Pancreatic Cell News Volume 10.14 | Apr 16 2019

TOP STORY

A Multiscale Map of the Stem Cell State in Pancreatic Adenocarcinoma

Researchers used RNA sequencing (seq), chromatin immunoprecipitation-seq, and genome-wide CRISPR analysis to map the molecular dependencies of pancreatic cancer stem cells, highly therapy-resistant cells that preferentially drove tumorigenesis and progression. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

JUND Regulates Pancreatic β Cell Survival during Metabolic Stress

Using a panel of diabetes-associated stressors, JUND was found to be upregulated in mouse islets cultured with high concentrations of glucose and free fatty acid, but not after treatment with hydrogen peroxide or thapsigargin. [Mol Metab] Full Article

Apolipoprotein A-I Improves Pancreatic β-Cell Function Independent of the ATP-Binding Cassette Transporters ABCA1 and ABCG1

Apolipoprotein A-I (apoA-I) treatment improved glucose-stimulated insulin secretion in β-double knockout but not control mouse islets. Plasma lipid and lipoprotein levels and islet cholesterol levels were also unaffected by treatment with apoA-I. [FASEB J] Abstract

Delivery of Pancreatic Digestive Enzymes into the Gastrointestinal Tract by Pancreatic Exocrine Tissue Transplant

Human induced pluripotent stem cells were differentiated into pancreatic exocrine cells by stage-specific treatment with growth factors and chemical compounds, and the differentiated pancreatic cells were implanted into the gastric submucosal space of nude rats. [Sci Rep] Full Article

Identification of a Hinge Residue Controlling Islet Amyloid Polypeptide Self-Assembly and Cytotoxicity

Researchers studied structure-self-assembly relationships focusing on position 21 to gain detailed insights into the molecular mechanisms of islet amyloid polypeptide self-assembly and to probe the conformational nature of the toxic assemblies associated with β-cell death. [J Biol Chem] Abstract | Full Article

PANCREATIC CANCER

Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF

Scientists report that combined ablation of EGFR and c-RAF expression resulted in complete regression of a significant percentage of pancreatic ductal adenocarcinoma tumors driven by Kras/Trp53 mutations in genetically engineered mice. [Cancer Cell] Abstract | Press Release | Graphical Abstract

A Direct Podocalyxin-Dynamin-2 Interaction Regulates Cytoskeletal Dynamics to Promote Migration and Metastasis in Pancreatic Cancer Cells

Using mass spectrometry, bioinformatics analysis, co-immunoprecipitation, and pulldown assays, investigators discovered a novel, direct binding interaction between the cytoplasmic tail of podocalyxin and the large GTPase dynamin-2 at its GTPase, middle, and pleckstrin homology domains. [Cancer Res] Abstract

Chaperone-Mediated Autophagy Degradation of IGF-1Rβ Induced by NVP-AUY922 in Pancreatic Cancer

The authors found that the heat shock protein 90 α inhibitor NVP-AUY922 effectively downregulated and destabilized the insulin-like growth factor 1 receptor (IGF-1R) β protein, substantially reduced the levels of downstream signaling molecules, and resulted in growth inhibition and apoptosis in IGF-1Rβ-overexpressing pancreatic cancer cells. [Cell Mol Life Sci] Abstract

Development of an Anti-BAG3 Humanized Antibody for Treatment of Pancreatic Cancer

Researchers showed that the humanized anti-BAG3 antibody, named BAG3-H2L4, abrogated BAG3 binding to macrophages and subsequent release of IL-6. Furthermore, it specifically localized into tumor tissues and significantly inhibited the growth of MiaPaCa-2 pancreatic cancer cell xenografts. [Mol Oncol] Abstract | Full Article

Specific Protein 1 (SP1) Regulates the Epithelial-Mesenchymal Transition via Lysyl Oxidase-Like 2 (LOXL2) in Pancreatic Ductal Adenocarcinoma

In MIA Paca-2 cells, silencing of SP1 induced a reduction of LOXL2 expression, whereas LOXL2 silencing did not lead to a decrease in the expression of SP1. Chromatin immunoprecipitation assay demonstrated the binding of SP1 to LOXL2 promoter. [Sci Rep] Full Article

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Epigenetics in Human Obesity and Type 2 Diabetes

The authors summarize epigenetic signatures obtained from human tissues of relevance for metabolism in relation to obesity and type 2 diabetes. [Cell Metab] Full Article

Protein Tyrosine Phosphatases: Promising Targets in Pancreatic Ductal Adenocarcinoma

Investigators discuss the role of protein tyrosine phosphatases in tumorigenesis as tumor suppressor and oncogenic proteins. They focus on the differential expression of these proteins in pancreatic ductal adenocarcinoma, as well as their clinical implications and possible targeting for pharmacological inhibition in cancer therapy. [Cell Mol Life Sci] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

OPKO Reports Additional Oxyntomodulin, OPK-88003, Results From Phase II Diabetes and Obesity Trial

OPKO Health, Inc. reported additional results from the per protocol patient population from the Phase II dose escalation trial of OPK-88003 to treat type 2 diabetes and obesity. [OPKO Health, Inc.] Press Release

Sernova Announces First Transplantation of Therapeutic Cells in Cell Pouch for the Company’s Phase I/II US Clinical Study for Diabetes

Sernova Corp. announced the first Cell Pouch™ transplant of insulin-producing cells in its US Phase I/II clinical trial evaluating the safety and efficacy of the Cell Pouch for clinical islet transplantation in type 1 diabetes. [Sernova Corp.] Press Release

Influential Senator Asks NSF for Data on Threat from Foreign Influences

The National Science Foundation (NSF) has joined the list of federal agencies that Senator Chuck Grassley has asked for explanations of how they are preventing foreign scientists from ripping off US taxpayers. [ScienceInsider] Editorial

Indonesian Mega-Science Agency in the Balance as Election Begins

Indonesians will vote in a national election that pits two old rivals against each other. The stakes are high for science. President Joko Widodo says that if he is re-elected, he will overhaul how much of the country’s research is organized and funded. The main opposition candidate has been silent on science so far. [Nature News] Editorial

NEW 2^nd Arab African International Cancer Congress (AAICC)
October 10-11, 2019
Cairo, Egypt

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Position – Molecular Biology and Cancer Research (Augusta University)

Postdoctoral Research Affiliate – Pancreatic Cancer Research (Roswell Park)

Clinical Professor – Diabetes (Univesity of Southern Denmark)

Postdoctoral Researcher – Beta-Cell Regeneration in Zebrafish (Karolinska Institutet)

Postdoctoral Research Fellow – Type 2 Diabetes and Obesity (Harvard Medical School/Boston Children’s Hospital)

Postdoctoral Fellowship – Regenerative Medicine and Metabolic Biology (Indiana Biosciences Research Institute)

Research Positions – Pancreatic Beta-Cells (Université de Montréal)

Postdoctoral Position – Diabetes (University of Minnesota)

Postdoctoral Fellow – Pancreatic Development & Islet Biology (Vanderbilt University)

Postdoctoral Fellow – Neuroscience and Diabetes (The Child Health Institute of New Jersey)

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