Pancreatic Cell News Volume 8.03 | Jan 24 2017

TOP STORY

Genomic Deletion of Malic Enzyme 2 Confers Collateral Lethality in Pancreatic Cancer

The authors sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. They showed that ME3 depletion selectively kills ME2-null pancreatic ductal adenocarcinoma cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Glucagon Receptor Inhibition Normalizes Blood Glucose in Severe Insulin-Resistant Mice

The authors demonstrated that glucagon receptor blockade with monoclonal antibody normalized blood glucose in a mouse model of extreme insulin resistance and hyperglycemia. [Proc Natl Acad Sci USA] Abstract

ATF5 Regulates β-Cell Survival during Stress

Scientists showed that Atf5, a close but less-studied relative of Atf4, is also a target of pancreas/duodenum homeobox protein 1 (PDX1) and is critical for β-cell survival under stress conditions. Pdx1 deficiency led to decreased Atf5 transcript, and primary islet ChIP-sequencing localized PDX1 to the Atf5 promoter, implicating Atf5 as a PDX1 target. [Proc Natl Acad Sci USA] Abstract

PLIN2 is a Key Regulator of the Unfolded Protein Response and Endoplasmic Reticulum Stress Resolution in Pancreatic β Cells

Investigators showed that perilipin 2 (PLIN2) modulates the unfolded protein response and endoplasmic reticulum (ER) stress in pancreatic β cells. PLIN2 expression goes up when β cells are exposed to a lipid load or to chemical ER stress inducers. Downregulation of PLIN2 ameliorates the effects of fatty acid- and chemical-induced ER stress, whereas PLIN2 overexpression exacerbates them. [Sci Rep] Full Article

Loss of Cyclin Dependent Kinase 2 in the Pancreas Links Primary β-Cell Dysfunction to Progressive Depletion of β-Cell Mass and Diabetes

Investigators showed that the cell cycle regulator, cyclin-dependent kinase 2, couples primary β-cell dysfunction to the progressive deterioration of β-cell mass in diabetes. [J Biol Chem] Abstract | Full Article

Osteopontin Affects Insulin Vesicle Localization and Ca²⁺ Homeostasis in Pancreatic Beta Cells from Female Mice

Researchers investigated the role of osteopontin (OPN) in insulin secretion using an OPN knock out mouse model. [PLoS One] Full Article

PANCREATIC CANCER

Tumor-Derived Interleukin 35 Promotes Pancreatic Ductal Adenocarcinoma Cell Extravasation and Metastasis by Inducing ICAM1 Expression

Researchers demonstrated that interleukin 35 (IL-35) is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients.” [Nat Commun] Full Article

Inhibition of Group 1 p21-Activated Kinases Suppresses Pancreatic Stellate Cell Activation and Increases Survival of Mice with Pancreatic Cancer

Investigators examined the role of p21-activated kinase 1 in pancreatic stellate cells (PSCs) and in the interaction of PSCs with pancreatic cancer cells. [Int J Cancer] Abstract

Oncogenic KRAS Targets MUC16/CA125 in Pancreatic Ductal Adenocarcinoma

Scientists demonstrated that high CA125 serum levels and expression levels of MUC16 are predictive of poor prognosis. MUC16 was also validated as a downstream target of KRAS, and their expression strongly correlated with each other in vitro and in vivo. Mechanistically, the KRAS/ERK axis induced upregulation of MUC16 and shedding of CA125 via its effector c-Myc in SW1990 and PANC-1 pancreatic cancer cells. [Mol Cancer Res] Abstract

The G Protein-Coupled Receptor RAI3 Is an Independent Prognostic Factor for Pancreatic Cancer Survival and Regulates Proliferation via STAT3 Phosphorylation

To elucidate the function of GPRC5A (RAI3) overexpression, scientists analyzed siRNA based knock-down and transfected cells using proliferation and migration assays. [PLoS One] Full Article

Beta-Cell Fragility as a Common Underlying Risk Factor in Type 1 and Type 2 Diabetes

There is a growing appreciation that they may share an etiopathological factor, namely the role of variation in beta-cell sensitivity to stress factors. Increased sensitivity increases the risk of beta-cell death or insulin secretion dysfunction. The authors review the beta-cell fragility model that proposes that this variation contributes to the risk of developing either type 1 or type 2 diabetes, in the presence of immunological and/or metabolic stress factors. [Trends Mol Med] Abstract

Therapeutic Potential of Curcumin in Treatment of Pancreatic Cancer: Current Status and Future Perspectives

Investigators summarize the current knowledge about possible molecular mechanisms of curcumin in pancreatic ductal adenocarcinoma with particular emphasis on preclinical/clinical studies in pancreatic cancer treatment. [J Cell Biochem] Abstract

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

ARMO BioSciences Presents New Phase Ib Clinical Data for AM0010 in Advanced Pancreatic Cancer Patients

ARMO BioSciences, Inc. presented new Phase Ib clinical data on the company’s lead investigational immuno-oncology drug AM0010. In the Phase Ib clinical trial, 21 patients with advanced pancreatic cancer were treated with AM0010 in combination with FOLFOX. [Press release from ARMO BioSciences, Inc. discussing research presented at the 2017 Gastrointestinal Cancers Symposium, San Francisco] Press Release

Pamrevlumab Pancreatic Cancer Clinical Data

FibroGen, Inc. announced that updated results from an ongoing clinical study of pamrevlumab in combination with standard-of-care chemotherapy in patients with locally advanced pancreatic ductal adenocarcinoma. [Press release from FibroGen, Inc. American Society of Clinical Oncology (ASCO) 2017 Gastrointestinal Cancers Symposium] Press Release

2017 Sees Five New UK Projects for Pancreatic Cancer Research

Five research projects with potential to make a real difference to tackling pancreatic cancer have been awarded grants by the national charity Pancreatic Cancer Research Fund, worth over £800k in total. [Pancreatic Cancer Research Fund] Press Release

ProtoKinetix Announces Investigator Sponsored Human Clinical Trial Application Using AAGP™ Has Been Approved by Health Canada

ProtoKinetix, Incorporated announced that the Governors of the University of Alberta have received a “No Objection Letter” from Health Canada to its Clinical Trial Application entitled: “Clinical Study using Antiaging Glycopeptide (PKX-001) in Islet Transplantation”. This authorization will allow the clinical trial group to enroll patients into the study. The study will test the effects of using PKX-001 on islet cells treated prior to transplantation into human test subjects as an addition to the already established Edmonton Protocol for the treatment of Type 1 Diabetes. [Protokinetix Inc. (Business Wire, Inc.)] Press Release

Caris Life Sciences and the Lustgarten Foundation Collaborate to Support Immunotherapy Clinical Trial for Pancreatic Cancer

Caris Life Sciences and the Lustgarten Foundation are collaborating to support a clinical trial evaluating the impact of immunotherapy in the treatment of pancreatic cancer. Caris is providing clinical trial enrollment services to identify potential trial candidates based on biomarker expression results and facilitate communication between treating physicians and study investigators. [Caris Life Sciences] Press Release

Enteris, Sanofi to Develop Oral Therapeutic for Type 2 Diabetes

Enteris BioPharma, Inc. announced the initiation of a feasibility study agreement with Sanofi to leverage Enteris’ proprietary and patented oral peptide and small molecule delivery platform, Peptelligence™, to develop an oral formulation of one of Sanofi’s preclinical stage peptides. [Enteris BioPharma, Inc.] Press Release

Biotech Firm Backs Controversial CRISPR Challenger

A major enzyme manufacturer has signed an agreement with a Chinese university to explore uses for a protein claimed to be a powerful alternative to the popular genome-editing tool CRISPR–Cas9. Several scientists have failed to reproduce the results of the paper that first made the claim and doubt that the protein, NgAgo, works as a gene editor. [Nature News] Editorial

Scientists Join Massive Protest against Trump

The women in white lab coats didn’t expect to be treated like celebrities. The group of scientists, dozens strong, came to Washington DC to join the Women’s March, a massive protest against the brand-new US President, Donald Trump. But as they navigated the dense crowd near the National Air and Space Museum, the researchers were greeted by shouts of “We love science!” Eager strangers asked the scientists to pose for photographs with the signs they carried, which bore slogans such as “Stand up 4 Science” and “Science does not discriminate.” [Nature News] Editorial

Wanted: A Leader for the Toughest Job in Global Health

Global health watchers will pay close attention to Geneva, Switzerland when the World Health Organization (WHO) will announce the final three candidates to take the agency’s top job. The decision by WHO’s Executive Board, made up of representatives of 34 member states, follows months of behind-the-scenes jockeying, campaigning by the candidates, and intense speculation. It will be followed in May by a final vote by WHO’s 194 member states. [ScienceInsider] Editorial

NEW Gordon Research Conference – Pancreatic Diseases
June 18-23, 2017
Waterville Valley, United States

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

NEW Postdoctoral Fellow – Pancreatic Beta Cell Biology and Regeneration (Icahn School of Medicine at Mount Sinai)

NEW Postdoctoral Associate – Pancreatic Cancer (University of Miami)

Senior Scientist – Pancreatic Cell Research (STEMCELL Technologies Inc.)

Research Scientist – Protein Misfolding and Toxicity (The George Washington University)

Postdoctoral Research Scientist – Diabetes and Inflammation (Two Positions)

Postdoctoral Research Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Oncogenic Signaling Pathways of Colorectal/Pancreatic Cancer (German Cancer Research Center)

Postdoctoral Position – Pancreatic Cancer (University of Liege)

Scientist – Insulin Secretion (Helmholtz Association)

Postdoctoral Researcher – Genome Regulation and Diabetes (August Pi i Sunyer Biomedical Research Institute)

Principle Scientist – Translational Development (Celgene Corporation)

Assistant Professor – Molecular Therapeutics (Dartmouth College/Geisel School of Medicine)

Vice President – Pancreatic Cancer Disease Lead (Celgene Corporation)

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