Pancreatic Cell News 8.27 July 11, 2017 | |
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TOP STORYResearchers established a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate. [Cancer Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)DIABETES & PANCREATITISRecruitment of Epac2A to Insulin Granule Docking Sites Regulates Priming for Exocytosis Using quantitative high-resolution microscopy scientists found that cAMP elevation caused rapid binding of Epac2A to the β-cell plasma membrane, where it accumulated specifically at secretory granules and rendered them more prone to undergo exocytosis. [Diabetes] Abstract | Press Release Investigators found that Gnb5 knockout in mice or in the insulin-secreting MIN6 cell line almost completely eliminated insulinotropic activity of muscarinic cholinergic receptor M3 (M3R). Moreover, overexpression of Gβ5-RGS7 strongly promoted M3R-stimulated insulin secretion. [FASEB J] Abstract | Press Release Probing the Missing Mature β-Cell Proteomic Landscape in Differentiating Patient IPSC-Derived Cells The authors demonstrated that insulin-positive cells can be generated in vitro from human induced pluripotent stem cells (hiPSCs) derived from patients carrying a non-sense HNF4A mutation, proving for the first time, that a human HNF4A mutation is neither blocking the expression of the insulin genes nor the development of insulin-producing cells in vitro. [Sci Rep] Full Article Scientists hypothesized that palmitate simultaneously stimulates secretion of glucagon and insulin at fasting glucose concentrations. They hypothesized that concomitant hypersecretion of glucagon and insulin was also contributed by reduced somatostatin secretion. They found that basal glucagon, insulin and somatostatin secretion and respiration from human islets, became enhanced during palmitate treatment at normoglycemia. [Sci Rep] Full Article Presence of Diabetes Autoantigens in Extracellular Vesicles Derived From Human Islets Researchers report the caspase-independent production of extracellular vesicles (EV) by human islets in culture, and the characterization of diabetes autoantigens glutamic acid decarboxylase 65 and zinc transporter 8, as well as the β-cell resident glucose transporter, present within the EV. [Sci Rep] Full Article PANCREATIC CANCERResearchers demonstrated that collagen served as a proline reservoir for pancreatic ductal adenocarcinoma (PDAC) cells to use as a nutrient source when other fuels are limited. They showed that PDAC cells were able to take up collagen fragments, which could promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributed to PDAC cell metabolism. [Nat Commun] Full Article The authors report an alternative mechanism by which integrin-linked kinase post-transcriptionally modulates the expression of MUC1-C by maintaining its protein stability in pancreatic cancer cells. They found that integrin-linked kinase (ILK) acts in concert with STAT3 to facilitate IL-6-mediated upregulation of MUC1-C; ILK depletion was equally effective as STAT3 depletion in abolishing IL-6-induced MUC1-C overexpression without disturbing the phosphorylation or cellular distribution of STAT3. [Oncogenesis] Full Article Scientists aimed to investigate the biological role of miR-372 in human pancreatic adenocarcinoma (HPAC). They found that the expression of miR-372 was markedly down-regulated in HPAC cells compared to adjacent normal tissues. [Cancer Sci] Abstract Researchers aimed to verify the hypothesis that up-regulation of microRNA-300 targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition of pancreatic cancer cells by regulating the Wnt/β-catenin signaling pathway. [J Cell Biochem] Abstract Investigators examined the impact of extracellular matrix (ECM) proteins on pancreatic ductal adenocarcinoma (PDAC) cancer stem cells. They quantified the effect of ECM proteins, β1-integrin, and focal adhesion kinase (FAK) on clonogenic PDAC growth and migration in vitro and tumor initiation, growth, and metastasis in vivo in nude mice using shRNA and overexpression constructs as well as small molecule FAK inhibitors. [PLoS One] Full Article | |
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REVIEWSInsulin Action and Resistance in Obesity and Type 2 Diabetes Nutritional excess is a major forerunner of type 2 diabetes. It enhances the secretion of insulin, but attenuates insulin’s metabolic actions in the liver, skeletal muscle and adipose tissue. However, conflicting evidence indicates a lack of knowledge of the timing of these events during the development of obesity and diabetes, pointing to a key gap in our understanding of metabolic disease. The author reviews alternate viewpoints and recent results on the temporal and mechanistic connections between hyperinsulinemia, obesity and insulin resistance. [Nat Med] Abstract Visit our reviews page to see a complete list of reviews in the pancreatic cell research field. | |
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SCIENCE NEWSARMO BioSciences Presents Clinical Data on Immunotherapy AM0010 in Advanced Pancreatic Cancer ARMO BioSciences, Inc. announced clinical data on its lead investigational immuno-oncology drug AM0010. AM0010 is being evaluated in an ongoing Phase I/Ib clinical trial that has enrolled 352 advanced cancer patients and in a Phase III clinical trial that is enrolling patients with advanced pancreatic cancer. [Press release from ARMO BioSciences, Inc. discussing research presented at the 2017 ESMO 19th World Congress on Gastrointestinal Cancer, Barcelona] Press Release | |
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INDUSTRY NEWSZydus Receives Tentative Approval From the USFDA for Sitagliptin and Metformin Hydrochloride Tablets Zydus Cadila has received the tentative approval from the USFDA to market Sitagliptin and Metformin Hydrochloride Tablets. This is a fixed dose combination of two anti-diabetic drugs indicated for Type II diabetes mellitus and will be produced at the group’s formulations manufacturing facility at the Pharma SEZ in Ahmedabad. [Zydus Cadila] Press Release FibroGen Granted Orphan Drug Designation for Pamrevlumab in the Treatment of Pancreatic Cancer FibroGen, Inc. announced that the U.S. Food and Drug Administration has granted Orphan Drug Designation status to pamrevlumab, the company’s first-in-class antibody, for the treatment of pancreatic cancer. [FibroGen, Inc.] Press Release BioLineRx Ltd. announced that Genentech has commenced a Phase Ib/II study for BL-8040 in combination with atezolizumab, Genentech’s anti-PDL1 cancer immunotherapy agent, evaluating the combination in metastatic pancreatic ductal adenocarcinoma. [BioLineRx Ltd.] Press Release | |
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POLICY NEWSWhite House’s Dwindling Science Office Leaves Major Research Programs in Limbo US President Donald Trump has pledged to shrink the federal government, and he seems to be starting with science. Nearly six months after taking office, Trump has not chosen a science adviser, and the White House’s Office of Science and Technology Policy has dwindled from around 130 staff members under former president Barack Obama to 35. [Nature News] Editorial French Scientist Fined for Failure to Disclose Industry Ties In an unprecedented court case in Paris, an eminent French lung specialist has been fined €50,000 and given a six-month suspended jail sentence because he didn’t disclose his ties to the oil industry during a Senate air-pollution inquiry. [Nature News] Editorial Trump Administration Chooses Georgia Physician to Lead US Public-Health Agency Obstetrician and gynecologist Brenda Fitzgerald will direct the US Centers for Disease Control and Prevention, Secretary of Health and Human Services Tom Price announced. [Nature News] Editorial
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EVENTSNEW Cold Spring Harbor Stem Cell Biology Meeting Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Senior Scientific Officer – Pancreatic Cancer (Cancer Research UK Beatson Institute) NEW Senior/Principal Scientist – Stem Cell Research (Plasticell Ltd) Postdoctoral Fellow – Integrative Computational Biology (Wellcome Trust Sanger Institute) Group Leader – Cancer Research (University of Lille) Postdoctoral Scholarship – Diabetes Research (Lund University) Postdoctoral Position – Pancreatic Cell Research (Inserm) Postdoctoral Research Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center) PhD Position – Health/Biomedical Sciences (University of Auckland) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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