Pancreatic Cell News Volume 6.26 | Jul 7 2015

The Ia-2β Intronic miRNA, miR-153, Is a Negative Regulator of Insulin and Dopamine Secretion through Its Effect on the Cacna1c Gene in Mice
Scientists confirmed that Cacna1c mRNA and protein are downregulated by miR-153 mimics and upregulated by miR-153 inhibitors in insulin-secreting freshly isolated mouse islets, in the insulin-secreting mouse cell line MIN6 and in the dopamine-secreting cell line PC12. [Diabetologia] Abstract

Combination of DPP-4 Inhibitor and PPARγ Agonist Exerts Protective Effects on Pancreatic β-Cells in Diabetic db/db Mice through the Augmentation of IRS-2 Expression
Researchers investigated the effects of long- and short-term treatment with pioglitazone and/or alogliptin on β-cells in diabetic db/db mice. [Mol Cell Endocrinol] Abstract

Expression Mechanism of Tryptophan Hydroxylase 1 in Mouse Islets during Pregnancy
Scientists performed 5′-RACE and identified β-cell-specific transcription initiation sites for tryptophan hydroxylase 1. Prolactin enhanced the expression of mRNA containing these exons; however, reporter gene plasmids containing the proximal 5′-flanking region of these exons did not show prolactin responsiveness in MIN6 cells. [J Mol Endocrinol] Abstract

Demethylation of the MafB Promoter in a Compromised β-Cell Model
The authors investigated a rat β-cell line of INS-1 cells with late-passage numbers, which showed extremely low expression of MafA and insulin, as an in vitro model of compromised β-cells. In these INS-1 cells, the mRNA expression and the promoter activity of MafB were upregulated compared with the early-passage (‘conventional’) INS-1 cells. [J Mol Endocrinol] Abstract

Inhibition of Calcium Influx Reduces Dysfunction and Apoptosis in Lipotoxic Pancreatic β-Cells via Regulation of Endoplasmic Reticulum Stress
Investigators examined whether regulation of fatty acids-triggered calcium influx could protect pancreatic β-cells from lipotoxicity. They found that both nifedipine and diazoxide protected MIN6 pancreatic β-cells and primary cultured murine islets from palmitic acid-induced apoptosis. [PLoS One] Full Article

PANCREATIC CANCER

TLR7 and TLR8 Expression Increases Tumor Cell Proliferation and Promotes Chemoresistance in Human Pancreatic Cancer
Researchers determined the role of both toll-like receptor (TLR)7 and TLR8 expression and signaling in tumor cell proliferation and chemoresistance in pancreatic cancer. Expression of TLR7/TLR8 in UICC stage I-IV pancreatic cancer, chronic pancreatitis, normal pancreatic tissue and human pancreatic cancer cell line was examined. [Int J Oncol] Abstract | Full Article

Mechanism of Ascorbate-Induced Cell Death in Human Pancreatic Cancer Cells: Role of Bcl-2, Beclin 1 and Autophagy
Researchers investigated the anticancer effect of ascorbate in MIA-PaCa-2 human pancreatic cancer cells using both in vitro and in vivo models, with a focus on assessing the role of oxidative stress and autophagy as important mechanistic elements in its anticancer actions. [Planta Med] Abstract

Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors
Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase, with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, scientists observed extended survival with frequent total regression of autochthonous and orthotopic pancreatic ductal adenocarcinoma tumors. [Cancer Immunol Res] Abstract | Press Release

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CTCA at Western Launches 3^rd New Clinical Trial Combining Immunotherapy with Chemotherapy
Cancer Treatment Centers of America^® (CTCA) at Western Regional Medical Center (Western) has begun a new Phase Ib/II clinical trial using a new immunotherapy treatment for patients with advanced kidney, non-small cell lung cancer, pancreatic cancer and colorectal carcinoma. [Cancer Treatment Centers of America^® (EurekAlert!)] Press Release

Aduro Biotech Announces Immunotherapy Regimen Successfully Passes Futility Analysis in Phase IIb ECLIPSE Trial in Metastatic Pancreatic Cancer
Aduro Biotech, Inc. announced that an independent Data Monitoring Committee recommended that the Phase IIb ECLIPSE trial of its novel LADD and GVAX immunotherapies continue as planned without modification based on the successful outcome of a pre-specified futility analysis. [Aduro Biotech, Inc.] Press Release

Amarna Therapeutics Teaming Up with Austrian CBmed in the Development of Immunotherapies
Amarna Therapeutics announced that it has entered into a cooperation with Austrian Center for Biomarker Research in Medicine (CBmed), for the development of immunotherapies against acute lymphoblastic leukemia, obesity, diabetes mellitus type 2 and atherosclerotic cardiovascular disease. [Amarna Therapeutics B.V.] Press Release

Intercontinental Oncology Partnership Brings Access to Specialized Cancer Care to Nigeria
Roswell Park Cancer Institute (RPCI) and Lakeshore Cancer Center (LCC) have announced an affiliation that will see Roswell Park faculty providing clinical consultations to assist LCC oncologists, who will also have access to both training at RPCI and continuing professional education seminars they can participate in remotely. [Roswell Park Cancer Institute] Press Release

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Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellowship – Pancreatic Beta Cell Biology and Regeneration, Relating to Diabetes (Mount Sinai School of Medicine)

Postdoctoral Fellowship – Immunopathogenesis of Type 1 Diabetes (Tongji Medical College)

PhD Student – Diabetes (Danish Diabetes Academy)

Research Associate – Cancer Therapeutics (University of Cambridge)

Postdoctoral Position – Adipocyte Development (German Institute of Human Nutrition)

Postdoctoral Research Associate – Type 1 Diabetes and Other Autoimmune Diseases (Benaroya Research Institute at Virginia Mason)

Postdoctoral Position – Cancer (MD Anderson Cancer Center)

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