Pancreatic Cell News Volume 6.39 | Oct 6 2015

Ca²⁺ Influx through L-Type Ca²⁺ Channels and Ca²⁺-Induced Ca²⁺ Release Regulate cAMP Accumulation and Epac1-Dependent ERK 1/2 Activation in INS-1 Cells
Investigators showed that glucose-stimulated ERK 1/2 phosphorylation is slowed and reduced in INS-1 cells expressing the intracellular II-III loop of the L-type Ca²⁺ channel Ca_v1.2 compared to INS-1 cells. [Mol Cell Endocrinol] Abstract

Nck1 Deficiency Improves Pancreatic β Cell Survival to Diabetes-Relevant Stresses by Modulating PERK Activation and Signaling
Researchers report that Nck1-deficient MIN6 cells display normal overall morphology while, as expected, increased number of secretory granules. Furthermore, they demonstrated that cell survival to diabetes-relevant stresses is increased, while cell viability in response to chemical endoplasmic reticulum stress inducers is not changed. [Cell Signal] Abstract

ATP Release, Generation and Hydrolysis in Exocrine Pancreatic Duct Cells
The authors investigated whether pancreatic duct cells release adenosine triphosphate (ATP) locally and whether they enzymatically modify extracellular nucleotides/sides. They also explored which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan-1, and online luminescence measurement, they detected fast ATP release in response to pH changes, bile acid, mechanical stress and hypo-osmotic stress. [Purinergic Signal] Abstract

BH3-Only Protein Bmf Is Required for the Maintenance of Glucose Homeostasis in an In Vivo Model of HNF1α-MODY Diabetes
Through the knockout of bmf in a transgenic mouse model with dominant-negative mutant of hepatocyte nuclear factor 1α (DNHNF-1α) suppression of HNF-1α function in pancreatic beta-cells, scientists examined the effect of loss-of-function of this BH3-only protein on the disease pathology and progression, and further elucidated the role of Bmf in mediating DNHNF-1α-induced beta-cell loss. [Cell Death Discov] Full Article

PANCREATIC CANCER

APC Haploinsufficiency Coupled with p53 Loss Sufficiently Induces Mucinous Cystic Neoplasms and Invasive Pancreatic Carcinoma in Mice
Investigators report for the first time that functional adenomatous polyposis coli (APC) is required for the growth and maintenance of pancreatic islets and maturation. [Oncogene] Abstract

DKK3 Blocked Translocation of β-Catenin/EMT Induced by Hypoxia and Improved Gemcitabine Therapeutic Effect in Pancreatic Cancer Bxpc-3 Cell
The authors examined the expression of dickkopf-related protein 3 (DKK3) in six human pancreatic cancer cell lines, 75 pancreatic cancer and 75 adjacent non-cancerous tissues. Dickkopf-related protein 3 was frequently silenced and methylation in pancreatic cancer cell lines. [J Cell Mol Med] Abstract

Downstream Mediators of the Intratumoral Interferon Response Suppress Antitumor Immunity, Induce Gemcitabine Resistance and Associate with Poor Survival in Human Pancreatic Cancer
The interferon-γ (IFNγ) response within and on key cells of the pancreatic cancer (PC) microenvironment was evaluated. IFNγ induced expression of human leukocyte antigen class I and II on PC cell lines, primary pancreatic cancer epithelial cells and patient-derived tumor-associated stroma, concomitant with an upregulation of PDL1 in the absence of CD80 and CD86 expression. [Cancer Immunol Immunother] Abstract

Polyphenols from Marine Brown Algae Target Radiotherapy-Coordinated EMT and Stemness-Maintenance in Residual Pancreatic Cancer
Utilizing pancreatic cancer (PC)- cancer stem cells grown ex vivo and a mouse model of residual-PC, scientists investigated the benefits of seaweed polyphenols in regulating stemness-maintenance. [Stem Cell Res Ther] Full Article

New Avenues for Improving Pancreatic Ductal Adenocarcinoma (PDAC) Treatment: Selective Stroma Depletion Combined with Nano Drug Delivery
The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell. The two opposing schools of thought – non-depletion of the stroma vs its depletion – to better drug efficacy are discussed. [Cancer Lett] Abstract

The Role of S100 Proteins and Their Receptor RAGE in Pancreatic Cancer
The authors discuss the potential role of S100 proteins and their receptor, receptor for advanced glycation end products (RAGE), in the development and progression of pancreatic cancer. [Biochim Biophys Acta] Abstract

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Immunovia, OHSU Collaborating on Early Detection Test for Pancreatic Cancer
Immunovia AB and the Knight Cancer Institute at Oregon Health & Science University (OHSU) formed a collaboration to confirm, validate and commercialize a blood test for the early diagnosis of pancreatic cancer. The test called IMMray™ PanCan-d analyzes a patient’s immune system for early signs of disease. [Immunovia AB] Press Release

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Clinical Research Fellow – Pancreatic Cancer (Cancer Research UK Manchester Institute)

Marketing Manager – Oncology (Celgene Corporation)

Postdoctoral Fellowship – Action in Obesity and Diabetes Pathogenesis (National Institutes of Health Diabetes)

Postdoctoral Fellow – Diabetes and Metabolism (Johns Hopkins University)

Postdoctoral Position – Pancreatic Cancer (University of California, San Diego)

Postdoctoral Position – Diabetes (Harvard Medical School)

Postdoctoral Position – Diabetes Research (Inserm)

Postdoctoral Position – Diabetes Research (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Research Fellow – Translational Research Program (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Scientist – Pancreatic Cancer (Columbia University)

Postdoctoral Research Fellow – Development and Pathogenesis of Pancreatic Cancer (University College London)

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