Pancreatic Cell News Volume 6.15 | Apr 21 2015

Phagocyte-Like NADPH Oxidase (Nox2) Promotes Activation of p38MAPK in Pancreatic β-Cells under Glucotoxic Conditions: Evidence for a Requisite Role of Ras-Related C3 Botulinum Toxin Substrate 1 (Rac1)
Researchers investigated roles of Nox2 in the regulation of downstream stress kinase (p38MAPK) activation under high glucose conditions in normal rodent islets and INS-1 832/13 cells. [Biochem Pharmacol] Abstract

Generation and Characterization of Transgenic Mice Expressing Mouse Ins1 Promoter for Pancreatic β Cell-Specific Gene Overexpression and Knockout
Scientists showed that Cre-mediated recombination and reverse tetracycline regulatable transactivator (rtTA)-mediated activation could be efficiently detected at E13.5 when models were crossed with reporter mice. The Cre and rtTA expression was restricted to β-cells without leakage in the brain and other tissues. [Endocrinology] Abstract | Full Article

MiR-375 Promotes Redifferentiation of Adult Human β Cells Expanded In Vitro
Scientists hypothesized that restoration of microRNA (miR)-375 expression in expanded β-cell-derived cells may contribute to their redifferentiation. They demonstrated that overexpression of miR-375 alone leads to activation of β-cell gene expression, reduced cell proliferation, and a switch from N-cadherin to E-cadherin expression, which characterizes mesenchymal-epithelial transition. [PLoS One] Full Article

Dopamine Modulates Insulin Release and Is Involved in the Survival of Rat Pancreatic Beta Cells
Investigators analyzed whether dopamine is a regulator of the proliferation and apoptosis of rat pancreatic beta cells after glucose-stimulated insulin secretion. [PLoS One] Full Article

PANCREATIC CANCER

The MiR-17-92 Cluster Counteracts Quiescence and Chemoresistance in a Distinct Subpopulation of Pancreatic Cancer Stem Cells
Scientists found the microRNA (miR)-17-92 cluster to be downregulated in chemoresistant cancer stem cells (CSCs) versus non-CSCs and demonstrated its crucial relevance for CSC biology. [Gut] Full Article

Xanthohumol-Mediated Suppression of Notch1 Signaling Is Associated with Antitumor Activity in Human Pancreatic Cancer Cells
Researchers assessed the efficacy of xanthohumol (XN) on pancreatic cancer cell lines against cell growth in real time and using colony forming assays. Treatment with XN resulted in reduction in cellular proliferation in a dose and time dependent manner. [Mol Cancer Ther] Abstract

The Involvement of Insulin-Like Growth Factor 2 Binding Protein 3 (IMP3) in Pancreatic Cancer Cell Migration, Invasion, and Adhesion
Using siRNA, the authors examined the effect of IMP3 inhibition on the motility, invasive ability, and matrix adhesion of pancreatic ductal adenocarcinoma cells. They also evaluated the expression of cytoskeleton-associated genes following IMP depletion. [BMC Cancer] Full Article

The Basic Helix-Loop-Helix Transcription Factor E47 Reprograms Human Pancreatic Cancer Cells to a Quiescent Acinar State with Reduced Tumorigenic Potential
Researchers queried whether pancreatic ductal adenocarcinoma (PDA) cells can be reprogrammed to revert to their original quiescent acinar cell state by shifting key transcription programs. In human PDA cells, E47 activity triggered stable G0/G1 arrest, which required the cyclin-dependent kinase inhibitor p21 and the stress response protein TP53INP1. [Pancreas] Abstract | Download Full Article | Press Release

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Tokai Pharmaceuticals Announces Preclinical Results from the University of Maryland Showing Galeterone and Analogs Inhibit Pancreatic Cancer Cell Growth
Tokai Pharmaceuticals, Inc. announced that scientists presented preclinical data showing that galeterone and novel analogs of galeterone inhibited growth, survival and migration of human pancreatic ductal adenocarcinoma cells. [Press release from the Tokai Pharmaceuticals, Inc. discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2015, Philadelphia] Press Release

Halozyme Presents New Preclinical Data at the American Association for Cancer Research Annual Meeting, Announces Clinical Data Presentation
Halozyme Therapeutics, Inc., a biotechnology company developing novel oncology and drug-delivery therapies, shared highlights of new data. [Press release from the Halozyme Therapeutics, Inc. discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2015, Philadelphia] Press Release

First-in-Human Phase I Trial of MM-141 Demonstrates Activity in Biomarker Positive Patients
Merrimack Pharmaceuticals, Inc. announced updated clinical data from a multi-arm Phase I study of MM-141, a bispecific antibody targeting IGF-1R and ErbB3. [Press release from the Merrimack Pharmaceuticals, Inc. discussing research presented at the American Association of Cancer Research (AACR) Annual Meeting 2015, Philadelphia] Press Release

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Imugene Files New HER-Vaxx Patent
Imugene Limited announced the filing of a new provisional patent titled, “A Vaccine Composition and Uses Thereof” (application number 2015901375), potentially extending HER-Vaxx patent life to 2036. [Imugene Limited] Press Release

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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)

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Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Mechanisms of Cell Death of Normal Tissue Stem Cells (Memorial Sloan Kettering Cancer Center)

Postdoctoral Position – Image-Guided Drug Delivery (Eindhoven University of Technology)

Research Assistant Professor – Protein Misfolding and Toxicity (George Washington University)

Director – Center of Emphasis in Diabetes and Metabolism (Texas Tech University Health Sciences Center)

Postdoctoral Position – Obesity & Diabetes (INSERM U892)

Postdoctoral Positions – Developmental Biology (Joslin Diabetes Center)

Postdoctoral Fellow – Type 2 Diabetes (Harvard Medical School)

Tenure-Track Immunology Faculty Position – Diabetes (University of Connecticut Health Center)

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