Volume 5.14 | Apr 15

Pancreatic Cell News 5.14 April 15, 2014
Pancreatic Cell News
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Mutant p53 Drives Pancreatic Cancer Metastasis through Cell-Autonomous PDGF Receptor ß Signaling
Scientists showed that sustained expression of mutant p53 is required to maintain the prometastatic phenotype of a murine model of pancreatic cancer, a highly metastatic disease that frequently displays p53 mutations. Blocking platelet-derived growth factor receptor b signaling by RNA interference or by small molecule inhibitors prevented pancreatic cancer cell invasion in vitro and metastasis formation in vivo. [Cell]
Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Expression of Human Cationic Trypsinogen (PRSS1) in Murine Acinar Cells Promotes Pancreatitis and Apoptotic Cell Death
Scientists developed a novel transgenic murine model system using wild-type human PRSS1 or two hereditary pancreatitis-associated mutants to determine whether expression of human cationic trypsinogen in murine acinar cells promotes pancreatitis. [Cell Death Dis] Full Article

Pancreatic ß-Cell Na+ Channels Control Global Ca2+ Signaling and Oxidative Metabolism by Inducing Na+ and Ca2+ Responses that Are Propagated into Mitochondria
Researchers showed that tetrodotoxin inhibits glucose-dependent depolarization and blocks cytosolic Na+ and Ca2+ responses and their propagation into mitochondria. Their results showed that communication of the Na+ channels with mitochondria shape both global Ca2+ and metabolism signals linked to insulin secretion in ß cells. [FASEB J] Abstract

Distinct Requirements for Beta-Catenin in Pancreatic Epithelial Growth and Patterning
To resolve the potential roles of ß-catenin in development of multipotent pancreatic progenitor cells and ß-cells, scientists generated pancreas- and pre-endocrine-specific ß-catenin knockout mice. Pancreas-specific loss of ß-catenin produced not only a dramatic reduction in acinar cell numbers, but also a significant reduction in ß-cell mass. [Dev Biol] Abstract

The Immunoregulation Effect of Alpha 1-Antitrypsin Prolong ß-Cell Survival after Transplantation
The authors established a ß cell line (NIT-hAAT) that stably expresses human alpha 1-antitrypsin. Interestingly, in a cytotoxic T lymphocyte-killing assay, they found that hAAT reduced apoptosis and inflammatory cytokine production in NIT-1 cells and regulated the Th1/Th2 cytokine balance in vitro. [PLoS One] Full Article

17ß-Estradiol Protects against Glucosamine-Induced Pancreatic ß-Cell Dysfunction
Researchers investigated changes in insulin production and ß-cell apoptosis in pancreatic islets after glucosamine (GlcN) treatment in rats with or without ovariectomy and used MIN-6 cells to investigate the protective effects and molecular mechanisms of 17ß-estradiol in GlcN-induced ß-cell dysfunction. [Menopause] Abstract

MANF Is Indispensable for the Proliferation and Survival of Pancreatic ß Cells
Scientists generated mesencephalic astrocyte-derived neurotrophic factor (MANF)-deficient mice that strikingly develop severe diabetes due to progressive postnatal reduction of ß cell mass, caused by decreased proliferation and increased apoptosis. [Cell Rep] Full Article | Graphical Abstract


Impaired c-Jun N-Terminal Protein Kinase Signaling Cooperates with KrasG12D Expression to Accelerate Pancreatic Ductal Adenocarcinoma
Researchers demonstrated the cooperative interaction of endogenous expression of KrasG12D with loss-of-function mutations in mitogen-activated protein kinase kinase 4 (mkk4) or both, mkk4 and mkk7 genes in the pancreas. [Cancer Res] Abstract | Full Article

CHIP Is a Novel Tumor Suppressor in Pancreatic Cancer through Targeting EGFR
Researchers showed that carboxyl terminus of heat shock protein 70-interacting protein (CHIP) interacts and ubiquitinates epidermal growth factor receptor (EGFR) for proteasome-mediated degradation in pancreatic cancer cells, thereby inhibiting the activation of EGFR downstream pathway. [Oncotarget] Abstract

Resistance to the Tyrosine Kinase Inhibitor Axitinib Is Associated with Increased Glucose Metabolism in Pancreatic Adenocarcinoma
Scientists showed that human cell lines and mouse pancreatic adenocarcinoma cell lines obtained from the spontaneous pancreatic cancer mouse model were sensitive to axitinib. [Cell Death Dis] Full Article

Measurement of Protein Kinase B Activity in Single Primary Human Pancreatic Cancer Cells
An optimized peptide substrate was used to measure protein kinase B activity in single cells. The system was validated in three model pancreatic cancer cell lines before application to cells from a human pancreatic adenocarcinomas propagated in nude mice. [Anal Chem] Abstract

Pancreatic Cancer Stem-Like Cells Display Aggressive Behavior Mediated via Activation of FoxQ1
Researchers found that isolated triple-marker positive cells of human pancreatic cancer MiaPaCa-2 and L3.6pl cells behave as cancer stem-like cells (CSLCs). These CSLCs exhibit aggressive behavior such as increased cell growth, migration, clonogenicity, and self-renewal capacity. [J Biol Chem] Abstract | Full Article

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Nutrient Regulation of Glucagon Secretion: Involvement in Metabolism and Diabetes
The authors present a summary of established concepts as well as new information about the regulation of a-cells by glucose, amino acids, fatty acids and other nutrients, focusing especially on glucagon release, glucagon synthesis and a-cell survival. [Nutr Res Rev] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
LX4211 Achieves Positive Results in Type 1 Diabetes Clinical Trial
Lexicon Pharmaceuticals, Inc. announced positive, top-line results in a Phase II clinical trial of LX4211 in type 1 diabetes, which achieved the primary endpoint of reducing mealtime insulin use as well as several secondary endpoints, including improved glycemic control. [Lexicon Pharmaceuticals, Inc.] Press Release

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Halozyme Announces Clinical Hold of PEGPH20 Pancreatic Cancer Trial Following Voluntary Halt of Trial by Halozyme
Halozyme Therapeutics, Inc. announced that the United States Food and Drug Administration informed the company yesterday that a clinical hold has been placed on patient enrollment and dosing of PEGPH20 in an ongoing Phase II trial evaluating PEGPH20 in patients with pancreatic cancer. [Halozyme Therapeutics, Inc.] Press Release

Nuvilex Engages ViruSure to Establish Cell Banks for Phase IIb Clinical Trials in Pancreatic Cancer
Nuvilex, Inc. reported that it has signed a Master Services Agreement with ViruSure GmbH to develop and maintain Master, Working and End of Production Cell Banks. These cell banks are necessary steps in the production of the cells to be encapsulated using the Cell-in-a-Box® technology for Nuvilex’s Phase IIb clinical trials in advanced, inoperable pancreatic cancer to be conducted in Australia. [GlobeNewswire, Inc.]
Press Release

Boehringer Ingelheim and Eli Lilly and Company Announce New Drug Application Filing in the U.S. for the Combination Tablet of Empagliflozin and Linagliptin
Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company announced the U.S. Food and Drug Administration accepted the filing of the New Drug Application for the combination tablet of empagliflozin and linagliptin for the treatment of adults with type 2 diabetes. [Boehringer Ingelheim GmbH] Press Release

Stand Up to Cancer Research Funding Opportunities
The American Association for Cancer Research (AACR), on behalf of Stand Up To Cancer (SU2C) and Cancer Research UK, is accepting applications for SU2C-Cancer Research UK Translational Research Fellowships that will offer up to $315,000 each in research funding. [The American Association for Cancer Research]
Press Release
NIH Stem-Cell Program Closes
Stem-cell researchers at the US National Institutes of Health (NIH) have been left frustrated and confused following the demise of the agency’s Center for Regenerative Medicine. [Nature News] Editorial

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 18th International Congress on Toxicology In Vitro ESTIV2014
June 10-13, 2014
Egmond aan Zee, Netherlands

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW Staff Scientist and Postdoctoral Fellow – Beta Cell Biology and Diabetes Research (Sanford Research/USD)

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

Postdoctoral Research Associate – Extracellular Microenvironment in Cancer (Institute of Translational Medicine, University of Liverpool)

PhD Studentship – Functional Role of MicroRNA in Vascular Complications of Diabetes (University of Edinburgh)

Postdoctoral Position – Diabetes (TAMHSC)

Senior Research Coordinator (Joslin Diabetes Center)

Diabetes Researchers – Pathway to Stop Diabetes (American Diabetes Association)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

Postdoctoral Position – Diabetes (Université de Sherbrooke)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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