Pancreatic Cell News Volume 9.13 | Apr 3 2018

TOP STORY

Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer

Pancreatic ribonuclease (RNase) is a secreted enzyme critical for host defense. Investigators discovered an intrinsic RNase function, serving as a ligand for epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase, in pancreatic ductal adenocarcinoma. [Cancer Cell] Abstract | Graphical Abstract

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DIABETES & PANCREATITIS

Establishment of Human Pluripotent Stem Cell-Derived Pancreatic β-Like Cells in the Mouse Pancreas

Scientists generated xenogeneic human pancreatic β-like cells in the mouse pancreas by orthotopic transplantation of stem cell-derived β-like cells into the pancreas of neonatal mice. [Proc Natl Acad Sci USA] Abstract

The Resident Macrophages in Murine Pancreatic Islets Are Constantly Probing Their Local Environment, Capturing Beta Cell Granules and Blood Particles

Researchers studied the interactions between the resident macrophages of pancreatic islets with beta cells and the blood vasculature. They also examined the immunological consequences of such interactions. [Diabetologia] Full Article

Vitamin A-Coupled Liposomes Carrying TLR4-Silencing shRNA Induce Apoptosis of Pancreatic Stellate Cells and Resolution of Pancreatic Fibrosis

Pancreatic stellate cells (PSCs) can be activated by Toll-like receptor 4 (TLR4) responses to its ligands and they contribute to the formation of pancreatic fibrosis. To ensure the efficient delivery of RNAi therapeutic agents to PSCs, vitamin A-coupled liposomes were used as drug carriers to deliver plasmids expressing TLR4-specific short hairpin RNA (shRNA) to treat pancreatic fibrosis. [J Mol Med (Berl)] Abstract

Culturing Functional Pancreatic Islets on α5-Laminins and Curative Transplantation to Diabetic Mice

The authors developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1–3 cells in thickness and remained normoxic and functional for at least 7 days in culture. [Matrix Biol] Abstract

PANCREATIC CANCER

Immune Cell Production of Interleukin 17 Induces Stem Cell Features of Pancreatic Intraepithelial Neoplasia Cells

In studies of mouse and human pancreatic tumors and precursors, investigators found immune cell-derived interleukin 17 (IL17) to regulate development of tuft cells and stem cell features of pancreatic cancer cells via increased expression of doublecortin like kinase 1, POU class 2 homeobox 3, ALDH1A1, and IL17 receptor C. [Gastroenterology] Abstract

Targeting Galectin-1 Inhibits Pancreatic Cancer Progression by Modulating Tumor-Stroma Crosstalk

Scientists identified galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in pancreatic ductal adenocarcinoma stroma, as a major driver of pancreatic cancer progression. In vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted human pancreatic stellate cell lead to impaired tumor formation and metastasis in mice. [Proc Natl Acad Sci USA] Abstract

SMAD4 Gene Mutation Renders Pancreatic Cancer Resistance to Radiotherapy through Promotion of Autophagy

The authors investigated the role of SMAD4 deficiency in pancreatic cancer cells’ response to radiotherapy. SMAD4-depleted pancreatic cancer cells were more resistant to radiotherapy based on clonogenic survival assay. [Clin Cancer Res] Abstract

Basement Membrane Destruction by Pancreatic Stellate Cells Leads to Local Invasion in Pancreatic Ductal Adenocarcinoma

Researchers elucidated the mechanism of stromal invasion of pancreatic ductal adenocarcinoma (PDAC), using organoids. From resected PDAC specimens, they established human PDAC organoids, which developed ductal and basement membrane structures. [Cancer Lett] Abstract

Tetrandrine Inhibits Deregulated Cell Cycle in Pancreatic Cancer Cells: Differential Regulation of p21^Cip1/Waf1, p27^Kip1 and Cyclin D1

Investigators showed that tetrandrine (TET) inhibits proliferation of the pancreatic cancer (PaCa) cells and inhibits PaCa tumor growth. TET increased levels of p21^Cip1/Waf1 and p27^Kip1, had no effect on the levels of CDK4/6 proteins and decreased the levels of cyclin D1 and pRb proteins. [Cancer Lett] Abstract | Graphical Abstract

Development of Primary Human Pancreatic Cancer Organoids, Matched Stromal and Immune Cells and 3D Tumor Microenvironment Models

Scientists developed and characterized pancreatic cancer organoids and multi-cell type organotypic co-culture models to demonstrate their applicability to the study of pancreatic cancer. [BMC Cancer] Full Article

Immunotherapy for Pancreatic Cancer: A Long and Hopeful Journey

The authors describe the roles of immune cells and the immunosuppressive microenvironment in the development of pancreatic cancer, as well as the preclinical and clinical outcomes and benefits and considerations of recent passive and active immunotherapeutic approaches. [Cancer Lett] Abstract

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ARMO BioSciences Announces Positive Outcome of First Interim Analysis in SEQUOIA Phase III Pancreatic Cancer Study

ARMO BioSciences, Inc. announced the completion of the first interim analysis in its Phase III SEQUOIA study in patients with pancreatic cancer. [ARMO BioSciences, Inc.] Press Release

Tyme Announces First Site Open for Its Phase II Trial with SM-88 in Pancreatic Cancer

Tyme Technologies, Inc. announced that the first site for the Phase II clinical trial evaluating SM-88 therapy for metastatic pancreatic cancer is open and additional clinical sites are scheduled to open within the coming weeks. [Tyme Technologies, Inc.] Press Release

ActoBio Therapeutics Greenlighted by FDA to Commence a Phase Ib/IIa Trial with AG019 for the Treatment of Early Onset Type 1 Diabetes

ActoBio Therapeutics, a wholly owned subsidiary of Intrexon Corporation, has been granted allowance by the FDA for their Investigational New Drug application to initiate a Phase Ib/IIa study for the treatment of early onset type 1 diabetes (T1D) with AG019, an innovative disease-modifying approach to induce immune tolerance in T1D. [Intrexon Corporation] Press Release

CTSA Grant Renewal Totals $21 Million

University of Iowa leaders announced the renewal of a $21 million grant of a Clinical and Translational Science Award (CTSA) from the National Center for Advancing Translational Sciences at the National Institutes of Health. [University of Iowa Carver College of Medicine] Press Release

French Universities Cancel Subscriptions to Springer Journals

French research organizations and universities have canceled their subscriptions to Springer journals, due to an impasse in fee negotiations between the publisher and Couperin.org, a national consortium representing more than 250 academic institutions in France. [The Scientist] Editorial

EU Copyright Reforms Draw Fire from Scientists

An influential committee of the European Parliament is due to vote on changes to copyright regulations in the European Union (EU), but the latest drafts of the rules have triggered a wave of criticism from open-science advocates. They say that the proposals will stifle research and scholarly communication. [Nature News] Editorial

Cancer Researcher at the Ohio State University Resigns following Multiple Misconduct Findings

A cancer researcher has resigned from The Ohio State University in Columbus after the institution determined he had committed misconduct in eight papers. His work in designing anticancer compounds had led to millions of dollars in funding and multiple patents, as well as two compounds in clinical trials. [ScienceInsider] Editorial

Cancer Researchers Push to Relax Rules for Clinical Trials

US government examines whether criteria for participating in drug studies unnecessarily exclude some people. [Nature News] Editorial

In Emotional Speech, CDC’s New Leader Vows to Uphold Science

Robert Redfield Jr., the new director of the Centers for Disease Control and Prevention (CDC), gave a deeply personal agency-wide address in which he repeatedly underscored the importance of science and data and said the CDC’s most critical public health mission is to protect Americans “from that which we don’t expect”. [The Washington Post] Editorial

NEW Cold Spring Harbor (CSH): Mechanisms & Models of Cancer
August 14-18, 2018
Cold Spring Harbor, New York, United States

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

NEW Research Fellow/Associate – Diabetes Research (Rutgers University)

NEW Postdoctoral Position – Pancreatic Cancer (Fox Chase Cancer Center)

Postdoctoral Scholar – Cancer (University of California, San Francisco)

Postdoctoral Position – Protein Biochemistry (Vlaams Instituut voor Biotechnologie)

Postdoctoal Fellow – Pancreatic Cell (Inserm)

Postdoctoral Fellow – Diabetes and Pancreatic Islet Biology (Vanderbilt University)

Postdoctoral Scientist – Epigenetic Mechanisms (Geneva University)

Postdoctoral Fellow – Epigenetic Regulation of Pancreatic Beta-Cell Mass (City of Hope)

Postdoctoral Positions – Pancreatic Cancer Cells (Fox Chase Cancer Center)

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