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Pancreatic Neoplasms: HELP
Articles by Wei Wang
Based on 67 articles published since 2010
(Why 67 articles?)
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Between 2010 and 2020, Wei Wang wrote the following 67 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review A Systematic Review and Meta-Analysis of Laparoscopic and Open Distal Pancreatectomy of Nonductal Adenocarcinomatous Pancreatic Tumor (NDACPT) in the Pancreatic Body and Tail. 2017

Yi, Xiaojiang / Chen, Sile / Wang, Wei / Zou, Liaonan / Diao, Dechang / Zheng, Yansheng / He, Yaobin / Li, Hongming / Luo, Lijie / Xiong, Wenjun / Wan, Jin. ·*Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine †Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China. ·Surg Laparosc Endosc Percutan Tech · Pubmed #28520652.

ABSTRACT: BACKGROUND: Currently, laparoscopic distal pancreatectomy is regarded as a safe and effective surgical approach for lesions in the body and tail of the pancreas. This review examined the evidence from published data of comparative studies of laparoscopic versus open distal pancreatectomy of nonductal adenocarcinomatous pancreatic tumor in pancreatic body and tail. METHODS: A systematic review of the studies comparing laparoscopic and open distal pancreatectomy was conducted. Comparative studies published between January 1996 and June 2016 were included. Studies were selected on the basis of specific inclusion and exclusion criteria. These 2 techniques were compared regarding several outcomes of interest, which were divided into preoperative, operative, postoperative, and pathologic characteristics, postoperative biomarker, and hospital stay cost. Sensitivity and subgroup analysis partially confirmed the robustness of these data. RESULTS: Ten comparative case-control studies involving 712 patients (53.7% laparoscopic and 46.3% open), who underwent a distal pancreatectomy were included. The results favored laparoscopy with regard to intraoperative blood loss (P=0.0001), the rate of blood transfusion (P=0.02), total hospital stay (P=0.004), postoperative hospital stay (P<0.0001), overall morbidity (P=0.0002), the rate of wound infection (P=0.05), time to initial feeds (P<0.0001), first flatus time (P=0.008), duration of pain-killer intake (P=0.0003), and C-reactive protein on postoperative day 1 (P=<0.0001). In the subgroup analysis, excluding western country studies, operation time changed to have a statistically significant difference between these 2 groups (P=0.02). CONCLUSIONS: Laparoscopic resection results in improved operative and postoperative outcomes compared with open surgery according to the results of the present meta-analysis. It may be a safe and feasible option for nonductal adenocarcinomatous pancreatic tumor patients in pancreatic body and tail. However, randomized controlled trials should be undertaken to confirm the relevance of these findings.

2 Review Increased Risk of Pancreatic Cancer Related to Gallstones and Cholecystectomy: A Systematic Review and Meta-Analysis. 2016

Fan, Yonggang / Hu, Jie / Feng, Bing / Wang, Wei / Yao, Guoliang / Zhai, Jingming / Li, Xin. ·From the *Departments of General Surgery and †Anesthesiology, The First Affiliated Hospital of Henan Science and Technology University, Luoyang, Henan Province; and ‡Department of Physiology, The Basic Medicine College of Weifang Medical University, Weifang, Shandong Province, China. ·Pancreas · Pubmed #26684857.

ABSTRACT: To investigate the potential roles of gallstones and cholecystectomy in pancreatic carcinogenesis, we performed the first meta-analysis of all currently published studies by pooling relative risks (RRs) with 95% confidence intervals (95% CIs). Stratified analysis by ethnicity, study design, and common adjusted factors were also conducted. Individuals with a history of gallstones and cholecystectomy were at increased risk of pancreatic cancer (RR, 1.39; 95% CI, 1.28-1.52; P < 0.001). Gallstones and cholecystectomy were also associated with an elevated risk of pancreatic cancer, respectively (for gallstones: RR, 1.70; 95% CI, 1.30-2.21; P < 0.001; for cholecystectomy: RR, 1.31; 95% CI, 1.19-1.43; P < 0.001). The positive association is observed among not only the Asian population but also whites. The pooled findings were further confirmed by sensitivity analysis and stratified analyses in case-control and cohort studies. Stratified analyses by different adjusted factors further showed that the increased risk of pancreatic cancer was independent of confounders including diabetes, obesity, smoking, and follow-up years of postcholecystectomy. A history of gallstones and cholecystectomy is a robust risk factor for pancreatic cancer. Gallstone disease or cholecystectomy alone is also an independent risk factor for pancreatic carcinogenesis.

3 Clinical Trial The efficacy and safety of modified FOLFIRINOX as first-line chemotherapy for Chinese patients with metastatic pancreatic cancer. 2019

Wang, Zhi-Qiang / Zhang, Fei / Deng, Ting / Zhang, Le / Feng, Fen / Wang, Feng-Hua / Wang, Wei / Wang, De-Shen / Luo, Hui-Yan / Xu, Rui-Hua / Ba, Yi / Li, Yu-Hong. ·Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China. · Department of Gastrointestinal Medical Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China. · Cancer Center, The First People's Hospital of Foshan, Foshan, 528000, Guangdong, People's Republic of China. · Department of Gastrointestinal Medical Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China. bayi@tjmuch.com. · Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China. liyh@sysucc.org.cn. ·Cancer Commun (Lond) · Pubmed #31068222.

ABSTRACT: BACKGROUND: Oxaliplatin, irinotecan, 5-fluorouracil, and L-leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 or 4 adverse events associated with the standard dosage of FOLFIRINOX limits its widespread use in clinical practice. In this study, we were to evaluate the efficacy and safety of a modified FOLFIRINOX regimen as a first-line chemotherapy for Chinese patients with metastatic PC. METHODS: Patients with histologically confirmed primary metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 were recruited to receive the modified FOLFIRINOX regimen (intravenous infusion of oxaliplatin, 65 mg/m RESULTS: Sixty-five patients were enrolled from July 2012 to April 2017 in three institutions, and they all received at least one cycle of chemotherapy, with a median of 8 cycles (range 1-12 cycles). No complete response was observed. Twenty-one (32.3%) patients had partial responses, and 27 (41.5%) had SD. The ORR and disease control rate of the study cohort was 32.3% and 73.8%. The estimated median overall survival and progression-free survival were 11.60 (95% confidence interval [CI] 8.76-14.44) and 5.77 (95% CI 5.00-6.54) months. Major grade 3 or 4 adverse events included neutropenia (12.3%) and diarrhea (6.2%). No treatment-related death was observed. CONCLUSIONS: Modified FOLFIRINOX was well-tolerated and might be a promising option as first-line therapy for Chinese patients with metastatic PC. Trial registration ClinicalTrials.gov, NCT02028806. Registered 7 January 2014, https://clinicaltrials.gov/ct2/show/NCT02028806.

4 Article The WW domains dictate isoform-specific regulation of YAP1 stability and pancreatic cancer cell malignancy. 2020

Guo, Qiang / Quan, Meiyu / Dong, Jinglai / Bai, Jing / Wang, Jie / Han, Rui / Wang, Wei / Cai, Yaxin / Lv, Yu-Qing / Chen, Qianjie / Xu, Huijing / Lyu, Han-Deng / Deng, Liancheng / Zhou, Depu / Xiao, Xueyuan / De Langhe, Stijn / Billadeau, Daniel D / Lou, Zhenkun / Zhang, Jin-San. ·School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. · Center for Precision Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. · Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing 100875, China. · Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, 35294-2182 AL, USA. · Division of Oncology Research, and Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN 55905, USA. · Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, China. ·Theranostics · Pubmed #32292505.

ABSTRACT: YAP1 is a key mediator of the Hippo pathway capable of exerting a profound effect on organ size as well as tumorigenesis. Alternative mRNA splicing of human YAP1 results in at least 8 protein isoforms that differ within the 2

5 Article Identification of pancreatic cancer type related factors by Weighted Gene Co-Expression Network Analysis. 2020

Wang, Wei / Xing, Haibo / Huang, Changxin / Pan, Hong / Li, Da. ·Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3# Eastern Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China. · Department of ICU, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Xiasha Campus, 368# Xiasha Road, Hangzhou, 310019, Zhejiang, People's Republic of China. · Department of Medical Oncology, Hangzhou Normal University Affiliated Hospital, Hangzhou, 310000, Zhejiang, People's Republic of China. · Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Xiasha Campus, 368# Xiasha Road, Hangzhou, 310019, Zhejiang, People's Republic of China. phltix@aliyun.com. · Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3# Eastern Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China. lidaonconew@zju.edu.cn. ·Med Oncol · Pubmed #32200436.

ABSTRACT: This study aims to identify the core modules associated with pancreatic cancer (PC) types and the ncRNAs and transcription factors (TFs) that regulate core module genes by weighted gene co-expression network analysis (WGCNA). WGCNA was used to analyze the union of genes related to PC in NCBI and OMIM databases and the differentially expressed genes screened by TCGA-PAAD database. Samples were clustered according to gene expression in gene modules and Fisher exact method was performed. GO and KEGG were used for enrichment analysis to visually display module genes and screen driver genes. Hypergeometric test method was used to calculate pivot nodes among ncRNAs, TFs and mRNA based on RAID 2.0 and TRRUST v2 databases. The blue and yellow modules were identified as the core modules associated with PC types. MST1R, TMPRSS, MIR198, SULF1, COL1A1 and FAP were the core genes in the modules. Hypergeometric test results showed that ANCR, miR-3134, MT1DP, LOC154449, LOC28329 and other ncRNAs were key factors driving blue module genes, while LINC-ROR, UCA1, SNORD114-4, HEIH, SNORD114-6 and other ncRNAs were key factors driving yellow module genes. TFs with significant regulatory effect on blue module included LCOR, PIAS4, ZEB1, SNAI2, SMARCA4, etc. and on yellow module included HOXC6, PER2, HOXD3, TWIST2, VHL, etc. The core modules associated with PC types were proved as yellow and blue modules, and important ncRNAs and TFs regulating yellow and blue modules were found. This study provides relevant evidence for further identification of PC types.

6 Article Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells. 2020

Wang, Wei / Liu, Bowei / Sun, Suofeng / Lan, Ling / Chen, Yu / Han, Shuangyin / Li, Xiuling / Li, Zhaoshen. ·Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, People's Republic of China. · Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, People's Republic of China. · Department of Gastroenterology, Nanhai Hospital, Southern Medical University, Foshan, Guangdong 528200, People's Republic of China. ·Onco Targets Ther · Pubmed #32158231.

ABSTRACT: Background: 5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Methods: Cell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect proliferation, apoptosis and migration in PANC-1 cells. The expressions of Bcl-2, Bax, cleaved caspase 3, PTEN, p-Akt and p-ERK in PANC-1 cells were detected with Western blot assay. Results: In this study, the inhibitory effects of 5-Fu on the proliferation, migration and invasion of PANC-1 cells were significantly enhanced following transfection with miR-486-5p antagonist. In addition, downregulation of miR-486-5p markedly enhanced the pro-apoptosis effect of 5-Fu on PANC-1 cells. Moreover, bioinformatics analysis and luciferase reporter assay identified that PTEN was the directly binding target of miR-486-5p. Meanwhile, downregulation of miR-486-5p markedly enhanced the anti-tumor effect of 5-Fu in PANC-1 cells via upregulation of the level of PTEN, and downregulation of the expressions of p-ERK and p-Akt. In vivo experiments confirmed that knockdown of miR-486-5p could enhance the anti-tumor effect of 5-Fu in PANC-1 xenograft model. Conclusion: We found that the downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Therefore, miR-486-5p antagonist plus 5-Fu might be considered as a potential therapeutic strategy for the treatment of pancreatic cancer.

7 Article Validation of European evidence-based guidelines and American College of Gastroenterology guidelines as predictors of advanced neoplasia in patients with suspected mucinous pancreatic cystic neoplasms. 2020

Sun, Liqi / Wang, Wei / Wang, Yang / Jiang, Fei / Peng, Lisi / Jin, Gang / Jin, Zhendong. ·Department of Gastroenterology, Changhai Hospital, Navy Military Medical University, Shanghai, China. · Department of Radiology, Changhai Hospital, Navy Military Medical University, Shanghai, China. · Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University, Shanghai, China. ·J Gastroenterol Hepatol · Pubmed #31900960.

ABSTRACT: BACKGROUND AND AIM: The European evidence-based guidelines (EEG) and American College of Gastroenterology Guidelines (ACGG) have been published to guide the management of pancreatic cystic lesions. We aim to evaluate the value of both guidelines in predicting advanced pancreatic cystic lesions (A-PCLs) with preoperatively imaging-suspected cystic mucinous pancreatic neoplasms (cMNs). METHODS: One hundred ninety-eight patients who underwent resections from 2013 to 2019 for suspected cMNs were retrospectively reviewed. Receiver operating characteristic curves were calculated and compared with measure diagnostic value. RESULTS: Sixty-two patients were diagnosed with A-PCLs pathologically. Cross-imaging modalities had comparable diagnostic accuracy to endoscopic ultrasound in type classification and A-PCLs prediction. Receiver operating characteristic curve comparison analyses showed that EEG absolute + MCN (EEG CONCLUSION: On the basis of cross-imaging evaluations, both sets of guidelines were found to be helpful in identifying A-PCLs in suspected cMNs with comparable performance. EEG

8 Article Efficacy of extended versus standard lymphadenectomy in pancreatoduodenectomy for pancreatic head adenocarcinoma. An update meta-analysis. 2019

Wang, Wei / He, Ying / Wu, Lun / Ye, Lin / Yao, Lichao / Tang, Zhigang. ·Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, PR China. · School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, Hubei Province, PR China. · Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, PR China. Electronic address: rm002251@whu.edu.cn. ·Pancreatology · Pubmed #31668841.

ABSTRACT: BACKGROUND: Surgical resection is the only possible cure for pancreatic cancer, it remains controversial whether extend lymphadenectomy in pancreatoduodenectomy (EPD) is better than standard lymphadenectomy in pancreatoduodenectomy (SPD). The aim of this study was to compare the efficacy of EPD with SPD for pancreatic head adenocarcinoma. METHODS: A specific search of online databases including PubMed, Web of Science, Embase, and Cochrane library was conducted from January 1990 to October 2018. Relative perioperative outcomes were synthesized. Single-arm meta-analysis was also performed. RESULTS: A total of eight studies involving 687 (342 vs 345) patients were included for analysis in our study. The number of lymph nodes harvested [24.54 vs 13.29; weighted mean difference (WMD) -10.69, P = 0.000], operative time (469.84 min vs 354.85 min; WMD -99.09, P = 0.000), and diarrhea (postoperative three months) [45.1% vs 18.2%; odds radio (OR) 0.20, P = 0.014] were significantly higher in patients who underwent EPD than SPD. The perioperative complications (35% vs 28.8%; OR 0.79, P = 0.186), tumor size (3.27 cm vs 3.248 cm; WMD -0.11, P = 0.256), lymph node metastasis (66% vs 55.9%; OR 0.71, P = 0.105), and positive margin (10.4% vs 11.3%; OR 1.28, P = 0.392) were no significant differences between EPD group and SPD group. Extended lymphadenectomy in pancreatoduodenectomy dose not contribute to the overall survival of patients with adenocarcinoma of the pancreatic head [hazard ratio (HR) 0.95; 95% CI 0.78-1.15; P = 0.61]. CONCLUSION: The update meta-analysis shows that EPD failed to improve the overall survival, may even lead to increased morbidity.

9 Article Cancer‑associated adipocytes exhibit distinct phenotypes and facilitate tumor progression in pancreatic cancer. 2019

Cai, Zhiwei / Liang, Yun / Xing, Chun / Wang, Hongwei / Hu, Pengfei / Li, Jialin / Huang, Haiyan / Wang, Wei / Jiang, Chongyi. ·Department of General Surgery, Huadong Hospital, Fudan University, Shanghai 200040, P.R. China. · Key Laboratory of Metabolism and Molecular Medicine of The Chinese Ministry of Education, Fudan University, Shanghai 200032, P.R. China. ·Oncol Rep · Pubmed #31638193.

ABSTRACT: Adipocyte infiltration in pancreatic cancer (PC) has been demonstrated to be independently associated with PC risk and an active contributor to tumor progression. However, to date, little is known about these unique pancreatic tumor‑surrounding adipocytes, or their response to cancer cells. The present study utilized an in vitro indirect coculture model in which the phenotypic changes of adipocytes following exposure to PC cells were directly observed. RNA‑sequencing was performed on 3T3‑L1 adipocytes cultured with or without Panc‑1 cancer cells, and significant changes were identified at the transcriptional level. In terms of delipidation and the impaired function of glucose and lipid metabolism, coculture with tumor cells resulted in an altered metabolic phenotype in mature adipocytes. In co‑cultured adipocytes, the appearance of fibroblast‑like cells was observed, and the mesenchymal cell differentiation pathway was enriched following the integrated analysis into the transcriptome. In addition, reverse transcription‑quantitative PCR analyses of co‑cultured adipocytes revealed a loss in gene expression of mature adipocyte markers, and a gain in gene expression of fibroblast‑specific markers. It was also confirmed that newly generated cancer‑associated adipocytes could facilitate the invasive capacities of the tumor, and may contribute to PC stromal remodeling. The present study supports a novel concept that reprogramming of stromal adipocytes orchestrated by PC cells may generate cancer‑associated adipocytes with activated phenotypes, which may ultimately drive pancreatic tumor progression.

10 Article The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. 2019

Aykut, Berk / Pushalkar, Smruti / Chen, Ruonan / Li, Qianhao / Abengozar, Raquel / Kim, Jacqueline I / Shadaloey, Sorin A / Wu, Dongling / Preiss, Pamela / Verma, Narendra / Guo, Yuqi / Saxena, Anjana / Vardhan, Mridula / Diskin, Brian / Wang, Wei / Leinwand, Joshua / Kurz, Emma / Kochen Rossi, Juan A / Hundeyin, Mautin / Zambrinis, Constantinos / Li, Xin / Saxena, Deepak / Miller, George. ·S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY, USA. · Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA. · Department of Medicine, New York University School of Medicine, New York, NY, USA. · Biology Department, Brooklyn College, CUNY, New York, NY, USA. · Biology and Biochemistry Programs, Graduate Center CUNY, New York, NY, USA. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY, USA. ds100@nyu.edu. · Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA. ds100@nyu.edu. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY, USA. george.miller@nyumc.org. · Department of Cell Biology, New York University School of Medicine, New York, NY, USA. george.miller@nyumc.org. ·Nature · Pubmed #31578522.

ABSTRACT: Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)

11 Article Management of the uncinate process via the artery first approach in laparoscopic pancreatoduodenectomy. 2019

Jiang, Chong-Yi / Liang, Yun / Wang, Hong-Wei / Hu, Peng-Fei / Cai, Zhi-Wei / Wang, Wei. ·Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, 20040, China. · Minimally Invasive Center, Huadong Hospital, Fudan University, Shanghai, China. ·J Hepatobiliary Pancreat Sci · Pubmed #31218822.

ABSTRACT: BACKGROUND: Uncinate process dissection is one of the major challenges for surgeons when performing laparoscopic pancreatoduodenectomy. This study aimed to evaluate the artery first approach for handling uncinate process dissection in laparoscopic pancreatoduodenectomy. METHODS: Between February 2015 and June 2018, a total of 91 consecutive patients without vascular encasement underwent selective laparoscopic pancreatoduodenectomy, including the first 26 consecutive cases treated with the conventional approach and the remaining 65 with the artery first approach applied for uncinate process dissection. Here, we present and analyze the surgical outcomes and the oncological results for the two groups. RESULTS: There was no significant difference between the two groups in operative time, intraoperative blood loss, the rate of conversion to open pancreatoduodenectomy, postoperative complications, mortality, as well as the number of lymph nodes retrieved in the malignancies. In contrast, the artery first approach group showed a statistically significant shorter resection time and a higher R0 resection rate when compared with the conventional group. CONCLUSIONS: The artery first approach is a safe and feasible technique that can be used for uncinate process management in laparoscopic pancreatoduodenectomy for patients without vascular encasement. It also has the advantage of increased rate of radical resection in the surgical intervention of relevant malignancies.

12 Article Specialized dendritic cells induce tumor-promoting IL-10 2019

Barilla, Rocky M / Diskin, Brian / Caso, Raul Caso / Lee, Ki Buom / Mohan, Navyatha / Buttar, Chandan / Adam, Salma / Sekendiz, Zennur / Wang, Junjie / Salas, Ruben D / Cassini, Marcelo F / Karlen, Jason / Sundberg, Belen / Akbar, Hashem / Levchenko, Dmitry / Gakhal, Inderdeep / Gutierrez, Johana / Wang, Wei / Hundeyin, Mautin / Torres-Hernandez, Alejandro / Leinwand, Joshua / Kurz, Emma / Rossi, Juan A Kochen / Mishra, Ankita / Liria, Miguel / Sanchez, Gustavo / Panta, Jyoti / Loke, P'ng / Aykut, Berk / Miller, George. ·S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA. · Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA. george.miller@nyumc.org. · Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA. george.miller@nyumc.org. ·Nat Commun · Pubmed #30926808.

ABSTRACT: The drivers and the specification of CD4

13 Article Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer. 2019

Yao, Wantong / Rose, Johnathon L / Wang, Wei / Seth, Sahil / Jiang, Hong / Taguchi, Ayumu / Liu, Jintan / Yan, Liang / Kapoor, Avnish / Hou, Pingping / Chen, Ziheng / Wang, Qiuyun / Nezi, Luigi / Xu, Zhaohui / Yao, Jun / Hu, Baoli / Pettazzoni, Piergiorgio F / Ho, I Lin / Feng, Ningping / Ramamoorthy, Vandhana / Jiang, Shan / Deng, Pingna / Ma, Grace J / Den, Peter / Tan, Zhi / Zhang, Shu Xing / Wang, Huamin / Wang, Y Alan / Deem, Angela K / Fleming, Jason B / Carugo, Alessandro / Heffernan, Timothy P / Maitra, Anirban / Viale, Andrea / Ying, Haoqiang / Hanash, Samir / DePinho, Ronald A / Draetta, Giulio F. ·Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Center for Co-Clinical Trials, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA. gdraetta@mdanderson.org. · Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. gdraetta@mdanderson.org. ·Nature · Pubmed #30918400.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) remains recalcitrant to all forms of cancer treatment and carries a five-year survival rate of only 8%

14 Article Should a standard lymphadenectomy include the No. 9 lymph nodes for body and tail pancreatic ductal adenocarcinoma? 2019

Zhou, Yiran / Lin, Jiewei / Wang, Wei / Chen, Hao / Deng, Xiaxing / Peng, Chenghong / Cheng, Dongfeng / Shen, Baiyong. ·Department of General Surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China. · Department of General Surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China. Electronic address: chengdf1059@163.com. · Department of General Surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China. Electronic address: shenby@shsmu.edu.cn. ·Pancreatology · Pubmed #30902419.

ABSTRACT: OBJECTIVES: This study aimed to use a retrospective data base to investigate whether a standard lymphadenectomy during distal pancreatectomy should include the No. 9 lymph nodes (LNs) for resectable pancreatic ductal adenocarcinoma (PDAC) located in the body and tail of the pancreas. METHODS: Data from 169 patients undergoing curative distal pancreatectomy for PDAC between Jan 1, 2013 and Dec 31, 2016 were collected. According to the tumor location, patients were divided into three groups: pancreatic neck tumor, pancreatic body and tail tumor with margin-to-bifurcation-distance (MTBD) ≤ 2.5 cm and pancreatic body and tail tumor with MTBD > 2.5 cm. The metastatic rate of the No. 9 LNs was compared among the 3 groups. The survival outcomes were analyzed. RESULTS: The involvement rate for No. 9 LNs was 20.7% (6/29) for pancreatic neck tumors, 17.6% (15/85) for body and tail tumors with MTBD ≤ 2.5 cm and 1.8% (1/55) for MTBD > 2.5 cm. The No. 9 LNs were significantly more frequently involved in neck or body and tail tumors with MTBD ≤2.5 cm than with the cases with MTBD >2.5 cm (OR 0.082, P = 0.016). No. 9 LN involvement was not associated with worse survival compared with survival associated with involvement of other LNs (P = 0.780). CONCLUSIONS: For PDAC located in the neck or in the body and tail of the pancreas with MTBD ≤ 2.5 cm, the involvement rate for No. 9 LNs is high. Standard lymphadenectomy should include the No. 9 LNs.

15 Article Downregulation of miR-183 inhibits the growth of PANC-1 pancreatic cancer cells 2019

Yang, Xiaoping / Wang, Wei / Zhang, Xiong / Zou, Qi / Cai, Lei / Yu, Bo. ·Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China. ·Exp Ther Med · Pubmed #30783438.

ABSTRACT: Pancreatic cancer (PC) is a common malignancy with a poorly understood pathogenesis. Currently, the efficacy of anti-PC therapies is insufficient, partially due to the chemoresistance of cancer cells. The present study aimed to elucidate the role of miR-183 in the proliferation, apoptosis, and chemosensitivity to 5-fluorouracil and gemcitabine of human PC cells and the associated mechanisms. PANC-1 cells were transfected with microRNA (miR)-183 inhibitors, and the effect of miR-183 on cell proliferation was evaluated via MTT assay. Apoptosis and cell cycle distribution were determined by flow cytometry.

16 Article Concurrent Pancreatic Metastasis From Lung Adenocarcinoma and Primary Cholangiocarcinoma on FDG PET/CT Imaging. 2019

Wang, Wei / Kan, Ying / Yang, Xu / Liu, Jie / Yang, Jigang. ·From the Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, China. ·Clin Nucl Med · Pubmed #30762824.

ABSTRACT: A 67-year-old man with a history of left upper lobe resection of poorly differentiated adenocarcinoma 1 year ago underwent FDG PET/CT for restaging. The images demonstrated a round cystic lesion with peripheral FDG uptake and centrally photopenic region. Additional focus of increased activity was detected in the left lobe of the liver. The patient underwent the Whipple and partial hepatectomy. The surgical pathology demonstrated concurrently the metastasis to the pancreas from the lung adenocarcinoma and a primary moderately differentiated cholangiocarcinoma.

17 Article Combined effect of 2018

Li, Dong / Jia, Yun-Ming / Cao, Pi-Kun / Wang, Wei / Liu, Bin / Li, Yu-Liang. ·Department of Interventional Medicine, The Second Hospital of Shandong University, Jinan, China. · Department of Interventional Medicine, Linzi District People's Hospital, Jinan, China. ·J Cancer Res Ther · Pubmed #30589026.

ABSTRACT: Subjects and Methods: PANC-1 cells were treated with Results: The cell growth could be significantly inhibited after the treatment with GEM or Conclusion: The combined treatment of

18 Article RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer. 2018

Wang, Wei / Marinis, Jill M / Beal, Allison M / Savadkar, Shivraj / Wu, Yue / Khan, Mohammed / Taunk, Pardeep S / Wu, Nan / Su, Wenyu / Wu, Jingjing / Ahsan, Aarif / Kurz, Emma / Chen, Ting / Yaboh, Inedouye / Li, Fei / Gutierrez, Johana / Diskin, Brian / Hundeyin, Mautin / Reilly, Michael / Lich, John D / Harris, Philip A / Mahajan, Mukesh K / Thorpe, James H / Nassau, Pamela / Mosley, Julie E / Leinwand, Joshua / Kochen Rossi, Juan A / Mishra, Ankita / Aykut, Berk / Glacken, Michael / Ochi, Atsuo / Verma, Narendra / Kim, Jacqueline I / Vasudevaraja, Varshini / Adeegbe, Dennis / Almonte, Christina / Bagdatlioglu, Ece / Cohen, Deirdre J / Wong, Kwok-Kin / Bertin, John / Miller, George. ·S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 435 East 30th Street, 4th Floor, New York, NY 10016, USA. · Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. · Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. · Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. · Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. Electronic address: john.j.bertin@gsk.com. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 435 East 30th Street, 4th Floor, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. Electronic address: george.miller@nyumc.org. ·Cancer Cell · Pubmed #30423296.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 (RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Targeting RIP1 reprogrammed TAMs toward an MHCII

19 Article SNX6 predicts poor prognosis and contributes to the metastasis of pancreatic cancer cells via activating epithelial-mesenchymal transition. 2018

Hu, Pengfei / Liang, Yun / Hu, Qiangsheng / Wang, Hongwei / Cai, Zhiwei / He, Jiaqi / Cai, Jianhua / Liu, Meng / Qin, Yi / Yu, Xianjun / Jiang, Chongyi / Zhang, Bo / Wang, Wei. ·Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, China. · Shanghai Pancreatic Cancer Institute, Shanghai, China. · Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China. · Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. ·Acta Biochim Biophys Sin (Shanghai) · Pubmed #30307473.

ABSTRACT: Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate around 6%. Though significant progress has been made in the availability of diagnostic techniques and treatment strategies, pancreatic cancer remains a disease of high mortality rate. Therefore, there is an urgent need for a better understanding of the molecular mechanisms that governs the oncogenesis and metastasis process of pancreatic cancer. In the present study, by using the Cancer Genome Atlas (TCGA) dataset analysis, we demonstrated that sorting nexin 6 (SNX6) serves as a biomarker for predicting prognosis of pancreatic cancer. In vitro studies demonstrated that silencing of SNX6 expression reduced cell proliferation, colony formation, invasion, and metastasis. Higher level of SNX6 helps maintain the mesenchymal properties, which renders migration and invasive capacities to pancreatic cancer cells. Moreover, in the process of TGF-β-induced epithelial to mesenchymal transition (EMT), the expression level of SNX6 was increased, and silencing of SNX6 expression could inhibit the TGF-β-induced EMT program. These results collectively uncovered a novel predictive marker for pancreatic cancer and provided the possible underlying molecular mechanism.

20 Article Discovery and Characterization of Dual Inhibitors of MDM2 and NFAT1 for Pancreatic Cancer Therapy. 2018

Wang, Wei / Qin, Jiang-Jiang / Voruganti, Sukesh / Nijampatnam, Bhavitavya / Velu, Sadanandan E / Ruan, Ke-He / Hu, Ming / Zhou, Jianwei / Zhang, Ruiwen. ·Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas. rzhang27@central.uh.edu wwang4@central.uh.edu. · Drug Discovery Institute, University of Houston, Houston, Texas. · Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas. · Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas. · Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama. · Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, P.R. China. ·Cancer Res · Pubmed #30217928.

ABSTRACT: Overexpression and activation of the murine double minute 2 (MDM2) or nuclear factor of activated T cells 1 (NFAT1) oncoproteins frequently occur in pancreatic cancer. Most MDM2 inhibitors under development target MDM2-p53 binding and have little or no effect on cancers without functional p53, including pancreatic cancer. Some available compounds indirectly inhibit NFAT1 activity by interfering with calcineurin activity, but there are currently no specific inhibitors against NFAT1. Here we performed a high-throughput virtual and cell-based screening to yield a lead compound (MA242) that can directly bind both MDM2 and NFAT1 with high affinity, induce their protein degradation, and inhibit NFAT1-mediated transcription of

21 Article IL22RA1/STAT3 Signaling Promotes Stemness and Tumorigenicity in Pancreatic Cancer. 2018

He, Weizhi / Wu, Jinghua / Shi, Juanjuan / Huo, Yan-Miao / Dai, Wentao / Geng, Jing / Lu, Ping / Yang, Min-Wei / Fang, Yuan / Wang, Wei / Zhang, Zhi-Gang / Habtezion, Aida / Sun, Yong-Wei / Xue, Jing. ·State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. · Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. · Shanghai Center for Bioinformation Technology & Shanghai Engineering Research Center of Pharmaceutical Translation, Shanghai, China. · Department of General Surgery & Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. · State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China. · Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California. jingxue@sjtu.edu.cn syw0616@126.com aidah@stanford.edu. · Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. jingxue@sjtu.edu.cn syw0616@126.com aidah@stanford.edu. · State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. jingxue@sjtu.edu.cn syw0616@126.com aidah@stanford.edu. ·Cancer Res · Pubmed #29572224.

ABSTRACT: Chronic inflammation is a feature of pancreatic cancer, but little is known about how immune cells or immune cell-related signals affect pancreatic cancer stemness and development. Our previous work showed that IL22/IL22RA1 plays a vital role in acute and chronic pancreatitis progression by mediating cross-talk between immune cells and acinar cells or stellate cells, respectively. Here, we find IL22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of patients with pancreatic cancer. The IL22RA1

22 Article The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. 2018

Pushalkar, Smruti / Hundeyin, Mautin / Daley, Donnele / Zambirinis, Constantinos P / Kurz, Emma / Mishra, Ankita / Mohan, Navyatha / Aykut, Berk / Usyk, Mykhaylo / Torres, Luisana E / Werba, Gregor / Zhang, Kevin / Guo, Yuqi / Li, Qianhao / Akkad, Neha / Lall, Sarah / Wadowski, Benjamin / Gutierrez, Johana / Kochen Rossi, Juan Andres / Herzog, Jeremy W / Diskin, Brian / Torres-Hernandez, Alejandro / Leinwand, Josh / Wang, Wei / Taunk, Pardeep S / Savadkar, Shivraj / Janal, Malvin / Saxena, Anjana / Li, Xin / Cohen, Deirdre / Sartor, R Balfour / Saxena, Deepak / Miller, George. ·Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York. · National Gnotobiotic Rodent Research Center, University of North Carolina, Chapel Hill, North Carolina. · Department of Epidemiology and Health Promotion, NYU College of Dentistry, New York, New York. · Department of Biology, Brooklyn College and the Graduate Center (CUNY), Brooklyn, New York, New York. · Department of Medicine, New York University School of Medicine, New York, New York. · Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York. george.miller@nyumc.org ds100@nyu.edu. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York. george.miller@nyumc.org ds100@nyu.edu. · Department of Medicine, Microbiology, and Immunology, University of North Carolina, Chapel Hill, North Carolina. ·Cancer Discov · Pubmed #29567829.

ABSTRACT: We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4

23 Article Upregulated long non-coding RNA SPRY4-IT1 predicts dismal prognosis for pancreatic ductal adenocarcinoma and regulates cell proliferation and apoptosis. 2018

Yao, Yue / Gao, Ping / Chen, Lili / Wang, Wei / Zhang, Jinchao / Li, Qiang / Xu, Yi. ·Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, Harbin 150086, China. · Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. · Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: qiangli@hrbmu.edu.cn. · Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, Harbin 150086, China. Electronic address: xuyi@hrbmu.edu.cn. ·Gene · Pubmed #29551494.

ABSTRACT: Recently, long noncoding RNAs (lncRNAs) have been emerged as pivotal regulators in various human cancers, including pancreatic ductal adenocarcinoma (PDAC). SPRY4-intronic transcript 1 (SPRY4-IT1) was reported to be upregulated in some kind of human cancers. Here, we elucidated the biological functions and possible clinical values of SPRY4-IT1 on PDAC. In present study, expression of SPRY4-IT1 in PDAC tissues and corresponding normal tissues were explored by qRT-PCR experiments. The link between SPRY4-IT1 expression levels and clinicopathological significance was further analyzed. In addition, the oncogenic role of SPRY4-IT1 was detected both in vitro and in vivo. The results demonstrated that SPRY4-IT1 was abnormally upregulated in PDAC tissues and cell lines. Tumor stage and differentiation grade was closely correlated with SPRY4-IT1 expression. Additionally, decreased SPRY4-IT1 contributed to tumor suppressive effect through attenuating cell growth, clonogenic ability and facilitating apoptosis via Bcl-2/caspase-3 pathway in PANC1 and Capan-2 cells. Furthermore, the xenograft study confirmed the tumor proliferation-promoting role of SPRY4-IT1 in PANC1 cells. Taken together, these findings indicated that SPRY4-IT1 is a potential therapeutic target and prognosis biomarker for the patients with PDAC.

24 Article A novel scoring system predicts postsurgical survival and adjuvant chemotherapeutic benefits in patients with pancreatic adenocarcinoma: Implications for AJCC-TNM staging. 2018

Liu, Liang / Xu, Hua-Xiang / He, Min / Wang, Wei / Wang, Wen-Quan / Wu, Chun-Tao / Wei, Rong-Qiang / Liang, Yun / Gao, He-Li / Liu, Chen / Xu, Jin / Long, Jiang / Ni, Quan-Xing / Shao, Cheng-Hao / Wang, Jian / Yu, Xian-Jun. ·Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China. · Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. · Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, China. · Department of Pancreatic-Biliary Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China. ·Surgery · Pubmed #29548773.

ABSTRACT: BACKGROUND: We evaluated the application of the latest 8 METHODS: This multicenter study involved 1,223 consecutive patients who underwent margin-negative pancreatectomy for PC. A scoring system was devised based on AJCC pathologic parameters and biologic markers and defined using a Cox proportional hazards model. Prognostic accuracies were evaluated by concordance index (C-index) and Akaike information criterion (AIC). RESULTS: The 8 CONCLUSION: Postoperative CA19-9 levels and tumor grade are two well-known PC biologic markers that could be incorporated into a standard AJCC staging system to refine risk stratification and predict OS benefit from adjuvant chemotherapy in resected PC.

25 Article Inhibiting β-Catenin by β-Carboline-Type MDM2 Inhibitor for Pancreatic Cancer Therapy. 2018

Qin, Jiang-Jiang / Wang, Wei / Li, Xin / Deokar, Hemantkumar / Buolamwini, John K / Zhang, Ruiwen. ·Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United States. · Center for Drug Discovery, University of Houston, Houston, TX, United States. · Department of Pharmaceutical Sciences, College of Pharmacy, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States. ·Front Pharmacol · Pubmed #29387014.

ABSTRACT: The β-catenin and MDM2 oncoproteins are overexpressed and constitutively activated in human pancreatic cancer and contribute to its initiation, progression, and metastasis. The Wnt/β-catenin signaling pathway strongly interacts with the MDM2-p53 signaling pathway, accelerating the tumorigenesis and its development. Therefore, therapies inhibiting both β-catenin and MDM2 are suggested to be ideal treatments for patients with advanced pancreatic cancer. We have recently identified a novel class of β-carboline compounds as the specific and potent MDM2 inhibitors, including a lead compound SP141. In the present study, we utilized SP141 as an exemplary β-carboline compound to characterize β-catenin as a molecular target of the β-carboline compounds and to demonstrate an important role of β-catenin in the anticancer activity of β-carboline. We found that the silencing of either β-catenin or MDM2 largely reduced the anticancer activity of SP141 while the double silencing of both genes almost completely blocked SP141's activity. SP141 directly bound to β-catenin and inhibited its expression and activity in pancreatic cancer cells

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