Volume 4.26 | Jul 9

Pancreatic Cell News 4.26 July 9, 2013
Pancreatic Cell News
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TOP STORY
CTGF Antagonism with mAb FG-3019 Enhances Chemotherapy Response without Increasing Drug Delivery in Murine Ductal Pancreas Cancer
Scientists used a chemical inhibitor of cytidine deaminase to stabilize and thereby artificially elevate gemcitabine levels in murine pancreatic ductal adenocarcinoma (PDA) tumors without disrupting the tumor microenvironment. Inhibition of cytidine deaminase raised the levels of activated gemcitabine within PDA tumors without stimulating neoplastic cell killing or decreasing the growth of tumors, whereas FG-3019 increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. [Proc Natl Acad Sci USA] Abstract | Full Article
Differentiation Doesn't Have to be Difficult - Get Easy, Standardized hPSC Differentiation
 
PUBLICATIONS (Ranked by impact factor of the journal)
DIABETES

Mutual Effect of Subcutaneously Transplanted Human Adipose-Derived Stem Cells and Pancreatic Islets within Fibrin Gel
Researchers evaluated whether fibrin gel with human adipose-derived stem cells (hADSCs) and rat pancreatic islets could cure diabetes mellitus when transplanted into the subcutaneous space of diabetic mice. The hADSCs did not directly differentiate into endothelial cells, but showed evidence of differentiation toward insulin-secreting cells. [Biomaterials] Abstract

Endoplasmic Reticulum Stress Sensitizes Pancreatic Beta Cells to Interleukin-1ß-Induced Apoptosis via Bim/A1 Imbalance
Scientists investigated whether mild endoplasmic reticulum (ER) stress also sensitizes beta cells to cytokine-induced apoptosis. Cyclopiazonic acid-induced ER stress enhanced the interleukin-1ß apoptosis in INS-1E and primary rat beta cells. This was not prevented by XBP1 knockdown, indicating the dissociation between the pathways leading to inflammation and cell death. [Cell Death Dis] Full Article

Pten Controls ß-Cell Regeneration in Aged Mice by Regulating Cell Cycle Inhibitor p16ink4a
Tissue regeneration diminishes with age, concurrent with declining hormone levels including growth factors such as insulin-like growth factor-1. Scientists investigated the molecular basis for such decline in pancreatic ß-cells where loss of proliferation occurs early in age, and is proposed to contribute to the pathogenesis of diabetes. They studied the regeneration capacity of ß-cells in mouse model where PI3K/AKT pathway downstream of insulin/insulin-like growth factor-1 signaling, is upregulated by genetic deletion of Pten (phosphatase and tensin homologue deleted on chromosome 10) specifically in insulin producing cells. [Aging Cell] Abstract

Global Gene Expression Profiling of Pancreatic Islets in Mice during Streptozotocin-Induced ß-Cell Damage and Pancreatic Glp-1 Gene Therapy
Researchers analyzed the mechanisms of streptozotocin (STZ)-induced diabetes and glucagon-like peptide-1-(glp-1)-mediated ß-cell protection in STZ-treated mice. One week after multiple low-dose STZ administrations, pancreatic ß-cells showed impaired insulin expression, while maintaining expression of nuclear Nkx6.1. [Dis Model Mech] Abstract | Full Article

Blockage of Progesterone Receptor Effectively Protects Pancreatic Islet Beta Cell Viability
Investigators found that progesterone receptor (PR) activation increased the pro-inflammatory cytokines (PIC)-induced injury in Min6 cells, and PR blockage with siRNA interference protected the cells from damage. Moreover, the new discovered PR antagonist SC51089 effectively improved cell survival by reducing the PIC-stimulated cell apoptosis in Min6 cells. [Steroids] Abstract

PANCREATIC CANCER

PARP-1 Regulates Resistance of Pancreatic Cancer to TRAIL Therapy
Researchers aimed to identify combination therapies that enhance the efficacy of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy; and investigated the underlying mechanisms. Poly(ADP-ribose) polymerase-1 (PARP-1) was found highly expressed in the TRA-8-resistant PANC-1 and Suit-2 cells, compared with TRA-8-sensitive BxPc-3 and MiaPaca-2. [Clin Cancer Res] Abstract

Clinical Impact of Pentraxin Family Expression on Prognosis of Pancreatic Carcinoma
Using pancreatic carcinoma cell lines and gene transfectant, scientists measured long pentraxin (PTX3) level in culture solution and carried out cellular migration assay in vitro. Elevated PTX3 production was observed in several cell lines, and a direct relationship between migratory activity and PTX3 level was identified in vitro. [Brit J Cancer] Abstract

Profilin1 Sensitizes Pancreatic Cancer Cells to Irradiation by Inducing Apoptosis and Reducing Autophagy
Researchers demonstrated how profilin1 affected pancreatic cancer radiosensitivity. Researchers showed profilin1 was down-regulated in pancreatic cancer cells after exposure to radiation, and re-expression of profilin1 suppressed tumor cell viability and increased DNA damage following irradiation. [Curr Mol Med] Abstract

miR-210 Regulates the Interaction between Pancreatic Cancer Cells and Stellate Cells
Researchers aimed to clarify the role of microRNAs (miRNAs) in the interaction between pancreatic stellate cells (PSCs) and pancreatic cancer cells. miR-210 was identified as an upregulated miRNA by co-culture with PSCs. Conditioned media of PSCs activated ERK and Akt, but not hypoxia-inducible factor-1a pathway. [Biochem Biophys Res Commun] Abstract

Silencing of GATA6 Suppresses SW1990 Pancreatic Cancer Cell Growth In Vitro and Up-Regulates Reactive Oxygen Species
Investigators studied the role of GATA6 expression on proliferation and apoptosis of pancreatic cancer cells and the role of reactive oxygen species. RNA interference against GATA6 successfully inhibited mRNA and protein expression of GATA6 in the SW1990 pancreatic cancer cell line. [Dig Dis Sci] Abstract

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REVIEWS
Incretin Action in the Pancreas: Potential Promise, Possible Perils, and Pathological Pitfalls
The authors review recent advances and controversies in incretin hormone action in the pancreas and contrast established mechanisms with areas of uncertainty. Furthermore, they highlight methodological challenges and pitfalls and outline key areas requiring additional scientific investigation. [Diabetes] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
 
INDUSTRY NEWS
Oramed Enrolls First Patient in Its Phase IIa U.S. Oral Insulin Clinical Trial
Oramed Pharmaceuticals Inc. announced that the first patient has been enrolled in a Phase IIa trial of ORMD-0801, an orally ingestible insulin capsule, on patients with type 2 diabetes. [Oramed Pharmaceuticals Inc] Press Release

Eli Lilly and Company and Boehringer Ingelheim Announce Regulatory Submission for New Insulin Glargine Biosimilar Product
Eli Lilly and Company and Boehringer Ingelheim announced that the companies’ marketing authorization application for LY2963016, an investigational basal insulin for the treatment of type 1 and type 2 diabetes, has been accepted for review by the European Medicines Agency. [Boehringer Ingelheim] Press Release

Seven-Year Pancreatic Cancer Survivor Named Chair of the National Board of Directors of the Pancreatic Cancer Action Network
The Pancreatic Cancer Action Network announced Laurie MacCaskill has been appointed Chair of the National Board of Directors of the organization, effective July 1. MacCaskill is the first pancreatic cancer patient to hold this position. [Pancreatic Cancer Action Network] Press Release

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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)

Therapeutic Goods Administration (Australia)
 
EVENTS
NEW American Pancreatic Association (APA) 2013 Annual Meeting
October 30 – November 2, 2013
Miami, United States

Visit our events page to see a complete list of events in the hematopoietic community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Electrophysiologist (University of Alberta)

Postdoctoral Position – Pluripotent Stem Cells to Islets (INSERM)

Postdoctoral Research Fellow – Platelet Biology and Diabetes (Thomas Jefferson University, Cardeza Foundation for Hematologic Research)

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

Diabetes UK PhD Studentship (Diabetes UK)

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

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


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