Volume 6.06 | Feb 17

Pancreatic Cell News 6.06 February 17, 2015
Pancreatic Cell News
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Dual PI3K/mTOR Inhibitors Induce Rapid Over-Activation of the MEK/ERK Pathway in Human Pancreatic Cancer Cells through Suppression of mTORC2
Researchers demonstrated that treatment of PANC-1 or MiaPaCa-2 pancreatic ductal adenocarcinoma cells with the dual PI3K/mTOR kinase inhibitor NPV-BEZ235 blocked mTORC1/S6K activation, mTORC1/4E-BP1 and mTORC2-mediated AKT phosphorylation at Ser473, in a concentration-dependent manner. [Mol Cancer Ther] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Overcoming Insulin Insufficiency by Forced Follistatin Expression in β-Cells of db/db Mice
Scientists describe a therapeutic strategy to preserve β-cell function by overexpression of follistatin (FST) using an AAV vector in diabetic mouse model. Overexpression of FST in the pancreas of db/db mouse increased β-cell islet mass, decreased fasting glucose level, alleviated diabetic symptoms, and essentially doubled lifespan of the treated mice. [Mol Ther] Abstract

Expression of the Kynurenine Pathway Enzymes in the Pancreatic Islet Cells. Activation by Cytokines and Glucolipotoxicity
Using normal rat islets and the INS-1 β-cell line, scientists demonstrated for the first time that only some TKP genes are constitutively expressed, both in β-cells as well as non β-cells. [Biochim Biophys Acta] Abstract

Impact of Sox9 Dosage and Hes1-Mediated Notch Signaling in Controlling the Plasticity of Adult Pancreatic Duct Cells in Mice
Using Sox9-IRES-CreERT2 knock-in mice as a model, researchers analyzed how plasticity is controlled in adult ducts. Adult duct cells in these mice express less Sox9 than do wild-type mice but Hes1 equally. Acinar cell differentiation was accelerated by Hes1 inactivation, but suppressed by NICD induction in adult Sox9-expressing cells. [Sci Rep] Full Article

Non-Receptor Tyrosine Kinase Inhibitors Enhances β-Cell Survival by Suppressing the PKCδ Signal Transduction Pathway in Streptozotocin-Induced β-Cell Apoptosis
Scientists determined the effects of GNF-2, GNF-5 on pancreatic β-cell death caused by streptozotocin (STZ). STZ treatment causes apoptosis of INS-1 cells by activation of intracellular reactive oxygen species, c-jun N-terminal kinase, caspase 3, and caspase 3-dependent activation of protein kinase C delta (PKCδ). [Cell Signal] Abstract


S100A4 Promotes Pancreatic Cancer Progression through a Dual Signaling Pathway Mediated by Src and Focal Adhesion Kinase
The effects of loss or gain of S100A4 were examined in pancreatic cancer cell lines. S100A4 downregulation remarkably reduces cell migration and invasion, inhibits proliferation, and induces apoptosis in pancreatic tumor cells. [Sci Rep] Full Article

Cofilin-Phosphatase Slingshot-1L (SSH1L) Is Over-Expressed in Pancreatic Cancer (PC) and Contributes to Tumor Cell Migration
Slingshot-1L (SSH1L) expression was shown to be up-regulated in PC cell lines with high metastatic potential. Loss of SSH1L expression was associated with an increase in the phosphorylation of cofilin-1 at serine-3 and further inhibit cell migration (but not proliferation) in KLM1, PANC-1 and MIAPaCa-2. [Cancer Lett] Abstract

Restoration of TRAIL-Induced Apoptosis in Resistant Human Pancreatic Cancer Cells by a Novel FAK Inhibitor, PH11
Researchers showed that treatment with PH11, a novel focal adhesion kinase inhibitor in association with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) rapidly induces apoptosis in TRAIL-resistant PANC-1 cells, but not in normal human fibroblast cells. [Cancer Lett] Abstract

Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas
To study telomere shortening in precancerous pancreatic lesions, scientists measured telomere lengths using quantitative fluorescence in situ hybridization in the normal pancreatic duct epithelium, pancreatic intraepithelial neoplasias (PanINs), and cancers. [PLoS One] Full Article

ZGDHu-1 Suppresses the Proliferation of PANC-1 Pancreatic Cancer Cells via Apoptosis and G2/M Cell Cycle Arrest
Using an MTT assay, scientists found that ZGDHu-1 significantly suppressed the proliferation of PANC-1 cells in a time- and dose-dependent manner. [Oncol Rep] Abstract

Free Cell Stem Cell Poster: Directed Differentiation of ESCs/iPSCs
Combination Immunotherapies for Type 1 Diabetes Mellitus
The authors summarize the available data about combination immunotherapies in type 1 diabetes mellitus, particularly addressing their clinical importance. The available data supporting the use of registered drugs, such as proton pump inhibitors and incretin-based agents, that have been shown to induce β-cell regeneration are also discussed. [Nat Rev Endocrinol] Abstract

Diabetes Mellitus – Advances and Challenges in Human β-Cell Proliferation
The authors discuss the physiology of normal human β-cell replication, the molecular mechanisms that regulate the cell cycle in human β cells, the upstream intracellular signaling pathways that connect them to cell surface receptors on β cells, the epigenetic mechanisms that control human β-cell proliferation and unbiased approaches for discovering novel molecules that can drive human β-cell proliferation. [Nat Rev Endocrinol] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
JDRF and Janssen to Drive Novel Type 1 Diabetes Research Concept
JDRF announced its support of an innovative scientific approach of Janssen Research & Development, LLC and the company’s Disease Interception Accelerator group, designed to support novel initiatives of disease interception – or changing the path of the disease before a person is clinically diagnosed. [JDRF]
Press Release

Oncolytics Biotech® Inc. Announces Receipt of Orphan Drug Designation from the U.S. FDA for Pancreatic Cancer
Oncolytics Biotech® Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for its lead product candidate, REOLYSIN®, for the treatment of pancreatic cancer. [Oncolytics Biotech® Inc.] Press Release

Kaul Foundation Donates $7 Million for UAB Personalized Medicine Institute
The Hugh Kaul Foundation has donated $7 million to the University of Alabama at Birmingham (UAB) to establish the Hugh Kaul Personalized Medicine Institute at UAB. [University of Alabama at Birmingham]
Press Release

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NEW Cellular Dynamics & Models
March 3-6, 2015
Cold Spring Harbor, United States

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW Postdoctoral Position – Endothelial Dysfunction and Diabetes (Weill Cornell Medical College in Qatar)

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

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Director – Vector Production (Sangamo BioSciences, Inc.)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Professor – Type 1 Diabetes (Karolinska Institute)

Assistant/Associate Professor – Endocrinology, Diabetes and Metabolism Research (University of Pennsylvania)

PhD Scholarships – Diabetes (Danish Diabetes Academy)

Postdoctoral Fellow – Wnt Signaling in Development and Disease (Van Andel Research Institute)

Postdoctoral Research Fellow – Post-Transcriptional Gene Regulation Governing Cancer Cell Behavior (Fred Hutchinson Cancer Research Center)

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