Pancreatic Cell News Volume 3.42 | Oct 23 2012

DIABETES

Oral Delivery of Bioencapsulated Exendin-4 Expressed in Chloroplasts Lowers Blood Glucose Level in Mice and Stimulates Insulin Secretion in Beta-TC6 Cells
Researchers expressed exendin-4 (EX4) as a cholera toxin B subunit (CTB)-fusion protein in tobacco chloroplasts to facilitate bioencapsulation within plant cells and transmucosal delivery in the gut via GM1 receptors present in the intestinal epithelium. Chloroplast-derived CTB-EX4 showed increased insulin secretion similar to the commercial EX4 in beta-TC6, a mouse pancreatic cell line. [Plant Biotechnol J] Abstract

Role of Calcium-Independent Phospholipase A2 (iPLA2β) in Human Pancreatic Islet β-Cell Apoptosis
To examine if islet β-cells are susceptible to ER stress and undergo iPLA2β-mediated apoptosis, scientists assessed the ER stress response in human pancreatic islets. They report that the iPLA2β protein is expressed predominantly in the β-cells of human islets and that thapsigargin-induced ER stress promotes β-cell apoptosis, as reflected by increases in activated caspase-3 in the β-cells. [Am J Physiol Endocrinol Metab] Abstract

Differential and Day-Time Dependent Expression of Nuclear Receptors RORα, RORβ, RORγ and RXRα in the Rodent Pancreas and Islet
The retinoic-acid-related receptor family of orphan receptors (RORs) act as transcriptional activators or repressors. Researchers described differential expression of the orphan receptors RORα, RORβ and RORγ and of the nuclear retinoid receptor RXRα in the pancreas and islet of rats. [Mol Cell Endocrinol] Abstract

Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice
The authors previously identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell function in young mice. Here, they aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. [PLoS One] Full Article

PANCREATIC CANCER

The NAD+-Dependent Histone Deacetylase SIRT6 Promotes Cytokine Production and Migration in Pancreatic Cancer Cells by Regulating Ca2+ Responses
Scientists determined whether SIRT6 is involved in conferring an inflammatory phenotype to cancer cells and to define the mechanisms linking SIRT6 to inflammation. They showed that SIRT6 enhances the expression of pro-inflammatory cyto/chemokines and promotes cell migration in pancreatic cancer cells by enhancing Ca2+ responses. [J Biol Chem] Abstract | Full Article

EGFR and HER2 Inhibition in Pancreatic Cancer
Researchers investigated the effect of lapatinib, a selective inhibitor of EGFR/HER2 tyrosine kinases, on pancreatic cancer cell lines both alone and in combination with chemotherapy. [Invest New Drugs] Abstract

Tissue Tolerable Plasma (TTP) Induces Apoptosis in Pancreatic Cancer Cells In Vitro and In Vivo
The authors investigated the effects of TTPs on the human pancreatic cancer cell line Colo-357 and PaTu8988T and the murine cell line 6606PDA in vitro as well as in the in vivo tumor chorio-allantoic membrane assay using Colo-357. [BMC Cancer] Abstract | Full Article

BML-275, an AMPK Inhibitor, Induces DNA Damage, G2/M Arrest and Apoptosis in Human Pancreatic Cancer Cells
Adenosine monophosphate-activated protein kinase (AMPK) is a principal intracellular energy sensor which regulates energy producing pathways and energy requiring pathways when the cellular AMP/ATP ratio is altered. BML-275, a well-known inhibitor of AMPK, has been found to induce apoptosis in myeloma, glioma and prostate cancer cells. Here scientists investigated BML-275 for its antitumor effect(s) in human pancreatic cancer cell lines. [Int J Oncol] Abstract

REVIEWS

Insulin Gene Therapy from Design to Beta Cell Generation
Despite the fact that insulin injection can protect diabetic patients from developing diabetes-related complications, recent meta-analyses indicate that rapid and long-acting insulin analogues only provide a limited benefit compared with conventional insulin regarding glycemic control. As insulin deficiency is the main sequel of type-1 diabetes (T1D), transfer of the insulin gene-by-gene therapy is becoming an attractive treatment modality even though T1D is not caused by a single genetic defect. [Expert Rev Mol Med] Abstract

Insulin and Type 1 Diabetes: Immune Connections
The authors summarize current knowledge concerning insulin, its role in beta-cell autoimmunity as initial target antigen, its recognition by autoantibodies and autoreactive T cells and the detection of these immune responses to provide biomarkers for clinical trials employing insulin as an immune modulatory agent. [Eur J Endocrinol] Abstract | Full Article

Threshold Pharmaceuticals Announces Agreement with U.S. FDA on a Special Protocol Assessment for Planned Phase III Trial of TH-302 in Combination with Gemcitabine in Advanced Pancreatic Cancer
Threshold Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has reached agreement with the U.S. affiliate of Merck KGaA, Darmstadt, Germany, Threshold’s partner for the development and commercialization of TH-302, covering a Special Protocol Assessment for a phase III randomized trial of TH-302 in patients with metastatic or locally advanced unresectable pancreatic cancer. [Threshold Pharmaceuticals Inc.] Press Release

Van Andel Institute Scientist to Lead Search for Pancreatic Cancer Clues
The National Cancer Institute has chosen a Van Andel Institute scientist to head a $2.3 million project to develop new molecular biomarkers for pancreatic cancer. Brian Haab. Ph.D., Head of Van Andel Institute’s Laboratory of Cancer Immunodiagnostics, will lead the five-year study in collaboration with David Smith, Ph.D. of Emory University. [Van Andel Institute] Press Release

Association Establishes the AABB Center for Cellular Therapies
AABB (formerly the American Association of Blood Banks) has established the AABB Center for Cellular Therapies, a functional unit within AABB that will focus on activities designed to foster patient safety and responsible innovation in the cellular therapy and regenerative medicine field. [AABB] Press Release

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)

NEW Workshop on Approval and Commercialization of Advanced Therapy Medicinal Products in Europe
November 15, 2012
Berlin, Germany

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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.)

Scientific Communications & Publishing Coordinator (STEMCELL Technologies, Inc.)

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

Postdoctoral Position – Diabetes Research (Monash University)

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

Postdoctoral Position – Cholesterol Homeostasis in Pancreatic Islets (Centre of Molecular Medicine and Therapeutics)

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

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

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