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Pancreatic Neoplasms: HELP
Articles by Wei Xu
Based on 18 articles published since 2010
(Why 18 articles?)
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Between 2010 and 2020, Wei Xu wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Endoscopic ultrasound elastography for differentiating between pancreatic adenocarcinoma and inflammatory masses: a meta-analysis. 2013

Li, Xiang / Xu, Wei / Shi, Jian / Lin, Yong / Zeng, Xin. ·Xiang Li, Jian Shi, Yong Lin, Xin Zeng, Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. ·World J Gastroenterol · Pubmed #24115828.

ABSTRACT: AIM: To evaluate the accuracy of endoscopic ultrasound (EUS) elastography for differentiating between pancreatic ductal adenocarcinoma (PDAC) and pancreatic inflammatory masses (PIM). METHODS: Electronic databases (updated to December 2012) and manual bibliographical searches were carried out. A meta-analysis of all diagnostic clinical trials evaluating the accuracy of EUS elastography in differentiating PDAC from PIM was conducted. Heterogeneity was assessed among the studies. The meta-analysis was performed to evaluate the accuracy of EUS elastography in differentiating PDAC from PIM in homogeneous studies. RESULTS: Ten studies involving 781 patients were included in the analysis. Significant heterogeneity in sensitivity was observed among the studies (Cochran Q test = 24.16, df = 9, P = 0.0041, I (2) = 62.8%), while heterogeneity in specificity was not observed (Cochran Q test = 5.93, df = 9, P = 0.7473, I (2) = 0.0%). The area under the curve under the Sports Rights Owners Coalition was 0.8227. Evaluation of heterogeneity suggested that the different diagnostic standards used in the included studies were the source of heterogeneity. In studies using the color pattern as the diagnostic standard, the pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic OR were 0.99 (0.97-1.00), 0.76 (0.67-0.83), 3.36 (2.39-4.72), 0.03 (0.01-0.07) and 129.96 (47.02-359.16), respectively. In studies using the hue histogram as the diagnostic standard, the pooled sensitivity, specificity, positive LR, negative LR and diagnostic OR were 0.92 (0.89-0.95), 0.68 (0.57-0.78), 2.84 (2.05-3.93), 0.12 (0.08-0.19) and 24.69 (12.81-47.59), respectively. CONCLUSION: EUS elastography is a valuable method for the differential diagnosis between PDAC and PIM. And a preferable diagnostic standard should be explored and improvements in specificity are required.

2 Review Endoscopic ultrasound elastography for differentiation of benign and malignant pancreatic masses: a systemic review and meta-analysis. 2013

Xu, Wei / Shi, Jian / Li, Xiang / Zeng, Xin / Lin, Yong. ·Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China. ·Eur J Gastroenterol Hepatol · Pubmed #23169307.

ABSTRACT: BACKGROUND: Endoscopic ultrasound (EUS) elastography is a novel method for visualization of tissue elasticity modulus during a conventional EUS examination. The reported yield of EUS elastography for the differentiation of benign and malignant pancreatic masses has shown variable results. The objective of this study was to assess the accuracy of EUS elastography by pooling data of available trials. METHODS: The Medline, PubMed, Embase, and Cochrane Central Trials databases were used to retrieve all the studies that assessed the diagnostic accuracy of EUS elastography for the differentiation of benign and malignant pancreatic masses. Pooling was carried out using a fixed-effect model when significant heterogeneity was not present; otherwise, the random-effect model was used. If there were less than four studies using the same diagnostic standard, forest plots were constructed without pooling. RESULTS: In six studies using the qualitative color pattern as the diagnostic standard, the sensitivity was 99% (95% confidence interval 98-100%) and the specificity was 74% (95% confidence interval 65-82%). The area under the curve under the summary receiver-operating characteristic was 0.9624. In three studies using the quantitative hue histogram value as the diagnostic standard, the sensitivity was 85-93% and the specificity was 64-76%. CONCLUSION: EUS elastography is a promising noninvasive technique for the differentiation of pancreatic masses with a high sensitivity, and may prove to be a valuable complementary method to EUS-FNA.

3 Article Linc-RoR promotes proliferation, migration, and invasion via the Hippo/YAP pathway in pancreatic cancer cells. 2020

Chen, Wei / Wang, Huizhi / Liu, Yawen / Xu, Wei / Ling, Chen / Li, Yafang / Liu, Junqiang / Chen, Mengjiao / Zhang, Youli / Chen, Baoding / Gong, Aihua / Xu, Min. ·Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China. · Department of Ultrasound, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China. · Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, China. ·J Cell Biochem · Pubmed #31452251.

ABSTRACT: Large intergenic noncoding RNA regulator of reprogramming (Linc-RoR) was first identified as a regulator to increase the emergence of induced pluripotent stem cells through reprogramming differentiated cells and is abnormal expression in a variety of malignant tumors. However, the function of Linc-RoR in pancreatic cancer progression needs further clarification. The data from this study demonstrated that Linc-RoR knockdown suppressed cell proliferative capacity and colony formation, while Linc-RoR overexpression promoted these behaviors. In particular, Linc-RoR overexpression promoted the level of mesenchymal markers, inhibited the expression of epithelial markers, as well as enhanced pancreatic cancer cells migration and invasion, whereas Linc-RoR knockdown inhibited the expression of mesenchymal markers, promoted the expression of epithelial markers, as well as weakened pancreatic cancer cells migration and invasion. Further study revealed that Linc-RoR knockdown brought about a significant fall in YAP phosphorylation and a rise in total YAP, while Linc-RoR overexpression produced the opposite results. Specifically, Linc-RoR promoted YAP in the cytoplasm into the nucleus. Taken together, we conjectured that Linc-RoR promoted proliferation, migration, and invasion of pancreatic cancer cells by activating the Hippo/YAP pathway. YAP might be an underlying target of Linc-RoR and mediate epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC); thus, Linc-RoR might be a very meaningful biomarker for PC.

4 Article Augmenting the therapeutic efficacy of adenosine against pancreatic cancer by switching the Akt/p21-dependent senescence to apoptosis. 2019

Yang, Dongqin / Zhang, Qi / Ma, Yunfang / Che, Zhihui / Zhang, Wenli / Wu, Mengmeng / Wu, Lijun / Liu, Fuchen / Chu, Yiwei / Xu, Wei / McGrath, Mary / Song, Chunhua / Liu, Jie. ·Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai, China. Electronic address: kobesakura@fudan.edu.cn. · Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai, China. · Department of Library, Fudan University, Shanghai, China. · The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. · Department of Immunology of School of Basic Medical Sciences, Fudan University, Shanghai, China. · Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. · Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai, China. Electronic address: jieliu@fudan.edu.cn. ·EBioMedicine · Pubmed #31495718.

ABSTRACT: BACKGROUND: There are many reports of the anti-tumour effects of exogenous adenosine in gastrointestinal tumours. Gemcitabine, a first line agent for patients with poor performance status, and adenosine have structural similarities. For these reasons, it is worth exploring the therapeutic efficacy of adenosine and its underlying mechanism in pancreatic cancer. METHODS: Tumour volumes and survival periods were measured in a patient-derived xenograft (PDX) model of pancreatic cancer. The Akt-p21 signalling axis was blocked by p21 silencing or by the Akt inhibitor GSK690693. The combined effect of GSK690693 and adenosine was calculated by the Chou-Talalay equation and verified by measuring fluorescent areas in orthotopic models. FINDINGS: Among the PDX mice, the tumour volume in the adenosine treatment group was only 61% of that in the saline treatment group. Adenosine treatment in combination with the Akt inhibitor, GSK690693, or the silencing of p21 to interfere with the Akt-p21 axis can switch the senescence-to-apoptosis signal and alleviate drug resistance. A GSK690693-adenosine combination caused 37.4% further reduction of tumour fluorescent areas in orthotopic models compared with that observed in adenosine monotherapy. INTERPRETATION: Our data confirmed the therapeutic effect of adenosine on pancreatic cancer, and revealed the potential of Akt inhibitors as sensitization agents in this treatment. FUND: The work is supported by grants from the National Natural Science Foundation of China to Dongqin Yang (81572336, 81770579) and Jie Liu (81630016, 81830080), and jointly by the Development Fund for Shanghai Talents (201660).

5 Article Circulating lncRNA ABHD11-AS1 serves as a biomarker for early pancreatic cancer diagnosis. 2019

Liu, Yawen / Feng, Wen / Liu, Wenyu / Kong, Xiangyu / Li, Lei / He, Junbo / Wang, Dawei / Zhang, Meiting / Zhou, Gai / Xu, Wei / Chen, Wei / Gong, Aihua / Xu, Min. ·Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China. · Department of Gastroenterology, Songjiang Hospital Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 201600, China. · Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. · Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. · Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China. ·J Cancer · Pubmed #31333792.

ABSTRACT:

6 Article Establishment of pancreatic cancer patient-derived xenograft models and comparison of the differences among the generations. 2019

Xu, Wei / Yang, Xiao-Wei / Zhao, Zheng-Yun / Dong, Bin / Guan, Xiao-Ya / Tian, Xiu-Yun / Qian, Hong-Gang / Hao, Chun-Yi. ·Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute No. 52 Fucheng Road, Haidian District, Beijing 100142, China. · Department of Hepatobiliary Intervention, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University Beijing, China. · Department of Chemistry, Durham University Stockton Road, Durham DH1 3LE, U.K. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Center Laboratory, Peking University Cancer Hospital & Institute Beijing, China. ·Am J Transl Res · Pubmed #31217882.

ABSTRACT: Tumor samples of pancreatic ductal adenocarcinoma patients, who underwent resection surgery, were implanted into NOD/SCID mice to construct pancreatic cancer patient-derived xenograft (PDX) models and explore the biological changes in the different generations of PDXs. Ten PDXs were successfully generated, and the tumor formation rate of F1 PDXs was found to be 38.46%, which was lower than F2 (77.78%) and F3 (71.43%) PDXs. In addition, latent periods of tumorigenesis of F2 and F3 PDXs were significantly shorter, compared to that in F1 PDXs (

7 Article Perineural invasion is related to p38 mitogen-activated protein kinase pathway activation and promotes tumor growth and chemoresistance in pancreatic cancer. 2019

Gu, Jiangning / Xu, Wei / Peng, Chenghong / Zhu, Youwei / Wang, Di / Wang, Xuelong / Li, Ying / Wei, Gang / Zhang, Zhiqiang / Zhong, Yiming / Zhao, Shulin / Shi, Minmin / Cheng, Dongfeng / Ying, Xiayang / Jin, Jiabin / Chen, Hao. ·Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China. · Research Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China. · Department of Scientific Research, Eyes & ENT Hospital of Fudan University, Shanghai, China. · Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. ·J Cell Biochem · Pubmed #30756419.

ABSTRACT: Metastasis is a key component of cancer progression and is strongly associated with poor prognosis. Perineural invasion is thought to be related to pain, tumor recurrence, and other conditions. However, the exact molecular mechanism is unclear. This study was conducted to identify the key components and signaling pathways involved in the perineural invasion of pancreatic cancer and alterations in the phenotype after the interaction between the dorsal root ganglion (DRG) and pancreatic cancer cells. The results indicated that the p38 mitogen-activated protein kinase signaling pathway was activated after coculture of the DRG and pancreatic cancer cells and lead to the promotion of cell growth and chemoresistance.

8 Article CDK8 regulates the angiogenesis of pancreatic cancer cells in part via the CDK8-β-catenin-KLF2 signal axis. 2018

Wei, Ran / Kong, Lingdong / Xiao, Yuhong / Yuan, Huiping / Song, Yi / Wang, Jia / Yu, Huihuan / Mao, Shengxun / Xu, Wei. ·The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, China. · The Queen Mary Clinical Medical College, Nanchang University, Nanchang, Jiangxi, China. · Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, China. · Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 330006 Nanchang, Jiangxi, China. Electronic address: xu_wei111@126.com. ·Exp Cell Res · Pubmed #29856990.

ABSTRACT: BACKGROUND: CDK8 is associated with the transcriptional Mediator complex and has been shown to regulate several transcription factors implicated in cancer. As a pancreatic cancer oncogene, the role of CDK8 in cancer angiogenesis remains unclear. Here, we investigated the contribution of CDK8 in pancreatic cancer angiogenesis and examined the underlying molecular mechanisms. METHODS: CDK8 expression was evaluated via immunohistochemistry, western blotting, and qRT-PCR in relation to the clinicopathological characteristics of pancreatic cancer patients. The effects of silencing or overexpressing CDK8 on cancer angiogenesis were assessed in vitro by western blotting assays in pancreatic cancer cell lines and in vivo with nude mice xenograft models. RESULTS: Compared with adjacent normal tissues, pancreatic cancer tissues showed upregulation of CDK8 expression, which was inversely correlated with T grade, liver metastasis, size, lymph node metastasis and poor survival. CDK8 overexpression promoted angiogenesis in pancreatic cancer via activation of the CDK8-β-catenin-KLF2 signaling axis, as demonstrated by the upregulation and downregulation of signals representing the rate-limiting steps in angiogenesis. Silencing CDK8 inhibited angiogenesis in pancreatic cancer in vitro. Additionally, these results were confirmed in nude mice xenograft models in vivo. CONCLUSIONS: CDK8 promotes angiogenesis in pancreatic cancer via activation of the CDK8-β-catenin-KLF2 signaling axis, thus providing valid targets for the treatment of pancreatic cancer.

9 Article Clinical data combined with radiological imaging improves the accuracy of TNM staging of pancreatic body and tail adenocarcinoma. 2017

Xu, Wei / Jiang, Bo / Yin, Xinmin. ·Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Changsha, China. ·Patient Prefer Adherence · Pubmed #29042755.

ABSTRACT: PURPOSE: Pancreatic body and tail adenocarcinoma (PBTA) remains one of the deadliest cancers, and current radiological modalities still have limitations on the staging of PBTA. Improving PBTA staging will contribute to the management of this disease. PATIENTS AND METHODS: Clinicopathological characteristics of 91 surgically treated PBTA patients were retrospectively retrieved. Clinical data associated with postoperative tumor staging (pTNM) were assessed using ordinal logistic regression model. Discriminant analysis was performed using function formula based on multivariate analysis results; further cross-validation was conducted by Bootstrap methods. RESULTS: Multivariate analysis showed that carbohydrate antigen 19-9 ≥955.0 U/L, albumin, and alkaline phosphatase/total bilirubin ratio were independent factors contributing to improved accuracy of pTNM staging. Discriminant analysis exhibited better performance and showed that the probability of accurate prediction of pTNM stage was 90.6% and the probability of cross-validation was 85.9%. After excluding patients with preoperative diagnosis of stage IV disease, the probability of accurate prediction of pTNM stage was 86.1% and the probability of cross-validation was 75.0%. CONCLUSION: The combination of imaging and clinical data has higher accuracy in staging PBTA than radiological data alone. A model proposed in this study will improve the management of PBTA.

10 Article Clinical and Magnetic Resonance Imaging Features of Solid Pseudopapillary Tumor of the Pancreas in Male Patients. 2017

Zhong, Yan / Wang, Hai-Yi / Linghu, En-Qiang / Sun, Yu-Fa / Xu, Wei / Ma, Lu / Ye, Hui-Yi. ·Department of Radiology,Hainan Branch of Chinese PLA General Hospital,Sanya,Hainan 572013,China. · Department of Radiology, Chinese PLA General Hospital,Beijing 100853,China. · Department of Gastroenterology and Hepatology, Chinese PLA General Hospital,Beijing 100853,China. · Health Division of Guard Bureau,Joint Staff Department of Central Military Commission,Beijing 100017,China. ·Zhongguo Yi Xue Ke Xue Yuan Xue Bao · Pubmed #28877823.

ABSTRACT: Objective To analyze the clinical and magnetic resonance imaging(MRI)findings of solid pseudopapillary tumor(SPT)of the pancreas in male patients. Methods Clinical and MRI features of 51 patients with pathologically-proved SPT were retrospectively analyzed.The following MRI features of the lesions were analyzed:location,maximal diameter,shape,margin,capsule,solid and cystic components,signal intensity characteristics,and enhancement patterns.Results The average maximal diameter of the SPT in male patients was significantly smaller [(3.9±1.6)cm vs.(6.3±3.9)cm,P=0.035]than that of SPT in female patients.Pure solid tumors were signiciantly more common in male patients(8/14)than in female patients(9/37)(P=0.037).T

11 Article Incidents and adverse events of endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions. 2017

Du, Chen / Chai, Ning-Li / Linghu, En-Qiang / Li, Hui-Kai / Sun, Yu-Fa / Xu, Wei / Wang, Xiang-Dong / Tang, Ping / Yang, Jing. ·Chen Du, Ning-Li Chai, En-Qiang Linghu, Hui-Kai Li, Xiang-Dong Wang, Ping Tang, Jing Yang, Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China. ·World J Gastroenterol · Pubmed #28852320.

ABSTRACT: AIM: To evaluate the diagnostic value and safety mainly regarding incidents of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic cystic lesions (PCLs). METHODS: A total of 150 consecutive patients with suspected PCLs were prospectively enrolled from April 2015 to November 2016. We finally enrolled 140 patients undergoing EUS-FNA. We compared the diagnostic accuracy of EUS-FNA and pathological diagnosis, which is regarded as the gold standard, for PCLs. Patients undergoing EUS-FNA at least 1 wk preoperatively were monitored for incidents and adverse events to evaluate its safety. RESULTS: There were 88 (62.9%) women and 52 (37.1%) men among 140 patients, with a mean age of 50.1 (± 15.4) years. There were 67 cysts located in the head/uncinate of the pancreas and 67 in the body/tail, and 6 patients had at least 1 cyst in the pancreas. There were 75 patients undergoing surgery and 55 undergoing EUS-FNA with interval at least 1 wk before other operations, with 3 patients undergoing the procedure twice. The accuracy of EUS-FNA in differentiating benign and malignant lesions was 97.3% (73/75), while the accuracy of characterizing PCL subtype was 84.0% (63/75). The incident rate was 37.9% (22/58), whereas only 1 AE was observed in 58 cases. CONCLUSION: EUS-FNA is effective and safe for diagnosis of PCLs, however procedure-related incidents are common. Caution should be taken in patients undergoing EUS-FNA.

12 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.

13 Article BRM polymorphisms, pancreatic cancer risk and survival. 2016

Segedi, Maja / Anderson, Laura N / Espin-Garcia, Osvaldo / Borgida, Ayelet / Bianco, Teresa / Cheng, Dangxiao / Chen, Zhuo / Patel, Devalben / Brown, M Catherine / Xu, Wei / Reisman, David / Gallinger, Steven / Cotterchio, Michelle / Hung, Rayjean / Liu, Geoffrey / Cleary, Sean P. ·Department of Surgery, University of British Columbia, Vancouver, BC, Canada. · Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada. · Mount Sinai Hospital-Lunenfeld Research Institute, Toronto, ON, Canada. · Medical Oncology, University of Florida, Gainesville, FL. · Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON, Canada. · Princess Margaret Cancer Centre-University Health Network-Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada. Geoffrey.Liu@uhn.ca. ·Int J Cancer · Pubmed #27487558.

ABSTRACT: Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM-1321), create MEF2D transcription binding sites that lead to epigenetic silencing of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex. BRM suppression can be reversed pharmacologically.(1) Our group and others have reported associations with lung, head and neck, hepatocellular cancer risk,(1-3) and with lung and esophageal cancer prognosis (ASCO 2013; abstract 11057 & 4077). Herein, we assessed risk and survival associations with pancreatic cancer. A provincial population-based case-control study was conducted with 623 histologically confirmed pancreatic adenocarcinoma cases and 1,192 age/gender distribution-matched controls.(4) Survival of cases was obtained through the Ontario Cancer Registry. Logistic and Cox proportional hazard regression models were fitted, adjusting for relevant covariates. Median age was 65 y; 52% were male; Stage I (8%), II (55%), III (14%), IV (23%); 53% after curative resection, 79% after chemotherapy; and 83% had died. In the risk analysis, adjusted odds ratios (aOR) were 1.01 (95% CI: 0.1-2.0) and 0.96 (95% CI: 0.7-1.3) for the homozygotes of BRM-741 and BRM-1321, respectively; aOR of double-homozygotes was 1.11 (95% CI: 0.80-1.53), compared to the double-wildtype. For the survival analysis, adjusted hazard ratios (aHR) were 2.19 (95% CI: 1.9-2.5) for BRM-741 and 1.94 (95% CI: 1.7-2.2) for BRM-1321, per unit increase in variant alleles. Compared with the double-wildtype, aHR for carrying no, one, and two double-homozygotes were 2.14 (95% CI: 1.6-2.8), 4.17 (95% CI: 3.0-5.7), 8.03 (95% CI: 5.7-11.4), respectively. In conclusion, two functional promoter BRM polymorphisms were not associated with pancreatic adenocarcinoma risk, but are strongly associated with survival.

14 Article Toward targeted therapy in chemotherapy-resistant pancreatic cancer with a smart triptolide nanomedicine. 2016

Wang, Cheng / Liu, Biao / Xu, Xuelian / Zhuang, Bo / Li, Hongxia / Yin, Jiaqi / Cong, Mengyi / Xu, Wei / Lu, Aiping. ·Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China. · Institute for Advancing Translational Medicine in Bone and Joint Diseases, Jockey Club School of Chinese Medicine Building, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong. · Department of Pharmacy, Shandong Provincial Qian Foshan Hospital, Jinan, China. · Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. ·Oncotarget · Pubmed #26840019.

ABSTRACT: Chemoresistance is the major impediment for treating pancreatic cancer. Herb-derived compound triptolide (TP) can inhibit proliferation of chemo-resistant pancreatic cancer (CPC) cell lines through multiple mechanisms, which exhibited superior anticancer efficacy compared with gemcitabine. However, toxicity due to non-specific exposure to healthy tissues hindered its clinical translation. Herein we successfully achieved targeting CPC cells and avoiding exposure to healthy tissues for TP by nucleolin-specific aptamer (AS1411) mediated polymeric nanocarrier. We conjugated AS1411 aptamer to carboxy terminated poly(ethylene glycol)-block-poly(d, l-lactide) (HOOC-PEG-PDLLA), then prepared AS1411-PEG-PDLLA micelle loading TP (AS-PPT) through solid dispersion technique. AS-PPT showed more antitumor activity than TP and equivalent specific binding ability with gemcitabine-resistant human pancreatic cancer cell (MIA PaCa-2) to AS1411 aptamer in vitro. Furthermore, we studied the distribution of AS-PPT (Cy3-labed TP) at tissue and cellular levels using biophotonic imaging technology. The results showed AS1411 facilitated TP selectively accumulating in tumor tissues and targeting CPC cells. The lifetime of the MIA PaCa-2 cell-bearing mice administrated with AS-PPT was efficiently prolonged than that of the mice subjected to the clinical anticancer drug Gemzar® in vivo. Such work provides a new strategy for overcoming the drug resistance of pancreatic cancer.

15 Article Gemcitabine plus S-1: a hopeful frontline treatment for Asian patients with unresectable advanced pancreatic cancer. 2015

Cao, Chunxiang / Kuang, Meng / Xu, Wei / Zhang, Xunlei / Chen, Jinfei / Tang, Cuiju. ·Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou. · Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing. · Department of Oncology, Nantong Tumor Hospital, Nantong. · Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing tangcuiju2013@163.com jinfeichen@sohu.com. ·Jpn J Clin Oncol · Pubmed #26518328.

ABSTRACT: OBJECTIVE: Gemcitabine-based chemotherapy is widely used for unresectable advanced pancreatic cancer which contains locally advanced and metastatic pancreatic cancer. We performed meta-analysis to examine whether gemcitabine plus S-1 could improve treatment efficacy as first-line chemotherapy for those patients when compared with gemcitabine alone. METHODS: STATA was used to estimate the summary hazard ratios or odds ratios and their 95% confidence intervals. Heterogeneity among trials was examined by Cochran's χ(2) test. Publication bias was evaluated by Begg's and Egger's tests. Subgroup analysis based on the extent of disease was performed. RESULTS: Four randomized controlled trials including 878 Asian patients were analyzed. In total meta-analysis, gemcitabine plus S-1 significantly improved overall survival (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96; P = 0.015), progression-free survival (hazard ratio, 0.64; 95% confidence interval, 0.55-0.74; P < 0.001), overall response rate (odds ratio, 3.00; 95% confidence interval, 2.04-4.41; P < 0.001) and disease control rate (odds ratio, 1.78; 95% confidence interval, 1.32 to 2.39; P < 0.001), and was associated with more but manageable hematologic (leukocytopenia, neutropenia, thrombocytopenia) and non-hematologic (diarrhea, stomatitis, nausea, rash) adverse events. In subgroup analysis, gemcitabine plus S-1, comparing with gemcitabine, significantly improved overall survival in locally advanced patients (hazard ratio, 0.69; 95% confidence interval, 0.48 to 0.99; P = 0.022) but not in metastatic patients (hazard ratio, 0.75; 95% confidence interval, 0.46-1.23; P = 0.256). CONCLUSION: This meta-analysis confirmed the survival benefits of gemcitabine plus S-1 as first-line treatment for unresectable advanced pancreatic cancer at least in Asia, while good Eastern Cooperative Oncology group performance status was warranted. Importantly, we highlighted the significant overall survival benefit of gemcitabine plus S-1 in locally advanced patients but not in metastatic patients.

16 Article Mutated K-ras activates CDK8 to stimulate the epithelial-to-mesenchymal transition in pancreatic cancer in part via the Wnt/β-catenin signaling pathway. 2015

Xu, Wei / Wang, Ziwei / Zhang, Wei / Qian, Kun / Li, Hui / Kong, Dequan / Li, Yuqiang / Tang, Yucheng. ·Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. · Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. Electronic address: wangziwei571@sina.com. ·Cancer Lett · Pubmed #25305448.

ABSTRACT: Cyclin-dependent kinase 8 (CDK8), a gene encoding the cyclin-dependent kinase (CDK) component of the Mediator complex, is known as a colon cancer oncogene. Our recent study showed that CDK8 plays an important role in the formation of pancreatic cancer, but the CDK8 expression levels were not completely identical in different pancreatic cancer samples. The level of CDK8 expression depended on whether the K-ras gene was mutated; its expression was much higher in samples carrying a K-ras mutation than in wild-type K-ras samples. Moreover, CDK8 expression was reduced following mutated K-ras knockdown in K-ras-mutated pancreatic cancer cells, whereas CDK8 expression was increased following expression of mutated K-ras in wild-type K-ras cells. Our study demonstrates that mutated K-ras stimulates CDK8 expression, possibly by regulating HIF-1α, and both CDK8 and mutated K-ras were confirmed to promote cell proliferation and prevent apoptosis in vitro. Additionally, we found that both CDK8 and mutated K-ras promote the invasion and migration of pancreatic cancer cells via the positive regulation of the Wnt/β-catenin signaling pathway, thereby increasing the expression of Snail1 and ZEB1, which act as important stimulating factors of the epithelial-to-mesenchymal transition (EMT). Finally, knockdown of either CDK8 or mutated K-ras contributed to attenuated pancreatic cancer growth in BALB/c nude mice. In conclusion, these findings demonstrate that mutated K-ras promotes CDK8 expression and that the regulatory effects of CDK8 on the EMT are partially attributed to the Wnt/β-catenin signaling pathway.

17 Article Negative methylation status of vimentin predicts improved prognosis in pancreatic carcinoma. 2014

Zhou, Yi-Feng / Xu, Wei / Wang, Xia / Sun, Jin-Shan / Xiang, Jing-Jing / Li, Zhao-Shen / Zhang, Xiao-Feng. ·Yi-Feng Zhou, Xia Wang, Jing-Jing Xiang, Xiao-Feng Zhang, Department of Digestive Medicine, The First People's Hospital of Hangzhou, Hangzhou 310006, Zhejiang Province, China. ·World J Gastroenterol · Pubmed #25278713.

ABSTRACT: AIM: To determine the existence of a potential relationship between the methylation state of the Vimentin gene and its prognostic value in pancreatic cancer. METHODS: Sixty-four primary tumor specimens and normal tissues were collected consecutively from pancreatic cancer patients during surgery at Hangzhou First People's Hospital and Affiliated Hospital of the Logistics University of the Chinese People's Armed Police Force. DNA was extracted from the samples and subsequently quantitative methylation-specific polymerase chain reaction was used to detect the Vimentin methylation status of the samples. All of the patients were followed up to December 2012. χ(2) test, Kaplan-Meier survival and Cox regression statistical models were used. RESULTS: Out of 64 pancreatic cancer tissues, 21 were marked as Vimentin methylation-positive, and 43 were marked as Vimentin methylation-negative. The location of pancreatic carcinoma was related to the Vimentin methylation state. The pathological T staging (P < 0.001), adjuvant chemotherapy (P = 0.003) and the Vimentin methylation state (P = 0.037) were independent prognostic factors. CONCLUSION: In our study, Vimentin methylation status can predict the prognosis of pancreatic cancer patients. However, additional experiments and clinical trials are needed to accurately validate this observation.

18 Article A new endoscopic ultrasonography image processing method to evaluate the prognosis for pancreatic cancer treated with interstitial brachytherapy. 2013

Xu, Wei / Liu, Yan / Lu, Zheng / Jin, Zhen-Dong / Hu, Yu-Hong / Yu, Jian-Guo / Li, Zhao-Shen. ·Wei Xu, Zheng Lu, Zhen-Dong Jin, Yu-Hong Hu, Zhao-Shen Li, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. ·World J Gastroenterol · Pubmed #24151368.

ABSTRACT: AIM: To develop a fuzzy classification method to score the texture features of pancreatic cancer in endoscopic ultrasonography (EUS) images and evaluate its utility in making prognosis judgments for patients with unresectable pancreatic cancer treated by EUS-guided interstitial brachytherapy. METHODS: EUS images from our retrospective database were analyzed. The regions of interest were drawn, and texture features were extracted, selected, and scored with a fuzzy classification method using a C++ program. Then, patients with unresectable pancreatic cancer were enrolled to receive EUS-guided iodine 125 radioactive seed implantation. Their fuzzy classification scores, tumor volumes, and carbohydrate antigen 199 (CA199) levels before and after the brachytherapy were recorded. The association between the changes in these parameters and overall survival was analyzed statistically. RESULTS: EUS images of 153 patients with pancreatic cancer and 63 non-cancer patients were analyzed. A total of 25 consecutive patients were enrolled, and they tolerated the brachytherapy well without any complications. There was a correlation between the change in the fuzzy classification score and overall survival (Spearman test, r = 0.616, P = 0.001), whereas no correlation was found to be significant between the change in tumor volume (P = 0.663), CA199 level (P = 0.659), and overall survival. There were 15 patients with a decrease in their fuzzy classification score after brachytherapy, whereas the fuzzy classification score increased in another 10 patients. There was a significant difference in overall survival between the two groups (67 d vs 151 d, P = 0.001), but not in the change of tumor volume and CA199 level. CONCLUSION: Using the fuzzy classification method to analyze EUS images of pancreatic cancer is feasible, and the method can be used to make prognosis judgments for patients with unresectable pancreatic cancer treated by interstitial brachytherapy.