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Pancreatic Neoplasms: HELP
Articles by J. Wu
Based on 6 articles published since 2010
(Why 6 articles?)
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Between 2010 and 2020, J. Wu wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Vertically integrated translational studies of PDX1 as a therapeutic target for pancreatic cancer via a novel bifunctional RNAi platform. 2014

Wu, J / Liu, S / Yu, J / Zhou, G / Rao, D / Jay, C M / Kumar, P / Sanchez, R / Templeton, N / Senzer, N / Maples, P / Nemunaitis, J / Brunicardi, F C. ·Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Gradalis, Carrollton, TX, USA. · 1] Gradalis, Carrollton, TX, USA [2] Mary Crowley Cancer Research Center, Dallas, TX, USA. ·Cancer Gene Ther · Pubmed #24457987.

ABSTRACT: RNA interference (RNAi) represents a powerful, new tool for scientific investigation as well as a promising new form of targeted gene therapy, with applications currently in clinical trials. Bifunctional short hairpin RNA (shRNA) are synthetic RNAi molecules, engineered to utilize multiple endogenous RNAi pathways to specifically silence target genes. Pancreatic and duodenal homeobox 1 (PDX1) is a key regulator of pancreatic development, β-cell differentiation, normal β-cell function and pancreatic cancer. Our aim is to review the process of identifying PDX1 as a specific, potential RNAi target in pancreatic cancer, as well as the underlying mechanisms and various forms of RNAi, with subsequent testing and development of PDX1-targeted bifunctional shRNA therapy.

2 Article Activation of PPARα by clofibrate sensitizes pancreatic cancer cells to radiation through the Wnt/β-catenin pathway. 2018

Xue, J / Zhu, W / Song, J / Jiao, Y / Luo, J / Yu, C / Zhou, J / Wu, J / Chen, M / Ding, W-Q / Cao, J / Zhang, S. ·School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China. · Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China. · Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou, China. · Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China. · Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China. · Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA. ·Oncogene · Pubmed #29059162.

ABSTRACT: Radiotherapy is emerging as an important modality for the local control of pancreatic cancer, but pancreatic cancer cell radioresistance remains a serious concern. Peroxisome proliferator-activated receptor α (PPARα) is a member of the PPAR nuclear hormone receptor superfamily, which can be activated by fibrate ligands. The clinical relevance of PPARα and its biological function in pancreatic cancer radiosensitivity have not been previously described. In this study, we examined PPARα expression in tissue samples of pancreatic cancer patients. We found significantly higher expression of PPARα in pancreatic cancer tissues than in tumor-adjacent tissues and that the PPARα expression level is inversely associated with higher overall patient survival rate. We further observed that PPARα activation by its agonist clofibrate sensitizes pancreatic cancer cells to radiation by modulating cell cycle progression and apoptosis in several pancreatic cancer cell lines. Small interfering RNA-mediated PPARα silencing and PPARα blockade by the antagonist GW6471 abolish the effect of clofibrate on radiosensitization. An in vivo study showed that PANC1 xenografts treated with clofibrate are more sensitive to radiation than untreated xenografts. mRNA profiling by microarray analysis revealed that the expression of PTPRZ1 and Wnt8a, two core components of the β-catenin pathway, is downregulated by clofibrate. Chromatin immunoprecipitation analysis confirmed that clofibrate abrogates the binding of nuclear factor-κB to the PTPRZ1 and Wnt8a promoters, ultimately decreasing Wnt/β-catenin signaling activity, which is associated with radiosensitivity. Overall, we demonstrate that PPARα is overexpressed in pancreatic cancer tissues and clofibrate-mediated PPARα activation sensitizes pancreatic cancer cells to radiation through the Wnt/β-catenin pathway.

3 Article A case of IgG4-related retroperitoneal fibrosis with multiple involvement. 2017

Zheng, Y-K / Gu, N-Y / Wu, J / Fang, X / Zhang, C / Li, Q-Y. ·Department of ICU, Hangzhou hospital, Nanjing Medical University, Hangzhou 310006, Zhejiang, China. · Department of Internal Medicine, Hangzhou geriatric hospital, Hangzhou 310006, Zhejiang, China. · Department of Internal Medicine, Hangzhou hospital, Nanjing Medical University, Hangzhou 310006, Zhejiang, China. · Department of Vascular Surgery, Hangzhou hospital, Nanjing Medical University, Hangzhou 310006, Zhejiang, China. · Department of Endocrinology, Hangzhou hospital, Nanjing Medical University, Hangzhou 310006, Zhejiang, China. · Department of Pathology, Hangzhou hospital, Nanjing Medical University, Hangzhou 310006, Zhejiang, China. ·Cell Mol Biol (Noisy-le-grand) · Pubmed #28886329.

ABSTRACT: To increase awareness of IgG4-related retroperitoneal fibrosis (IgG4-RRPF) and reduce clinical misdiagnosis. We report a 79-year-old man with multiple organs involvement of IgG4-RRPF, who developed right lower extremity edema, hemoptysis and fever. The abdomen computed tomography (CT) scan image showed lymph nodes enlargement. The positron emission tomography/CT scan image showed pancreatic malignancy with multiple nodal lymph node metastasis, lung fibroblast proliferation, and right lung apex bullae. The chest CT scan image showed pulmonary multiple lymph nodes with calcification in the mediastinum. Posterior peritoneum magnetic resonance imaging showed the body and tail of the pancreas parenchymatous mass. The serum IgG4 concentration was high. The fibrous connective tissue with IgG4-positive plasma cells infiltration in the left supraclavicular lymph node biopsy was found. Fiberoptic bronchoscopy showed diffuse alveolar hemorrhage, and the transbronchial lung biopsy found no cancer cells. The patient was treated with glucocorticoids and immunosuppressive agents. After 2 months treatment, the patient showed rapid improvement. This is a case of IgG4-RRPF with multiple organs involvement. Glucocorticoid is the first-line treatment.

4 Article Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. 2017

Richards, K E / Zeleniak, A E / Fishel, M L / Wu, J / Littlepage, L E / Hill, R. ·Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA. · Department of Biological Sciences, Harper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA. · Integrated Biomedical Sciences Program, University of Notre Dame, South Bend, IN, USA. · Department of Pediatrics, Indiana University School of Medicine, Indiana University, Indianapolis, IN, USA. · Department of Pharmacology, Indiana University, Indianapolis, IN, USA. · Indiana University Simon Cancer Center, Indianapolis, IN, USA. · Department of Toxicology, Indiana University, Indianapolis, IN, USA. · Department of Chemistry, University of Notre Dame, Notre Dame, IN, USA. · Department of Biochemistry, University of Notre Dame, Notre Dame, IN, USA. ·Oncogene · Pubmed #27669441.

ABSTRACT: Cancer-associated fibroblasts (CAFs) comprise the majority of the tumor bulk of pancreatic ductal adenocarcinomas (PDACs). Current efforts to eradicate these tumors focus predominantly on targeting the proliferation of rapidly growing cancer epithelial cells. We know that this is largely ineffective with resistance arising in most tumors following exposure to chemotherapy. Despite the long-standing recognition of the prominence of CAFs in PDAC, the effect of chemotherapy on CAFs and how they may contribute to drug resistance in neighboring cancer cells is not well characterized. Here, we show that CAFs exposed to chemotherapy have an active role in regulating the survival and proliferation of cancer cells. We found that CAFs are intrinsically resistant to gemcitabine, the chemotherapeutic standard of care for PDAC. Further, CAFs exposed to gemcitabine significantly increase the release of extracellular vesicles called exosomes. These exosomes increased chemoresistance-inducing factor, Snail, in recipient epithelial cells and promote proliferation and drug resistance. Finally, treatment of gemcitabine-exposed CAFs with an inhibitor of exosome release, GW4869, significantly reduces survival in co-cultured epithelial cells, signifying an important role of CAF exosomes in chemotherapeutic drug resistance. Collectively, these findings show the potential for exosome inhibitors as treatment options alongside chemotherapy for overcoming PDAC chemoresistance.

5 Article Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma. 2016

Zhou, G / Yu, J / Wang, A / Liu, S-H / Sinnett-Smith, J / Wu, J / Sanchez, R / Nemunaitis, J / Ricordi, C / Rozengurt, E / Brunicardi, F C. ·Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA, USA. cbrunicardi@mednet.ucla.edu. ·Curr Mol Med · Pubmed #26695692.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most potent and perilous diseases known, with a median survival rate of 3-5 months due to the combination of only advanced stage diagnosis and ineffective therapeutic options. Metformin (1,1-Dimethylbiguanide hydrochloride), the leading drug used for type 2 diabetes mellitus, emerges as a potential therapy for PDAC and other human cancers. Metformin exerts its anticancer action via a variety of adenosine monophosphate (AMP)-activated protein kinase (AMPK)- dependent and/or AMPK-independent mechanisms. We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action. Metformin inhibited PDX-1 expression at both protein and mRNA levels and PDX-1 transactivity as well in PDAC cells. Extracellular signal-regulated kinase (ERK) was identified as a PDX-1-interacting protein by antibody array screening in GFP-PDX-1 stable HEK293 cells. Co-transfection of ERK1 with PDX-1 resulted in an enhanced PDX-1 expression in HEK293 cells in a dose-dependent manner. Immunoprecipitation/Western blotting analysis confirmed the ERK-PDX-1 interaction in PANC-1 cells stimulated by epidermal growth factor (EGF). EGF induced an enhanced PDX-1 expression in PANC-1 cells and this stimulation was inhibited by MEK inhibitor PD0325901. Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells. Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling.

6 Article hsa-miR-520h downregulates ABCG2 in pancreatic cancer cells to inhibit migration, invasion, and side populations. 2010

Wang, F / Xue, X / Wei, J / An, Y / Yao, J / Cai, H / Wu, J / Dai, C / Qian, Z / Xu, Z / Miao, Y. ·Laboratory of General Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, PR China. ·Br J Cancer · Pubmed #20628378.

ABSTRACT: BACKGROUND: Expression of ABCG2 is normally absent or low in the pancreas, but high in human pancreatic cancer cells. The mechanism by which ABCG2 is altered in human cancers remains unknown. METHODS: We investigated ABCG2 expression in four pancreatic cancer cell lines, and used three microRNA (miRNA) target prediction programmes, and information from the existing literature to predict and identify hsa-miR-520h as an miRNA that targets ABCG2. The function of this miRNA was investigated by transient transfection of the pancreatic cancer cell line PANC-1 with oligonucleotides that mimic hsa-miR-520h. RESULTS: Results showed that both mRNA and protein levels of ABCG2 were reduced, indicating that it was a target of hsa-miR-520h. Introduction of hsa-miR-520h mimics into PANC-1 cells also resulted in inhibition of cell migration and invasion, and reduction of side population cells. Cell proliferation, cell cycle progression and apoptosis were not affected. CONCLUSIONS: We propose that the effects of hsa-miR-520h may be, at least in part, caused by its regulation of ABCG2. Thus, our findings provide a new insight into the function of miRNA in the regulation of ABCG2 expression in pancreatic cancer. Gene therapy using miRNA mimics may therefore be useful as a pancreatic cancer therapy.