Pancreatic Cell News 8.00 January 3, 2017 | |
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TOP STORYDirect Evidence for Cancer-Cell-Autonomous Extracellular Protein Catabolism in Pancreatic Tumors Investigators utilized miniaturized plasma exchange to deliver labeled albumin to tissues in live mice, and they demonstrated that breakdown of albumin contributes to the supply of free amino acids in pancreatic tumors. They also delivered albumin directly into tumors using an implantable microdevice. [Nat Med] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)DIABETES & PANCREATITISResearchers examined whether physiological insulinostatic adrenaline action is mediated via the transient receptor potential melastatin 2 (TRPM2) channel, a type of non-selective cation channels (NSCCs), in β-cells. Results showed that physiological concentrations of adrenaline strongly suppressed glucose-induced and incretin-potentiated cAMP production and insulin secretion, and inhibited NSCCs current and membrane excitability via the α2A-adrenoceptor in wild-type mice; however, in TRPM2-knockout mice insulin secretion was not attenuated. [Diabetes] Abstract Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells The authors showed that human beta cells produce and secrete serotonin when stimulated with increases in glucose concentration. Serotonin secretion from beta cells decreased cyclic AMP levels in neighboring alpha cells via 5-HT1F receptors and inhibited glucagon secretion. [Cell Rep] Full Article | Graphical Abstract HMGB1 Modulation in Pancreatic Islets Using a Cell-Permeable A-Box Fragment Investigators demonstrated that high-mobility group-box-1 (HMGB1) protein could be bound to its A-box fragment with higher binding affinity, resembling anti-HMGB1 antibody. To be used as a pharmaceutical protein ex vivo, TAT-labeled HMGB1 A-box-His6 was structurally modified for cellular membrane penetration. [J Control Release] Abstract Researchers investigated whether adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) prevents beta cell apoptosis and inflammation in diabetes. APPL1 preserved beta cell mass by reducing beta cell apoptosis upon treatment with multiple-low-dose streptozotocin. [Diabetologia] Abstract Reciprocal Regulation of mTOR Complexes in Pancreatic Islets from Humans with Type 2 Diabetes While mechanistic target of rapamycin complex 1 (mTORC1) mediates beta cell growth and expansion, its hyperactivation has been observed in pancreatic islets from animal models of type 2 diabetes and leads to beta cell loss. The authors sought to determine whether such mTORC1 activation occurs in humans with type 2 diabetes or in metabolically stressed human islets and whether mTORC1 blockade can restore beta cell function of diabetic islets. [Diabetologia] Abstract PANCREATIC CANCERResearchers found that expression of the actomyosin regulatory ROCK1 and ROCK2 kinases increased with tumor progression in human and mouse pancreatic tumors, while elevated ROCK1/ROCK2 expression in human patients, or conditional ROCK2 activation in a KrasG12D/p53R172H mouse pancreatic ductal adenocarcinoma model, was associated with reduced survival. [EMBO Mol Med] Full Article HDAC2 Promotes Loss of Primary Cilia in Pancreatic Ductal Adenocarcinoma Investigators found that inhibition or silencing of histone deacetylase 2 (HDAC2) restores primary cilia formation in pancreatic ductal adenocarcinoma cells. Inactivation of HDAC2 resulted in decreased Aurora A expression, which promoted disassembly of primary cilia. They further showed that HDAC2 controls ciliogenesis independently of Kras, which facilitates Aurora A expression. [EMBO Rep] Abstract ARF6, Induced by Mutant Kras, Promotes Proliferation and Warburg Effect in Pancreatic Cancer By using the Cancer Genome Atlas dataset analysis, scientists demonstrated that the small guanosine triphosphatase ADP-ribosylation factor 6 (ARF6) serves as a biomarker for predicting prognosis of pancreatic cancer. In vitro studies demonstrated that silencing ARF6 expression reduced cell proliferation and attenuated the Warburg effect. [Cancer Lett] Abstract The authors showed for that CD147 interacts with membrane transporters beyond monocarboxylate transporters and exhibits a protective role for several of its interacting partners. The interactions with transmembrane small molecule and ion transporters identified indicate a central role of CD147 in pancreatic cancer metabolic reprogramming, particularly with respect to amino acid anabolism and calcium signaling. [Oncotarget] Full Article Researchers showed that deletion of CRABP-II in pancreatic ductal adenocarcinoma cells by CRISPR/Cas9 does not affect cancer cell proliferation, but decreases cell migration and invasion. Gene expression microarray analysis revealed that interleukin 8 (IL-8) is one of the top genes whose expression is down-regulated upon CRABP-II deletion, while expression of MMP-2 and MMP-14, two targets of IL-8 are also significantly down-regulated. [Oncotarget] Full Article | |
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REVIEWSMicroenvironment in Determining Chemo-Resistance in Pancreatic Cancer: Neighborhood Matters The authors systematically focus on the role played by the different microenvironmental components in determining chemoresistance of pancreatic tumors. Heterogeneity of the tumor, the dense fibroblastic stroma, and the aggressive biology of the tumor all contribute to the chemoresistant phenotype. [Pancreatology] Abstract Visit our reviews page to see a complete list of reviews in the pancreatic cell research field. | |
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INDUSTRY NEWSLexicon Pharmaceuticals, Inc. announced that its pivotal inTandem2 Phase III clinical trial of sotagliflozin met its primary endpoint, showing a statistically significant reduction in A1C at 24 weeks in patients with type 1 diabetes on optimized insulin therapy. [Lexicon Pharmaceuticals, Inc.] Press Release ARMO BioSciences, Inc. announced that the European Commission has granted the company’s lead investigational immuno-oncology drug AM0010 Orphan designation for the treatment of pancreatic cancer. ARMO plans to initiate enrollment of an international pivotal Phase III clinical trial, using AM0010 in combination with FOLFOX as second-line therapy in patients with advanced metastatic pancreatic cancer. [ARMO BioSciences, Inc.] Press Release The National Institute of Diabetes and Digestive and Kidney Diseases has awarded Penn Medicine a $12 Million, four-year grant to establish the Human Pancreas Analysis Program (HPAP). HPAP is focused on procuring and phenotyping pancreatic tissues from individuals with or at risk for Type 1 diabetes, Type 2 diabetes, or other types of pancreatic islet dysfunction characterized by changes in beta cell mass. [Penn Medicine] Press Release | |
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POLICY NEWSArgentina’s Researchers Occupy Science Ministry Hundreds of young researchers occupied Argentina’s science ministry in Buenos Aires last month, angry at budget cuts that they say have denied them permanent jobs at the country’s National Scientific and Technical Research Council. The occupation was the most extreme action yet by Argentinian scientists after months of protests at last year’s budget, the first under President Mauricio Macri. And the occupation seems to have paid off, in part: many of those involved have been offered extensions to their fellowships. [Nature News] Editorial Scientists in Germany, Peru and Taiwan to Lose Access to Elsevier Journals Thousands of scientists in Germany, Peru and Taiwan are preparing for a new year without online access to journals from the Dutch publishing giant Elsevier. Contract negotiations in both Germany and Taiwan broke down in December, while Peru’s government has cut off funding for a licence. [Nature News] Editorial
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EVENTSNEW Keystone Symposium: Lipidomics and Bioactive Lipids in Metabolism and Disease Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Position – Pancreatic Cancer (University of Liege) Senior Scientist – Pancreatic Cell Research (STEMCELL Technologies Inc.) Scientist – Insulin Secretion (Helmholtz Association) Principle Scientist – Translational Development (Celgene Corporation) Postdoctoral Researcher – Cell Biology (Northwestern University) Postdoctoral Researcher – Pancreatic Cancer (Karlsruhe Institute of Technology) Postdoctoral Researcher – Diabetes Research (Karolinska Institutet) Assistant Professor – Molecular Therapeutics (Dartmouth College/Geisel School of Medicine) Postdoctoral Research Associate – Structural Biology (Arizona State University) Faculty Position – Cancer Immunology (University of New Mexico) Assistant Professor – Cancer Cell Biology (North Dakota State University) Vice President – Pancreatic Cancer Disease Lead (Celgene Corporation) 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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