Pancreatic Cell News Volume 5.02 | Jan 21 2014

Targeting the Cell Cycle Inhibitor p57^Kip2 Promotes Adult Human ß Cell Replication
Researchers hypothesized that targeting p57^Kip2 could stimulate adult human ß cell replication. Indeed, when they suppressed CDKN1C expression in human islets obtained from deceased adult organ donors and transplanted them into hyperglycemic, immunodeficient mice, ß cell replication increased more than three-fold. [J Clin Invest] Full Article | Press Release

A Common Functional Regulatory Variant at a Type 2 Diabetes Locus Upregulates ARAP1 Expression in the Pancreatic Beta Cell
Measurement of allele-specific mRNA levels in human pancreatic islet samples heterozygous for rs11603334 showed that the type 2 diabetes-risk and proinsulin-decreasing allele is associated with increased ARAP1 expression. Scientists evaluated four candidate functional SNPs for allelic effects on transcriptional activity by performing reporter assays in rodent pancreatic beta cell lines. [Am J Hum Genet] Abstract

Phosphatidylinositol 4,5-Biphosphate (PIP2) Modulates Interaction of Syntaxin-1A with Sulfonylurea Receptor 1 to Regulate Pancreatic Beta-Cell ATP-Sensitive Potassium Channels
Researchers assessed whether PIP2’s actions on activating KATP channels is contributed by sequestering syntaxin (Syn)-1A from binding SUR1. In vitro binding showed PIP2 dose-dependently disrupted Syn-1A-SUR1 complexes, corroborated by in vivo Forster resonance energy transfer assay showing disruption of SUR1(-EGFP)/Syn-1A(-mCherry) interaction along with increased Syn-1A cluster formation. [J Biol Chem]
Abstract | Full Article

GSK-3ß Phosphorylates and Stabilizes HLXB9 in Insulinoma Cells to Form a Targetable Mechanism of Controlling Insulinoma Cell Proliferation
Scientists previously reported the pro-apoptotic ß-cell differentiation factor HLXB9 as a downstream target of menin. Here they showed that GSK-3ß inactivates the pro-apoptotic activity of HLXB9 by phosphorylating HLXB9 at Ser-78/Ser-80. [J Cell Biol] Abstract | Full Article

Compliant 3D Microenvironment Improves ß-Cell Cluster Insulin Expression through Mechanosensing and ß-Catenin Signaling
Scientists showed a significant increase in insulin mRNA expression of 3D primary mouse islet-derived and Min6-derived ß-cell clusters grown on compliant 0.1 kPa scaffolds. Moreover, these compliant 0.1 kPa scaffolds also increase glucose sensitivity in Min6-derived ß-cell clusters as demonstrates by the increased glucose stimulation index. [Tissue Eng Part A] Abstract

Pancreatic Acinar Cells-Derived Cyclophilin A Promotes Pancreatic Damage by Activating NF-?B Pathway in Experimental Pancreatitis
Researchers investigated the role of Cyclophilin A (CypA) in experimental acute pancreatitis induced by administration of sodium taurocholate. CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. [Biochem Biophys Res Commun] Abstract

PANCREATIC CANCER

Protease-Activated Receptor-1 Drives Pancreatic Cancer Progression and Chemoresistance
Utilizing an orthotopic pancreatic cancer model in which tumor cells are protease activated receptor (PAR)-1 positive whereas stromal cells are PAR-1 negative, researchers showed that PAR-1 expression in the microenvironment drives progression and induces chemoresistance of pancreatic cancer. [Int J Cancer] Abstract

CBP Mediated FOXO-1 Acetylation Inhibits Pancreatic Tumor Growth by Targeting SirT
Researchers investigated the potential mechanism of capsaicin-mediated apoptosis in pancreatic cancer cells. Capsaicin treatment phosphorylated JNK, FOXO1 and BIM in BxPC-3, AsPC-1 and L3.6PL cells. [Mol Cancer Ther] Abstract

Antitumor Activity of Gemcitabine Can Be Potentiated in Pancreatic Cancer through Modulation of TLR4/NF-?B Signaling by 6-Shogaol
Scientists investigated whether 6-shogaol could suppress pancreatic cancer progress and potentiate pancreatic cancer to gemcitabine treatment in vitro and in vivo. They found that 6-shogaol prevented the activation of toll like receptor 4 (TLR4)/NF-?B signaling. [AAPS J] Abstract

Antiproliferative Effects of Carbon Monoxide on Pancreatic Cancer
In vitro studies were performed on human pancreatic cancer cells treated with a carbon monoxide-releasing molecule or its inactive counterpart, or exposed to carbon monoxide gas. Both carbon monoxide-releasing molecule and carbon monoxide exposure significantly inhibited proliferation of human pancreatic cancer cells. [Dig Liver Dis] Abstract

Magnetic Catechin-Dextran Conjugate as Targeted Therapeutic for Pancreatic Tumor Cells
Catechin-dextran conjugated with Endorem increased the intracellular concentration of the drug and it induced apoptosis in 98% of pancreatic tumor cells placed under magnetic field. [J Drug Target] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

Aduro Announces Phase II Clinical Trial Results Demonstrating Statistically Significant Survival Benefit in Pancreatic Cancer Patients Treated with Its Novel Immunotherapies
Aduro BioTech, Inc. announced the presentation of safety and efficacy data from a randomized Phase II clinical trial of its novel immunotherapy product candidates, CRS-207 and GVAX Pancreas, in metastatic pancreatic cancer patients. [Press release from Aduro BioTech, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Conference, San Francisco] Press Release

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AstraZeneca and Bristol-Myers Squibb Diabetes Alliance Provides $5 Million Grant for American Diabetes Association’s Pathway to Stop Diabetes Research Initiative
AstraZeneca and Bristol-Myers Squibb Company announced that the companies’ U.S. Diabetes Alliance is providing a three-year grant to the American Diabetes Association’s Pathway to Stop Diabetes program. [Bristol-Myers Squibb Company] Press Release

The HUB Foundation for Organoid Technology and STEMCELL Technologies Sign Agreement on the Manufacturing of Cell Culture Media for Organoids
The HUB Foundation for Organoid Technology announced that it has signed a licensing agreement with STEMCELL Technologies Inc. for the manufacturing and worldwide distribution of cell culture media for growing Organoids. [STEMCELL Technologies Inc.] Press Release

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

Postdoctoral Research Assistant in Physiology – Pancreatic Islet Cell Electrophysiology (University of Gothenburg)

PhD Scholarship Positions – Diabetes & Obesity Research (Virginia Polytechnic Institute and State University)

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)

Postdoctoral Position – Pancreatic Cancer Research (University of Texas Health Science Center at San Antonio)

Research Assistant/Associate Professor Position – Division of Diabetes, Endocrinology and Metabolism (Vanderbilt Medical Center)

Clinical MD – Clinical Development Program for Oncology and Autoimmune Diseases (Immunomedics, Inc.)

Chief Medical Officer – Novel Therapeutics in Oncology and Autoimmune Disease (Immunomedics, Inc.)

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