Pancreatic Cell News 8.06 February 14, 2017 | |
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TOP STORYScientists Identify Aggressive Pancreatic Cancer Cells and Their Vulnerability Researchers identified a gatekeeper protein that prevents pancreatic cancer cells from transitioning into a particularly aggressive cell type and also found therapies capable of thwarting those cells when the gatekeeper is depleted. [Press release from the University of Texas MD Anderson Cancer Center discussing online prepublication in Nature] Press Release | Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)DIABETES & PANCREATITISThe authors investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. They found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6.1+ stage, leading to impaired formation of glucose-responsive β-like cells. [Cell Stem Cell] Abstract | Graphical Abstract Investigators identified a population of β cells during the progression of type 1 diabetes in non-obese diabetic (NOD) mice that survived immune attack. This population developed from normal β cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival were activated in these cells. [Cell Metab] Abstract | Graphical Abstract Using the endodermal progenitor stem cell culture system to bypass the developmental block at the endoderm stage, scientists differentiated cell lines with mutations in one or both GATA6 alleles into β-like cells but with reduced efficiency. GATA6 mutant β-like cells failed to secrete insulin upon glucose stimulation and demonstrated defective insulin processing. [Stem Cell Reports] Full Article Researchers investigated the effect and mechanism of tributyltin (TBT) exposure at noncytotoxic doses relevant to human exposure on β-cell function in vitro and in vivo. Unlike previous studies, TBT at noncytotoxic concentrations significantly increased glucose-stimulated insulin secretion and intracellular Ca2+ in β-cells. [Arch Toxicol] Abstract Inflammatory Stress of Pancreatic Beta Cells Drives Release of Extracellular Heat Shock Protein 90α Investigators hypothesized heat shock protein (HSP)90α could be released from beta cells in response to cellular stress and inflammation associated with the earliest stages of type 1 diabetes. Human beta cell lines and cadaveric islets released HSP90α in response to stress induced by treatment with a combination of pro-inflammatory cytokines including IL-1β, TNF-α, and IFN-γ. Mechanistically, HSP90α release was found to be driven by cytokine-induced endoplasmic reticulum stress mediated by c-Jun N-terminal kinase, a pathway that can eventually lead to beta cell apoptosis. [Immunology] Abstract PANCREATIC CANCERTo characterize pure HG-PanIN, the authors analyzed 23 isolated HG-PanIN lesions occurring in the absence of pancreatic ductal adenocarcinoma. Whole-exome sequencing of five of these HG-PanIN lesions revealed a median of 33 somatic mutations per lesion, with a total of 318 mutated genes. [J Pathol] Abstract Chemoproteomic Screening of Covalent Ligands Reveals UBA5 as a Novel Pancreatic Cancer Target Researchers discovered a covalent ligand DKM 2-93 that impairs pancreatic cancer cell survival and in vivo tumor growth through covalently modifying the catalytic cysteine of the ubiquitin-like modifier activating enzyme 5 (UBA5), thereby inhibiting its activity as a protein that activates the ubiquitin-like protein UFM1 to UFMylate proteins. [ACS Chem Biol] Abstract Scientists evaluated the roles of lysophosphatidic acid (LPA)1 and LPA3 in cellular functions during tumor progression in pancreatic cancer cells. LPA1 and LPA3 knockdown cells were generated from PANC-1 cells. The cell motile and invasive activities of PANC-1 cells were inhibited by LPA1 and LPA3 knockdown. [Exp Cell Res] Abstract | |
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REVIEWSScientists review the recent advances regarding the regulatory roles and mechanisms of stroma biology, especially the cellular components such as pancreatic stellate cells, macrophages, neutrophils, adipocytes, epithelial cells, pericytes, mast cells, and lymphocytes, in pancreatic cancer. [Cancer Lett] Abstract The authors summarize recent evidences on the cardio-renal and metabolic benefits of specific Na+/glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes. [J Diabetes Investig] Full Article Visit our reviews page to see a complete list of reviews in the pancreatic cell research field. | |
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INDUSTRY NEWSThe label for Eli Lilly and Company’s once-weekly Trulicity® is now updated to include use in combination with basal insulin for adults with type 2 diabetes. The U.S. Food and Drug Administration included the changes to the approved product labeling to reflect this important information for prescribers. [Eli Lilly and Company] Press Release MabVax Therapeutics Studies Lead Investigational Drug MVT-5873 with Halozyme PEGPH20 MabVax Therapeutics Holdings, Inc. announced results from a pre-clinical study evaluating the potential benefits of using MabVax’s HuMab-5B1antibody, MVT-5873, currently in Phase I clinical trials for the treatment of metastatic pancreatic cancer with Halozyme Therapeutic’s investigational drug PEGPH20, which targets the tumor microenvironment potentially allowing increased access of co-administered cancer drug therapies to solid tumors. [MabVax Therapeutics Holdings, Inc.] Press Release Cancer Research UK announces that four international teams are the first recipients of its global £100 million Grand Challenge competition, which aims to overcome the biggest challenges facing cancer researchers in a global effort to beat cancer sooner. [Cancer Research UK] Press Release | Video | |
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POLICY NEWSUS Science Advisers Outline Path to Genetically Modified Babies Modified human embryos should be allowed if researchers meet strict criteria, says long-awaited National Academies report. [Nature News] Editorial German Scientists Regain Access to Elsevier Journals A stand-off in which dozens of German universities declined to pay for access to journals from publishing giant Elsevier has been partially resolved. [Nature News] Editorial Debate Erupts over Plan to Create Another Online Destination for Biology Preprints A plan to create a new repository for biomedical and biology preprints has earned the endorsement of nearly a dozen major science funders, including government agencies, major foundations, and research charities. But it also has sparked a debate about whether an existing preprint repository, bioRxiv.org, should be the natural home for such material. [ScienceInsider] Editorial Lawsuit Aims to Force USDA to Repost Scrubbed Animal Welfare Records Put the records back on the internet. That’s the demand made in a lawsuit filed against the U.S. Department of Agriculture (USDA) by an animal law expert at Harvard University, together with the People for the Ethical Treatment of Animals and several other animal welfare groups. The plaintiffs allege that USDA violated the federal Freedom of Information Act when it removed thousands of animal welfare inspection reports and other records from a publicly accessible website. [ScienceInsider] Editorial
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EVENTSNEW Gordon Research Conference: Cell Growth & Proliferation Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Position – Pancreatic Cancer (Cold Spring Harbor Laboratory) Senior Scientist – Pancreatic Cell Research (STEMCELL Technologies Inc.) Postdoctoral Research Scientist – Diabetes Research (University of Oxford) Postdoctoral Fellow – Islet Function/Regeneration (Toronto General Research Institute) Postdoctoral Associate – Pancreatic Cancer (University of Miami) Postdoctoral Research Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center) Postdoctoral Position – Pancreatic Cancer (University of Liege) Principle Scientist – Translational Development (Celgene Corporation) Assistant Professor – Molecular Therapeutics (Dartmouth College/Geisel School of Medicine) 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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Home Pancreatic Cell News Volume 8.06 | Feb 14 2017