Pancreatic Cell News Volume 9.33 | Aug 21 2018

TOP STORY

Dual Reporter Genetic Mouse Models of Pancreatic Cancer Identify an Epithelial-to-Mesenchymal Transition-Independent Metastasis Program

The established metastases were primarily composed of cancer cells without evidence for a partial epithelial-to-mesenchymal transition (EMT) program, as assessed by the fate mapping approach. In contrast, metastatic cancer cells exhibiting a partial EMT program were restricted to isolated single cancer cells or micrometastases. [EMBO Mol Med] Full Article | Graphical Abstract

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DIABETES & PANCREATITIS

Contribution of the Long Non-Coding RNA H19 to Neonatal and Adult Rodent β-Cell Mass Expansion

Scientists revealed that the expression of the long non-coding RNA H19 was controlled by the transcription factor E2F1 and was profoundly downregulated during the post-natal period. H19 silencing decreased newborn β-cell expansion while its re-expression promoted proliferation of adult β-cells via a mechanism involving the microRNA let-7 and the activation of Akt. [Diabetes] Abstract

Angiotensin II Induces Cholesterol Accumulation and Impairs Insulin Secretion by Regulating ABCA1 in Beta Cells

Angiotensin II suppressed the promoter activity of ATP-binding cassette transporter A1 (ABCA1)-an effect that was abrogated by PD98095, a specific inhibitor of MEK. Liver X receptor (LXR) enhanced ABCA1 promoter activity, and angiotensin II decreased the nuclear abundance of LXR protein. [J Lipid Res] Abstract | Full Article

Estradiol Prevents High Glucose-Induced β-Cell Apoptosis by Decreased BTG2 Expression

SiRNA-B-cell translocation gene 2 (BTG₂) significantly reduced cell apoptosis, cleaved-caspase 3, and Bax, compared to the siRNA-control in INS-1 cells cultured under high glucose conditions. Researchers further demonstrated that BTG₂ promoter activity was activated under high glucose conditions whereas estrogen significantly reduced it. [Sci Rep] Full Article

Characterization of Induced Tissue-Specific Stem Cells from Pancreas by a Synthetic Self-Replicative RNA

A single VEE-RF RNA transfection into mouse pancreatic tissue resulted in efficient generation of induced tissue-specific stem cells from pancreas with genetic markers of endoderm and pancreatic progenitors and differentiation into insulin-producing cells more efficiently than embryonic stem cells. [Sci Rep] Full Article

Regulation of the β-Cell Inflammasome and Contribution to Stress-Induced Cellular Dysfunction and Apoptosis

High extracellular K⁺ reduced cytokine-induced apoptosis and NO production and restored cytokine-inhibited accumulated insulin-secretion. Knock-down of the ASC interaction domain common for NLRP1 and 3 improved insulin secretion and ameliorated IL-1β and/or glucolipotoxicity-induced cell death and reduced cytokine-induced NO-production. [Mol Cell Endocrinol] Abstract | Graphical Abstract

Attenuation of High Glucose Induced Apoptotic and Inflammatory Signaling Pathways in RIN-m5F Pancreatic β Cell Lines by Hibiscus rosa sinensis L. Petals and Its Phytoconstituents

The ethyl acetate fraction of Hibiscus rosa sinensis petals elevated the release of insulin in pancreatic cells and modulated apoptotic signaling cascades. It significantly reduced NF-κB nuclear translocation, thereby down-regulating the expressions of major inflammatory cytokines and up-regulating expressions of pancreatic β-cell functional genes. [J Ethnopharmacol] Abstract | Graphical Abstract

Leptospermum Flavescens Sm. Protect Pancreatic β Cell Function from Streptozotocin Involving Apoptosis and Autophagy Signaling Pathway in In Vitro and In Vivo Case Study

The methanolic extract of Leptospermum flavescens (MELF) was found to increase INS-1 β cell viability and insulin secretion against streptozotocin. MELF exhibited anti-hyperglycemic activity in diabetic rats where apoptosis and autophagy protein expression was found to be suppressed in pancreatic β islets. [J Ethnopharmacol] Abstract | Graphical Abstract

Effect of Nociceptin on Insulin Release in Normal and Diabetic Rat Pancreas

Isolated islets from non-diabetic and diabetic rats were used to determine the effect of nociceptin (NC) on insulin release. NC was discerned in islet cells of non-diabetic control and diabetic rat pancreata. NC co-localized only with insulin in pancreatic beta cells. NC did not co-localize with either glucagon or somatostatin or pancreatic polypeptide. [Cell Tissue Res] Abstract

PANCREATIC CANCER

USP9X Inhibition Improves Gemcitabine Sensitivity in Pancreatic Cancer by Inhibiting Autophagy

The authors found that the expression of ubiquitin-specific peptidase 9X (USP9X) in pancreatic cancer cells was positively correlated with gemcitabine resistance, and that inhibition of USP9X by WP1130 sensitized pancreatic cancer cells to gemcitabine. Gemcitabine induced autophagy, and blocking autophagy with chloroquine improved sensitivity to gemcitabine. [Cancer Lett] Abstract

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Designer Hydrogels: Shedding Light on the Physical Chemistry of the Pancreatic Cancer Microenvironment

Owing to its critical roles on governing pancreatic ductal adenocarcinoma (PDAC) progression and treatment outcome, the tumor microenvironment and its interplay with cancer cells are increasingly studied. Investigators summarize recent efforts in using 3D hydrogels for fundamental studies on cell-matrix or cell-cell interactions in PDAC. [Cancer Lett] Abstract

Biomarkers of Islet Beta Cell Stress and Death in Type 1 Diabetes

The authors outline current literature, limitations and future directions for promising circulating markers of beta cell stress and death in type 1 diabetes, including markers indicating abnormal prohormone processing, circulating RNAs and circulating DNAs. [Diabetologia] Abstract

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Novocure and US Oncology Research Announce Collaboration on PANOVA-3 Trial for Patients with Advanced Pancreatic Cancer

Novocure and US Oncology Research are collaborating on PANOVA-3, a Phase III pivotal trial testing the efficacy of tumor treating fields combined with nab-paclitaxel and gemcitabine in patients with unresectable locally advanced pancreatic cancer. [Novocure] Press Release

Xeris Pharmaceuticals and OHSU Conducting Artificial Pancreas Clinical Trial Using Xeris’ Novel Ready-to-Use Liquid Glucagon

Xeris Pharmaceuticals, Inc. announced that Jessica Castle, M.D., an associate professor of medicine in the OHSU School of Medicine and OHSU Harold Schnitzer Diabetes Health Center in Portland, Oregon, is conducting a clinical trial with a dual-hormone artificial pancreas using Xeris’ ready-to-use liquid glucagon to evaluate a new closed-loop algorithm. [Xeris Pharmaceuticals, Inc.] Press Release

Novo Nordisk Acquires Ziylo Ltd to Accelerate Its Development of Glucose Responsive Insulins

Ziylo and Novo Nordisk A/S announced that Novo Nordisk has acquired all of the shares of Ziylo, a University of Bristol spin-out company based at Unit DX science incubator in Bristol, UK. Ziylo has been pioneering the use of its platform technology – synthetic glucose binding molecules – for therapeutic and diagnostic applications. [Novo Nordisk A/S] Press Release

NIH Awards $6.5 Million to NDRI for Recovery of Human Tissues and Organs for Research

The National Institutes of Health (NIH) have awarded $6,591,480 to the National Disease Research Interchange (NDRI) to support continued national leadership with the recovery and distribution of human organs and tissues for medical research. [National Disease Research Interchange] Press Release

Hundreds of Chimps at the NIH Await Retirement. This Senator Wants to Help

Sen. Bill Cassidy is trying to help hundreds of chimpanzees enjoy an easy retirement in his home state of Louisiana. The Republican is pushing for an amendment to a major appropriations bill winding its way through Congress that would force the National Institutes of Health (NIH) to make good on a 2015 promise to move all its chimps out of research facilities. [STAT News] Editorial

As Primate Research Drops in Europe, Overseas Options Appeal

A combination of public opposition, intense regulations, and rising costs in the EU make conditions in China and elsewhere attractive for studying monkeys. [The Scientist] Editorial

Salk Institute Asks Judge to Narrow Scope of Gender-Discrimination Suit

Lawyers representing the Salk Institute for Biological Studies went to court on 17 August in San Diego, California, asking a judge to narrow the scope of a gender-discrimination lawsuit filed by molecular biologist Beverly Emerson. [Nature News] Editorial

Top Geneticist Loses £3.5-Million Grant in First Test of Landmark Bullying Policy

One of the world’s largest research-funding charities has revoked a £3.5-million (US$4.5-million) grant awarded to a top cancer geneticist, Nazneen Rahman, following allegations that she bullied scientists and other staff when she worked at the Institute of Cancer Research in London. [Nature News] Editorial

NEW Stem Cells & Organoids in Development & Disease
February 20-22, 2019
Amsterdam, Netherlands

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NEW Caspar Wistar Fellows – Cancer Biology (The Wistar Institute)

Postdoctoral Researcher – Diabetes Research (UC San Diego School of Medicine)

Postdoctoral Associate – Protein-Protein Interactions in Islets (Stanford Burmham Prebys Medical Discovery Institute)

Postdoctoral Associate – Biology of the Pancreas and Diabetes (University of Minnesota)

Assistant/Associate/Full Professor – Diabetes & Neuroscience (Indiana University School of Medicine)

Postdoctoral Position – Beta Cell Research (Helmholtz Zentrum Munchen)

Postdoctoral Positions – Pancretic Cancer Research (The University of Texas MD Anderson Cancer Center)

Lecturer/ Professor/ Clinical Academic – Diabetes (University of Exeter)

Postdoctoral Positions – Immunology of Diabetes (Cochin Institute)

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

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