Pancreatic Cell News Volume 10.28 | Jul 23 2019

TOP STORY

ZRANB3 Is an African-Specific Type 2 Diabetes Locus Associated with Beta-Cell Mass and Insulin Response

Knockdown or genomic knockout of the zebrafish ortholog resulted in reduction in pancreatic β-cell number which researchers demonstrated to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 β-cells resulted in impaired insulin secretion in response to high glucose, implicating Zranb3 in β-cell functional response to high glucose conditions. [Nat Commun] Full Article | Press Release

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Mitochondrial GTP Links Nutrient Sensing to β Cell Health, Mitochondrial Morphology, and Insulin Secretion Independent of OxPhos

Mitochondrial GTP (mtGTP) synthesized by succinyl-CoA synthetase (SCS) was hydrolyzed via mitochondrial PEPCK to make phosphoenolpyruvate, a high-energy metabolite that integrated TCA cycling and anaplerosis with glucose-stimulated insulin secretion. Several strategies, including xenotopic overexpression of yeast mitochondrial GTP/GDP exchanger and human ATP and GTP-specific SCS isoforms, demonstrated the importance of the mtGTP cycle. [Cell Rep] Full Article | Graphical Abstract

Myc Is Required for Adaptive ß-Cell Replication in Young Mice but Is Not Sufficient in One-Year-Old Mice Fed with a High-Fat Diet

Mechanistically, PKCζ, ERK1/2, mTOR and PP2A were key regulators of the Myc response in pancreatic ß-cells. DNA methylation analysis showed hypomethylation of cell cycle genes that were Myc targets in islets from young mice fed with a short- term high fat diet. [Diabetes] Abstract

Pancreatic Ductal Cells May Have a Negative Effect on Human Islet Transplantation

Isolated islets were purified by handpicking. Ductal cells were purified by magnetic cell sorting and then clustered into ductal pancreatospheres (DPS). Islets, DPS, and islets + DPS were cultured and glucose-stimulated insulin secretion, β-cell apoptosis, and gene expression was determined. [PLoS One] Full Article

PANCREATIC CANCER

Protein Arginine Methyltransferase 3-Induced Metabolic Reprogramming Is a Vulnerable Target of Pancreatic Cancer

The protein arginine methyltransferase 3 (PRMT3) protein level of human pancreatic tumors was detected by immunoblotting and immunohistochemical staining. PRMT3-associated proteins and the methylation sites on the proteins were investigated using mass spectrometry. [J Hematol Oncol] Full Article

LATS1/2 Suppress NFκB and Aberrant EMT Initiation to Permit Pancreatic Progenitor Differentiation

Investigators made the unexpected finding that Hippo suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling in pancreatic progenitors to permit cell differentiation and epithelial morphogenesis. They found that pancreas-specific deletion of the large tumor suppressor kinases 1 and 2 (LATS1/2) from mouse progenitor epithelia resulted in failure to differentiate key pancreatic lineages: acinar, ductal, and endocrine. [PLoS Biol] Full Article

Application of a MYC Degradation Screen Identifies Sensitivity to CDK9 Inhibitors in KRAS-Mutant Pancreatic Cancer

Researchers used a previously developed, flow cytometry-based assay that screened a library of >800 protein kinase inhibitors and identified compounds that promoted either the stability or degradation of MYC in a KRAS-mutant pancreatic cancer cell line. They validated compounds that stabilized or destabilized MYC and then focused on one compound, UNC10112785, that induced the substantial loss of MYC protein in both two-dimensional (2D) and 3D cell cultures. [Sci Signal] Full Article

lncRNA TP53TG1 Promotes Pancreatic Ductal Adenocarcinoma Development by Acting as a Molecular Sponge of miR-96

Scientists identified TP53TG1 was highly expressed in pancreatic ductal adenocarcinoma (PDAC) and was a novel regulator of PDAC development. Knockdown of TP53TG1 inhibited proliferation, induced apoptosis, decreased migration and invasion in PDAC cells, whereas enhanced expression of TP53TG1 had the opposite effects. [Cancer Sci] Abstract

Diagnostic Potential of Hypermethylation of the Cysteine Dioxygenase 1 Gene (CDO1) Promoter DNA in Pancreatic Cancer

Three studies, including cell experiments, tissue validation and pilot testing for pancreatic cytology, were conducted. Promoter DNA methylation value of CDO1 was quantified by quantitative methylation‐specific PCR. [Cancer Sci] Abstract

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The Relationship between Pancreatic Cancer and Hypercoagulability: A Comprehensive Review on Epidemiological and Biological Issues

Although the relationship between pancreatic cancer and hypercoagulability is well described, the underlying pathological mechanism(s) and the interplay between these pathways remain a matter of intensive study. The authors summarize existing data on epidemiology and pathogenesis of thrombotic complications in pancreatic cancer with a particular emphasis on novel pathophysiological pathways. [Br J Cancer] Abstract

Metabolomics Analysis of Nutrient Metabolism in β-Cells

The islets of Langerhans harbor multiple endocrine cell-types that continuously respond to circulating nutrient levels in order to adjust their secretion of catabolic and anabolic hormones. Stimulus-secretion coupling in these cells is largely of metabolic nature, i.e. metabolism of nutrient fuels yields signals that trigger and amplify secretion of hormones. [J Mol Biol] Abstract | Graphical Abstract

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PharmaCyte Biotech and UTS Creating Advanced Version of Melligen Cells to Treat Diabetes

PharmaCyte Biotech, Inc. announced it has entered into a new research agreement with the University of Technology Sydney (UTS) in Australia to create a new version of Melligen cells for the treatment of diabetes with the potential to express higher levels of insulin. [PharmaCyte Biotech, Inc.] Press Release

Rafael Pharmaceuticals Announces Expansion into Israel of Pivotal Phase III Trial (AVENGER 500) of CPI-613^®️ (Devimistat) in Combination with Modified FOLFIRINOX as First-Line Treatment for Patients with Metastatic Pancreatic Cancer

Rafael Pharmaceuticals, Inc. announced the expansion of its Phase III clinical trial for patients with metastatic pancreatic cancer into Israel. The multicenter, open-label, randomized pivotal trial is evaluating the efficacy and safety of Rafael’s lead compound CPI-613^®️ in combination with modified FOLFIRINOX as first-line therapy in patients with metastatic adenocarcinoma of the pancreas. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release

Sun BioPharma, Inc. Provides an Update on Ongoing Front-Line Pancreatic Cancer Clinical Trial

Sun BioPharma, Inc. provided an update on the company’s current clinical trial. Following successful conclusion of the first SBP-101 dose escalation study in heavily pretreated pancreatic cancer patients that showed SBP-101 could be administered safely as monotherapy, a second Phase I safety study was undertaken to evaluate the addition of SBP-101 to front line gemcitabine and nab-paclitaxel treatment. [Sun BioPharma, Inc. (GlobeNewswire, Inc.)] Press Release

Budget Deal Raises Hopes for US Research Agencies

A new budget deal between the White House and congressional leaders means US research agencies could receive increases on the order of the 4% to 5% that Democrats have already proposed for next year. [ScienceInsider] Editorial

What Boris Johnson’s Leadership Could Mean for Science

Boris Johnson has been selected as the United Kingdom’s new prime minister — and is poised to lead the country out of the European Union. At the forefront of many scientists’ minds are questions about how Johnson’s leadership, including his support for a ‘no deal’ Brexit, will affect research. They fear that British science has much to lose from a messy departure from the EU. [Nature News] Editorial

University of Adelaide Investigates Ancient DNA Lab

The University of Adelaide has launched an investigation in to the work environment of the Australian Centre for Ancient DNA. The lab is run by an evolutionary molecular biologist Alan Cooper; it’s the second time a university has investigated allegations of misconduct in a lab he has led. [The Scientist] Editorial

NEW 2019 National Cancer Research Institute Cancer Conference
November 3-5, 2019
Glasgow, United Kingdom

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NEW Research Assistant – Department of Surgical Oncology (MD Anderson Cancer Center)

Research Associate – Pathology and Treatment of Diabetes (King’s College London)

Postdoctoral Fellowship – Jak-Stat Signaling in Prostate/Pancreatic Cancer (Medical College of Wisconsin)

PhD Studentship – Type 2 Diabetes (University of Roehampton)

Research Scientist – Endocrine Pancreas Development (Helmholtz Zentrum München)

Postdoctoral Position – Immunology (Roswell Park Cancer Institute)

Postdoctoral Researcher – Pancreas Cancer Research (Fred Hutchinson Cancer Research Center)

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

Postdoctoral Fellow – Cancer Drug Response Research (University of Texas at Austin)

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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