Pancreatic Cell News Volume 9.24 | Jun 19 2018

TOP STORY

NFκB in Pancreatic Stellate Cells Reduces Infiltration of Tumors by Cytotoxic T Cells and Killing of Cancer Cells, via Upregulation of CXCL12

In vitro expression of p50 by pancreatic stellate cells (PSCs) reduced T-cell migration toward and killing of cancer cells. When cultured with cancer cells, control PSCs expressed 10-fold higher levels of CXCL12 than p50–/– PSCs. The CXCL12 inhibitor increased migration of T cells toward KrasG12D/+; Trp53 R172H/+; Pdx-1cre cells in culture. [Gastroenterology] Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets

Investigators showed that glucagon secretion in low glucose conditions is maintained by fatty acid metabolism in both mouse and human islets, and that inhibiting this metabolic pathway profoundly decreases glucagon output by depolarizing α cell membrane potential and decreasing action potential amplitude. They demonstrated that this is not mediated by the K_ATP channel, but instead due to reduced operation of the Na⁺-K⁺ pump. [Cell Rep] Full Article | Graphical Abstract

miR-149 Negative Regulation of mafA Is Involved in the Arsenite-Induced Dysfunction of Insulin Synthesis and Secretion in Pancreatic Beta Cells

Exposure of Min6 cells to low levels of arsenite led to lower glucose-stimulated insulin secretion in a dose- and time-dependent fashion. In arsenite-exposed Min6 cells, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (mafA) activity was lowered by the increase of its target miRNA, miR-149. Luciferase assays illustrated an interaction between miR-149 and the mafA 3′ untranslated region. [Toxicol Sci] Abstract

Melatonin Attenuates Endoplasmic Reticulum Stress in Acute Pancreatitis

Inositol-requiring 1α-mediated Jun N-terminal kinase/nuclear factor-kappa B pathway were activated early in AR42J cells and rat acute pancreatitis models. Melatonin significantly inhibited the expression of proinflammatory cytokines. Western blot and immunohistochemical results all indicated that melatonin regulated apoptosis-related protein expression. [Pancreas] Abstract

Spexin Modulates Functions of Rat Endocrine Pancreatic Cells

Insulin secretion from cultured cells and isolated islets was reduced by spexin at 16 mM glucose level. Spexin treatment showed an increase in cultured cells and pancreatic islets cell viability and proliferation as well as an increase in proliferating cell nuclear antigen protein level. In contrast, a decrease in insulin and pancreatic duodenal homeobox-1 gene expression was found. [Pancreas] Abstract

PANCREATIC CANCER

Regulation of Epithelial Plasticity Determines Metastatic Organotropism in Pancreatic Cancer

Investigators demonstrated, using multiple mouse models, that liver and lung metastatic organotropism is dependent upon p120catenin (p120ctn)-mediated epithelial identity. RNA-seq demonstrated differential induction of pathways associated with metastasis and epithelial-to-mesenchymal transition in p120ctn-deficient versus p120ctn-wild-type cells. [Dev Cell] Full Article

Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer

The authors mapped tumor hypoxia by both immunofluorescence and phosphorescence lifetime imaging of oxygen-sensitive nanoparticles and demonstrated that these hypoxic regions move transiently around the tumor. To overlay this microenvironmental information with drug response, they applied a FRET biosensor for Akt activity, which is a key effector of the PI3K pathway. [Cell Rep] Full Article | Press Release | Graphical Abstract

Loss of Linc01060 Induces Pancreatic Cancer Progression through Vinculin-Mediated Focal Adhesion Turnover

Linc01060 inhibited pancreatic cancer proliferation and invasion in vitro and in vivo. Vinculin overexpression inhibited Linc01060KD-mediated increases in FAK and paxillin phosphorylation, whereas vinculin knockdown reversed the Linc01060-mediated repression of FAK and inactivation of focal adhesion turnover. [Cancer Lett] Abstract

Linc00462 Promotes Pancreatic Cancer Invasiveness through the miR-665/TGFBR1-TGFBR2/SMAD2/3 Pathway

Researchers demonstrated that linc00462 was a target of miR-665. Linc00462 overexpression enhanced the expression levels of TGFBR1 and TGFBR2, and thus activated the SMAD2/3 pathway in pancreatic cancer cells. [Cell Death Dis] Full Article

Overexpression of CBX3 in Pancreatic Adenocarcinoma Promotes Cell Cycle Transition-Associated Tumor Progression

The authors showed that chromobox protein homolog 3 (CBX3) may be associated with cell cycle transition of pancreatic adenocarcinoma (PAAD) cells, and cyclin-dependent kinase 1 (CDK1) and proliferating cell nuclear antigen may mediate the tumor-promoting action of CBX3. CDK1 knockdown attenuated the cell cycle transition, proliferation and invasion of CBX3-overexpressing PAAD cells. [Int J Mol Sci] Full Article

Targeting the Incretin/Glucagon System with Triagonists to Treat Diabetes

Investigators discuss the range of tissue targets and added benefits afforded by the inclusion of each glucose-dependent insulinotropic peptide and glucagon. They discuss considerations for the development of sequence intermixed dual- and tri-agonists, highlighting the importance of evaluating balanced signaling at the targeted receptors. [Endocr Rev] Abstract

The Hepatic Pre-Metastatic Niche in Pancreatic Ductal Adenocarcinoma

Even before the onset of pancreatic cancer cell dissemination, soluble factors and extracellular vesicles secreted by the primary tumor, and possibly even premalignant lesions, help shape a supportive niche in the liver by providing vascular docking sites for circulating tumor cells, enhancing vascular permeability, remodeling the extracellular matrix and recruiting immunosuppressive inflammatory cells. [Mol Cancer] Full Article

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

Adocia to Present Six Abstracts

Adocia announced that six abstracts covering its diabetes portfolio have been accepted for presentation. [Press release from Adocia discussing research to be presented at the American Diabetes Association 78^th Scientific Sessions, Orlando] Press Release

Novo Nordisk to Present 39 Abstracts

Novo Nordisk announced that the company will share data from 39 abstracts discussing a breadth of new clinical, real-world and patient perspectives data across its portfolio of pipeline and marketed products. [Press release from Novo Nordisk (PR Newswire Association LLC.) discussing research to be presented at the American Diabetes Association 78^th Scientific Sessions, Orlando] Press Release

Kallyope and Novo Nordisk Announce Collaboration to Discover Novel Therapeutics for Obesity and Diabetes

Kallyope Inc. and Novo Nordisk A/S announced that they have entered into a research collaboration and option agreement to discover novel peptide therapeutics to treat obesity and diabetes. [Kallyope Inc.] Press Release

FDA Acceptance of IND to Advance Phase III Clinical Trial COMPETE with Solucin^® for Treatment of GEP-NET in the U.S.

ITM Isotopen Technologien München AG, announced that the FDA has accepted the company’s investigational new drug application (IND) to advance its innovative radiopharmaceutical Solucin^®, into a Phase III clinical trial in the U.S.. [ITM Isotopen Technologien München AG] Press Release

PharmaCyte Biotech Successfully Completes Another FDA Required Study Necessary for Submitting Investigational New Drug Application

PharmaCyte Biotech, Inc. announced that it has successfully completed the comprehensive characterization of its proprietary cell clone known as 22P1G. The cells from the Master Cell Bank will serve as the active pharmaceutical ingredient in the company’s Cell-in-a Box^® capsules that will be used (together with low doses of the cancer prodrug ifosfamide) for the treatment of locally advanced, non-metastatic, inoperable pancreatic cancer in its planned clinical trial. [PharmaCyte Biotech Inc.] Press Release

U.S. Legislators Back Larger Facilities Budget for NSF

The National Science Foundation (NSF) in Alexandria, Virginia, is in line for a budget increase of 4% to 5% next year. That assessment is based on bills approved recently by the spending committees in both chambers of Congress. Lawmakers have also signaled support for growing the account that NSF uses to build major new scientific facilities. [ScienceInsider] Editorial

Why the Medical Research Grant System Could Be Costing Us Great Ideas

The medical research grant system in the United States, run through the National Institutes of Health, is intended to fund work that spurs innovation and fosters research careers. In many ways, it may be failing. [The New York Times] Editorial

House Bill Gives NIH a 3% Boost in 2019, to $38.3 Billion

A draft bill released by a House of Representatives spending panel would give the National Institutes of Health (NIH) in Bethesda, Maryland, a $1.25 billion raise in 2019, to $38.3 billion. That is 3% more than this year’s level and $4.1 billion more than President Donald Trump’s administration had requested. [ScienceInsider] Editorial

New Zealand Appoints First Female Chief Scientific Adviser

The New Zealand government has appointed biochemist Juliet Gerrard as its next chief scientific adviser — the first woman to hold the position. [Nature News] Editorial

Bill to Encourage Generic-Drug Development Passes a Key Hurdle

A key Senate committee voted to advance legislation that aims to spur the development of new generic drugs and in turn, lower drug prices. [Stat News] Editorial

NEW Keystone Symposia: Drivers of Type 2 Diabetes – From Genes to Environment
October 7-11, 2018
Seoul, South Korea

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

NEW Postdoctoral Fellow – Cellular Biology of Pancreatic Cancer (The Francis Crick Institute)

Assistant or Associate Professor (Tenure Track) – Immunopathology of Metabolic Diseases )

Postdoctoral Research Scientist – Metabolic Homeostasis Research (London Institute of Medical Sciences)

Postdoctoral Position – Human Pluripotent Stem Cell-Based Cell Therapy in Type 1 Diabetes (University of Copenhagen)

Postdoctoral Researcher – Pancreatic Islets & Beta Cell Transplantation (Karolinska Institutet)

Postdoctoral Positions – Translational Diabetes Research (Partner of German Center for Diabetes Research)

Postdoctoral Scholars – Structural Biology (The University of Chicago)

EBPOD Fellowship – Pancreatic Cancer Analysis (European Molecular Biology Laboratory)

Postdoctoral Positions – Immunology of Diabetes (Cochin Institute)

Postdoctoral Position – Functional Genomics of Insulin Resistance (Stanford University)

Postdoctoral Fellows – Diabetes Complications & Epigenetics (St. Michael’s Hospital)

Doctoral Thesis Positions – Diabetes Research (International Helmholtz Research School for Diabetes)

Doctoral Thesis Position – Genomics of Pancreatic Cancer and Pancreatic Development (Universitatsklinikum Ulm)

Associate Professor or Professor – Biomedical Metabolics (The Ohio State University Wexner Medical Center)

Postdoctoral Scholar – Glucose Homeostasis, Obesity & Type 2 Diabetes (University of California – San Francisco)

Postdoctoral Fellow – Molecular Medicine (City of Hope)

Doctoral Thesis Position – Diabetes Research (Universite Libre de Bruxelles)

Pioneer Award Postdoctoral Fellowships – Pancreatic Cancer (University of Miami Miller School of Medicine)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral Fellow – Epigenetic Regulation of Pancreatic Beta-Cell Mass (City of Hope)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Pancreatic Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.