-miR-1266 hsa-miR-1293, and hsa-miR-4772) could be used as a prognostic marker for pancreatic adenocarcinoma.

9 Article Comparison of Totally 3-Dimensional Laparoscopic Pancreaticoduodenectomy and Open Pancreaticoduodenectomy. 2018

Zhang, Hang / Guo, Xingjun / Xia, Jia / Zhu, Feng / Shen, Ming / Wang, Xin / Wang, Min / Qin, Renyi. · ·Pancreas · Pubmed #29683967.

ABSTRACT: OBJECTIVE: The aim of this study was to evaluate the safety, feasibility, and oncologic outcomes of 3-dimensional total laparoscopic pancreaticoduodenectomy (3D-TLPD). METHODS: Data of all patients who underwent 3D-TLPD (n = 202) or open pancreaticoduodenectomy (OPD) (n = 213) at a single institution between October 2014 and December 2016 were reviewed. We evaluated the safety, feasibility, and oncologic outcomes of 3D-TLPD compared with OPD. RESULTS: The mean operative times in the 3D-TLPD and OPD groups were comparable (P = 0.322). The estimated blood loss and perioperative transfusion rate were similar in both groups, as were the morbidity and mortality rates (P > 0.050). The mean number of analgesic administered and the mean length of hospital and intensive care unit stay were lower (P < 0.001) and shorter (P < 0.001, P = 0.009) in the 3D-TLPD group than in the OPD group, respectively. The surgical resection margins and the number of lymph nodes harvested did not differ between the 2 groups; however, a significant difference was observed in pathological results. CONCLUSIONS: Three-dimensional TLPD had the typical advantages of minimally invasive abdominal procedures, such as shorter hospital stays. It is technically safe and feasible and has comparable operative times and similar oncologic outcomes to those of OPD.

10 Article Regulatory B cells induced by pancreatic cancer cell-derived interleukin-18 promote immune tolerance via the PD-1/PD-L1 pathway. 2018

Zhao, Yan / Shen, Ming / Feng, Yecheng / He, Ruizhi / Xu, Xiaodong / Xie, Yu / Shi, Xiuhui / Zhou, Min / Pan, Shutao / Wang, Min / Guo, Xingjun / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ·Oncotarget · Pubmed #29599908.

ABSTRACT: Dysregulation of regulatory B cells (Bregs), a type of immunosuppressive lymphocyte, are associated with development of autoimmune diseases and cancers. Bregs produce immune tolerance-inducing cell surface molecules and tolerogenic cytokines (interleukin [IL]-10 and transforming growth factor-beta). We previously showed that levels of the inflammatory cytokine IL-18 were increased in patients with pancreatic cancer. In the present study study, we found that pancreatic cancer cell-derived IL-18 increases Breg-induced immunosuppression. IL-18 also promoted B-cell proliferation and IL-10 expression

11 Article Pancreaticoduodenectomy for borderline resectable pancreatic head cancer with a modified artery-first approach technique. 2017

Wang, Min / Zhang, Hang / Zhu, Feng / Peng, Feng / Wang, Xin / Shen, Ming / Qin, Ren-Yi. ·Department of Pancreatic-Biliary Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ryqin@tjh.tjmu.edu.cn. ·Hepatobiliary Pancreat Dis Int · Pubmed #28381388.

ABSTRACT: BACKGROUND: The treatment of borderline resectable pancreatic head cancer (BRPHC) is still controversial and challenging. The artery-first approaches are described to be the important options for the early determination. Whether these approaches can achieve an increase R0 rate, better bleeding control and increasing long-term survival for BRPHC are still controversial. We compared a previously reported technique, a modified artery-first approach (MAFA), with conventional techniques for the surgical treatment of BRPHC. METHODS: A total of 117 patients with BRPHC undergone pancreaticoduodenectomy (PD) from January 2013 to June 2015 were included. They were divided into an MAFA group (n=78) and a conventional-technique group (n=39). Background characteristics, operative data and complications were compared between the two groups. RESULTS: Mean operation time was significantly shorter in the MAFA group than that in the conventional-technique group (313 vs 384 min; P=0.014); mean volume of intraoperative blood loss was significantly lower in the MAFA group than that in the conventional-technique group (534 vs 756 mL; P=0.043); and mean rate of venous resection was significantly higher in the conventional-technique group than that in the MAFA group (61.5% vs 35.9%; P=0.014). Pathologic data, early mortality and morbidity were not different significantly between the two groups. CONCLUSIONS: MAFA is safe, simple, less time-consuming, less intraoperative blood loss and less venous resection, and therefore, may become a standard surgical approach to PD for BRPHC with the superior mesenteric vein-portal vein involvement but without superior mesenteric artery invasion.

12 Article Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin. 2017

Xu, Xiao Dong / Zhao, Yan / Zhang, Min / He, Rui Zhi / Shi, Xiu Hui / Guo, Xing Jun / Shi, Cheng Jian / Peng, Feng / Wang, Min / Shen, Min / Wang, Xin / Li, Xu / Qin, Ren Yi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tjxuxiaodong@163.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. zhaoy2401@163.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. zm0911work@163.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. heruizhi@aliyun.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 18771146878@163.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. amjoyguo@126.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. chengj1010@sina.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. nicholas.peng7@gmail.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. wangmin0013128@aliyun.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. shenming-2002@163.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. xwangtjh@163.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. kuai_1985@hotmail.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ryqin@tjh.tjmu.edu.cn. ·Int J Mol Sci · Pubmed #28208617.

ABSTRACT: Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.

13 Article Imbedding pancreaticojejunostomy used in pure laparoscopic pancreaticoduodenectomy for nondilated pancreatic duct. 2017

Wang, Min / Xu, Simiao / Zhang, Hang / Peng, Shuyou / Zhu, Feng / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, Hubei, China. · Department of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. · Department of General Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310016, People's Republic of China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, Hubei, China. zfjch1977@sina.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, Hubei, China. ryqin@tjh.tjmu.edu.cn. ·Surg Endosc · Pubmed #28078460.

ABSTRACT: BACKGROUND: LPD has been cautiously regarded as feasible and safe for resection and reconstruction. However, anastomosis of the remnant pancreas is still thought to be a critical obstacle to the dissemination of LPD in general practice. This study presents a new technique of pancreaticojejunostomy for nondilated pancreatic duct and evaluates its safety and reliability. METHODS: From July 2014 to June 2015, a total of 52 patients underwent LPD with the new technique. A modified technique of duct-to-mucosa PJ was performed with transpancreatic interlocking mattress sutures, named the imbedding duct-to-mucosa PJ. Then the morbidity and mortality was calculated. RESULTS: This technique was applied in 52 patients after LPD all with nondilated pancreatic duct (1-3 mm). The mean operation time was 4.6 h (range, 3.5-8.3 h) and the median time for the anastomosis was 37 min (range, 24-53 min). Operative mortality was zero, and morbidity was 21.2 % (n = 11), including hemorrhage (n = 3, 5.8 %), biliary fistula (n = 1, 1.9 %), pulmonary infection (n = 1, 1.9 %), delayed gastric emptying (n = 2, 3.8 %), abdominal abscess caused by biliary fistula or PF formation (n = 2, 3.8 %), and POPF (n = 2, 3.8 %). Two patients developed a pancreatic fistula (one type A, one type B) classified according to the International Study Group on Pancreatic Fistula. CONCLUSIONS: The described technique is a simple and safe reconstruction procedure after LPD, especially for patients with nondilated pancreatic duct.

14 Article MiRNA-145 increases therapeutic sensibility to gemcitabine treatment of pancreatic adenocarcinoma cells. 2016

Lin, Yong / Ge, Xin / Wen, Yiyang / Shi, Zhu-Mei / Chen, Qiu-Dan / Wang, Min / Liu, Ling-Zhi / Jiang, Bing-Hua / Lu, Yuan. ·Department of Laboratory Medicine, Huashan Hospital of Fudan University, Shanghai, China. · The Department of Clinical Laboratory, Central Laboratory, Jing'an District Centre Hospital of Shanghai, Huashan Hospital of Fudan University Jing'An Branch, Shanghai, China. · State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention, and Treatment Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, China. · Ninggao Personalized Medicine and Technology Innovation Center, Nanjing, China. · Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. · Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States of America. ·Oncotarget · Pubmed #27765914.

ABSTRACT: Pancreatic adenocarcinoma is one of the most leading causes of cancer-related deaths worldwide. Although recent advances provide various treatment options, pancreatic adenocarcinoma has poor prognosis due to its late diagnosis and ineffective therapeutic multimodality. Gemcitabine is the effective first-line drug in pancreatic adenocarcinoma treatment. However, gemcitabine chemoresistance of pancreatic adenocarcinoma cells has been a major obstacle for limiting its treatment effect. Our study found that p70S6K1 plays an important role in gemcitabine chemoresistence. MiR-145 is a tumor suppressor which directly targets p70S6K1 for inhibiting its expression in pancreatic adenocarcinoma, providing new therapeutic scheme. Our findings revealed a new mechanism underlying gemcitabine chemoresistance in pancreatic adenocarcinoma cells.

15 Article Dual Inhibition of Topoisomerase II and Tyrosine Kinases by the Novel Bis-Fluoroquinolone Chalcone-Like Derivative HMNE3 in Human Pancreatic Cancer Cells. 2016

Ma, Yong-Chao / Wang, Zhi-Xin / Jin, Shao-Ju / Zhang, Yan-Xin / Hu, Guo-Qiang / Cui, Dong-Tao / Wang, Jiang-Shuan / Wang, Min / Wang, Fu-Qing / Zhao, Zhi-Jun. ·Clinical Medical Institute of Luohe Medical College, Luohe, Henan, P.R. China. · The First Affiliated Hospital of Luohe Medical College, Luohe, Henan, P.R. China. · Tumor Occurrence and Prevention Research Innovation team of Luohe, Luohe, Henan, P.R. China. · Basic Medical Institute of ZhengZhou University, ZhengZhou, Henan, P.R. China. · Institute of pharmacology of Luohe Medical College, Luohe, Henan, P.R. China. · Basic Medical Institute of Luohe Medical College, Luohe, Henan, P.R. China. · Institute of Chemistry and Biology of Henan University, Kaifeng, Henan, P.R. China. ·PLoS One · Pubmed #27760157.

ABSTRACT: Both tyrosine kinase and topoisomerase II (TopII) are important anticancer targets, and their respective inhibitors are widely used in cancer therapy. However, some combinations of anticancer drugs could exhibit mutually antagonistic actions and drug resistance, which further limit their therapeutic efficacy. Here, we report that HMNE3, a novel bis-fluoroquinolone chalcone-like derivative that targets both tyrosine kinase and TopII, induces tumor cell proliferation and growth inhibition. The viabilities of 6 different cancer cell lines treated with a range of HMNE3 doses were detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was determined using Hoechst 33258 fluorescence staining and the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. The expression of activated Caspase-3 was examined by immunocytochemistry. The tyrosine kinase activity was measured with a human receptor tyrosine kinase (RTK) detection kit using a horseradish peroxidase (HRP)-conjugated phosphotyrosine (pY20) antibody as the substrate. The topoisomerase II activity was measured using agarose gel electrophoresis with the DNA plasmid pBR322 as the substrate. The expression levels of the P53, Bax, Bcl-2, Caspase-3, -8, -9, p-cSrc, c-Src and topoisomerase II proteins were detected by western blot analysis. The proliferation of five of the six cancer cell lines was significantly inhibited by HMNE3 at 0.312 to 10 μmol/L in a time- and dose-dependent manner. Treatment of the Capan-1 and Panc-1 cells with 1.6 to 3.2 μM HMNE3 for 48 h significantly increased the percentage of apoptotic cells (P<0.05), and this effect was accompanied by a decrease in tyrosine kinase activity. HMNE3 potentially inhibited tyrosine kinase activity in vitro with an IC50 value of 0.64±0.34 μmol/L in Capan-1 cells and 3.1±0.86 μmol/L in Panc-1 cells. The activity of c-Src was significantly inhibited by HMNE3 in a dose- and time-dependent manner in different cellular contexts. Compared with the control group, HMNE3 induced increased expression of cellular apoptosis-related proteins. Consistent with cellular apoptosis data, a significant decrease in topoisomerase IIβ activity was noted following treatment with HMNE3 for 24 h. Our data suggest that HMNE3 induced apoptosis in Capan-1 and Panc-1 cells by inhibiting the activity of both tyrosine kinases and topoisomerase II.

16 Article Simultaneous inhibition of the ubiquitin-proteasome system and autophagy enhances apoptosis induced by ER stress aggravators in human pancreatic cancer cells. 2016

Li, Xu / Zhu, Feng / Jiang, Jianxin / Sun, Chengyi / Zhong, Qing / Shen, Ming / Wang, Xin / Tian, Rui / Shi, Chengjian / Xu, Meng / Peng, Feng / Guo, Xingjun / Hu, Jun / Ye, Dawei / Wang, Min / Qin, Renyi. ·a Department of Biliary-Pancreatic Surgery , Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China. · b Department of Hepatic-Biliary-Pancreatic Surgery , Hubei Cancer Hospital , Wuhan , China. · c Department of Biliary-Hepatic Surgery , Affiliated Hospital of Guiyang Medical College , Guizhou , China. · d Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas , TX , USA. · e Department of Colon Cancer , Tianjin Medical University Cancer Institute and Hospital , Tianjin , China. · f Department of Oncology , Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China. ·Autophagy · Pubmed #27308733.

ABSTRACT: In contrast to normal tissue, cancer cells display profound alterations in protein synthesis and degradation. Therefore, proteins that regulate endoplasmic reticulum (ER) homeostasis are being increasingly recognized as potential therapeutic targets. The ubiquitin-proteasome system and autophagy are crucially important for proteostasis in cells. However, interactions between autophagy, the proteasome, and ER stress pathways in cancer remain largely undefined. This study demonstrated that withaferin-A (WA), the biologically active withanolide extracted from Withania somnifera, significantly increased autophagosomes, but blocked the degradation of autophagic cargo by inhibiting SNARE-mediated fusion of autophagosomes and lysosomes in human pancreatic cancer (PC) cells. WA specifically induced proteasome inhibition and promoted the accumulation of ubiquitinated proteins, which resulted in ER stress-mediated apoptosis. Meanwhile, the impaired autophagy at early stage induced by WA was likely activated in response to ER stress. Importantly, combining WA with a series of ER stress aggravators enhanced apoptosis synergistically. WA was well tolerated in mice, and displayed synergism with ER stress aggravators to inhibit tumor growth in PC xenografts. Taken together, these findings indicate that simultaneous suppression of 2 key intracellular protein degradation systems rendered PC cells vulnerable to ER stress, which may represent an avenue for new therapeutic combinations for this disease.

17 Article Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer. 2016

Guo, Xingjun / Zheng, Lei / Jiang, Jianxin / Zhao, Yan / Wang, Xin / Shen, Ming / Zhu, Feng / Tian, Rui / Shi, Chengjian / Xu, Meng / Li, Xu / Peng, Feng / Zhang, Hang / Feng, Yechen / Xie, Yu / Xu, Xiaodong / Jia, Wei / He, Ruizhi / Xie, Chencheng / Hu, Jun / Ye, Dawei / Wang, Min / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Oncology, The Sidney Kimmel Cancer Center, and the Skip Viragh Center for Pancreatic Cancer Research & Clinical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, The Sidney Kimmel Cancer Center, and the Skip Viragh Center for Pancreatic Cancer Research & Clinical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of hepatic-biliary-pancreatic surgery, Renmin Hospital of Wuhan University, Wuhan, China. · Department of Bioengineering and Therapeutic Sciences, University of Minnesota, Minneapolis, Minnesota. · Department of Colon Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. · Department of Oncology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. ryqin@tjh.tjmu.edu.cn wangmin0013128@aliyun.com. ·Clin Cancer Res · Pubmed #27297583.

ABSTRACT: PURPOSE: We sought to find new immune-based treatments for pancreatic cancer. EXPERIMENTAL DESIGN: We detected IL18 expression in plasma and specimens from patients with pancreatic cancer. We then investigated whether IL18 had a therapeutic effect for pancreatic cancer in vitro and in vivo and any underlying mechanisms. RESULTS: Higher plasma IL18 was associated with longer overall survival (OS), but higher IL18 in pancreatic cancer tissues was associated with shorter OS and increased invasion and metastasis. Recombinant IL18 alone had no antitumor effect in the syngeneic mice with orthotopically transplanted tumors and promoted tumors in immunocompromised mice; it also facilitated immune responses in vitro and in vivo by augmenting the activity of cytotoxic T cells and NK cells in peripheral blood and lymph nodes. However, IL18 promoted the proliferation and invasion of pancreatic cancer cells, in vitro and in vivo, through the NF-κB pathway. Nevertheless, by coadministrating IL18 with BAY11-7082, an NF-κB inhibitor, we were able to prevent the procancerous effects of IL18 and prolong the survival time of the mice. CONCLUSIONS: IL18 has both cancer-promoting and cancer-suppressing functions. Although its single-agent treatment has no therapeutic effect on pancreatic cancer, when combined with the NF-κB pathway inhibitor, IL18 improved survival in a murine pancreatic cancer model. Our study implies the possibility of a combinational immunotherapy that uses IL18 and targets NF-κB pathway. Clin Cancer Res; 22(23); 5939-50. ©2016 AACR.

18 Article Circulating myeloid-derived suppressor cells in patients with pancreatic cancer. 2016

Xu, Xiao-Dong / Hu, Jun / Wang, Min / Peng, Feng / Tian, Rui / Guo, Xing-Jun / Xie, Yu / Qin, Ren-Yi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ryqin@tjh.tjmu.edu.cn. ·Hepatobiliary Pancreat Dis Int · Pubmed #26818550.

ABSTRACT: BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co-cultured with normal peripheral blood mononuclear cells (PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS: CD14+/CD11b+/HLA-DR- MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the serum of patients with pancreatic cancer. CONCLUSIONS: MDSCs were tumor related: tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.

19 Article Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1. 2016

Guo, Xingjun / Wang, Min / Zhao, Yan / Wang, Xin / Shen, Ming / Zhu, Feng / Shi, Chengjian / Xu, Meng / Li, Xu / Peng, Feng / Zhang, Hang / Feng, Yechen / Xie, Yu / Xu, Xiaodong / Jia, Wei / He, Ruizhi / Jiang, Jianxin / Hu, Jun / Tian, Rui / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China. · Department of Hepatic-Biliary-Pancreatic Surgery, Hubei Cancer Hospital, Wuhan City, People's Republic of China. · Department of Colon Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China. jinguxiong@gmail.com. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, 430030, Hubei Province, People's Republic of China. ryqin@tjh.tjmu.edu.cn. ·Clin Exp Med · Pubmed #26084985.

ABSTRACT: The conserved polarity complex, which comprises partitioning-defective proteins Par3, Par6, and the atypical protein kinase C, affects various cell-polarization events, including assembly of tight junctions. Control of tight junction assembly is closely related to invasion and migration potential. However, as the importance of conserved polarity complexes in regulating pancreatic cancer invasion and metastasis is unclear, we investigated their role and mechanism in pancreatic cancers. We first detect that the key protein of the conserved polarity complex finds that only Par3 is down-regulated in pancreatic cancer tissues while Par6 and aPKC show no difference. What is more, Par3 tissues level was significantly and positively associated with patient overall survival. Knocking-down Par3 promotes pancreatic cancer cells invasion and migration. And Par3 requires interaction with Tiam1 to affect tight junction assembly, and then affect invasion and migration of pancreatic cancer cells. Then, we find that tight junction marker protein ZO-1 and claudin-1 are down-regulated in pancreatic cancer tissues. And the relationship of the expression of Par3 and ZO-1 in pancreatic cancer tissue is linear correlation. We establish liver metastasis model of human pancreatic cancer cells in Balb/c nude mice and find that knocking down Par3 promotes invasion and metastasis and disturbs tight junction assembly in vivo. Taken together, these results suggest that the Par3 regulates invasion and metastasis in pancreatic cancers by controlling tight junction assembly.

20 Article Expression and significance of HIF-1α and HIF-2α in pancreatic cancer. 2015

Wang, Min / Chen, Mei-Yuan / Guo, Xing-Jun / Jiang, Jian-Xin. ·Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. · Department of Hepatic-biliary-pancreatic Surgery, Hubei Cancer Hospital, Wuhan, 430079, China. · Department of Hepatic-biliary-pancreatic Surgery, Hubei Cancer Hospital, Wuhan, 430079, China. jjx731003@163.com. ·J Huazhong Univ Sci Technolog Med Sci · Pubmed #26670439.

ABSTRACT: The expression levels of hypoxia-inducible factor 1alpha (HIF-1α) and HIF-2α in pancreatic cancer (PC) and their association with clinicopathologic characteristics were investigated in order to elucidate their roles in the development of PC. HIF-1α and HIF-2α mRNA levels in 20 patients with PC were detected by quantitative real-time polymerase chain reaction. The expression of HIF-1α and HIF-2α protein in samples from other 90 patients with PC was measured by immunohistochemistry. Correlations between the expression of HIF-1α or HIF-2α and clinicopathologica features and prognosis were analyzed. The expression of both HIF-1α and HIF-2α mRNA was up-regulated in most cancer tissues (P<0.05). HIF-1α staining was weakly positive in most cancer tissues and strongly positive in adjacent pancreas tissues (P<0.05). Clinicopathologic analysis revealed that relatively strong HIF-1α expression in cancer tissues was related to greater invasion (P<0.05), higher tumor pathologic stage (P<0.05), higher American Joint Committee on Cancer (AJCC) stage (P<0.05) and shorter overall survival time (P<0.05). Conversely, HIF-2α staining was strongly positive in most cancer tissues and weakly positive in adjacent pancreas tissues. Clinicopathologic analysis revealed that relatively strong HIF-2α expression in cancer tissues was related to less invasion (P<0.05), lower tumor pathologic stage (P<0.05), lower AJCC stage (P<0.05) and longer overall survival time (P<0.05). Moreover, the HIF-1α(high)/HIF-2α(low) group showed a shorter survival time than the HIF-1α(low)/HIF-2α(high) group. In conclusion, although HIF-1α and HIF-2α mRNA expression patterns are the same, their protein expression patterns are significantly different and they play different roles in PC. Combined analysis of HIF-1α and HIF-2α expression might be useful to predict the prognosis of patients with PC.

21 Article Upregulation of miR-181c contributes to chemoresistance in pancreatic cancer by inactivating the Hippo signaling pathway. 2015

Chen, Meiyuan / Wang, Min / Xu, Simiao / Guo, Xingjun / Jiang, Jianxin. ·Department of Hepatic-Biliary-Pancreatic Surgery, Hubei Cancer Hospital, Wuhan, Hubei, 430079, China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. · Department of Endocrinology and Metabolism, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. ·Oncotarget · Pubmed #26561204.

ABSTRACT: The Hippo signaling pathway plays a crucial role in regulating tissue homeostasis, organ size, tumorigenesis and cancer chemoresistance when deregulated. Physiologically, the Hippo core kinase cassette that consists of mamma-lian STE20-like protein kinase 1/2 (MST1/2), and large tumour suppressor 1/2 (LATS1/2), together with the adaptor proteins Salvador homologue 1 (SAV1) and MOB kinase activator 1 (MOB1), tightly restricts the activities of homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) to low levels. However, how the Hippo kinase cassette core components are simultaneously inhibited, to exhibit constitutively inactivated Hippo signaling and activated YAP/TAZ in cancer remains puzzling. Herein, we reported that miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-181c in the progression of pancreatic cancer, but also may represent a new therapeutic target and prognostic marker.

22 Article Upregulation of microRNA‑138‑5p inhibits pancreatic cancer cell migration and increases chemotherapy sensitivity. 2015

Yu, Chao / Wang, Min / Chen, Meiyuan / Huang, Yang / Jiang, Jianxin. ·Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China. · Department of Biliary‑Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China. ·Mol Med Rep · Pubmed #26135834.

ABSTRACT: The present study investigated the role of microRNA (miR)‑138‑5p in regulating carcinoma migration and sensitivity to chemotherapy in pancreatic cancer. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to assess the expression levels of miR‑138‑5p in pancreatic cancer cell lines and primary carcinoma tissues from human patients. A lentiviral vector, containing miR‑138‑5p mimics (lv‑miR‑138‑m) or miR‑138‑5p inhibitor (lv‑miR‑138‑i), was used to either upregulate or downregulate the expression levels of miR‑138‑5p in PANC‑1 cells, respectively. The effects of miR‑138‑3p regulation on pancreatic cancer cell migration and sensitivity to chemotherapy were examined. The predicted targeting of miR‑138‑5p on vimentin (VIM) was assessed by western blotting in PANC‑1 cells. VIM was subsequently downregulated using small interfering (si)RNA to determine its effect on miR‑138‑5p‑modulated pancreatic cancer cell development. The expression levels of miR‑138‑5p were downregulated in pancreatic cancer cell lines and primary carcinoma tissues. In PANC‑1 cells, lentivirus-mediated upregulation of miR‑138‑5p inhibited cancer cell migration and increased cell chemosensitivity to 5‑fluorouracil (5‑FU). By contrast, downregulation of miR‑138‑5p promoted cancer cell migration and decreased cell chemosensitivity to 5‑FU. A luciferase assay revealed that VIM was a direct target of miR‑138‑5p. Western blotting demonstrated that VIM was downregulated upon the upregulation of miR‑138‑5p in PANC‑1 cells. siRNA‑mediated downregulation of VIM inhibited pancreatic cancer cell migration in the control and miR‑138‑5p downregulated PANC‑1 cells. The present study demonstrated that miR‑138‑5p is important in regulating pancreatic cancer development, possibly through targeting VIM.

23 Article pERK1/2 silencing sensitizes pancreatic cancer BXPC-3 cell to gemcitabine-induced apoptosis via regulating Bax and Bcl-2 expression. 2015

Wang, Min / Lu, Xingjiao / Dong, Xueguang / Hao, Fengyun / Liu, Zimin / Ni, Guangzhen / Chen, Dong. ·Department of Clinical Laboratory, People's Hospital of Laiwu, Laiwu, Shangdong, China. wangminjyk@126.com. · Department of Internal Neurology, People's Hospital of Zhangqiu, ZhangQiu, Shangdong, China. luxj08@163.com. · Department of Clinical Laboratory, People's Hospital of Laiwu, Laiwu, Shangdong, China. dongxgwf@yeah.net. · Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China. cancerhly@163.com. · Department of Clinical Laboratory, People's Hospital of Weifang, Weifang, Shangdong, China. cancerhly@163.com. · Department of Clinical Laboratory, People's Hospital of Laiwu, Laiwu, Shangdong, China. qyfylzm@126.com. · Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China. qyfylzm@126.com. · Department of Clinical Laboratory, People's Hospital of Weifang, Weifang, Shangdong, China. zhangyong2013226@126.com. · Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China. chendd820@126.com. ·World J Surg Oncol · Pubmed #25880226.

ABSTRACT: BACKGROUND: Our previous study has demonstrated that knockdown of activated ERK1/2(pERK1/2) sensitizes pancreatic cancer cells to chemotherapeutic drug gemcitabine (Gem) treatment. However, the details of this survival mechanism remain undefined. It has also shown that Bcl-2 confers resistance and Bax sensitizes to gemcitabine-induced apoptosis in pancreatic cancer cells. Furthermore, the extracellular signaling-regulated kinase (ERK) signaling pathway regulates Bcl-2/Bax expression ratio. We therefore tested the hypothesis that pancreatic cancer cells are resistant to gemcitabine and this resistance is due to activation of ERK1/2 and subsequent upregulation of Bcl-2 and downregulation of Bax. METHODS: Pancreatic cancer cell BXPC-3 was used in the study. The effect of pharmacological inhibition of ERK1/2 on resistance of pancreatic cancer cells to apoptosis induced by treatment with gemcitabine was analyzed. The following methods were utilized: TUNEL and ELISA were used to detect apoptosis. Western blot was used to detect the protein expression. RESULTS: Gemcitabine treatment enhanced the activity of ERK1/2 in the BXPC-3 cells. Inhibition of the ERK1/2 by PD98059 could downregulate Bcl-2 and upregulate Bax and was associated with restoration of sensitivity to gemcitabine in BXPC-3 cells. Depletion of endogenous Bcl-2 expression by specific small interfering RNA transfection significantly increased gemcitabine-induced cell apoptosis. Combined treatment with PD98059 and Bax siRNA transfection could decrease gemcitabine-induced ERK1/2 and Bax activation, which subsequently resulted in decreased apoptosis. CONCLUSIONS: The upregulation of ERK1/2-dependent Bcl-2 and downregulation of ERK1/2-dependent Bax can protect human pancreatic cancer cells from gemcitabine-induced apoptosis. Targeting the ERK1/2-Bax/Bcl-2 pathway may in part lead to sensitization of pancreatic cancer to gemcitabine.

24 Article MicroRNA-138-5p regulates pancreatic cancer cell growth through targeting FOXC1. 2015

Yu, Chao / Wang, Min / Li, Zhipeng / Xiao, Jie / Peng, Feng / Guo, Xingjun / Deng, Yazhu / Jiang, Jianxin / Sun, Chengyi. ·Department of Hepatobiliary Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou Province, 550004, China. ·Cell Oncol (Dordr) · Pubmed #25875420.

ABSTRACT: PURPOSE: The prognosis of pancreatic cancer ranks among the worst of all cancer types, which is primarily due to the fact that during the past decades little progress has been made in its diagnosis and treatment. Here, we set out to investigate the role of microRNA 138 (miR-138-5p) in the regulation of pancreatic cancer cell growth and to assess its role as putative therapeutic target. METHODS: qRT-PCR was used to examine the expression of miR-138-5p in 8 pancreatic cancer cell lines and 18 primary human pancreatic cancer samples. A lentivirual vector containing miR-138-5p mimics (lv-miR-138-5p) was used to exogenously over-express miR-138-5p in the pancreatic cancer cells lines Capan-2 and PANC-1. The effect of this over-expression on cell proliferation was examined using an in vitro propidium iodide fluorescence assay. Capan-2 cells exogenously over-expressing miR-138-5p were transplanted into nude mice to examine its in vivo effect on tumor growth. A predicted target of miR-138-5p (FOXC1) was first validated using a luciferase assay and, subsequently, down-regulated by siRNA to assess its effect on pancreatic cancer cell growth. RESULTS: We found that miR-138-5p was markedly down-regulated in both pancreatic cancer cell lines and primary human pancreatic cancer samples, compared to a human pancreas ductal epithelial (HPDE) cell line and normal pancreatic tissues, respectively (P < 0.05). In addition, we found that in the pancreatic cancer cells lines Capan-2 and PANC-1 lentiviral transfection of miR-138-5p mimicked up-regulation of the endogenous expression of miR-138-5p and, concomitantly, inhibited cancer cell proliferation (P < 0.05). The exogenous over-expression of miR-138-5p also led to a significant inhibition of tumor formation in vivo. Using a luciferase assay, we found that miR-138-5p directly targets FOXC1. In conformity with this notion, we found that FOXC1 was down-regulated upon miR-138-5p over-expression in pancreatic cancer cells. Finally, we found that silencing of FOXC1 by siRNA had an inhibitory effect on pancreatic cancer cell growth. CONCLUSIONS: Our data indicate that miR-138-5p may play an important role in regulating pancreatic cancer cell growth, possibly through targeting FOXC1. Over-expression of miR-138-5p may serve as a novel approach for the treatment of patients with pancreatic cancer.

25 Article Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells. 2015

Li, Xu / Zhu, Feng / Jiang, Jianxin / Sun, Chengyi / Wang, Xin / Shen, Ming / Tian, Rui / Shi, Chengjian / Xu, Meng / Peng, Feng / Guo, Xingjun / Wang, Min / Qin, Renyi. ·Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. · Department of Biliary-Hepatic Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou, China. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: wangmin0013128@yahoo.com.cn. · Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: ryqin@tjh.tjmu.edu.cn. ·Cancer Lett · Pubmed #25444914.

ABSTRACT: Application of oxaliplatin for the treatment of pancreatic cancer (PC) is restricted owing to its toxic side effects and drug resistance. We investigated how withaferin A (WA), a bioactive component isolated from the medicinal plant Withania somnifera, acts synergistically with oxaliplatin on human PC in vitro and in vivo. We found that WA enhanced oxaliplatin-induced growth suppression and apoptosis in PC cells dramatically through a mechanism involving mitochondrial dysfunction and inactivation of the PI3K/AKT pathway. Combination treatment resulted in significant accumulation of intracellular reactive oxygen species (ROS). Pretreatment of cells with the ROS scavenger N-acetylcysteine completely blocked the apoptosis induced by combination treatment, and recovered expression of AKT inactivation, which revealed the important role of ROS in apoptosis and AKT regulation. In vivo, combination therapy showed the strongest anti-tumor effects compared with single agents, without obvious additional toxicity. These results support the notion that combination treatment with oxaliplatin and WA could facilitate development of an effective strategy for PC treatment.

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