Volume 3.45 | Nov 13

Pancreatic Cell News 3.45 November 13, 2012
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs 
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TOP STORY
Secreted Frizzled-Related Protein 4 Reduces Insulin Secretion and Is Overexpressed in Type 2 Diabetes
Researchers explored the pathophysiology of type 2 diabetes by analyzing global gene expression in human pancreatic islets. [Cell Metab] Abstract | Graphical Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

DIABETES

The Peri-Islet Basement Membrane, a Barrier to Infiltrating Leukocytes in Type 1 Diabetes in Mouse and Human
Investigators provided the first comprehensive analysis of the extracellular matrix composition of peri-islet capsules, composed of the peri-islet basement membrane (BM) and subjacent interstitial matrix (IM), in development of type 1 diabetes in NOD mice and in human type 1 diabetes. The data demonstrate global loss of peri-islet BM and IM components only at sites of leukocyte infiltration into the islet. [Diabetes] Abstract

Insights Into the Molecular Mechanism for Type 2 Diabetes Susceptibility at the KCNQ1 Locus from Temporal Changes in Imprinting Status in Human Islets
By use of quantitative PCR and pyrosequencing of human adult islet and fetal pancreas samples, researchers investigated the imprinting status of regional transcripts and aimed to determine whether type 2 diabetes risk alleles influence regional DNA methylation and gene expression. [Diabetes] Abstract

Oestrogens Improve Human Pancreatic Islet Transplantation in a Mouse Model of Insulin Deficient Diabetes
During pancreatic islet transplantation, the female hormone 17β-oestradiol synergistic actions contribute to enhancing human islet-graft survival, revascularization and functional mass. [Diabetologia]
Abstract | Full Article

Syntaxin-3 Regulates Newcomer Insulin Granule Exocytosis and Compound Fusion in Pancreatic Beta Cells
Mouse pancreatic islets and INS-1 cells were treated with adenovirus carrying Syntaxin-3 (Syn-3) or small interfering RNA targeting Syn-3 in order to examine insulin secretion by radioimmunoassay. The localization and distribution of insulin granules were examined by confocal and electron microscopy. [Diabetologia] Abstract | Full Article

ALDH1B1 Is a Potential Stem/Progenitor Marker for Multiple Pancreas Progenitor Pools
In the adult pancreas researchers identified rare ALDH1B1+ cells that become abundant following pancreas injury in either the caerulein or streptozotocin paradigms. Blocking aldehyde dehydrogenase (ALDH) catalytic activity in pancreas embryonic explants resulted in reduced size of the explants and accelerated differentiation suggesting for the first time that ALDH activity may be necessary in the developing pancreas for the maintenance and expansion of progenitor pools. [Dev Biol] Abstract

PANCREATIC CANCER

Common Genetic Variants in the CLDN2 and PRSS1PRSS2 Loci Alter Risk for Alcohol-Related and Sporadic Pancreatitis
Researchers reported two pancreatitis risk associations at genome-wide significance identified and replicated at PRSS1PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. [Nat Genet]
Abstract | Press Release

MiR-197 Induces Epithelial-Mesenchymal Transition in Pancreatic Cancer Cells by Targeting p120 Catenin
Assessing the difference of miRNA expression profiles of invasive ductal adenocarcinoma (IDA), intraductal papillary mucinous adenoma and carcinoma, researchers newly identified miR-197 as an up-regulated miRNA specifically in IDA. Expression of miR-197 in pancreatic cancer cells resulted in the induction of epithelial-mesenchymal transition along with the down-regulation of p120 catenin which is a putative target of miR-197. [J Cell Physiol] Abstract

Extracellular Signal-Regulated Kinase Pathway and Sheddases Play an Essential Role in Ethanol-Induced CX3CL1 Release in Pancreatic Stellate Cells
Investigators aimed to determine the effects of cytokines, pathogen-associated molecular patterns, and ethanol and its metabolites on fractalkine (CX3CL1) secretion by pancreatic stellate cells. [Lab Invest] Abstract

Sulforaphane Regulates Self-Renewal of Pancreatic Cancer Stem Cells through the Modulation of Sonic Hedgehog-GLI Pathway
Investigators showed for the first time that sulforaphane treatment resulted in a significant reduction in the tumor growth of orthotopically implanted primary pancreatic cancer stem cells isolated from human pancreatic tumors into the pancreas of NOD/SCID/IL2Rgamma mice, which is mediated through the modulation of Sonic hedgehog-GLI signaling. [Mol Cell Biochem] Abstract

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REVIEWS

Signaling Danger: Endoplasmic Reticulum Stress and the Unfolded Protein Response in Pancreatic Islet Inflammation
Recent evidence, discussed in this review, indicates that both saturated fats and inflammatory mediators such as cytokines trigger the unfolded protein response in pancreatic beta cells. [Diabetologia]
Abstract | Full Article
SCIENCE NEWS
OncoMed Pharmaceuticals Announces Presentations of Anti-Notch2/3 and Demcizumab Clinical Data
The oral presentation, “A First-in-Human Phase I Study to Evaluate the Fully Human Monoclonal Antibody OMP-59R5 (anti-Notch2/3) Administered Intravenously to Patients with Advance Solid Tumors” was presented. In the clinical trial, OMP-59R5 was generally well tolerated, with diarrhea as the main treatment-related and dose-related adverse event. Based on these data, OncoMed has advanced Anti-Notch2/3 into an ongoing Phase Ib/II “ALPINE” trial (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) in first-line advanced pancreatic cancer patients. [Press release from OncoMed Pharmaceuticals, Inc. discussing research presented at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Dublin] Press Release
INDUSTRY NEWS

Kancera Reports Inhibitory Effects on Pancreatic Cancer in Animal Studies
Kancera reported that the company’s first generation of PFKFB3 inhibiting compounds reduces growth of pancreatic cancer in a pre-clinical animal study. [Kancera AB] Press Release

£20 Million Investment for UK Synthetic Biology Research
In a move that could potentially revolutionize major UK industries and help us to meet serious social and environmental challenges, the Biotechnology and Biological Sciences Research Council has announced an unprecedented £20M worth of synthetic biology projects. [Biotechnology and Biological Sciences Research Council] Press Release

POLICY NEWS

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)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS
NEW International Conference of Personalized Medicine and Targeted Therapies in Cancer
January 31-February 2, 2013
Sharjah, United Arab Emirates

Visit our events page to see a complete list of events in the pancreatic cell community.
JOB OPPORTUNITIES

Quality Control Operations Coordinator (STEMCELL Technologies, Inc.)

Research Technologist – Cell Separation (STEMCELL Technologies, Inc.)

Product Manager – Hematopoietic (STEMCELL Technologies, Inc.)

Product Quality Scientist (STEMCELL Technologies, Inc.)

Scientist – Endothelial Cell Research (STEMCELL Technologies, Inc.)

Postdoctoral Position – Beta Cell Biology and Translational Research (University of California, Los Angeles)

Postdoctoral Position – Signaling Pathways Pancreatic Beta-Cells (CNRS – Centre National de la Recherche Scientifique)

Postdoctoral Position – Beta Cell Biology (Umea Center for Molecular Medicine)

Postdoctoral Position – Tumor Stem Cells (Cancer Institute of New Jersey)

Postdoctoral Position – Pancreatic Cancer Research (University of Notre Dame, Department of Biological Sciences)

Postdoctoral Fellow – Beta-Cell Regeneration in Zebrafish (Karolinska Institute, Cell and Molecular Biology)


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