Volume 6.39 | Oct 6

Pancreatic Cell News 6.39 October 6, 2015
Pancreatic Cell News
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TOP STORY
PAX4 Gene Transfer Induces α-to-β Cell Phenotypic Conversion and Confers Therapeutic Benefits for Diabetes Treatment
Researchers found that Pax4 delivered by adenoviral vector, Ad5.Pax4, induced insulin expression and reduced glucagon expression in αTC1.9 cells. More importantly, these cells exhibited glucose-stimulated insulin secretion, a key feature of functional β-cells. [Mol Ther] Abstract
Take the &quote;if&quote; out of &quote;diff&quote;: reduce variability when differentiating to definitive endoderm.
 
PUBLICATIONS (Ranked by impact factor of the journal)
DIABETES & PANCREATITIS

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 Cav1.2 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

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REVIEWS
Pre-Clinical Models of Pancreatic Ductal Adenocarcinoma
The authors review current preclinical models for human pancreatic ductal adenocarcinoma (PDA). In addition, they discuss potential applications of the recently developed pancreatic ductal organoids, three-dimensional culture systems and organoid-based xenografts as new preclinical models for PDA. [J Pathol] Abstract

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

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
 
INDUSTRY NEWS
PTC Therapeutics Submits European Application For Translarna™ for Cystic Fibrosis
PTC Therapeutics, Inc. announced that the European Medicines Agency has validated the submission of a variation for a new indication for Translarna™ (ataluren) for the treatment of nonsense mutation cystic fibrosis for patients not taking chronic inhaled aminoglycoside antibiotics. [PTC Therapeutics, Inc.] Press Release

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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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 European Society for Medical Oncology (ESMO) Asia 2015 Congress
December 18-21, 2015
Singapore, Singapore

Visit our events page to see a complete list of events in the pancreatic cell community.
 
JOB OPPORTUNITIES
NEW Research Associate – Pancreatic Cancer Modelling (University College London)

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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