Pancreatic Cell News Volume 4.22 | Jun 11 2013

DIABETES

Synergistic Expression of the CXCL10 Gene in Response to IL-1β and IFN-γ Involves NF-κB, Phosphorylation of STAT1 at Tyr⁷⁰¹, and Acetylation of Histones H3 and H4
Researchers determined the molecular mechanisms required for expression of the CXCL10 gene in response to IL-1β and IFN-γ using rat islets and β cell lines. IL-1β induced the expression of the CXCL10 gene and promoter activity, whereas the combination of IL-1β plus IFN-γ was synergistic. [J Immunol] Abstract

Dendritic Cell-Dependent In Vivo Generation of Autoregulatory T Cells by Antidiabetogenic MHC Class II
Investigators showed that expression of I-E on dendritic cells of NOD mice promotes the differentiation of MHC promiscuous autoreactive CD4⁺ clonotypes into antidiabetogenic autoregulatory T cells. [J Immunol] Abstract

Pancreatic Acinar Cell NF-κB Activation Due to Bile Acid Exposure Is Dependent on Calcineurin
Investigators examined the role of the downstream Ca²⁺ target calcineurin on NF-Kappa B (NF-κB) translocation. They showed that the NF-κB inhibitor Bay 11-7082 blocked translocation and injury. [J Biol Chem] Abstract | Full Article

One Year of Sitagliptin Treatment Protects against Islet Amyloid-Associated Beta-Cell Loss and Does Not Induce Pancreatitis or Pancreatic Neoplasia in Mice
Scientists investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and beta-cell toxicity, and induced pancreatic ductal proliferation, pancreatitis and/or pancreatic metaplasia/neoplasia. [Am J Physiol Endocrinol Metab] Abstract

Obestatin Enhances In Vitro Generation of Pancreatic Islets through Regulation of Developmental Pathways
Scientists investigated whether obestatin may promote in vitro β-cell generation from mouse pancreatic islet-derived precursor cells. Treatment of cultured islets of Langerhans with obestatin enriched cells expressing the mesenchymal/neuronal marker nestin, which is associated with pancreatic precursors. [PLoS One]
Full Article

PANCREATIC CANCER

EVI1 Oncogene Promotes KRAS Pathway through Suppression of MicroRNA-96 in Pancreatic Carcinogenesis
By tracking a potential regulator of another feature of pancreatic ductal adenocarcinoma (PDAC) precursors, acquisition of foregut or gastric epithelial gene signature, researchers report that aberrant overexpression of ecotropic viral integration site 1 (EVI1) oncoprotein, which is usually absent in normal pancreatic duct, is a widespread marker across the full spectrum of human PDAC precursors and PDAC. [Oncogene] Abstract

Powerful Inhibition of Experimental Human Pancreatic Cancers by Receptor Targeted Cytotoxic LH-RH Analog AEZS-108
The authors determined LH-RH receptor presence in human pancreatic cancer samples by immunohistochemistry and, in three human pancreatic cancer lines, by binding assays and Western blotting. Cytotoxic LH-RH analogs powerfully inhibited growth of all three tumor lines in nude mice; AN-152 was significantly stronger than doxorubicin on Panc-1 and CFPAC-1 cancers. [Oncotarget] Abstract

An Undesired Effect of Chemotherapy: Gemcitabine Promotes Pancreatic Cancer Cell Invasiveness through ROS-Dependent, NF-κB- and HIF-1α-Mediated Upregulation of CXCR4
Recently, scientists have shown that CXCL12/CXCR4 signaling plays an important role in gemcitabine-resistance of pancreatic cancer (PC) cells. Here, they explored the effect of gemcitabine on this resistance mechanism. Their data demonstrated that gemcitabine induces CXCR4 expression in two PC cell lines in a dose- and time- dependent manner. [J Biol Chem] Abstract | Full Article

M2-Polarized Tumor-Associated Macrophages Promoted Epithelial-Mesenchymal Transition in Pancreatic Cancer Cells, Partially through TLR4/IL-10 Signaling Pathway
Scientists showed that coculture with M2-polarized tumor-associated macrophages increased fibroblastic morphology, upregulated mesenchymal markers vimentin and snail at the mRNA and protein levels, and increased proliferation, migration, and metalloproteinase (MMP)2 and MMP9 proteolytic activity in pancreatic cancer cells. [Lab Invest] Abstract

Role of the eIF4E Binding Protein 4E-BP1 in Regulation of the Sensitivity of Human Pancreatic Cancer Cells to TRAIL and Celastrol-Induced Apoptosis
Scientists examined the effects of celastrol and tumor necrosis factor α-related death-inducing ligand (TRAIL) in several pancreatic cancer cell lines. In cells that are normally resistant to TRAIL synergistic effects of TRAIL plus celastrol on commitment to apoptosis and inhibition of protein synthesis were observed. [Biol Cell] Abstract

REVIEWS

The Case for Virus-Induced Type 1 Diabetes
The established role of inflammation in the insulitic process and the increasing evidence in support of the contribution of viral infections to a proinflammatory islet scenario are strongly suggestive that viruses may indeed contribute to beta-cell damage and dysfunction, thus setting the stage for the design of antiviral strategies (e.g. vaccines and antiviral drugs) aimed at protecting the beta-cells. [Curr Opin Endocrinol Diabetes] Abstract

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Targovax AS Raises $3.6 Million in Private and Public Support for TG01 Pancreatic Cancer Vaccine Development
Targovax announced that it has raised a total of $3.6 million to accelerate development of its RAS mutation-targeted therapeutic cancer vaccine pipeline, specifically lead candidate TG01 for pancreatic cancer. [Business Wire] Press Release

Arena Pharmaceuticals Reports on Launch of BELVIQ® (lorcaserin HCl) CIV for Chronic Weight Management in Adults Who Are Overweight with a Comorbidity or Obese
Arena Pharmaceuticals, Inc. reported on the launch of BELVIQ in the United States. BELVIQ is approved by the US Food and Drug Administration for use as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index of 30 kg/m² or greater, or 27 kg/m² or greater in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes). [Arena Pharmaceuticals, Inc.] Press Release

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NEW Cold Spring Harbor Laboratory: Cell Signaling in Metabolism, Inflammation and Cancer
September 2-6, 2013
Suzhou, China

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NEW Postdoctoral Researcher – Experimental diabetes and Protein Research (Lund University/Experimental Medical Science)

NEW Director of Cell Processing Facility (S L Collins Associates, Inc.)

Diabetes UK PhD Studentship (Diabetes UK)

Postdoctoral Fellow – Beta Cell Biology (Sanford Research/University of South Dakota)

PhD Scholarships – Diabetes (Danish Diabetes Academy)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

PhD Positions – Molecular Mechanisms Controlling Acinar Cell Proliferation (University Hospital Zuerich)

Postdoctoral Researcher (The University of Texas Health Science Center at San Antonio)

Research Associate – Progression and Metastasis of Pancreatic and Breast Cancer (University of North Carolina at Charlotte)

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