Pancreatic Cell News Volume 10.13 | Apr 9 2019

TOP STORY

Ring1b-Dependent Epigenetic Remodeling Is an Essential Prerequisite for Pancreatic Carcinogenesis

Relevance of Ring1b-catalysed H2AK119ub in acinar cell reprogramming was studied in an inducible Ring1b knockout mouse model. CRISPR/Cas9-mediated Ring1b ablation as well as drug-induced Ring1b inhibition were functionally characterized in pancreatic cancer cells. [Gut] Abstract

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DIABETES & PANCREATITIS

Glucose Controls Glucagon Secretion by Directly Modulating cAMP in Alpha Cells

Researchers investigated the role of the intracellular messenger cAMP in alpha-cell-intrinsic glucose regulation of glucagon release. Subplasmalemmal cAMP and Ca²⁺ concentrations were recorded in isolated and islet-located alpha cells using fluorescent reporters and total internal reflection microscopy. [Diabetologia] Full Article

Cytokine-Induced Translocation of GRP78 to the Plasma Membrane Triggers a Pro-Apoptotic Feedback Loop in Pancreatic Beta Cells

Scientists demonstrated translocation of glucose-regulated protein (GRP78) to the surface of human EndoC-βH1 cells and primary human islets upon cytokine exposure, in analogy to observations in rodent INS-1E and MIN6 beta cell lines. They demonstrated that both GRP78 signaling domains initiated pro-apoptotic signaling cascades in beta cells. [Cell Death Dis] Full Article

The Direct Effect of Lobeglitazone, a New Thiazolidinedione, on Pancreatic Beta Cells: A Comparison With Other Thiazolidinediones

INS-1 cells were incubated at a high-glucose concentration with various concentrations of troglitazone, rosiglitazone, pioglitazone, and lobeglitazone. Apoptosis and proliferation of beta cells, markers for ER stress and glucose-stimulated insulin secretion were assessed. [Diabetes Res Clin Pract] Abstract

PANCREATIC CANCER

NMIIA Promotes Tumor Growth and Metastasis by Activating the Wnt/β-Catenin Signaling Pathway and EMT in Pancreatic Cancer

Non-muscle myosin IIA (NMIIA) regulated β-catenin mediated EMT to promote the proliferation, migration, invasion, and sphere formation of pancreatic cancer cells in vitro and in vivo. NMIIA controlled the β-catenin transcriptional activity by interacting with β-catenin. Moreover, MEK/ERK signaling was critical in MLC2 phosphorylation, which could mediate NMIIA activity and regulate Wnt/β-catenin signaling. [Oncogene] Abstract

Tumor-Associated Macrophage-Secreted 14-3-3ζ Signals via AXL to Promote Pancreatic Cancer Chemoresistance

Primary human pancreatic ductal adenocarcinoma (PDAC) cultures were treated with conditioned media (CM) from monocyte-derived macrophage cultures incubated with apoptotic PDAC cells (MØ^ApopCM). MØ^ApopCM pretreatment rendered naïve PDAC cells resistant to gemcitabine- or abraxane-induced apoptosis. [Oncogene] Abstract

CD90 Highly Expressed Population Harbors a Stemness Signature and Creates an Immunosuppressive Niche in Pancreatic Cancer

Investigators report that CD90 was expressed on both stromal and tumor cells and that high expression of CD90 was related to a poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). The CD90 highly expressed population in PDAC cells harbored high stemness features and tumorigenicity. [Cancer Lett] Abstract

ARHGAP4 Regulates the Cell Migration and Invasion of Pancreatic Cancer by the HDAC2/β-Catenin Signaling Pathway

Mechanistically, ARHGAP4 interacted with and ubiquitinates histone deacetylase 2 (HDAC2), which in turn inhibited β-catenin activation. Furthermore, treatment of CAY10683, a HDAC2 inhibitor, and XAV939, a Wnt/β-catenin pathway inhibitor, attenuated the effects of ARHGAP4 silencing on pancreatic cancer cells. [Carcinogenesis] Abstract

Upregulation of LASP2 Inhibits Pancreatic Cancer Cell Migration and Invasion Through Suppressing TGF-β-Induced EMT

Scientists demonstrated that LIM and SH3 protein 2 (LASP2) was downregulated in pancreatic cancer (PC) tissues and cell lines. In addition, upregulation of LASP2 inhibited PC cell migration and invasion. They also found that LASP2 upregulation reversed tumor growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) in PC cells. [J Cell Biochem] Abstract

Ocoxin Oral Solution Exerts an Antitumoral Effect in Pancreatic Cancer and Reduces the Stromal-Mediated Chemoresistance

Ocoxin oral solution (OOS) enhanced the cytotoxic effect of paclitaxel and gemcitabine, while it ameliorated the chemoresistance induced by fibroblast-derived soluble factors in human pancreatic cancer cells. The OOS also promoted the regulation of the expression of genes that were altered in pancreatic carcinoma and slowed down 266-6 cell pancreatic tumor development in vivo. [Pancreas] Abstract

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Role of the P2X7 Receptor in the Pathogenesis of Type 2 Diabetes and Its Microvascular Complications

P2X7 receptors can be found in many tissues and organs, where they mediate several biological functions. The authors summarize the current knowledge about the role of this receptor in the pathogenesis of type 2 diabetes, in which the key clinical features are impaired insulin secretion and sensitivity, hyperglycemia, coexistence of other cardiovascular risk factors such as dyslipidemia and hypertension, and subclinical inflammation. [Curr Opin Pharmacol] Abstract

Deciphering Role of FGFR Signaling Pathway in Pancreatic Cancer

Investigators describe recent advances of the FGFR signaling pathway in pancreatic carcinogenesis and progression. Moreover, they highlight the available chemical inhibitors of the FGFR pathway for potential treatment of pancreatic cancer. [Cell Prolif] Full Article

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Moleculin Announces Preclinical Pancreatic Cancer Data Presented

Moleculin Biotech, Inc. announced that preclinical data supporting activity of its STAT3-inhibiting Immune/Transcription Modulators was presented by Dr. Waldemar Priebe, Founder and Chair of the Scientific Advisory Board of Moleculin, Inc. [Press release from Moleculin Biotech, Inc. discussing research presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR), Atlanta] Press Release

Clovis Oncology Announces Interim Results From Rubraca^® (Rucaparib) Phase II Study in Advanced Pancreatic Cancer and Nonclinical Data in Multiple Solid Tumor Types for Rucaparib and Lucitanib Presented

Clovis Oncology, Inc. announced multiple presentations. These include presentation of interim results from an investigator-initiated Phase II trial of Rubraca^® in platinum-sensitive patients with advanced pancreatic cancer. [Press release from Clovis Oncology, Inc. discussing research presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR), Atlanta] Press Release

Immunovia and University College of London Sign Agreement to Extend Validation Studies of IMMray™ PanCan-D for Early Signs and Symptoms

Immunovia announced that Prof. Stephen Pereira and his team at the institute for Liver and Digestive Health, University College London will extend the prospective collection of blood samples funded by Immunovia and that started with the PanSYM-1 pilot study. [Immunovia] Press Release

Sun Pharma Launches Ready-to-Infuse INFUGEM in the US

Sun Pharmaceutical Industries Ltd. announced that INFUGEM™, for intravenous use, is now commercially available in the US. INFUGEM, the first chemotherapy product that comes in a premixed, ready-to-infuse formulation, was approved by the FDA in July 2018 in combination with other drugs for the treatment of breast, ovarian, non-small cell lung cancers, and as a single agent for the treatment of pancreatic cancer. [Sun Pharmaceutical Industries Ltd.(Business Wire, Inc.)] Press Release

Poxel and Sumitomo Dainippon Pharma Announce Positive Top-Line Results for Imeglimin Phase III Trial (TIMES 1) in Japan for the Treatment of Type 2 Diabetes

POXEL SA and Sumitomo Dainippon Pharma Co., Ltd, announced positive top-line Phase III data results for the Imeglimin TIMES 1 trial for the treatment of type 2 diabetes in Japan. Referred to as TIMES (Trials of IMeglimin for Efficacy and Safety), the Imeglimin Phase III program in Japan includes three pivotal trials to evaluate Imeglimin’s efficacy and safety in over 1,100 patients. [POXEL SA] Press Release

Adocia Announces Positive Topline Results for the First Clinical Study of ADO09, a New Co-Formulation of Pramlintide and a Prandial Insulin Analog, in People with Type 1 Diabetes

Adocia announced positive topline pharamacodynamic and safety results from the first Phase I study of ADOO0, a ready-to-use, pH 4, co-formulation at fixed ratio of pramlintide, the only FDA-approved analog of amylin, and A12G human insulin analog, a rapid-acting insulin that is known to be the main circulating metabolite of insulin glargine. [Adocia] Press Release

Racism Rife at Top South African University, Says Report

A damning report that says racism is entrenched at the University of Cape Town has reignited discussions about how to erase the divisive legacy of colonialism at South Africa’s top research institutions. [Nature News] Editorial

FDA, New York Attorney General Go After Stem Cell Clinics

On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [The Scientist] Editorial

NEW Keystone Symposia: Cancer Stem Cells: Advances in Biology & Clinical Translation
October 13-17, 2019
Hong Kong, China

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NEW Postdoctoral Research Affiliate – Pancreatic Cancer Research (Roswell Park)

NEW Clinical Professor – Diabetes (Univesity of Southern Denmark)

Postdoctoral Researcher – Beta-Cell Regeneration in Zebrafish (Karolinska Institutet)

Postdoctoral Research Fellow – Type 2 Diabetes and Obesity (Harvard Medical School/Boston Children’s Hospital)

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 Position – Diabetes (University of Minnesota)

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

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

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