Volume 4.46 | Nov 26

Pancreatic Cell News 4.46 November 26, 2013
Pancreatic Cell News
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Desnutrin/ATGL Activates PPARδ to Promote Mitochondrial Function for Insulin Secretion in Islet β Cells
Researchers showed that desnutrin ablation via RIP-Cre or RIP-CreER results in hyperglycemia with impaired glucose-stimulated insulin secretion. Due to decreased lipolysis, islets have higher TAG content but lower free FA levels. [Cell Metab] Abstract | Full Article | Graphical Abstract
Take the "if" out of "diff": Reduce variability when differentiating to endothelial cells
PUBLICATIONS ( Ranked by impact factor of the journal)

Reporter Islets in the Eye Reveal the Plasticity of the Endocrine Pancreas
Researchers describe the application of a natural body window that successfully reports on the properties of in situ pancreatic islets. As proof of principle, they transplanted “reporter islets” into the anterior chamber of the eye of leptin-deficient mice. [Proc Natl Acad Sci USA] Abstract

High Glucose Exposure Promotes Activation of Protein Phosphatase 2A in Rodent Islets and INS-1 832/13 β-Cells by Increasing the Posttranslational Carboxylmethylation of Its Catalytic Subunit
Scientists report activation of protein phosphatase 2A (PP2A) in normal rat islets and insulin-secreting INS-1 832/13 cells under the duress of hyperglycemic conditions. Small interfering RNA-mediated knockdown of the catalytic subunit of PP2A markedly attenuated glucose-induced activation of PP2A. [Endocrinology] Abstract

A Novel Gene Delivery Method Transduces Porcine Pancreatic Duct Epithelial Cells
Scientists catheterized the umbilical artery of wild-type newborn pigs and delivered an adeno-associated virus serotype 9 vector expressing green-fluorescent protein or vehicle to the celiac artery, the vessel that supplies major branches to the pancreas. [Gene Ther] Abstract

Activation of PPARβ/δ Protects Pancreatic β Cells from Palmitate-Induced Apoptosis by Upregulating the Expression of GLP-1 Receptor
Researchers showed that peroxisome proliferator-activated receptor (PPAR)β/δ activation decreased apoptosis in β cells and robustly stimulated glucagon-like peptide-1 receptor (GLP-1R) expression under lipotoxic conditions. GW501516 enhanced glucose-stimulated insulin secretion impaired by palmitate through stimulation of GLP-1R expression in β cells. [Cell Signal] Abstract

R-Spondin1 Deficiency Enhances [Beta]-Cell Neogenesis in a Murine Model of Diabetes
Scientints hypothesized that R-spondin1 (Rspo1) deficiency enhances [beta]-cell neogenesis in streptozotocin (STZ)-induced diabetes. [beta]-cell mass, islet number, and islet size distribution did not differ between STZ-induced Rspo1+/+ and Rspo1-/- mice, but Rspo1-/- animals had reduced [beta]-cell apoptosis and increased numbers of insulin-positive ductal cells, indicating [beta]-cell neogenesis. [Pancreas] Abstract


Low CHD5 Expression Activates the DNA Damage Response and Predicts Poor Outcome in Patients Undergoing Adjuvant Therapy for Resected Pancreatic Cancer
Researchers evaluated the relationship of CHD5 expression with DNA damage response activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. [Oncogene] Abstract

Overexpression of Calreticulin Contributes to the Development and Progression of Pancreatic Cancer
Scientists studied the clinicopathological significance for Calreticulin expression in pancreatic cancer (PC), and its functional relationship with other signaling genes in regulating the biological behavior of PC cells. [J Cell Physiol] Abstract

Histone Deacetylase 6 and Cytoplasmic Linker Protein 170 Function Together to Regulate the Motility of Pancreatic Cancer Cells
Researchers found that histone deacetylase 6 (HDAC6), a member of the class II HDAC family, is highly expressed at both protein and mRNA levels in human pancreatic cancer tissues. [Protein Cell] Abstract

Heat-Shock Protein 90 Inhibitors Synergistically Enhance Melanoma Differentiation-Associated Gene-7-Mediated Cell Killing of Human Pancreatic Carcinoma
Scientists examined possible antitumor effects of adenoviruses expressing melanoma differentiation-associated gene-7/interleukin-24 (Ad-mda-7) and a heat-shock protein 90 (Hsp90) inhibitor to human pancreatic carcinoma cells. Ad-mda-7 and an Hsp90 inhibitor, geldanamycin (GA), produced cytotoxic effects, and a combinatory use of Ad-mda-7 and GA further achieved synergistic effects. [Cancer Gene Ther] Abstract

Sineoculis Homeobox Homolog 1 Protein Overexpression as an Independent Biomarker for Pancreatic Ductal Adenocarcinoma
To investigate the clinicopathological significance of sineoculis homeobox homolog 1 (SIX1) expression in pancreatic ductal adenocarcinoma (PDAC), and to further identify its role as a potential biomarker and therapeutic target in PDAC, 103 PDAC tissue samples and 45 normal pancreatic tissue samples were immunohistochemically stained for SIX1 protein. The localization of SIX1 protein was detected in Panc-1 cancer cells using immunofluorescence staining. [Exp Mol Pathol] Abstract

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Pathophysiology of Chronic Pancreatitis
Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. [ World J Gastroenterol] Full Article

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Xigduo™ (Dapagliflozin and Metformin Hydrochloride) Receives Positive CHMP Opinion in the European Union for the Treatment of Type 2 Diabetes
AstraZeneca and Bristol-Myers Squibb announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of Xigduo™ for adults aged 18 and older with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in patients inadequately controlled on their current metformin-based treatment regimen or who are currently being treated with the combination of dapgliflozin and metformin as separate tablets. [AstraZeneca] Press Release

Celgene Receives Positive CHMP Opinion for ABRAXANE® in Combination with Gemcitabine as Treatment for Patients with Metastatic Pancreatic Cancer
Celgene International Sàrl announced that the European Medicines Agency’s: Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for ABRAXANE in combination with gemcitabine for first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas. [Celgene International Sàrl] Press Release

Berg Launches First-Ever Stratified Medicine Clinical Trial to Investigate Cancer Metabolism of Solid Tumors
Berg announced a first-of-its-kind Phase Ib clinical trial with Weill Cornell Medical College, Palo Alto Medical Foundation, and MD Anderson Cancer Center to study its investigational compound, BPM 31510, as a new cancer therapy for solid tumors. [PR Newswire Association LLC] Press Release

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NEW Molecular Medicine Tri-Conference 2014
February 9-14, 2014
San Francisco, United States

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NEW Faculty Fellowship – Diabetes Research (Joslin Diabetes Center)

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

Postdoctoral Fellow Positions – Beta Cell Maintenance in Health and Diabetes (Tel Aviv University)

Postdoctoral Fellow – Novel Genes in Pancreatic Beta Cell Function (University of California – San Francisco)

Postdoctoral Position – Cell Metabolism, Diabetes and Fatty Liver Disease (Boston University)

Postdoctoral Associate – Human and Mouse Stem Cell Biology, Pancreatic and Liver Specification and In Vitro Disease Modeling (Baylor College of Medicine)

Faculty Position – Department of Cellular & Structural Biology (The University of Texas Health Science Center at San Antonio)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

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