Pancreatic Cell News Volume 10.35 | Sep 10 2019

TOP STORY

ITGA5 Inhibition in Pancreatic Stellate Cells Attenuates Desmoplasia and Potentiates Efficacy of Chemotherapy in Pancreatic Cancer

Researchers investigated the therapeutic potential of integrin α5 (ITGA5) receptor in the pancreatic ductal adenocarcinoma (PDAC) stroma. ITGA5 was overexpressed in the tumor stroma from PDAC patient samples, and overexpression was inversely correlated with overall survival. In vitro, knockdown of ITGA5 inhibited differentiation of human pancreatic stellate cells and reduced desmoplasia in vivo. [Sci Adv] Full Article

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

ATF6 Regulates the Development of Chronic Pancreatitis by Inducing p53-Mediated Apoptosis

A humanized serine protease 1 transgenic mouse was established and treated with caerulein to mimic the development of chronic pancreatitis (CP), as evidenced by pathogenic alterations, collagen deposition, and increased expression of the inflammatory factors IL-6, IL-1β, and TNF-α. ATF6, XBP1, and CHOP expression levels were also increased during CP development in this model. Acinar cell apoptosis was also significantly increased, accompanied by upregulated p53 expression. [Cell Death Dis] Full Article

Characterization of Chelator-Mediated Recovery of Pancreatic Islets from Barium-Stabilized Alginate Microcapsules

EDTA, EGTA, and sodium citrate were used to dissolve single-layered Ba²⁺ alginate encapsulated islets and the rate of capsule breakdown calculated from analysis of imaging data. The effect of chelator exposure on islet viability and recovery was assessed using flow cytometry, while glucose-stimulated insulin release assay was used to measure effects on islet function. [Xenotransplantation] Abstract

Dezhou Donkey (Equus asinus) Milk a Potential Treatment Strategy for Type 2 Diabetes

Gastrointestinal digested donkey milk was simulated in vitro and its products of protein digestion were analyzed by SDS-PAGE. Researchers then performed cell viability assay, insulin secretion assay, animal experiments and ELISA assays to study the anti-diabetic effect of donkey milk in vitro and in vivo. [J Ethnopharmacol] Abstract | Graphical Abstract

PANCREATIC CANCER

Identification of Resistance Pathways Specific to Malignancy Using Organoid Models of Pancreatic Cancer

The authors evaluated the expression and activation of receptor tyrosine kinases in response to combined MEK and AKT inhibition in KPC mice and pancreatic ductal organoids. Additionally, they sought to determine the therapeutic efficacy of targeting resistance pathways induced by MEK and AKT inhibition in order to identify malignant-specific vulnerabilities. [Clin Cancer Res] Abstract

Predictive Signatures Inform the Effective Repurposing of Decitabine to Treat K-Ras-Dependent Pancreatic Ductal Adenocarcinoma

Mechanistically, decitabine efficacy was linked to K-RAS-driven dependency on nucleotide metabolism and its ability to specifically impair pyrimidine biosynthesis in K-RAS-dependent tumors cells. Investigators also showed that gene signatures related to K-RAS dependency might be prospectively used to inform on decitabine sensitivity in a selected subset of K-RAS-mutated pancreatic cancer patients. [Cancer Res] Abstract | Full Article

Synergistic Cytotoxicity and Co-Autophagy Inhibition in Pancreatic Tumor Cells and Cancer-Associated Fibroblasts by Dual Functional Peptide-Modified Liposomes

Due to the dense surrounding stroma and the high autophagy in pancreatic cancer, integrin ɑvβ3 targeting, acid environmental sensitive, TR peptide-modified liposomal platforms loaded with combined autophagy inhibiting hydroxychloroquine, and cytotoxic paclitaxel were designed to accomplish the aim of synergistically killing tumor cells while inhibiting stroma fibrosis. The results showed that TR peptide-modified liposomes had superior targeting and penetrating effects both in vitro and in vivo. [Acta Biomater] Full Article | Graphical Abstract

Phlda3 Regulates Beta Cell Survival during Stress

Scientists found that the mRNA levels of pleckstrin homology-like, domain family A, member 3 (Phlda3) were markedly upregulated in vivo in the islets of diabetic humans and mice. In vitro, exposure of MIN6 cells or islets to cytokines, palmitate, thapsigargin or ribose upregulated Phlda3 mRNA and protein levels, concurrent with the induction of endoplasmic reticulum stress and antioxidant genes. [Sci Rep] Full Article

One-Pot Synthesis of Substituted Pyrrole-Imidazole Derivatives with Anticancer Activity

Synthesized pyrrole-imidazole was collected by performing a mild reaction and a simple procedure, which could be applicable to a broad scope of functionalized anilines. The screening results demonstrated that compound 7e exhibited a high potency of anticancer activity in human pancreatic cancer cell lines PANC and ASPC-1. [Mol Divers] Abstract | Graphical Abstract

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Targeting Innate Immune Mediators in Type 1 and Type 2 Diabetes

The authors review recent advances in their understanding of the inflammatory pathogenesis of type 1 and type 2 diabetes from a translational angle and point out the critical gaps in knowledge that need to be addressed to guide drug development. [Nat Rev Immunol] Abstract

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Esperion Announces Positive Top-Line Results from Phase II Study of Bempedoic Acid/Ezetimibe Combination Tablet in Patients with Hypercholesterolemia and Type 2 Diabetes

Esperion announced positive top-line results from the Phase II bempedoic acid/ezetimibe combination tablet study. This was a randomized, double-blind, parallel group study assessing the efficacy and safety of the bempedoic acid/ezetimibe combination tablet compared to ezetimibe and placebo in 179 patients with both hypercholesterolemia and type 2 diabetes. [Esperion Therapeutics, Inc. (GlobeNewswire, Inc.)] Press Release

Fractyl Announces Positive Topline Results in the Revita-2 Clinical Trial in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

Fractyl Laboratories Inc. announced positive topline results from Revita-2, the first randomized, double-blind, sham-controlled, multicenter clinical trial of Fractyl’s Revita™ DMR. Data from patients with type 2 diabetes with and without nonalcoholic fatty liver disease show that Revita DMR, a minimally invasive, outpatient procedural therapy that resurfaces the duodenal mucosa, is safe and effective relative to a sham procedure. [Fractyl Laboratories Inc.] Press Release

Generex Biotechnology Signs Letter of Intent to Acquire 51% in ALTuCELL, Inc. and Their Cellular Therapy Product Altsulin^® with Patented Microencapsulation Technology for the Treatment of Type I Diabetes Mellitis

Generex Biotechnology Corporation announced that the company has signed a binding letter of intent to partner with ALTuCELL. The company’s proprietary and unique technology overcomes the major barriers to transplantation by a novel strategy utilizing patented microencapsulation technology, enabling a transplantable, cell-based therapy that avoids detection and rejection by the immune system. [Generex Biotechnology Corporation] Press Release

Elsevier Investigates Hundreds of Peer Reviewers for Manipulating Citations

The Dutch publisher Elsevier is investigating hundreds of researchers whom it suspects of deliberately manipulating the peer-review process to boost their own citation numbers. [Nature News] Editorial

Frontrunner to Lead FDA, Dogged by Controversies, Has Developed Knack for Confronting Them

Before he interviewed with President Trump to become FDA commissioner, Dr. Stephen Hahn had only been here once in a formal capacity: to apologize to Congress. [STAT News] Editorial

NEW NF-kB, JAK-STAT & MAPK in Health, Disease & Therapy
October 7-11, 2019
Suzhou, China

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NEW Postdoctoral Fellow – Pancreatic Cancer (The University of Alabama at Birmingham)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Position – Pancreatic Ductal Adenocarcinoma (IT University of Copenhagen)

Lab Aide – Pancreatic Cancer Research (Fred Hutchinson Cancer Research Center)

Research Technition – Diabetes, Allergies, and Lung Diseases (Helmholtz Zentrum München)

Postdoctoral Researcher – Auto-Immunity (Benaroya Research Institute)

Postdoctoral Researcher – Endocrinology, Diabetes, and Metabolism (The University of Alabama at Birmingham)

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

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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