Pancreatic Cell News Volume 10.15 | Apr 23 2019

TOP STORY

New Study Targets Achilles’ Heel of Pancreatic Cancer, with Promising Results

Researchers have uncovered the role of a signaling protein that may be the Achilles’ heel of pancreatic cancer. The findings show that pancreatic stellate cells — resident cells typically dormant in normal tissue — become activated and secrete proteins to form a shell around the tumor in an attempt to wall off and contain it. [Press release from Salk Institute discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Lipotoxicity Reduces β Cell Survival through Islet Stellate Cell Activation Regulated by Lipid Metabolism-Related Molecules

Lipotoxicity reduced the expression of lipid metabolism-related molecules in islet stellate cells (ISCs) treated with palmitic acid, especially sterol regulatory element-binding protein (SREBP)-1c. Overexpression of SREBP-1c in ISCs improved islet viability and insulin secretion in co-cultures. [Exp Cell Res] Abstract

Oleic Acid Ameliorates Palmitic Acid-Induced ER Stress and Inflammation Markers in Naive and Cerulein-Treated Exocrine Pancreas Cells

Acute exposure of AR42J and pancreatic acinar cells to different FAs and their combinations increased triglyceride accumulation. Palmitic acid significantly dose-dependently enhanced the unfolded protein response (UPR), immune factors and pancreatic lipase levels, as demonstrated by XBP1 splicing and elevation in UPR transcripts and protein levels. [Biosci Rep] Abstract | Full Article

Baicalein Attenuates Pancreatic Inflammatory Injury through Regulating MAPK, STAT 3 and NF-κB Activation

The therapeutic potential of baicalein and its mechanism were investigated in caerulein-induced acute pancreatitis in vivo and in vitro models. The authors found that baicalein treatment alleviated caerulein-induced pathological damage in the pancreas. [Int Immunopharmacol] Abstract | Graphical Abstract

MicroRNA-181c Inhibits Interleukin-6-Mediated Beta Cell Apoptosis by Targeting TNF-α Expression

Investigators analyzed a microarray with RNA from INS-1 beta cells treated with interleukin-6, and found that TNF-α mRNA was significantly upregulated. Inhibition of TNF-α expression by neutralizing antibodies significantly decreased annexin V staining in cells compared with those treated with a control antibody. [Molecules] Full Article | Graphical Abstract

PANCREATIC CANCER

Intrinsic Apoptosis Shapes the Tumor Spectrum Linked to Inactivation of the Deubiquitinase BAP1

Scientists showed that BAP1 inactivation caused apoptosis in mouse embryonic stem cells, fibroblasts, liver, and pancreatic tissue but not in melanocytes and mesothelial cells. Ubiquitin ligase RNF2, which silenced genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing expression of the prosurvival genes Bcl2 and Mcl1. [Science] Abstract

Disruption of Oncogenic Liver-Intestine Cadherin (CDH17) Drives Apoptotic Pancreatic Cancer Death

In vitro studies demonstrated that impairing CDH17 inhibited cell proliferation, colony formation, and motility by mechanistically modulating pro- and anti-apoptosis events in pancreatic cancer cells, as CDH17 suppression obviously increased expression of Bad, cytochrome C, cleaved caspase 3, and cleaved PARP, and reduced expression of Bcl-2, Survivin, and pAkt. [Cancer Lett] Abstract

Low Molecular Weight Heparin and Direct Oral Anticoagulants Influence Tumor Formation, Growth, Invasion and Vascularization by Separate Mechanisms

WM-266-4 melanoma and AsPC-1 pancreatic cancer cell lines were treated with Tinzaparin and Dalteparin, and Apixaban and Rivaroxaban and the rate of tumor formation, growth and invasion were measured in vitro. Tinzaparin and Daltepain reduced tumor formation and invasion by the cell lines in vitro, but with dissimilar potencies. [Sci Rep] Full Article

MicroRNA-1225 Inhibit Apoptosis of Pancreatic Cancer Cells via Targeting JAK1

The expression of miRNA-1225-5p (miR-1225) was upregulated in 20 human pancreatic cancer (PC) samples from acute myeloid leukemia patients with adverse prognosis and poor responses to therapy as well as in several human PC cell lines, as compared to that in healthy tissues, normal tissues, and normal pancreatic cells. [Cell Cycle] Abstract

Long Non-Coding RNA LINC01207 Silencing Suppresses AGR2 Expression to Facilitate Autophagy and Apoptosis of Pancreatic Cancer Cells by Sponging miR-143-5p

LINC01207 and AGR2 were highly expressed while miR-143-5p was poorly expressed in pancreatic cancer. Functionally, LINC01207 could bind to miR-143-5p, and AGR2 was a target gene of miR-143-5p. Importantly, silencing of LINC01207 up-regulated the expression of AGR2 by down-regulating miR-143-5p. [Mol Cell Endocrinol] Abstract

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Islet Inflammation in Type 2 Diabetes

Investigators provide an overview on the features of islet inflammation in diabetes and models of prediabetes. [Semin Immunopathol] Abstract

Therapeutic Challenges and Current Immunomodulatory Strategies in Targeting the Immunosuppressive Pancreatic Tumor Microenvironment

The authors summarize the evidence and unique properties of the tumor microenvironment in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. [J Exp Clin Cancer Res] Full Article

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

Hua Medicine Initiates First Combination Study of Dorzagliatin with SGLT-2 in the United States

Hua Medicine announced dosing of the first patient in a Phase I drug-drug interaction trial of dorzagliatin in patients with insufficiently controlled type 2 diabetes with metformin, DPP-4 inhibitor, or SGLT2 inhibitor, alone or in combination therapy. [Hua Medicine] Press Release

Orgenesis Announces Collaboration Agreement with Columbia University to Develop Cellular Vaccination Product Platform for Pancreatic, Hepatic and Cholangiocarcinoma Cancers

Orgenesis Inc. announced that it has entered into an agreement with Columbia University, by which it will fund research to develop a cellular vaccination product platform, which it has licensed from Columbia University, for pancreatic, hepatic and cholangiocarcinoma cancers. [Orgenesis, Inc.] Press Release

Gritstone Oncology Announces Clinical Acceleration of “Off-the-Shelf” Personalized Neoantigen Immunotherapy Program (SLATE) Following FDA Feedback

Gritstone Oncology, Inc. announced that following feedback from the FDA the SLATE Phase I clinical study may be accelerated by up to six months from the company’s prior expectations by leveraging pre-clinical data generated for the original GRANITE Investigational New Drug application. [Gritstone Oncology, Inc.] Press Release

Mateon Enters into Merger Agreement with Oncotelic

Mateon Therapeutics, Inc. and Oncotelic Inc. announced that they have entered into a definitive agreement with respect to a merger, creating a publicly traded immuno-oncology company with a robust pipeline of first in class TGF-β immunotherapies for late stage cancers such as gliomas, pancreatic cancer and melanoma. [Mateon Therapeutics, Inc.] Press Release

Harpoon Therapeutics Doses First Patient with a Mesothelin-Targeting T Cell Engager (HPN536) in Phase I/IIa Clinical Trial for Ovarian and Other Solid Tumor Cancers

Harpoon Therapeutics, Inc. announced that the first patient has been dosed with HPN536 in a Phase I/IIa clinical trial initially focused on ovarian cancer. HPN536 targets mesothelin, which is expressed on malignant cells of ovarian and pancreatic carcinoma, mesothelioma, non-small cell lung cancer and breast cancer. [Harpoon Therapeutics, Inc.] Press Release

AngioDynamics’ DIRECT Clinical Study Receives Institutional Review Board Approval for the Treatment of Stage III Pancreatic Cancer

AngioDynamics, Inc. announced that the company received central Institutional Review Board approval to conduct its NanoKnife^® Irreversible Electroporation “Direct IRE Cancer Treatment” clinical study (DIRECT). [AngioDynamics, Inc. (Business Wire, Inc.)] Press Release

Intensity Therapeutics Receives Fast Track Designation from US FDA for Development of INT230-6 as Treatment for Relapsed or Metastatic Triple Negative Breast Cancer

Intensity Therapeutics, Inc. announced that the FDA has granted Fast Track designation to the company’s development program evaluating INT230-6 for the treatment of patients with relapsed or metastatic triple negative breast cancer who have failed at least two prior lines of therapy. [Intensity Therapeutics, Inc.] Press Release

Three Researchers Ousted from MD Anderson

MD Anderson Cancer Center has ousted three researchers for violating granting agency policies, reports The Houston Chronicle. Last year, the National Institutes of Health notified the center of five grantees there who were under investigation, reports the Chronicle. The senior researchers violated confidentiality of peer review and disclosure of connections to foreign countries, specifically China, according to Science. [The Scientist] Editorial

Indian Scientists Launch Preprint Repository to Boost Research Quality

Researchers in India will soon have their own preprint repository where they can post manuscripts from any discipline. The founders of IndiaRxiv hope it will improve the quality of science in the country. [Nature News] Editorial

NEW World Congress on Gastrointestinal Cancer
July 3-6, 2019
Barcelona, Spain

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellowship – Pancreatic Cancer (Oregon Health and Science University)

NEW Postdoctoral Researcher – Exosomes in Atherosclerosis and Cardiovascular Disease (Northern California Institute for Research and Education)

NEW Postdoctoral Fellowship – Regenerative Medicine (Cornell University)

Postdoctoral Research Position – Molecular Biology and Cancer Research (Augusta University)

Postdoctoral Research Affiliate – Pancreatic Cancer Research (Roswell Park)

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)

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

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