Pancreatic Cell News Volume 10.37 | Sep 24 2019

TOP STORY

α-Ketoglutarate Links p53 to Cell Fate during Tumor Suppression

p53 induced transcriptional programs that were characteristic of premalignant differentiation, and this effect could be partially recapitulated by the addition of cell-permeable α-ketoglutarate (αKG). Increased levels of the αKG-dependent chromatin modification 5-hydroxymethylcytosine (5hmC) accompanied the tumor-cell differentiation that was triggered by p53, whereas decreased 5hmC characterized the transition from premalignant to de-differentiated malignant lesions that was associated with mutations in Trp53. [Nature] Abstract

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DIABETES & PANCREATITIS

A GLIS3-CD133-WNT Signaling Axis Regulates the Self-Renewal of Adult Murine Pancreatic Progenitor-Like Cells in Colonies and Organoids

Using an ex vivo colony/organoid culture system, scientists demonstrated that stem/progenitor-like cells had self-renewal and multilineage differentiation potential. They named these cells pancreatic colony-forming units because they could give rise to three-dimensional colonies. [J Biol Chem] Abstract

Lrrc55 Is a Novel Pro-Survival Factor in Pancreatic Islets

The authors found that Lrrc55 expression was upregulated by >60-fold during pregnancy in a prolactin receptor-dependent manner, and this increase was restricted only to the islets. Overexpression of Lrrc55 in β-cells had minimal effect on β-cell proliferation and glucose-stimulated insulin secretion, but protected β-cells from glucolipotoxicity-induced reduction in insulin gene expression. [Am J Physiol Endocrinol Metab] Abstract

Zinc Deficiency Alters the Susceptibility of Pancreatic Beta Cells (INS-1) to Arsenic Exposure

Zinc deficiency decreased cell proliferation by 30% in pancreatic INS-1 rat insulinoma cells. Arsenic exposure significantly decreased cell proliferation, and increased mRNA levels of genes involved in stress response and DNA damage. [Biometals] Abstract

miR-92a-3p Regulates Trypsinogen Activation via Egr1 in AR42J Cells

Researchers investigated the expression of microRNA (miR)-92a-3p and early growth response protein 1 (Egr1), and the effect of miR-92a-3p on trypsinogen activation in the pancreatic exocrine cell line AR42J. mRNA and miRNA microarrays were used to identify differentially expressed mRNAs and miRNAs in AR42J cells. [Mol Med Rep] Abstract | Download Full Article

PANCREATIC CANCER

LINC01232 Exerts Oncogenic Activities in Pancreatic Adenocarcinoma via Regulation of TM9SF2

Loss-of-function assays were carried out and the experimental results indicated that suppression of long intergenic non-protein coding RNA 1232 (LINC01232) hindered the deterioration of pancreatic adenocarcinoma by affecting cell proliferation and migration. Furthermore, the relationship between LINC01232 and its nearby gene transmembrane 9 superfamily member 2 was investigated. [Cell Death Dis] Full Article

TMEM158 Promotes Pancreatic Cancer Aggressiveness by Activation of TGFβ1 and PI3K/AKT Signaling Pathway

Investigators found that transmembrane protein 158 (TMEM158) was significantly upregulated in pancreatic cancer (PC) samples as well as PC cell lines. The overexpression of TMEM158 was significantly correlated with advanced clinicopathologic features and poorer prognosis of patients with PC in clinic. [J Cell Physiol] Abstract

Effect of Adenomatous Polyposis Coli Loss on Tumorigenic Potential in Pancreatic Ductal Adenocarcinoma

Using lentiviral shRNA, investigators successfully knocked down Adenomatous Polyposis Coli expression in six pancreatic cancer cell lines. No changes were observed in localization of β-catenin or reporter assays to assess β-catenin/TCF interaction. [Cells] Full Article

Interleukin 21 Receptor/Ligand Interaction Is Linked to Disease Progression in Pancreatic Cancer

In vitro data using pancreatic tumor cells lines showed that IL-21 activated ERK and STAT3 pathways and upregulated Blimp-1. Moreover, IL-21 increased invasion of tumor cell lines in a Blimp-1-dependent manner. [Cells] Full Article

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The Heterogeneous Pathogenesis of Type 1 Diabetes Mellitus

Multiple genetic and environmental factors found in variable combinations in individual patients are involved in the development of T1DM. Compared with the genetic factors, environmental factors that affect the development of T1DM are less well characterized but contact with particular microorganisms is emerging as an important factor. [Nat Rev Endocrinol] Abstract

“Omics” and “Epi-Omics” Underlying the β-Cell Adaptation to Insulin Resistance

Type 2 diabetes (T2D) is typically characterized by β-cell decompensation. The authors focus on summarizing the “omics” and “epi-omics” approaches that particularly focus on addressing the β-cell adaptation to insulin resistance and T2D. [Mol Metab] Full Article

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Zealand Pharma Achieves Primary and All Key Secondary Endpoints in Pediatric Phase III Trial with Dasiglucagon for Severe Hypoglycemia

Zealand Pharma A/S announced positive results in the pediatric Phase III trial with dasiglucagon for severe hypoglycemia in diabetes. Dasiglucagon is a potential first-in-class soluble glucagon analog invented and developed by Zealand. It is being developed in the ready-to-use HypoPal^® rescue pen: an auto-injector for easy, fast and effective treatment of severe hypoglycemia in people with diabetes. [Zealand Pharma A/S (GlobeNewswire, Inc.)] Press Release

Theraly Fibrosis Granted US Orphan Drug Designation for TLY012 for Chronic Pancreatitis

Theraly Fibrosis announced that the FDA has granted Orphan Drug Designation to TLY012 for the treatment of chronic pancreatitis. The company plans to initiate a Phase I/IIa clinical trial in 2020. [Theraly Fibrosis (Business Wire, Inc.)] Press Release

Mediator: French Weight-Loss Drug Trial over ‘up to 2,000’ Deaths Begins

A landmark French trial is due to begin to decide whether a diabetes pill prescribed for weight loss was behind the deaths of up to 2,000 people. Servier, the drug’s manufacturer, is accused of deceiving users over the killer side effects of a drug later used to treat overweight diabetics. [BBC] Editorial

Grad Student Unions Dealt Blow as Proposed New Rule Says Students Aren’t ‘Employees’

Graduate students are not “employees” with a right to unionize, according to a rule proposed today by the National Labor Relations Board (NLRB), an agency that’s tasked with enforcing US labor laws. If implemented, the rule would undercut a recent wave of grad student unionization efforts at private US universities. The NLRB will be accepting public comment on the announcement for 60 days. [ScienceMagazine] Editorial

Kashmir’s Communication Blackout Is a ‘Devastating Blow’ for Academics, Researchers Say

Six professors from India’s top science institutions have appealed to the government to lift the blockade of academic and research institutions in Indian-controlled Kashmir. The blockade has been a “devastating blow,” the six write in an open letter published September 18^th. [ScienceMagazine] Editorial

NEW AACR International Conference on Molecular Targets and Cancer Therapeutics
October 26-30, 2019
Boston, Massachusetts, United States

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NEW Group Leader – Diabetes Research (International Centre for Genetic Engineering and Biotechnology)

Faculty Position – Cancer Biology (Children’s Research Institute at UT Southwestern)

Postdoctoral Fellow – Pancreatic Cancer (The University of Alabama at Birmingham)

Postdoctoral Position – Pancreatic Ductal Adenocarcinoma (IT University of Copenhagen)

Lab Aide – Pancreatic Cancer Research (Fred Hutchinson Cancer Research Center)

Research Technition – Diabetes, Allergies, and Lung Diseases (Helmholtz Zentrum München)

Postdoctoral Researcher – Auto-Immunity (Benaroya Research Institute)

Postdoctoral Researcher – Endocrinology, Diabetes, and Metabolism (The University of Alabama at Birmingham)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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

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

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

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