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Pancreatic Neoplasms: HELP
Articles by Wei Zhang
Based on 47 articles published since 2010
(Why 47 articles?)
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Between 2010 and 2020, Wei Zhang wrote the following 47 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Meta-Analysis of the Correlation between Apparent Diffusion Coefficient and Standardized Uptake Value in Malignant Disease. 2017

Deng, Shengming / Wu, Zhifang / Wu, Yiwei / Zhang, Wei / Li, Jihui / Dai, Na / Zhang, Bin / Yan, Jianhua. ·Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China. · Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China. · Molecular Imaging Precision Medicine Collaborative Innovation Center, Shanxi Medical University, Taiyuan, China. ·Contrast Media Mol Imaging · Pubmed #29097924.

ABSTRACT: The objective of this meta-analysis is to explore the correlation between the apparent diffusion coefficient (ADC) on diffusion-weighted MR and the standard uptake value (SUV) of

2 Review Surgical treatment of hepato-pancreato-biliary disease in China: the Tongji experience. 2016

Zhang, Binhao / Dong, Wei / Luo, Hongping / Zhu, Xuanru / Chen, Lin / Li, Changhai / Zhu, Peng / Zhang, Wei / Xiang, Shuai / Zhang, Wanguang / Huang, Zhiyong / Chen, Xiao-Ping. ·Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery; Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, 430030, China. · Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery; Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, 430030, China. zyhuang@medmail.com.cn. · Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery; Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Public Health, Wuhan, 430030, China. chenxpchenxp@163.com. ·Sci China Life Sci · Pubmed #27585922.

ABSTRACT: Hepato-pancreato-biliary (HPB) tumors are common in China. However, these tumors are often diagnosed at intermediate/ advanced stages because of the lack of a systemic surveillance program in China. This situation creates many technical challenges for surgeons and increases the incidence of postoperative complications. Therefore, Dr. Xiao-Ping Chen has made many important technical improvements, such as Chen's hepatic portal occlusion method, the anterior approach for liver resection of large HCC tumors, the modified technique of Belghiti's liver-hanging maneuver, inserting biliary-enteric anastomosis technique, and invaginated pancreaticojujunostomy with transpancreatic U-sutures. These techniques are simple, practical, and easy to learn. Owing to these advantages, complicated surgical procedures can be simplified, and the curative effects are greatly improved. These improved techniques have been widely applied in China and will benefit many additional patients. In this review, we introduce our experience of surgically treating intermediate/advanced hepatocellular carcinoma (HCC), hilar cholangiocarcinoma (HC), and pancreatic carcinoma, mainly focusing on technical innovations established by Dr. Chen in HPB surgery.

3 Review MicroRNA Signaling Pathway Network in Pancreatic Ductal Adenocarcinoma. 2015

Sun, Longhao / Chua, Corrine Ying Xuan / Tian, Weijun / Zhang, Zhixiang / Chiao, Paul J / Zhang, Wei. ·Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA; The University of Texas Graduate School of Biomedical Sciences, Houston 77030, USA. · Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China. · Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA; The University of Texas Graduate School of Biomedical Sciences, Houston 77030, USA. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA; The University of Texas Graduate School of Biomedical Sciences, Houston 77030, USA; Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: wzhang@mdanderson.org. ·J Genet Genomics · Pubmed #26554910.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is considered to be the most lethal and aggressive malignancy with high mortality and poor prognosis. Their responses to current multimodal therapeutic regimens are limited. It is urgently needed to identify the molecular mechanism underlying pancreatic oncogenesis. Twelve core signaling cascades have been established critical in PDAC tumorigenesis by governing a wide variety of cellular processes. MicroRNAs (miRNAs) are aberrantly expressed in different types of tumors and play pivotal roles as post-transcriptional regulators of gene expression. Here, we will describe how miRNAs regulate different signaling pathways that contribute to pancreatic oncogenesis and progression.

4 Clinical Trial Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial. 2017

Alistar, Angela / Morris, Bonny B / Desnoyer, Rodwige / Klepin, Heidi D / Hosseinzadeh, Keyanoosh / Clark, Clancy / Cameron, Amy / Leyendecker, John / D'Agostino, Ralph / Topaloglu, Umit / Boteju, Lakmal W / Boteju, Asela R / Shorr, Rob / Zachar, Zuzana / Bingham, Paul M / Ahmed, Tamjeed / Crane, Sandrine / Shah, Riddhishkumar / Migliano, John J / Pardee, Timothy S / Miller, Lance / Hawkins, Gregory / Jin, Guangxu / Zhang, Wei / Pasche, Boris. ·Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. Electronic address: angela.alistar@atlantichealth.org. · Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Section on Surgical Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · UT Southwestern Medical Center, Department of Radiology, Dallas, TX, USA. · Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Biostatistics, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · Department of Chemistry, Cornerstone Pharmaceuticals, Cranbury, NJ, USA. · Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA. · Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. · Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. ·Lancet Oncol · Pubmed #28495639.

ABSTRACT: BACKGROUND: Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. METHODS: In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m FINDINGS: Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m INTERPRETATION: A maximum tolerated dose of CPI-613 was established at 500 mg/m FUNDING: Comprehensive Cancer Center of Wake Forest Baptist Medical Center.

5 Article None 2019

Jones, Martin R / Williamson, Laura M / Topham, James T / Lee, Michael K C / Goytain, Angela / Ho, Julie / Denroche, Robert E / Jang, GunHo / Pleasance, Erin / Shen, Yaoquing / Karasinska, Joanna M / McGhie, John P / Gill, Sharlene / Lim, Howard J / Moore, Malcolm J / Wong, Hui-Li / Ng, Tony / Yip, Stephen / Zhang, Wei / Sadeghi, Sara / Reisle, Carolyn / Mungall, Andrew J / Mungall, Karen L / Moore, Richard A / Ma, Yussanne / Knox, Jennifer J / Gallinger, Steven / Laskin, Janessa / Marra, Marco A / Schaeffer, David F / Jones, Steven J M / Renouf, Daniel J. ·BC Cancer, Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada. · Pancreas Centre British Columbia, Vancouver, Canada. · BC Cancer, Division of Medical Oncology, Vancouver, British Columbia, Canada. · Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada. · PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. · Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. · Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, British Columbia, Canada. · Pancreas Centre British Columbia, Vancouver, Canada. drenouf@bccancer.bc.ca. ·Clin Cancer Res · Pubmed #31068372.

ABSTRACT: PURPOSE: Gene fusions involving neuregulin 1 ( EXPERIMENTAL DESIGN: Forty-seven patients with pancreatic ductal adenocarcinoma received comprehensive whole-genome and transcriptome sequencing and analysis. Two patients with gene fusions involving RESULTS: Three of 47 (6%) patients with advanced pancreatic ductal adenocarcinoma were identified as CONCLUSIONS: This work adds to a growing body of evidence that

6 Article LncRNA SNHG16 promotes tumor growth of pancreatic cancer by targeting miR-218-5p. 2019

Liu, Songyang / Zhang, Wei / Liu, Kai / Liu, Yahui. ·Department of Hepatopancreatobiliary Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, PR China. · Department of Hepatopancreatobiliary Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, PR China. Electronic address: liuyahui588@aliyun.com. ·Biomed Pharmacother · Pubmed #30981105.

ABSTRACT: Small Nucleolar RNA Host Gene (SNHG16) is a novel cancer-related long noncoding RNA (lncRNA) and functions as an oncogene in a variety of cancers. Nonetheless, the expression patterns, biological function, and potential mechanisms in SNHG16 in pancreatic cancer (PC) remain rarely known. An increase in expression of SNHG16 in PC samples against adjacent normal tissues was shown here. Increased SNHG16 was linked intimately to the tumor-node-metastasis (TNM) stage, distant metastasis, tumor differentiation, and poor overall survival. Loss-of-function experiments revealed that SNHG16 knockdown suppressed the proliferation, formation of colonies, ability to migrate and invade in vitro, along with a lowered growth of the tumor in a mouse model. Mechanistically, SNHG16 might serve as a sponge competitive endogenous RNA (ceRNA) for miR-218-5p, thereby playing a role in regulating the expression of high mobility group box 1 (HMGB1) expression, a known direct miR-218-5p target in PC cells. These results provide novel insight into PC tumorigenesis and suggest that SNHG16 could serve as a likely therapeutic intervention in PC.

7 Article Adiponectin Suppresses Human Pancreatic Cancer Growth through Attenuating the β-Catenin Signaling Pathway. 2019

Jiang, Jinghui / Fan, Yingchao / Zhang, Wei / Shen, Yuling / Liu, Tingting / Yao, Ming / Gu, Jianren / Tu, Hong / Gan, Yu. ·State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 25/Ln. 2200 Xietu Road, Shanghai 200032, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, China. ·Int J Biol Sci · Pubmed #30745818.

ABSTRACT: Adipokines are emerging as a link between obesity and obesity-related cancers, including pancreatic cancer. Adiponectin is an abundant adipokine with pleiotropic beneficial roles in metabolic disorders. Low adiponectin levels are commonly observed in human obesity and have been associated with increased pancreatic cancer risk in prospective epidemiologic studies. Here, we investigated the direct effect of adiponectin on human pancreatic cancer

8 Article Aberrant FAM64A mRNA expression is an independent predictor of poor survival in pancreatic cancer. 2019

Jiao, Yan / Fu, Zhuo / Li, Yanqing / Zhang, Wei / Liu, Yahui. ·Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, P.R. China. · Department of Hand and Foot surgery, The First Hospital of Jilin University, Changchun, Jilin, P.R. China. · Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, P.R. China. ·PLoS One · Pubmed #30695070.

ABSTRACT: FAM64A, a marker of cell proliferation, has been investigated as a potential biomarker in several cancers. In the present study, we examined the value of FAM64A expression in the diagnosis and prognosis of pancreatic cancer through bioinformatics analysis of data obtained from The Cancer Genome Atlas (TCGA) database. The diagnostic value of FAM64A expression in pancreatic cancer tissue was deteremined through receiver operating characteristic (ROC) curve analysis, and based on the obtained cut-off value, patients were divided into two groups (high FAM64A expression and low FAM64A expression). Chi-square and Fisher exact tests were applied to identify associations between FAM64A expression and clinical features. Moreover, the effect of FAM64A expression in the survival of pancreatic cancer patients was observed by Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Our results showed that high FAM64A expression in pancreatic cancer was associated with survival status, overall survival (OS), and recurrence. The area under the ROC curve was 0.736, which indicated modest diagnostic value. Patients with higher FAM64A expression had significantly shorter OS and recurrence-free survival (RFS) times. Multivariate survival analysis demonstrated that high FAM64A expression was an independent risk factor for OS and RFS. GSEA identified mitotic spindles, myc targets, MTORC1 signaling, G2M checkpoint, E2F targets, DNA repair, glycolysis and unfolded protein response as differentially enriched with the high FAM64A expression phenotype. In conclusion, high FAM64A mRNA expression is an independent risk factor for poor prognosis in pancreatic cancer.

9 Article Identification of hub genes with diagnostic values in pancreatic cancer by bioinformatics analyses and supervised learning methods. 2018

Li, Chunyang / Zeng, Xiaoxi / Yu, Haopeng / Gu, Yonghong / Zhang, Wei. ·West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China. · Medical Big Data Center, Sichuan University, Chengdu, China. · West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China. weizhang005@126.com. · Medical Big Data Center, Sichuan University, Chengdu, China. weizhang005@126.com. ·World J Surg Oncol · Pubmed #30428899.

ABSTRACT: BACKGROUND: Pancreatic cancer is one of the most lethal tumors with poor prognosis, and lacks of effective biomarkers in diagnosis and treatment. The aim of this investigation was to identify hub genes in pancreatic cancer, which would serve as potential biomarkers for cancer diagnosis and therapy in the future. METHODS: Combination of two expression profiles of GSE16515 and GSE22780 from Gene Expression Omnibus (GEO) database was served as training set. Differentially expressed genes (DEGs) with top 25% variance followed by protein-protein interaction (PPI) network were performed to find candidate genes. Then, hub genes were further screened by survival and cox analyses in The Cancer Genome Atlas (TCGA) database. Finally, hub genes were validated in GSE15471 dataset from GEO by supervised learning methods k-nearest neighbor (kNN) and random forest algorithms. RESULTS: After quality control and batch effect elimination of training set, 181 DEGs bearing top 25% variance were identified as candidate genes. Then, two hub genes, MMP7 and ITGA2, correlating with diagnosis and prognosis of pancreatic cancer were screened as hub genes according to above-mentioned bioinformatics methods. Finally, hub genes were demonstrated to successfully differ tumor samples from normal tissues with predictive accuracies reached to 93.59 and 81.31% by using kNN and random forest algorithms, respectively. CONCLUSIONS: All the hub genes were associated with the regulation of tumor microenvironment, which implicated in tumor proliferation, progression, migration, and metastasis. Our results provide a novel prospect for diagnosis and treatment of pancreatic cancer, which may have a further application in clinical.

10 Article A systematic analysis of the association between Notch1 expression and the patients with digestive tract cancers. 2018

Zhang, Wei / Chen, Hong / Sun, Zhihui / Qiu, Chengyu / Xiao, Jingjie / Luo, Wenli / Liu, Da / Yan, Zhitao / Ou, Huajing / Wen, Xiaoman / Li, Ganxiong / Huang, Gang. ·Department of Gerontology, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832000, Xinjiang, PR China. · The First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, 161005, PR China. · Department of Physiology Medicine School of Shihezi University, Shihezi, 832000, Xinjiang, PR China. ·Biomark Med · Pubmed #30043645.

ABSTRACT: AIM: Notch1 expression remains controversial on digestive tract cancers. This meta-analysis was performed to assess the clinicopathological significance of Notch1 expression in individuals with digestive tract cancers, mainly involving esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), pancreatic cancer (PC) and colorectal cancer (CRC). METHODS: Available articles were searched from the online databases, and the meta-analysis was done using Review Manager software 5.3. RESULTS: 35 studies were included in this analysis (6187 samples). Notch1 is downregulated in esophageal squamous cell carcinoma (p < 0.00001), Notch1 expression at high levels was detected in GC (p = 0.02) and CRC (p < 0.001), and no significant difference exists between PC and normal tissue (p = 0.76). CONCLUSION: Notch1 overexpression in GC and CRC suggested aggressive biological behaviors, and Notch1 may be a biomarker in digestive tract cancers.

11 Article Oxygen-Self-Produced Nanoplatform for Relieving Hypoxia and Breaking Resistance to Sonodynamic Treatment of Pancreatic Cancer. 2017

Chen, Jie / Luo, Honglin / Liu, Yan / Zhang, Wei / Li, Hongxue / Luo, Tao / Zhang, Kun / Zhao, Yongxiang / Liu, Junjie. ·Affiliated Tumor Hospital of Guangxi Medical University , 71 He-di Road, Nanning 530021, People's Republic of China. · Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine , 301 Yan-chang-zhong Road, Shanghai 200072, People's Republic of China. · National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University , 6 Shuang-yong Road, Nanning, Guangxi 530021, People's Republic of China. ·ACS Nano · Pubmed #29236476.

ABSTRACT: Hypoxia as one characteristic hallmark of solid tumors has been demonstrated to be involved in cancer metastasis and progression, induce severe resistance to oxygen-dependent therapies, and hamper the transportation of theranostic agents. To address these issues, an oxygen-self-produced sonodynamic therapy (SDT) nanoplatform involving a modified fluorocarbon (FC)-chain-mediated oxygen delivery protocol has been established to realize highly efficient SDT against hypoxic pancreatic cancer. In this nanoplatform, mesopores and FC chains of FC-chain-functionalized hollow mesoporous organosilica nanoparticle carriers can provide sufficient storage capacity and binding sites for sonosensitizers (IR780) and oxygen, respectively. In vitro and in vivo experiments demonstrate the nanoplatform involving this distinctive oxygen delivery protocol indeed breaks the hypoxia-specific transportation barriers, supplies sufficient oxygen to hypoxic PANC-1 cells especially upon exposure to ultrasound irradiation, and relieves hypoxia. Consequently, hypoxia-induced resistance to SDT is inhibited and sufficient highly reactive oxygen species (ROS) are produced to kill PANC-1 cells and shrink hypoxic PANC-1 pancreatic cancer. This distinctive FC-chain-mediated oxygen delivery method provides an avenue to hypoxia oxygenation and holds great potential in mitigating hypoxia-induced resistance to those oxygen-depleted therapies, e.g., photodynamic therapy, radiotherapy, and chemotherapy.

12 Article [Dihydroartemisinin inhibits proliferation of pancreatic cancer JF-305 cells by regulating expression of apoptosis related proteins and production of reactive oxygen species]. 2017

Li, Ya-Wei / Zhang, Wei / Xu, Na / Li, Yan / Zhang, Hong / Lv, Shi-Jie / Zhu, Wen-He. ·Jilin Medical College, Jilin 132013, China. ·Zhongguo Zhong Yao Za Zhi · Pubmed #29139274.

ABSTRACT: To investigate the effect of dihydroartemisinin on apoptosis of human pancreatic cancer cell line JF-305 and the role of reactive oxygen species(ROS) in the apoptosis of JF-305 cells induced by dihydroartemisinin. MTT assays were used to detect effect of different concentrations of dihydroartemisinin on cells proliferation of JF-305 lines. Cell cycle was detected by flow cytometry, and the apoptotic morphology was observed by Hoechst 333258 fluorescence staining. Annexin V fluorescence staining was used to detect the apoptosis changes of JF-305 cells, while DCFH-DA was used to detect the changes of ROS during apoptosis process. Western blot was used to detect the protein expression changes of Bax, Bcl-2, Cleaved caspase-3, Cleaved caspase-9 and Cyto C. As compared with the control group, the JF-305 cells proliferation was inhibited significantly(P<0.05) after treatment with different concentrations of dihydroartemisimin for 48 h; cell cycle was blocked in the G2/M phase; apoptotic morphology of nuclear condensation, aggregation, and fragmentation was found, and the apoptosis ratio was increased(P<0.05). DCFH-DA detection showed that the cell ROS was increased significantly after dihydroartemisinin treatment(P<0.05). Western blot results showed that the expression of Bcl-2 protein was down-regulated; the expression of Bax protein was up-regulated; the ration of Bax/Bcl-2 was increased and the protein expression levels of Cleaved caspase-3, Cleaved caspase-9 and Cyto C were increased after dihydroartemisinin treatment. Therefore, dihydroartemisinin could induce apoptosis of JF-305 cells, and the possible mechanism may be related to the formation and increasing of ROS.

13 Article Comparison of endoscopic ultrasound guided fine needle aspiration and PET/CT in preoperative diagnosis of pancreatic adenocarcinoma. 2017

Lai, Jin-Ping / Yue, Yong / Zhang, Wei / Zhou, Yihua / Frishberg, David / Jamil, Laith H / Mirocha, James M / Guindi, Maha / Balzer, Bonnie / Bose, Shikha / Cao, Dengfeng / Lo, Simon / Fan, Xuemo / Rutgers, Joanne K. ·Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. Electronic address: jinpinglai@ufl.edu. · Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. · Department of Radiology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. · Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Division of Gastroenterology and Hepatology, Digestive Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Biostatistics Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Department of Pathology, Immunology and Laboratory Medicine, Washington University in St. Louis, St. Louis, MO 63130, USA. · Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: RutgersJK@cshs.org. ·Pancreatology · Pubmed #28501471.

ABSTRACT: BACKGROUND: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the procedure of choice to investigate and sample pancreatic masses for the preoperative diagnosis of pancreatic ductal adenocarcinoma (PDAC). The role of METHODS: Preoperative evaluation by PET/CT and EUS-FNA was performed on 25 patients with pancreatic solid lesions, who underwent a subsequent Whipple procedure or partial pancreatic resection. RESULTS: This series included 19 PDACs and 6 non-PDACs including 1 metastatic breast ductal adenocarcinoma, 2 low grade neuroendocrine tumors, 2 chronic pancreatitis and 1 gastrointestinal tumor abutting the pancreas. EUS-FNA correctly diagnosed 18 of 19 PDACs, 1 metastatic breast ductal adenocarcinoma and all 5 of the other non-PDAC cases. One case of well differentiated PDAC was negative on EUS-FNA. PET/CT provided excellent size and was positive in 14 of 19 PDACs and the metastatic breast ductal adenocarcinoma. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for EUS-FNA in diagnosis of selected pancreatic tumors were 91%, 100%, 100%, 50% and 92%, respectively, while they were 65%, 100%, 100%, 20% and 68% for PET/CT, respectively. CONCLUSIONS: Compared to PET/CT, EUS-FNA has a higher sensitivity and accuracy for preoperative diagnosis of PDAC. However, PET/CT provides excellent size, volume and stage information. A combination of both PET/CT and EUS will better help guide diagnosis and treatment of pancreatic adenocarcinoma.

14 Article eIF5A-PEAK1 Signaling Regulates YAP1/TAZ Protein Expression and Pancreatic Cancer Cell Growth. 2017

Strnadel, Jan / Choi, Sunkyu / Fujimura, Ken / Wang, Huawei / Zhang, Wei / Wyse, Meghan / Wright, Tracy / Gross, Emilie / Peinado, Carlos / Park, Hyun Woo / Bui, Jack / Kelber, Jonathan / Bouvet, Michael / Guan, Kun-Liang / Klemke, Richard L. ·Department of Pathology, University of California, San Diego, La Jolla, California. · Moores Cancer Center, University of California, San Diego, La Jolla, California. · Department of Medicine, University of California, San Diego, La Jolla, California. · Department of Pharmacology, University of California, San Diego, La Jolla, California. · Department of Biology, California State University Northridge, Northridge, California. · Department of Surgery, University of California, San Diego, La Jolla, California. · Department of Pathology, University of California, San Diego, La Jolla, California. rklemke@ucsd.edu. ·Cancer Res · Pubmed #28381547.

ABSTRACT: In pancreatic ductal adenocarcinoma (PDAC), mutant KRAS stimulates the translation initiation factor eIF5A and upregulates the focal adhesion kinase PEAK1, which transmits integrin and growth factor signals mediated by the tumor microenvironment. Although eIF5A-PEAK1 signaling contributes to multiple aggressive cancer cell phenotypes, the downstream signaling processes that mediate these responses are uncharacterized. Through proteomics and informatic analyses of PEAK1-depleted PDAC cells, we defined protein translation, cytoskeleton organization, and cell-cycle regulatory pathways as major pathways controlled by PEAK1. Biochemical and functional studies revealed that the transcription factors YAP1 and TAZ are key targets of eIF5A-PEAK1 signaling. YAP1/TAZ coimmunoprecipitated with PEAK1. Interfering with eIF5A-PEAK1 signaling in PDAC cells inhibited YAP/TAZ protein expression, decreasing expression of stem cell-associated transcription factors (STF) including Oct4, Nanog, c-Myc, and TEAD, thereby decreasing three-dimensional (3D) tumor sphere growth. Conversely, amplified eIF5A-PEAK1 signaling increased YAP1/TAZ expression, increasing expression of STF and enhancing 3D tumor sphere growth. Informatic interrogation of mRNA sequence databases revealed upregulation of the eIF5A-PEAK1-YAP1-TEAD signaling module in PDAC patients. Taken together, our findings indicate that eIF5A-PEAK1-YAP signaling contributes to PDAC development by regulating an STF program associated with increased tumorigenicity.

15 Article A prospective study on the safety and effectiveness of using lauromacrogol for ablation of pancreatic cystic neoplasms with the aid of EUS. 2017

Linghu, Enqiang / Du, Chen / Chai, Ningli / Li, Huikai / Wang, Zhiqiang / Sun, Yufa / Xu, Wei / Guo, Xu / Ning, Bo / Sun, Lihua / Zhang, Wei / Wang, Xiangdong / Tang, Ping / Feng, Jia. ·Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, China. · Department of Health Care, Central Guard Bureau, Beijing, China. ·Gastrointest Endosc · Pubmed #28365355.

ABSTRACT: BACKGROUND AND AIMS: With the development of imaging techniques, the detection rate of pancreatic cystic neoplasms (PCNs) has increased. The surgical morbidity and mortality rates of PCNs are quite high. This study is intended to evaluate the safety and effectiveness of a minimally invasive treatment, EUS-guided PCN ablation with lauromacrogol. METHODS: From April 2015 to May 2016, 120 patients with PCNs were enrolled to undergo EUS. We prospectively studied 29 of the 120 patients who underwent EUS-guided ablation with lauromacrogol. The follow-up contrast-enhanced CT or magnetic resonance image was conducted at 3 months and then 6 months after ablation. We determined the effectiveness of ablation by the changes in the volume of the cysts. RESULTS: Twenty-nine patients were enrolled in the study, and 7 of them underwent a second ablation; therefore, there were 36 treatments. The mean tumor diameter was 28.6 ± 14.5 mm preoperation, whereas the diameter postoperation was 13.4 ± 10.5 mm. Mild pancreatitis occurred in 2 patients and moderate fever in 1; they occurred in the cysts located in the head/uncinate. Among the 29 treatments with complete follow-up of 9 months (range, 3-15), 11 had complete response and 9 had partial response. The resolution rate was 37.9% (11/29) with 36.4% (8/22) in the cysts of the head/uncinate and 42.9% (3/7) in the body/tail (P > .05). CONCLUSIONS: EUS-guided PCN ablation with lauromacrogol is safe and efficient. Adverse event rates seem to be higher in the head/uncinate than in the body/tail, but their resolution rates are similar. Further studies involving larger populations and longer follow-ups are warranted.

16 Article Genome-scale analysis identifies GJB2 and ERO1LB as prognosis markers in patients with pancreatic cancer. 2017

Zhu, Tao / Gao, Yuan-Feng / Chen, Yi-Xin / Wang, Zhi-Bin / Yin, Ji-Ye / Mao, Xiao-Yuan / Li, Xi / Zhang, Wei / Zhou, Hong-Hao / Liu, Zhao-Qian. ·Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China. · Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China. ·Oncotarget · Pubmed #28177904.

ABSTRACT: Pancreatic cancer is a complex and heterogeneous disease with the etiology largely unknown. The deadly nature of pancreatic cancer, with an extremely low 5-year survival rate, renders urgent a better understanding of the molecular events underlying it. The aim of this study is to investigate the gene expression module of pancreatic adenocarcinoma and to identify differentially expressed genes (DEGs) with prognostic potentials. Transcriptome microarray data of five GEO datasets (GSE15471, GSE16515, GSE18670, GSE32676, GSE71989), including 117 primary tumor samples and 73 normal pancreatic tissue samples, were utilized to identify DEGs. The five sets of DEGs had an overlapping subset consisting of 98 genes (90 up-regulated and 8 down-regulated), which were probably common to pancreatic cancer. Gene ontology (GO) analysis of the 98 DEGs showed that cell cycle and cell adhesion were the major enriched processes, and extracellular matrix (ECM)-receptor interaction and p53 signaling pathway were the most enriched pathways according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Elevated expression of gap junction protein beta 2 (GJB2) and reduced endoplasmic reticulum oxidoreductase 1-like beta (ERO1LB) expression were validated in an independent cohort. Kaplan-Meier survival analysis revealed that GJB2 and ERO1LB levels were significantly associated with the overall survival of pancreatic cancer patients. GJB2 and ERO1LB are implicated in pancreatic cancer progression and can be used to predict patient survival. Therapeutic strategies targeting GJB2 and facilitating ERO1LB expression may deserve evaluation to improve prognosis of pancreatic cancer patients.

17 Article MIR506 induces autophagy-related cell death in pancreatic cancer cells by targeting the STAT3 pathway. 2017

Sun, Longhao / Hu, Limei / Cogdell, David / Lu, Li / Gao, Chao / Tian, Weijun / Zhang, Zhixiang / Kang, Ya'an / Fleming, Jason B / Zhang, Wei. ·a Department of Cancer Biology , Comprehensive Cancer Center of Wake Forest Baptist Medical Center , Winston-Salem , NC , USA. · b Department of Pathology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA. · c Department of General Surgery , Tianjin Medical University General Hospital , Tianjin , China. · d Department of Surgical Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA. ·Autophagy · Pubmed #28121485.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and lethal cancer. The role of autophagy in the pathobiology of PDAC is intricate, with opposing functions manifested in different cellular contexts. MIR506 functions as a tumor suppressor in many cancer types through the regulation of multiple pathways. In this study, we hypothesized that MIR506 exerted a tumor suppression function in PDAC by inducing autophagy-related cell death. Our results provided evidence that downregulation of MIR506 expression was associated with disease progression in human PDAC. MIR506 triggered autophagic flux in PDAC cells, which led to autophagy-related cell death through direct targeting of the STAT3 (signal transducer and activator of transcription 3)-BCL2-BECN1 axis. Silencing and inhibiting STAT3 recapitulated the effects of MIR506, whereas forced expression of STAT3 abrogated the effects of MIR506. We propose that the apoptosis-inhibitory protein BCL2, which also inhibits induction of autophagy by blocking BECN1, was inhibited by MIR506 through targeting STAT3, thus augmenting BECN1 and promoting autophagy-related cell death. Silencing BECN1 and overexpression of BCL2 abrogated the effects of MIR506. These findings expand the known mechanisms of MIR506-mediated tumor suppression to activation of autophagy-related cell death and suggest a strategy for using MIR506 as an anti-STAT3 approach to PDAC treatment.

18 Article Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression. 2017

Huang, Chongbiao / Li, Na / Li, Zengxun / Chang, Antao / Chen, Yanan / Zhao, Tiansuo / Li, Yang / Wang, Xiuchao / Zhang, Wei / Wang, Zhimin / Luo, Lin / Shi, Jingjing / Yang, Shengyu / Ren, He / Hao, Jihui. ·Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. · Senior Ward, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. · School of Medicine, Nankai University, Tianjin 300071, China. · Tianjin Hepingqu Gynaechology and Obstetrics Hospital, Tianjin 300000, China. · Department of Tissue Bank, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. · Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA. ·Nat Commun · Pubmed #28102193.

ABSTRACT: Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation. Mechanistically, IL-35 promotes ICAM1 overexpression through a GP130-STAT1 signalling pathway, which facilitates endothelial adhesion and transendothelial migration via an ICAM1-fibrinogen-ICAM1 bridge. In an orthotopic xenograft model, IL-35 promotes spontaneous pancreatic cancer metastasis in an ICAM1-dependent manner. Together, our results indicate additional functions of IL-35 in promoting PDAC metastasis through mediating ICAM1 expression.

19 Article Aspirin Use and Reduced Risk of Pancreatic Cancer. 2017

Risch, Harvey A / Lu, Lingeng / Streicher, Samantha A / Wang, Jing / Zhang, Wei / Ni, Quanxing / Kidd, Mark S / Yu, Herbert / Gao, Yu-Tang. ·Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. harvey.risch@yale.edu. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. · Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. · Wren Laboratories LLC, Branford, Connecticut. · Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii. ·Cancer Epidemiol Biomarkers Prev · Pubmed #27999143.

ABSTRACT: BACKGROUND: Few options besides the avoidance of smoking and obesity are available to prevent pancreatic cancer. The association between aspirin use and risk of pancreatic cancer has been inconsistent across studies. METHODS: We performed a population-based study of 761 case and 794 control subjects frequency matched on sex and age during 2006 to 2011 in Shanghai, China. Participants were asked about episodes of regular use of aspirin, tablets per day or week, and ages that the use started and stopped. Data were analyzed by unconditional logistic regression, with adjustments for age, sex, education, body mass index, years of cigarette smoking, cigarettes smoked per day, Helicobacter pylori CagA seropositivity, ABO blood group, and history of diabetes mellitus. Meta-regression was carried out to summarize the literature. RESULTS: Ever-regular use of aspirin was associated with lowered risk of pancreatic cancer: OR = 0.54; 95% confidence interval (CI), 0.40-0.73; P = 10 CONCLUSIONS: Regular use of aspirin thus appears to reduce risk of pancreatic cancer by almost half. IMPACT: People who take aspirin for prevention of other diseases likely also reduce their risk of pancreatic cancer. Aside from benefits for both cardiovascular disease and certain cancers, long-term aspirin use entails some risks of bleeding complications, which necessitates risk-benefit analysis for individual decisions about use. Cancer Epidemiol Biomarkers Prev; 26(1); 68-74. ©2016 AACR.

20 Article IGFBP2 Activates the NF-κB Pathway to Drive Epithelial-Mesenchymal Transition and Invasive Character in Pancreatic Ductal Adenocarcinoma. 2016

Gao, Song / Sun, Yan / Zhang, Xuebin / Hu, Limei / Liu, Yuexin / Chua, Corrine Yingxuan / Phillips, Lynette M / Ren, He / Fleming, Jason B / Wang, Huamin / Chiao, Paul J / Hao, Jihui / Zhang, Wei. ·Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Pancreatic Carcinoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P.R. China. · Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P.R. China. · Department of Pathology, Tianjin Huanhu Hospital, Tianjin, P.R. China. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Pancreatic Carcinoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P.R. China. wezhang@wakehealth.edu haojihui@tjmuch.com. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. wezhang@wakehealth.edu haojihui@tjmuch.com. · Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Winston-Salem, North Carolina. ·Cancer Res · Pubmed #27659045.

ABSTRACT: The molecular basis underlying the particularly aggressive nature of pancreatic ductal adenocarcinoma (PDAC) still remains unclear. Here we report evidence that the insulin-like growth factor-binding protein IGFBP2 acts as a potent oncogene to drive its extremely malignant character. We found that elevated IGFBP2 expression in primary tumors was associated with lymph node metastasis and shorter survival in patients with PDAC. Enforced expression of IGFBP2 promoted invasion and metastasis of PDAC cells in vitro and in vivo by inducing NF-κB-dependent epithelial-mesenchymal transition (EMT). Mechanistic investigations revealed that IGFBP2 induced the nuclear translocation and phosphorylation of the p65 NF-κB subunit through the PI3K/Akt/IKKβ pathway. Conversely, enforced expression of PTEN blunted this signaling pathway and restored an epithelial phenotype to PDAC cells in the presence of overexpressed IGFBP2. Overall, our results identify IGFBP2 as a pivotal regulator of an EMT axis in PDAC, the activation of which is sufficient to confer the characteristically aggressive clinical features of this disease. Cancer Res; 76(22); 6543-54. ©2016 AACR.

21 Article (‑)‑Epigallocatechin‑3‑gallate induces apoptosis in human pancreatic cancer cells via PTEN. 2016

Liu, Shi / Xu, Zhong-Ling / Sun, Li / Liu, Ying / Li, Cheng-Chong / Li, Hong-Mei / Zhang, Wei / Li, Cheng-Jun / Qin, Wei. ·Department of General Surgery, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161099, P.R. China. · Department of Oncology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161099, P.R. China. · Department of Pharmaceutical Science, Qiqihar Medical University, Qiqihar, Heilongjiang 161099, P.R. China. ·Mol Med Rep · Pubmed #27176210.

ABSTRACT: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a cancer suppressor gene and an important negative regulator in the phosphatidylinositide 3‑kinase (PI3K)/protein kinase B (Akt)/ mechanistic target of rapamycin (mTOR) signaling pathway. The PI3K/Akt/mTOR pathway can promote cancer cell survival, proliferation and progression. In the present study, the effects of (‑)‑epigallocatechin‑3‑gallate (EGCG) on PI3K/Akt/mTOR signaling in pancreatic cancer cells and PTEN knockdown cells were measured, in addition to assessing its therapeutic potential in pancreatic cancer. The apoptosis and proliferation of the cancer cells were examined by flow cytometry and Cell Counting kit‑8 assay, respectively. The expression of genes and proteins in the PI3K/Akt/mTOR signaling pathway were investigated by reverse transcription‑polymerase chain reaction and western blotting, respectively. The results suggested that the EGCG‑induced apoptosis, proliferation inhibition and downregulated expression of phosphorylated (p)‑Akt and p‑mTOR were partially attenuated in PTEN‑knockdown cells. In conclusion, the results indicated that EGCG is able to reduce proliferation and induce the apoptosis of pancreatic cancer cells associated with the expression of PTEN. Additionally, EGCG can suppress the expression of p‑Akt and p‑mTOR via PTEN to regulate the PI3K/Akt/mTOR pathway. The results suggest that EGCG may represent a potential treatment for pancreatic cancer, based on PTEN activation.

22 Article Menstrual and Reproductive Factors, Hormone Use, and Risk of Pancreatic Cancer: Analysis From the International Pancreatic Cancer Case-Control Consortium (PanC4). 2016

Lujan-Barroso, Leila / Zhang, Wei / Olson, Sara H / Gao, Yu-Tang / Yu, Herbert / Baghurst, Peter A / Bracci, Paige M / Bueno-de-Mesquita, H Bas / Foretová, Lenka / Gallinger, Steven / Holcatova, Ivana / Janout, Vladimír / Ji, Bu-Tian / Kurtz, Robert C / La Vecchia, Carlo / Lagiou, Pagona / Li, Donghui / Miller, Anthony B / Serraino, Diego / Zatonski, Witold / Risch, Harvey A / Duell, Eric J. ·From the *Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; †Department of Epidemiology, Shanghai Cancer Institute and Jiao Tong University, Shanghai, China; ‡Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; §Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI; ∥Public Health, Women's and Children's Hospital, Adelaide, SA, Australia; ¶University of California, San Francisco, San Francisco, CA; #National Institute for Public Health and the Environment (RIVM), Bilthoven; **Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands; ††Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; ‡‡Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; §§Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Institute and MF MU, Brno, Czech Republic; ∥∥University Health Network, Department of Surgery, University of Toronto, Toronto, Canada; ¶¶Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague; ##Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic; ***National Cancer Institute, Bethesda, MD; †††Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; ‡‡‡Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; §§§Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Greece; ∥∥∥Department of Epidemiology, Harvard School of Public Health, Boston, MA; ¶¶¶M.D. Anderson Cancer Center, University of Texas, Houston, TX; ###Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; ****Unit of Epidemiology and Biostatistics, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; ††††Cancer Center and Institute of Oncology, Warsaw, Poland; and ‡‡‡‡Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT. ·Pancreas · Pubmed #27088489.

ABSTRACT: OBJECTIVES: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC). METHODS: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates. RESULTS: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84). CONCLUSIONS: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary.

23 Article Identification of initial leads directed at the calmodulin-binding region on the Src-SH2 domain that exhibit anti-proliferation activity against pancreatic cancer. 2016

Tzou, Ywh-Min / Bailey, Sarah K / Yuan, Kaiyu / Shin, Ronald / Zhang, Wei / Chen, Yabing / Singh, Raj K / Shevde, Lalita A / Krishna, N Rama. ·Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, United States. · Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, United States. · Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, United States. · Southern Research, Birmingham, AL 35205, United States. · Vivo Biosciences, Inc., 1601 12th Ave South, Birmingham, AL 35205, United States. · Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, United States. · Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, United States. Electronic address: nrk@uab.edu. ·Bioorg Med Chem Lett · Pubmed #26803204.

ABSTRACT: Cellular calmodulin binds to the SH2 domain of Src kinase, and upon Fas activation it recruits Src into the death-inducing signaling complex. This results in Src-ERK activation of cell survival pathway through which pancreatic cancer cells survive and proliferate. We had proposed that the inhibition of the interaction of calmodulin with Src-SH2 domain is an attractive strategy to inhibit the proliferation of pancreatic cancer. Thus we have performed screening of compound libraries by a combination of methods and identified some compounds (initial leads) that target the calmodulin-binding region on the SH2 domain and inhibit the proliferation of pancreatic cancer cells in in vitro assays. Most of these compounds also exhibited varying degrees of cytotoxicity when tested against immortalized breast epithelial cell line (MCF10A). These initial leads are likely candidates for development in targeted delivery of compounds to cancer cells without affecting normal cells.

24 Article Tetraspanin 1 is involved in survival, proliferation and carcinogenesis of pancreatic cancer. 2015

Hou, Feng-Qiang / Lei, Xi-Feng / Yao, Jian-Long / Wang, Yi-Jin / Zhang, Wei. ·Department of General Surgery, The Weinan Central Hospital, Weinan, Shaanxi 714000, P.R. China. ·Oncol Rep · Pubmed #26370588.

ABSTRACT: Pancreatic cancer (PCC) is one of the most difficult cancers to treat and the 10th leading cause of cancer-related death in worldwide. Studies have demonstrated that the tetraspanin 1 (Tspan1) is overexpressed in various cancers and may be a potential therapeutic strategy for the treatment of different cancers. However, the possible role of Tspan1 in PCC is still unknown. In the present study, our data revealed that the increased Tspan1 in PCC tissues was associated with the clinicopathological features and survival rate of PCC patient. We also investigated the effects of Tspan1 gene knockdown on the biological behavior of human PCC. The expression of Tspan1 (detected by immunohistochemistry, qRT-PCR and western blot analysis) derived from human PCC tissues and cell lines (AsPC-1 and PANC-1), were significantly elevated compared with those of the control (P<0.05). Transfection with siRNA-targeting Tspan1 significantly decreased proliferation, increased the apoptosis and reduced migration and invasion of AsPC-1 and PANC-1 cells. The present study demonstrated that Tspan1 plays an important role in PCC carcinogenic progression, including migration and invasion. The siRNA targeting of Tspan1 may be a potential therapeutic strategy for the treatment of PCC.

25 Article Genomic expression profiling and bioinformatics analysis of pancreatic cancer. 2015

Han, Dong-Yan / Fu, Da / Xi, Hao / Li, Qian-Yu / Feng, Li-Jin / Zhang, Wei / Ji, Guo / Xiao, Jia-Cheng / Wei, Qing. ·Department of Pathology, Shanghai Tenth People's Hospital, Shanghai 200072, P.R. China. ·Mol Med Rep · Pubmed #26062681.

ABSTRACT: Pancreatic cancer is a polygenic disease and the fourth leading cause of cancer-associated mortality worldwide; however, the tumorigenesis of pancreatic cancer remains poorly understood. Research at a molecular level, which includes the exploration of biomarkers for early diagnosis and specific targets for therapy, may effectively aid in the diagnosis of pancreatic cancer in its early stages and in the development of targeted molecular‑biological approaches for treatment, thus improving prognosis. By conducting expression profiling in para‑carcinoma, carcinoma and relapse of human pancreatic tissues, 319 genes or transcripts with differential expression levels >3‑fold between these tissue types were identified. Further analysis with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that the translation, nucleus assembly processes and molecular functions associated with vitamin B6 and pyridoxal phosphate binding in pancreatic carcinoma were abnormal. Pancreatic cancer was additionally identified to be closely associated with certain autoimmune diseases, including type I diabetes mellitus and systemic lupus erythematosus.

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