Volume 5.05 | Feb 11

Pancreatic Cell News 5.05 February 11, 2014
Pancreatic Cell News
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Scientists Reprogram Skin Cells into Insulin-Producing Pancreas Cells
A cure for type 1 diabetes has long eluded even the top experts. Not because they do not know what must be done – but because the tools did not exist to do it. But now scientists have developed a technique in animal models that could replenish the very cells destroyed by the disease. [Press release from University of California, San Francisco discussing online prepublication in Cell Stem Cell]
Press Release | Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Pdx1 Maintains ß Cell Identity and Function by Repressing an a Cell Program
Scientists traced the fate of adult ß cells after Pdx1 deletion. As expected, ß-cell-specific removal of Pdx1 resulted in severe hyperglycemia within days. Surprisingly, a large fraction of Pdx1-deleted cells rapidly acquired ultrastructural and physiological features of a cells, indicating that a robust cellular reprogramming had occurred. [Cell Metab] Abstract | Graphical Abstract

Uncoupling of Cav1.2 from Ca2+-Induced Ca2+ Release and SK Channel Regulation in Pancreatic ß-Cells
Researchers investigated the role of Cav1.2 in pancreatic ß-cell function by expressing a Cav1.2 II-III loop/GFP fusion in INS-1 cells to disrupt channel-protein interactions. [Mol Endocrinol] Abstract

A Critical Role for the Neural Zinc Factor ST18 in Pancreatic Beta-Cell Apoptosis
Scientists demonstrated that, in the pancreas, ST18 expression is restricted to endocrine cells. The detection of ST18 expression in pancreatic ß-cells prompted them to investigate its regulation and its role in ß-cell mass and function. [J Biol Chem] Abstract | Full Article

Altered Pancreatic Growth and Insulin Secretion in WSB/EiJ Mice
Scientists examined whether defects in ß-cell mass or function could contribute to the low insulin levels in WSB mice. WSB mice had markedly increased insulin secretion from isolated islets in vitro. [PLoS One] Full Article

Aberrant Islet Unfolded Protein Response in Type 2 Diabetes
Researchers analyzed the expression of activating factor 6 and spliced X-box binding protein 1, and phosphorylation of eukaryotic initiation factor 2, to evaluate the three distinct branches of the unfolded protein response in the pancreatic islets of mice with diet- or genetic-induced obesity and insulin resistance. [Sci Rep] Full Article


Nuclear Translocation of FGFR1 and FGF2 in Pancreatic Stellate Cells Facilitates Pancreatic Cancer Cell Invasion
At the invasive front of human pancreatic cancer, FGF2 and FGFR1 localize to the nucleus in activated pancreatic stellate cells (PSCs) but not cancer cells. In vitro, inhibiting FGFR1 and FGF2 in PSCs, using RNAi or chemical inhibition, resulted in significantly reduced cell proliferation, which was not seen in cancer cells. [EMBO Mol Med] Full Article

Extracellular Superoxide Dismutase (EcSOD) Suppresses Hypoxia-Inducible Factor-1a (HIF-1a) in Pancreatic Cancer
Scientists hypothesized that EcSOD overexpression leads to changes in the O2•-/H2O2 balance modulating the redox status affecting signal transduction pathways. Both transient and stable overexpression of EcSOD suppressed the hypoxic accumulation of HIF-1a in human pancreatic cancer cells. [Free Radic Biol Med] Abstract

Antitumor Efficacy of a-Solanine against Pancreatic Cancer In Vitro and In Vivo
Researchers investigated the anti-carcinogenic effect of a-solanine against human pancreatic cancer cells. In vitro, a-solanine inhibited proliferation of PANC-1, sw1990, MIA PaCa-2 cells in a dose-dependent manner, as well as cell migration and invasion with atoxic doses. [PLoS One] Full Article

Redox-Responsive Targeted Gelatin Nanoparticles for Delivery of Combination wt-p53 Expressing Plasmid DNA and Gemcitabine in the Treatment of Pancreatic Cancer
Scientists developed a redox-responsive thiolated gelatin based nanoparticle system that efficiently delivers its payload in the presence of glutathione-mediated reducing intra-cellular environment and could be successfully used for site-specific wt-p53 expressing plasmid DNA as well as gemcitabine delivery by targeting epidermal growth factor receptor. [BMC Cancer] Abstract | Full Article

Different Responses of Human Pancreatic Adenocarcinoma Cell Lines to Oncolytic Newcastle Disease Virus Infection
In an effort to develop oncolytic virotherapy with Newcastle disease virus (NDV) for patients with pancreatic cancer, scientists evaluated the responses to NDV infection and interferon treatment of 11 different established human pancreatic adenocarcinoma cell lines (HPACs). They showed that all HPACs were susceptible to NDV. [Cancer Gene Ther] Abstract

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Toll-Like Receptors and NLRP3 as Central Regulators of Pancreatic Islet Inflammation in Type 2 Diabetes
The authors present evidence that Toll-like receptors 2 and 4 and the NLRP3 (Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain containing 3) inflammasome are triggers for islet inflammation in T2D and propose that the activation of macrophages by these triggers mediates islet endocrine cell dysfunction. [Immunol Cell Biol] Abstract

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Targovax TG01 Immunotherapy Reaches Phase IIa in Operable Pancreatic Cancer
Targovax announced that Phase I results of its RAS mutation-targeted cancer medicine TG01 in combination with chemotherapy for surgically resected pancreatic cancer, has triggered a $2 million milestone from current owners. [Targovax] Press Release

JDRF to Provide Additional Support for Upcoming Clinical Trial of ViaCyte’s Encapsulated Cell Therapy for Type 1 Diabetes
JDRF and ViaCyte, Inc. jointly announced that JDRF is providing additional milestone-based funding for the continued development of ViaCyte’s VC-01™ encapsulated cell therapy product candidate for the treatment of type 1 diabetes. [ViaCyte, Inc.] Press Release

Data on More than 10,000 Cancer Genomes Released by the International Cancer Genome Consortium
The International Cancer Genome Consortium announced that it has made available to the scientific community data from more than 10,000 cancer genomes. The data can be used by cancer researchers around the world to better understand the genomic basis of cancer, accelerate cancer research and aid in the development of more targeted treatments. [International Cancer Genome Consortium] Press Release

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Judges Side with FDA on Stem Cells
The D.C. Circuit Court of Appeals ruled that culturing a patient’s stem cells for therapeutic use falls under the aegis of the US Food and Drug Administration (FDA). FDA has said therapeutic stem cells should be regulated as drugs. [The Scientist] Editorial | Court Ruling

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW Clinical Translation of Stem Cells 2014
April 21-22, 2014
Palm Desert, United States

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW Postdoctoral Fellow – Stem Cell Biology (McEwen Centre for Regenerative Medicine/University Health Network)

Postdoctoral Associate Specialist – Human Pancreatic Stem Cell Research (The Nestlé Institute of Health Sciences)

Scientist Specialist – Diabetes/Metabolic Health (The Nestlé Institute of Health Sciences)

PhD Student – Beta-Cell ER Stress as Driver for Immune Activation in Early Type 1 Diabetes (KU Leuven)

Postdoctoral Research Scientist – Imaging GTPase Activation in Cancer (Cancer Research UK Beatson Institute in Glasgow)

Postdoctoral Research Scientist – RAC and RAL Signaling Downstream of KRAS Mutation in Pancreatic and Colon Cancer (Cancer Research UK Beatson Institute in Glasgow)

Postdoctoral Fellowship Position – Mechanisms of Action in Obesity and Diabetes Pathogenesis (NIH/NIDDK)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

PhD Student Position – Diabetes and Bone Regeneration (KU Leuven)

Postdoctoral Position – Development of Cellular Assays for Drug Development and Testing in Diabetes Treatment (Université de Sherbrooke)

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