Pancreatic Cell News Volume 3.41 | Oct 16 2012

DIABETES

Nifedipine Prevents Etoposide-Induced Caspase-3 Activation, Prenyl Transferase Degradation and Loss in Cell Viability in Pancreatic β-Cells
Investigators report that exposure of insulin-secreting INS 832/13 cells or normal rat islets to etoposide leads to significant activation of caspase-3 and subsequent degradation of the common α-subunit of farnesyl/geranylgeranyl transferases. [Apoptosis] Abstract

Glutathionylation State of Uncoupling Protein-2 and the Control of Glucose-Stimulated Insulin Secretion
The authors determined if glutathionylation is required for uncoupling protein-2 (UCP2) regulation of glucose-stimulated insulin secretion (GSIS). Using Min6 cells and pancreatic islets, they demonstrated that induction of glutathionylation not only deactivates UCP2-mediated proton leak but also enhances GSIS. [J Biol Chem] Abstract | Full Article

Regulation of the CCL2 Gene in Pancreatic β-Cells by IL-1β and Glucocorticoids: Role of MAP Kinase Phosphatase-1
Synthesis and secretion of the chemokine CCL2 from pancreatic β-cells in response to pro-inflammatory signaling pathways influences immune cell recruitment into the pancreatic islets. Therefore, the authors investigated the positive and negative regulatory components controlling expression of the CCL2 gene using isolated rat islets and INS-1-derived β-cell lines. [PLoS One] Full Article

Accelerated Antibody-Mediated Graft Loss of Rodent Pancreatic Islets after Pretreatment with Dexamethasone-Treated Immature Donor Dendritic Cells
Researchers assessed whether donor bone marrow-derived dexamethasone-treated dendritic cells could prolong islet allograft survival in a full major histocompatibility complex mismatch rat model. [Transplantation] Abstract

β1 Integrin-Extracellular Matrix Interactions Are Essential for Maintaining Exocrine Pancreas Architecture and Function
Scientists examined the role of β1 integrin in exocrine pancreatic structure and function. It was discovered that β1 integrin-deficient pancreatic acinar cells displayed decreased proliferation and increased apoptosis. Apoptosis was reduced to that of controls when isolated exocrine clusters were cultured in media supplemented with extracellular matrix proteins. [Lab Invest] Abstract

PANCREATIC CANCERR

Interactions of Everolimus and Sorafenib in Pancreatic Cancer Cells
Researchers examined the effects of everolimus and sorafenib on proliferation of the pancreatic cancer cell lines MiaPaCa-2 and Panc-1. Cell growth inhibition was evaluated in vitro for a range of concentrations of the drugs alone and in combination. [AAPS J] Abstract

A Novel EPAC Specific Inhibitor Suppresses Pancreatic Cancer Cell Migration and Invasion
The authors report the identification and characterization of ESI-09, a novel non-cyclic nucleotide exchange protein directly activated by cAMP (EPAC) antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated insulin secretion in pancreatic beta cells. [Mol Pharmacol] Abstract

Inhibition of Hydrogen Sulfide Synthesis Provides Protection for Severe Acute Pancreatitis Rats via Apoptosis Pathway
Scientists aimed to investigate the relationship between the synthesis of hydrogen sulfide and the pancreatic acinar cell apoptosis in severe acute pancreatitis rats, as well as analyze the potential apoptotic pathway involved in this process. [Apoptosis] Abstract

XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells
Using structure-based design, investigators developed a non-peptide cell-permeable, small molecule, termed as XZH-5, which targeted signal transducers and activators of transcription 3 (STAT3) phosphorylation. XZH-5 was found to inhibit STAT3 phosphorylation and induce apoptosis in human breast and pancreatic cancer cell lines expressing elevated levels of phosphorylated STAT3. [PLoS One] Full Article

Haloperidol Induces Demethylation and Expression of the Dual Specificity Phosphatase 6 Gene in MIA PaCa-2 Human Pancreatic Cancer Cells
The effects of haloperidol and 5-azacytidine on expression and methylation of dual specificity phosphatase 6 (DUSP6) was quantitatively measured in MIA PaCa-2 human pancreatic carcinoma cells, in which DUSP6 expression is suppressed due to intronic hypermethylation. The growth rate of MIA PaCa-2 cells were also examined after treatment with haloperidol or 5-azacytidine. [Life Sci] Abstract

REVIEWS

Nuvilex Reports Additional Safety and Efficacy Data from Second Phase II Pancreatic Cancer Trial
Nuvilex, Inc. announced the presentation of additional safety and efficacy data from a second phase II pancreatic cancer clinical trial. The trial data presented used the same encapsulated cytochrome P450 expressing cells followed by chemotherapy to treat pancreatic cancer that were used in the previously published trial and confirmed results generated in the previous trial. [Press release from Nuvilex, Inc. discussing research presented at the International Society for Cell and Gene Therapy of Cancer (ISCGT) 2012, Singapore] Press Release

NewLink Genetics Launches Phase III Clinical Trial of algenpantucel-L Immunotherapy in Patients with Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer
NewLink Genetics Corporation announced launching of an open-label, randomized, multi-institutional phase III study in patients with borderline resectable or locally advanced unresectable pancreatic cancer. The projected enrollment will be 280 subjects and patients will be randomized (1:1) to receive standard of care FOLFIRINOX plus or minus algenpantucel-L immunotherapy. [NewLink Genetics Corporation] Press Release

Pioneering iPS Cell Scientist Kazutoshi Takahashi Receives NYSCF – Robertson Prize in Stem Cell Research
The New York Stem Cell Foundation (NYSCF) will award a Japanese scientist with the NYSCF – Robertson Prize for his extraordinary achievements in translational stem cell research. This award will go to Kazutoshi Takahashi, PhD, Lecturer, Center for induced pluripotent stem  (iPS) Cell Research and Application at Kyoto University, for his vital contribution to iPS cell derivation. [The New York Stem Cell Foundation] 
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 Stem Cells and Metabolism
November 5-6, 2012
La Jolla, United States

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

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Postdoctoral Position – Type 1 Diabetes Research (Sanford Health/University of South Dakota)

Postdoctoral Position – Pancreatic Beta Cell Biology (CeMM – Research Center for Molecular Medicine of the Austrian Academy of Sciences)

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)

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