Pancreatic Cell News Volume 9.35 | Sep 4 2018

TOP STORY

L1CAM Induces Perineural Invasion of Pancreas Cancer Cells by Upregulation of Metalloproteinase Expression

By modeling the neural microenvironment, scientists found that L1 cell adhesion molecule (L1CAM) secreted from schwann cells acts as a strong chemoattractant to cancer cells, through activation of MAP kinase signaling. L1CAM also upregulated expression of metalloproteinase-2 (MMP-2) and MMP-9 by pancreatic ductal adenocarcinoma cells, through STAT3 activation. [Oncogene] Abstract

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DIABETES & PANCREATITIS

Protecting Pax6 3’UTR from MicroRNA-7 Partially Restores PAX6 in Islets from an Aniridia Mouse Model

Researchers showed that miR-7 and miR-375 targeted specific sites within the paired box 6 gene (Pax6) 3’UTR in a mouse pancreatic β-insulinoma cell line. Tough decoys against miR-7 and miR-375 increased expression of a mouse Pax6 3’UTR luciferase reporter and increased PAX6 protein levels in these cells. [Mol Ther Nucleic Acids] Abstract | Full Article | Graphical Abstract

Short-Term High Glucose Culture Potentiates Pancreatic Beta Cell Function

Glucose-stimulated insulin secretion was enhanced in a concentration-dependent manner in high glucose-cultured islets. This was associated with a positive effect on beta cell exocytotic capacity, a lower basal K_ATP conductance and a higher glucose sensitivity to fire action potentials. [Sci Rep] Full Article

Glucose Controls the Expression of Polypyrimidine Tract-Binding Protein 1 via the Insulin Receptor Signaling Pathway in Pancreatic β Cells

Polypyrimidine tract-binding protein 1 (PTBP1) levels in immortalized β cells established from wild-type (WT) mice were higher than levels in β cells established from insulin receptor (IR)-null (βIRKO) mice, and ectopic re-expression of IR-WT in βIRKO cells restored PTBP1 levels. [Mol Cells] Abstract

PANCREATIC CANCER

Nucleus-Targeted, Echogenic Polymersomes for Delivering a Cancer Stemness Inhibitor to Pancreatic Cancer Cells

Investigators prepared polymersomes from the dexamethasone-N3-polyethylene glycol (PEG)-polylactic acid (PLA) conjugate along with a synthesized stimuli-responsive polymer PEG-S-S-PLA. They encapsulated the cancer stemness inhibitor BBI608 in the vesicles and observed that the BBI608 encapsulated polymersomes reduced the viability of the BxPC3 cells to 43% in 3-D spheroid cultures. [Biomacromolecules] Abstract

Human Organoids Share Structural and Genetic Features with Primary Pancreatic Adenocarcinoma Tumors

Primary tumor- and PDX-derived organoids, and 2D cultures for in-depth genomic and histopathological comparisons to the primary tumor were created. Scientists demonstrated that organoids are primarily a clonal population. In drug response assays, organoids displayed patient-specific sensitivities. [Mol Cancer Res] Abstract

Identification and Characterization of TGFBI in Circulating Tumor Cell Subline from Pancreatic Cancer Cell Line

Panc-1-circulating tumor cells (CTCs) expressed transforming growth factor beta-induced (TGFBI), an extracellular matrix protein, more abundantly than did parent cells. Knockdown of TGFBI reduced cell migration and invasion abilities, whereas overexpression of TGFBI increased both abilities. [Cancer Sci] Abstract

Proteome Profiling of Primary Pancreatic Ductal Adenocarcinomas Undergoing Additive Chemoradiation Link ALDH1A1 to Early Local Recurrence and Chemoradiation Resistance

Specific inhibition of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) by A37 in combination with gemcitabine, radiation, and chemoradiation lowered cell viability and augmented cell death in MiaPaCa-2 and Panc 05.04 cells. ALDH1A1 silencing in both cell lines dampened cell proliferation, cell metabolism, and colony formation. [Transl Oncol] Full Article

BH3 Mimetic ABT-199 Enhances the Sensitivity of Gemcitabine in Pancreatic Cancer In Vitro and In Vivo

Gemcitabine decreased the expression of anti-apoptotic protein Mcl-1 but increased the expression of anti-apoptotic protein B cell CLL/lymphoma 2 (Bcl-2). ABT-199 downregulated the gemcitabine-induced production of Bcl-2 and increased the expression of pro-apoptotic protein Bcl-2 interacting protein. [Dig Dis Sci] Abstract

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Role of Biomarker Tests for Diagnosis of Neuroendocrine Tumors

In the past decade, methods for detecting circulating transcripts and tumor cells have been developed to improve the diagnosis of patients with neuroendocrine tumors (NETs). The authors review the latest research on biomarkers in the NET field to provide clinicians with a comprehensive overview of relevant diagnostic biomarkers that can be implemented in dedicated situations. [Nat Rev Endocrinol] Abstract

Immune Mechanisms and Pathways Targeted in Type 1 Diabetes

Investigators review emerging type 1 diabetes (T1D) biomarkers within the context of recent and ongoing T1D immunotherapy trials. They discuss responder/non-responder analyses in an effort to identify therapeutic mechanisms, define actionable pathways, and guide subject selection, drug dosing, and tailored combination drug therapy for future T1D trials. [Curr Diab Rep] Abstract

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

Ossianix and Novo Nordisk Sign Research and Option Agreement on Blood Brain Barrier Delivery Technology for Proteins in Diabetes and other Metabolic Diseases

Ossianix, Inc. announced a research collaboration and option agreement with Novo Nordisk to deliver therapeutic molecules in diabetes and other metabolic diseases across the blood brain barrier to the brain. Under the terms of the agreement, Ossianix will use its patented single domain VNAR antibodies to deliver a predefined number of therapeutic agents of Novo Nordisk. [Ossianix, Inc.] Press Release

$500K Grant Aids Exploration of Genetic Changes in Pancreatic Cancer for New Treatment Targets

A $500,000 grant awarded to Rutgers Cancer Institute of New Jersey surgical oncologist Darren R. Carpizo, MD, PhD, will aid the work of the physician-scientist in examining genetic changes in pancreatic cancer that could lead to new therapeutic targets. [Rutgers, The State University of New Jersey] Press Release

Hemispherx Releases Recently Manufactured Ampligen for Pancreatic Cancer Early Access Program in the Netherlands to Fill Stock Order

Hemispherx Biopharma, Inc. announced that the new Ampligen batch manufactured earlier this year is now released for patients’ use in the pancreatic cancer Early Access Program (EAP) in the Netherlands pursuant to the terms of the agreement with their EAP provider. [Hemispherx Biopharma, Inc.] Press Release

Glytec Receives Two More Patent Allowances for Its Insulin Optimization System

The United States Patent and Trademark Office has awarded Glytec two more patent allowances acknowledging the unique characteristics of its disruptive innovations. The allowances, which comprise a total of 52 claims, describe interactions between Glytec’s solution for insulin titration and multiple current and future-state connected diabetes technologies and health information systems, including devices, apps and other form factors for blood glucose measurement, insulin delivery and patient communication. [Glytec, LLC] Press Release

Radical Open-Access Plan Could Spell End to Journal Subscriptions

Research funders from France, the United Kingdom, the Netherlands and eight other European nations have unveiled a radical open-access initiative that could change the face of science publishing in two years — and which has instantly provoked protest from publishers. [Nature News] Editorial

World Bank Pours Hundreds of Millions into African Science

A World Bank scheme aimed at building grassroots research capacity in Africa will nearly double its budget with a third, and probably final, investment worth at least US$280 million. [Nature News] Editorial

Salk Gender-Discrimination Lawsuit to Go to Trial

Molecular biologist Beverly Emerson’s case against the Salk Institute will go to trial this December, after a judge threw out three of her claims but let one stand. Emerson, now a professor emerita at Salk, says she was for decades denied professional opportunities available to male faculty members at the institute. [The Scientist] Editorial

NEW 5^th National Cancer Institute Pancreatic Cancer Symposium
October 2-3, 2018
Bethesda, Maryland, United States

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

NEW Scientists – Diabetes Research (Qatar Biomedical Research Institute)

Postdoctoral Position – Human Microphysiology Systems of Pancreatic Islets (University of Pittsburgh Drug Discovery Institute)

Caspar Wistar Fellows – Cancer Biology (The Wistar Institute)

Postdoctoral Researcher – Diabetes Research (UC San Diego School of Medicine)

Postdoctoral Associate – Protein-Protein Interactions in Islets (Stanford Burmham Prebys Medical Discovery Institute)

Postdoctoral Associate – Biology of the Pancreas and Diabetes (University of Minnesota)

Assistant/Associate/Full Professor – Diabetes & Neuroscience (Indiana University School of Medicine)

Postdoctoral Position – Beta Cell Research (Helmholtz Zentrum Munchen)

Postdoctoral Positions – Pancretic Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Positions – Immunology of Diabetes (Cochin Institute)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

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