Volume 5.03 | Jan 28

Pancreatic Cell News 5.03 January 28, 2014
Pancreatic Cell News
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Axon Guidance Factor Slit2 Inhibits Neural Invasion and Metastasis in Pancreatic Cancer
Researchers examined the hypothesis that escaping from repellent Slit2-Robo signaling is essential to enable pancreatic ductal adenocarcinoma (PDAC) cells to appropriate their local stromal infrastructure for dissemination. Through immunohistochemical analysis, they detected Slit2 receptors Robo1 and Robo4 on epithelia, nerves and vessels in healthy pancreas and PDAC specimens, respectively. [Cancer Res] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

GLP-1R-Targeting Magnetic Nanoparticles for Pancreatic Islet Imaging
Researchers synthesized an exendin-4 conjugated magnetic iron oxide based nanoparticle probe targeting glucagon-like peptide-1 receptor (GLP-1R), which is highly expressed on the surface of pancreatic beta-cells. In vitro studies in ßTC-6 beta-cell line showed specific accumulation of the targeted probe compared to non-targeted. [Diabetes] Abstract

Cdc42/N-WASP Signaling Links Actin Dynamics to Pancreatic ß Cell Delamination and Differentiation
Using the developing mouse pancreas as a model system, scientists showed that ß cell delamination and differentiation are two independent events, which are controlled by Cdc42/N-WASP signaling. [Development] Abstract

Disulfide Stress: A Novel Type of Oxidative Stress in Acute Pancreatitis
Researchers analyzed redox status of thiols and aimed to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. [Free Radic Biol Med] Abstract

Autocrine C-Peptide Mechanism Underlying INS1 Beta Cell Adaptation to Oxidative Stress
Researchers tested the hypothesis that an autocrine activity of C-peptide similarly decreases reactive oxygen species (ROS) when INS1 beta cells are exposed to stressful conditions of diabetes. C-peptide significantly decreased high glucose- and H2O2-induced ROS and prevented apoptosis of INS1 beta cells. [Diabetes Metab Res Rev] Abstract

Contribution of Protein Kinase Ca in the Stimulation of Insulin by the Down-Regulation of Cavß Subunits
Examination of protein kinase C (PKC) isozymes in the pancreatic ß-cells of voltage-gated calcium (Cav)ß2- or ß3 small interfering RNA-injected mice showed that three PKC isozymes, viz., PKC a, ßII and ?, translocated to the membrane. [Endocrine] Full Article


Novel Bispecific Antibodies Increase ?d T-Cell Cytotoxicity against Pancreatic Cancer Cells
Researchers demonstrated that ?d T-cells isolated from patients with pancreatic ductal adenocarcinoma tumor infiltrates lyse pancreatic tumor cells after selective stimulation with phosphorylated antigens. [Cancer Res] Abstract

FOXM1c Promotes Pancreatic Cancer Epithelial-to-Mesenchymal Transition and Metastasis via Upregulation of Expression of the Urokinase Plasminogen Activator System
The effect of altered expression of Forkhead box M1 (FOXM1) and urokinase plasminogen activator receptor on epithelial-to-mesenchymal transition and metastasis was examined using animal models of pancreatic cancer. Pancreatic tumor specimens and cell lines predominantly overexpressed the FOXM1 isoform FOXM1c. [Clin Cancer Res] Abstract

Hedgehog Acyltransferase as a Target in Pancreatic Ductal Adenocarcinoma
Researchers showed that Hedgehog acyltransferase, the enzyme responsible for the attachment of palmitate onto Sonic hedgehog (Shh), is a novel target for inhibition of Shh signaling in pancreatic cancer cells. [Oncogene] Abstract

Tumor-Associated Macrophages Exhibit Pro- and Anti-Inflammatory Properties by Which They Impact on Pancreatic Tumorigenesis
Since a detailed analysis of tumor-associated macrophages (TAMs) in human pancreatic ductal adenocarcinoma (PDAC) development is still lacking, freshly isolated PDAC-derived TAMs were analyzed for their phenotype and impact on epithelial-mesenchymal-transition of benign and malignant pancreatic ductal epithelial cells. [Int J Cancer] Abstract

MicroRNA-148b and MicroRNA-152 Reactivate Tumor Suppressor Genes through Suppression of DNA Methyltransferase-1 Gene in Pancreatic Cancer Cell Lines
Scientists investigated the effect of microRNA (miR)-148b and -152 on reverting the tumorigenic phenotype of pancreatic cancer cell lines. In order to investigate whether miR-148b and -152 are involved in the regulation of DNMT-1, luciferase reporter assay was used and confirmed that the DNMT-1 mRNA could be a target for miR-148b and miR-152. [Cancer Biol Ther] Full Article

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Immune Modulation in Humans: Implications for Type 1 Diabetes Mellitus
Type 1 diabetes mellitus is the result of autoimmune destruction of pancreatic ß cells in genetically predisposed individuals with impaired immune regulation. The authors discuss the current knowledge on immune regulation and dysfunction in humans that is the basis of tissue-specific immune regulation as an alternative to generalized immune suppression. [Nat Rev Endocrinol] Abstract

Vertically Integrated Translational Studies of PDX1 as a Therapeutic Target for Pancreatic Cancer via a Novel Bifunctional RNAi Platform
Pancreatic and duodenal homeobox 1 (PDX1) is a key regulator of pancreatic development, ß-cell differentiation, normal ß-cell function and pancreatic cancer. The authors review the process of identifying PDX1 as a specific, potential RNA interference (RNAi) target in pancreatic cancer, as well as the underlying mechanisms and various forms of RNAi, with subsequent testing and development of PDX1-targeted bifunctional short hairpin RNA therapy. [Cancer Gene Ther] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
Human Trials in Two Years for Artificial Pancreas Invention
An artificial pancreas invented by a De Montfort University professor could have its first human trials within two years. Professor Joan Taylor’s creation ensures patients will no longer have to endure injections of insulin every day. [De Montfort University] Press Release

GSK Receives Positive Opinion from the CHMP in Europe for Once-Weekly EperzanTM (albiglutide) for the Treatment of Type 2 Diabetes
GlaxoSmithKline plc (GSK) announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion recommending marketing authorization for albiglutide, under the brand name EperzanTM. [GlaxoSmithKline plc] Press Release

Novocure Enrolls First Patient in Pilot Clinical Trial of NovoTTF™ Therapy Plus Gemcitabine for First-line Treatment of Advanced Pancreatic Adenocarcinoma
Novocure announced that the first patient has enrolled in the EF-20 Study, an open label, pilot clinical trial of NovoTTF Therapy plus gemcitabine as first-line therapy for patients with locally advanced and metastatic pancreatic adenocarcinoma. [PR Newswire Association LLC] Press Release

Minister Sherlock Opens Ireland’s First Human Use Stem Cell Manufacturing Facility at NUI Galway
The Centre for Cell Manufacturing Ireland at National University of Ireland Galway is the first ever facility on the island of Ireland to receive a license from the Irish Medicines Board to manufacture culture-expanded stem cells for human use. [National University of Ireland, Galway] Press Release

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NEW Keystone Symposia: Emerging Concepts and Targets in Islet Biology
April 6-11, 2014
Keystone, United States

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW PhD Student – Beta-Cell ER Stress as Driver for Immune Activation in Early Type 1 Diabetes (KU Leuven)

NEW Postdoctoral Research Scientist – Imaging GTPase Activation in Cancer (Cancer Research UK Beatson Institute in Glasgow)

NEW Postdoctoral Research Scientist – RAC and RAL Signaling Downstream of KRAS Mutation in Pancreatic and Colon Cancer (Cancer Research UK Beatson Institute in Glasgow)

Postdoctoral Fellowship Position – Mechanisms of Action in Obesity and Diabetes Pathogenesis (NIH/NIDDK)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

PhD Scholarship Positions – Diabetes & Obesity Research (Virginia Polytechnic Institute and State University)

PhD Student Position – Diabetes and Bone Regeneration (KU Leuven)

Postdoctoral Position – Development of Cellular Assays for Drug Development and Testing in Diabetes Treatment (Université de Sherbrooke)

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

Research Assistant/Associate Professor Position – Division of Diabetes, Endocrinology and Metabolism (Vanderbilt Medical Center)

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