Pancreatic Cell News Volume 10.11 | Mar 26 2019

TOP STORY

Balance of Two Enzymes Linked to Pancreatic Cancer Survival

Protein Kinase C (PKC) enzymes are crucial for a number of cellular activities, including cell survival, proliferation and migration. Researchers found that another enzyme, called PHLPP1, acted as a “proofreader” to keep careful tabs on PKC. In pancreatic cancer, they discovered that high PHLPP1 levels lead to low PKC levels, which is associated with poor patient survival. [Press release from University of California, San Diego discussing online prepublication in Molecular Cell] Press Release | Abstract | Graphical Abstract

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DIABETES & PANCREATITIS

Laser Capture Microdissection of Human Pancreatic Islets Reveals Novel eQTLs Associated with Type 2 Diabetes

Investigators identified expression quantitative trait loci (eQTLs) from human islets: 1,173 eQTLs from organ donors and 1,021 from surgical samples. eQTLs in LD with genome-wide association studies loci for type 2 diabetes and associated traits did not always implicate the nearest gene. [Mol Metab] Full Article

Point Mutations in the PDX1 Transactivation Domain Impair Human β-Cell Development and Function

Using an in vitro β-cell differentiation protocol, scientists demonstrated that both heterozygous PDX1^P33T/+, PDX1^C18R/+ and homozygous PDX1^P33T/P33T, PDX1^C18R/C18R mutations impaired β-cell differentiation and function. [Mol Metab] Full Article

Pancreatic Stone Protein/Regenerating Protein Is a Potential Biomarker for Endoplasmic Reticulum Stress in Beta Cells

Pancreatic stone protein/regenerating protein (PSP/reg) levels were elevated in cell culture and mouse models of Wolfram syndrome, a prototype of endoplasmic reticulum (ER) stress-induced diabetes. Moreover, PSP/reg expression was induced by canonical chemical inducers of ER stress, tunicamycin and thapsigargin. [Sci Rep] Full Article

Paeoniflorin Protects Pancreatic β Cells from STZ-Induced Damage through Inhibition of the p38 MAPK and JNK Signaling Pathways

Paeoniflorin (PF) resulted in a decrease in production of reactive oxygen species and MDA, and an increase in SOD activity in streptozotocin-treated INS-1 cells. Furthermore, PF inhibited the phosphorylation of p38 and JNK, which was induced by streptozotocin (STZ) in INS-1 cells. [Eur J Pharmacol] Abstract

PANCREATIC CANCER

Lysosome Inhibition Sensitizes Pancreatic Cancer to Replication Stress by Aspartate Depletion

Scientists performed a comprehensive pharmacological inhibition screen of the protein kinome and found that replication stress response inhibitors were synthetically lethal with chloroquine (CQ) in pancreatic ductal adenocarcinoma cells. CQ treatment reduced de novo nucleotide biosynthesis and induced replication stress. [Proc Natl Acad Sci USA] Abstract | Press Release

UHRF1 Promotes Aerobic Glycolysis and Proliferation via Suppression of SIRT4 in Pancreatic Cancer

The authors demonstrated that silencing ubiquitin like with plant homeodomain and ring finger domains 1 (UHRF1) significantly inhibited aerobic glycolysis in pancreatic cancer cells. Furthermore, they demonstrated that UHRF1 knockdown decreased hypoxia inducible factor (HIF) 1α levels and HIF1α targeted glycolytic genes. [Cancer Lett] Abstract

Vimentin-Positive Circulating Tumor Cells as a Biomarker for Diagnosis and Treatment Monitoring in Patients with Pancreatic Cancer

Researchers aimed to determine whether cell-surface vimentin could be a biomarker to isolate circulating tumor cells in pancreatic ductal adenocarcinoma. Vimentin was identified as highly expressed on the surface of mesenchymal-phenotype pancreatic tumor cells. [Cancer Lett] Abstract

Phosphorylation Regulates CAP1 (Cyclase-Associated Protein 1) Functions in the Motility and Invasion of Pancreatic Cancer Cells

Knockdown of CAP1 in cancer cells led to enhanced stress fibers, reduced cell motility and invasion into Matrigel. Phosphorylation of CAP1 at the S308/S310 tandem regulatory site was elevated in cancer cells, consistent with hyper-activated GSK3 reported in pancreatic cancer. [Sci Rep] Full Article

Genome-Wide CRISPR Screen Reveals PSMA6 to Be an Essential Gene in Pancreatic Cancer Cells

The authors used a negative-selection genome-wide CRISPR screen to identify essential genes in the PANC-1 human pancreatic carcinoma cell line. They validated the top hits with follow-up siRNA screens, using the HPNE, HPAF-II, AsPC-1, and Mia PaCa-2 cell lines. [BMC Cancer] Full Article

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The tRNA Epitranscriptome and Diabetes: Emergence of tRNA Hypomodifications as a Cause of Pancreatic β-Cell Failure

Investigators review recent findings that associate transfer RNA (tRNA) epitranscriptome perturbations with diabetes. [Endocrinology] Abstract

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Parker Institute to Share Pancreatic Cancer Trial Results, Microbiome and Immunotherapy Research, and New CAR-T Approaches

Just months after the first Nobel Prize for cancer immunotherapy was awarded, Parker Institute for Cancer Immunotherapy scientists will present the latest research driving the next generation of immune therapies. [Press release from Parker Institute discussing research to be presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

CalciMedica, Inc. to Present Study Population Profile from Its Initial Patient Study of Its CRAC Channel Inhibitor CM4620 in Acute Pancreatitis

The poster, titled “Patients with acute pancreatitis who have SIRS and hypoxemia at presentation have evidence of severe systemic and pancreatic inflammation”, was presented by Sudarshan Hebbar, MD, CalciMedica’s Chief Medical Officer. [Press release from CalciMedica, Inc. (PR Newswire Association LLC) discussing research presented at the 39^th International Symposium on Intensive Care and Emergency Medicine (ISICEM), Brussels] Press Release

Novo Nordisk Files Oral Semaglutide for US Regulatory Approval of Glycemic Control, as Well as for CV Risk Reduction for Oral Semaglutide and Ozempic^®

Novo Nordisk announced the submission of two New Drug Applications (NDAs) to the FDA for oral semaglutide, a once-daily glucagon-like peptide-1 analogue in a tablet, as well as a supplemental NDA for once-weekly semaglutide. [Novo Nordisk A/S] Press Release

FDA Issues Complete Response Letter for Zynquista™ (Sotagliflozin)

The FDA issued a Complete Response Letter regarding the New Drug Application for investigational Zynquista™, a dual SGLT1 and SGLT2 inhibitor for the treatment of adults with type 1 diabetes in combination with insulin. [Lexicon Pharmaceuticals, Inc.] Press Release

Duke University Settles Research Misconduct Lawsuit for $112.5 Million

Duke University will pay $112.5 million to the US government to settle a lawsuit brought by a former employee who alleged that the university included falsified data in applications and reports for federal grants worth nearly $200 million. The university will also take several steps “to improve the quality and integrity of research conducted on campus,” including the creation of a new advisory panel that will provide recommendations to the president, the Durham, North Carolina, institution said in a statement. [ScienceInsider] Editorial

Top US Institutes Still Aren’t Reporting Clinical-Trial Results on Time

Many leading US universities are breaking the law by failing to make public the results of clinical trials. A report found that 25 of the 40 universities that sponsor the most trials in the United States did not post study results on a public, government register within 12 months of completion, as is required by US law. [Nature News] Editorial

As Elsevier Falters, Wiley Succeeds in Open-Access Deal Making

Over the last few years, Project DEAL, a consortium that represents around 700 academic institutions in Germany, has been in negotiations for nationwide licensing agreements with three of the largest scholarly publishers – Elsevier, Springer Nature, and Wiley. [The Scientist] Editorial

NEW Obesity and NAFLD: Mechanisms and Therapeutics
February 23-27, 2020
Banff, Alberta, Canada

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NEW PhD Position – Pancreatic Cancer (Philipps-Universität Marburg)

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

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

Postdoctoral Fellowship – Pancreatic Islet Cells (Karolinska Institutet)

Postdoctoral Position – Diabetes (University of Minnesota)

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

Junior Scientists – Diabetes (Lund University)

Postdoctoral Position – Pancreatic Tissue Engineering (King’s College London)

Professor – Diabetes (University of California, San Diego)

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

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