Pancreatic Cell News Volume 8.12 | Mar 28 2017

TOP STORY

SerpinB2 Regulates Stromal Remodeling and Local Invasion in Pancreatic Cancer

Researchers showed that SerpinB2 is required by stromal cells for normal collagen remodeling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of pancreatic ductal adenocarcinoma cancer cells and SerpinB2^−/− mouse embryonic fibroblasts resulted in increased tumor growth, aberrant remodeling of the extracellular matrix and increased local invasion from the primary tumor. [Oncogene] Full Article

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Pancreatic Alpha Cell-Selective Deletion of Tcf7l2 Impairs Glucagon Secretion and Counter-Regulatory Responses to Hypoglycemia in Mice

Investigators explored the role of transcription factor 7-like 2 (TCF7L2) in the control of the counter-regulatory response to hypoglycemia by generating mice with selective deletion of the Tcf7l2 gene in pancreatic alpha cells. While glucose tolerance was unaffected in Tcf7l2AKO mice, glucose infusion rates were increased and glucagon secretion tended to be lower. [Diabetologia] Full Article

BACE2 Suppression Promotes β-Cell Survival and Function in a Model of Type 2 Diabetes Induced by Human Islet Amyloid Polypeptide Overexpression

The authors investigated the effect of β-site amyloid polypeptide (APP)-cleaving enzyme 2 (BACE2) modulation on β-cell alterations in a mouse model of type 2 diabetes induced by islet APP (IAPP) overexpression. When heterozygous mice carrying the human transcript of IAPP (hIAPP-Tg) crossed with BACE2-deficient mice, the animals presented a significant improvement in glucose tolerance accompanied with an enhanced insulin secretion, as compared to hIAPP-Tg mice. [Cell Mol Life Sci] Abstract

Elevated miR-130a/miR130b/miR-152 Expression Reduces Intracellular ATP Levels in the Pancreatic Beta Cell

Researchers showed that microRNA (miR)-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats. They demonstrated negative regulatory effects of the three miRs on pyruvate dehydrogenase E1 alpha and on glucokinase proteins, which are both involved in ATP production. [Sci Rep] Full Article

The Stress-Response Molecule NR4A1 Resists ROS-Induced Pancreatic β-Cells Apoptosis via WT1

Investigators showed that NR4A1 protein expression rapidly increased in MIN6 cells upon H₂O₂ treatment, and overexpression of NR4A1 in MIN6 cells conferred resistance to cell apoptosis induced by H₂O₂. [Cell Signal] Abstract

Downregulation of miR-139-5p Contributes to the Antiapoptotic Effect of Liraglutide on the Diabetic Rat Pancreas and INS-1 Cells by Targeting IRS1

It is not clear whether microRNA (miR)-139-5p contributes to the anti-apoptotic effect of liraglutide in β-cells. Scientists investigated the role of miR-139-5p on apoptosis of pancreatic β-cells. Their observations suggest that decreased miR-139-5p expression contributes to the anti-apoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1. [PLoS One] Full Article

PANCREATIC CANCER

miR-18a Counteracts AKT and ERK Activation to Inhibit the Proliferation of Pancreatic Progenitor Cells

Investigators demonstrated that miR-18a, but not the other members of the miR-17-92 gene cluster, inhibits the proliferation of pancreatic progenitor cells in vitro and ex vivo. miR-18a inhibits proliferation of adult pancreatic progenitor cells through arresting the cell cycle at G1 stage, indicating that miR-18a plays a role in keeping the adult pancreatic progenitor cells in quiescence. [Sci Rep] Full Article

The Over Expression of Long Non-Coding RNA ANRIL Promotes Epithelial-Mesenchymal Transition by Activating the ATM-E2F1 Signaling Pathway in Pancreatic Cancer: An In Vivo and In Vitro Study

The authors established pancreatic cancer (PC) rat models and ANRIL overexpression and interference plasmids were transfected. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. [Int J Biol Macromol] Abstract

Quantitative Visualization of Synchronized Insulin Secretion from 3D-Cultured Cells

Researchers demonstrated the effect of an antidiabetic drug, glibenclamide, on synchronized insulin secretion from 2D- and 3D-cultured Insulin-GLase (iGL) cells. A subclonal rat INS-1E cell line stably expressing iGL was established and a cluster of iGL cells showed oscillatory insulin secretion that was completely synchronized in response to high glucose. [Biochem Biophys Res Commun] Full Article

Marine Peptides as Potential Agents for the Management of Type 2 Diabetes Mellitus — A Prospect

Researchers try to understand the underlying mechanism involved and the structure characteristics of bioactive peptides responsible for its antidiabetic activities to prospect the utilization of rich marine organism proteins. [Mar Drugs] Full Article

CAR T-Cell Therapy for Pancreatic Cancer

The authors summarize the opportunities, challenges, and state of knowledge in targeting pancreatic cancer with chimeric antigen receptor (CAR) T-cell therapy. [J Surg Oncol] Abstract

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Protein Identified as Potential Druggable Target for Pancreatic Cancer

A protein known as arginine methyltransferase 1 may be a potential therapeutic target for pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer, and one of the most deadliest with a less than ten percent, five-year survival rate. Results from the study will be reported. [Press release from The University of Texas MD Anderson Cancer Center discussing research to be presented at the American Association for Cancer Research (AACR), Washington, D.C.] Press Release

Direct Tumor Vaccination Shown to Induce Anti-Tumor Immunity and Increase Survival in a Murine Model of Pancreatic Cancer

Building on their previous research focusing on vaccination within a tumor for the most common form of pancreatic cancer, investigators have shown that in a mouse model of early stage resected pancreatic cancer, intratumoral vaccination induces an anti-tumor response that results in a significant improvement in overall survival. [Press release from Rutgers Cancer Institute of New Jersey discussing research presented at the 70^th Annual Society of Surgical Oncology Cancer Symposium, Seattle] Press Release

FDA Provides Cornerstone Pharmaceuticals Approval to Initiate Pivotal Study for CPI-613, Its Metabolism-Directed Anticancer Compound

Cornerstone Pharmaceuticals, Inc. announced that following successful End-of-Phase I Type B meetings with the U.S. Food and Drug Administration (FDA), the company has been given a clear clinical and regulatory path forward to conduct pivotal trials of its lead compound, CPI-613, in patients with acute myeloid leukemia and pancreatic cancer. [Cornerstone Pharmaceuticals, Inc. (PR Newswire Association LLC.)] Press Release

Merrimack Initiates Phase I Study of MM-310 in Solid Tumors

Merrimack Pharmaceuticals, Inc. announced the enrollment of its first patient in a Phase I study of MM-310 in solid tumors. MM-310 is an antibody-directed nanotherapeutic that encapsulates a novel taxane and targets the EphA2 receptor, a protein which surveys suggest is overexpressed in 50-100% of many major tumor types, including prostate, ovarian, bladder, gastric, pancreatic and lung cancers. [Merrimack Pharmaceuticals, Inc.] Press Release

Europe Says University of California Deserves Broad Patent for CRISPR

The European Patent Office announced its “intention to grant a patent” to the University of California (UC) for its broad-based claims about the genome-editing tool popularly known as CRISPR. UC, on behalf of several parties, has been in a pitched battle with the Broad Institute of Cambridge, Massachusetts, over CRISPR patents, and the new decision marks a sharp departure from the position of the U.S. Patent and Trademark Office. [ScienceInsider] Editorial

Playing No Trump at AAAS Policy Forum

The relationship between U.S. scientists and the Trump administration hit a new low after organizers of a major annual science policy conference were unable to find anyone willing to discuss the president’s priorities. [ScienceInsider] Editorial

NIH Enables Investigators to Include Draft Preprints in Grant Proposals

Researchers should feel free to include preprints, or draft manuscripts that haven’t yet been gone through peer review, as part of their applications when they seek funding from the Bethesda, Maryland–based National Institutes of Health (NIH), the agency announced. [ScienceInsider] Editorial

NEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs
May 11-13, 2017
Heidelberg, Germany

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NEW Principle Investigator – Human Physiology and Experimental Medicine (University of Cambridge)

NEW Postdoctoral Fellow – Prostate/Pancreatic Cancer (Medical College of Wisconsin)

Senior Scientist – Pancreatic Cell Research (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Pancreatic Cancer Immunology (Memorial Sloan Kettering)

Postdoctoral Positions – Life Sciences (Helmholtz Zentrum München)

Associate Program Officer – Type 1 Diabetes (Helmsley Charitable Trust)

Postdoctoral Fellows – Diabetes Research (Icahn School of Medicine at Mount Sinai)

Bioinformatician/ Data Analyst – Beta Cell Biology (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

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

Research Positions – Mouse Genetics, Diabetes and Reprogramming (Inserm)

Postdoctoral Associate – Human Pancreatic Stem Cells (Nestlé)

Postdoctoral Fellowship – Beta Cell Regeneration (Helmholtz Zentrum München)

Postdoctoral Fellows – Cancer Epigenetics (Baylor Scott & White Research Institute)

Postdoctoral Position – Pancreatic Cancer (Cold Spring Harbor Laboratory)

Principle Scientist – Translational Development (Celgene Corporation)

Assistant Professor – Molecular Therapeutics (Dartmouth College/Geisel School of Medicine)

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