Pancreatic Cell News Volume 9.32 | Aug 14 2018

TOP STORY

PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism

PINK1-PARK2 pathway-mediated degradation of SLC25A37 and SLC25A28 increased mitochondrial iron accumulation, which led to the HIF1A-dependent Warburg effect and AIM2-dependent inflammasome activation in tumor cells. AIM2-mediated HMGB1 release further induced expression of CD274/PD-L1. [Dev Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Toll-Like Receptor 9 Negatively Regulates Pancreatic Islet Beta Cell Growth and Function in a Mouse Model of Type 1 Diabetes

Toll-like receptor 9 deficiency promoted pancreatic islet development and beta cell differentiation, leading to enhanced glucose tolerance, improved insulin sensitivity and enhanced first-phase insulin secretory response. This was, in part, mediated by upregulation of CD140a. [Diabetologia] Full Article

c-Src Regulates Cargo Transit via the Golgi in Pancreatic Acinar Cells

Stimulation of zymogen granule formation with dexamethasone activated Src and increased the Golgi area in acinar cells. While other Src family members had no effect on the Golgi markers P115 and GM130, active c-Src increased the Golgi area these stained, extending them into the ER. [Sci Rep] Full Article

Sirtuin 5 Overexpression Attenuates Glucolipotoxicity-Induced Pancreatic β Cells Apoptosis and Dysfunction

Chronic exposure to excess palmitate and glucose (High-PA-G) induced apoptosis and suppressed glucose-stimulated insulin secretion in β cells. SIRT5 overexpression significantly alleviated apoptosis under the High-PA-G condition, accompanied by suppressed caspase 3 activity and reduced malondialdehyde levels. [Exp Cell Res] Abstract

PANCREATIC CANCER

siRNA Knockdown of RRM2 Effectively Suppressed Pancreatic Tumor Growth Alone or Synergistically with Doxorubicin

Transfection of siRRM2 into PANC-1 dramatically repressed the formation of cell colonies by inducing cell cycle arrest at S-phase. When combined with doxorubicin (DOX), siRRM2 improved the efficacy 4 times than applying DOX alone, suggesting a well synergistic effect of siRRM2 and DOX. [Mol Ther Nucleic Acids] Full Article

Multicellular Spheroid Based on a Triple Co-Culture: A Novel 3D Model to Mimic Pancreatic Tumor Complexity

Researchers describe the conception and the characterization of a novel 3D tumor model, consisting of a triple co-culture of pancreatic cancer cells, fibroblasts and endothelial cells, which assembled to form a hetero-type multicellular tumor spheroid. They revealed the presence of a core rich in fibroblasts and fibronectin in which endothelial cells were homogeneously distributed. [Acta Biomater] Abstract | Graphical Abstract

iRGD-Guided Tumor-Penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer

Investigators showed that tumor-penetrating nanocomplexes effectively knockdown siRNA targets in pancreatic ductal adenocarcinoma (PDAC) cell lines and in an immunocompetent genetically-engineered mouse model of PDAC. They validated the tumor-penetrating ability in three-dimensional organoids and autochthonous tumors. [Mol Cancer Ther] Abstract

Gemcitabine Treatment Promotes Immunosuppressive Microenvironment in Pancreatic Tumors by Supporting the Infiltration, Growth, and Polarization of Macrophages

Cytokine profiling of gemcitabine-treated pancreatic cancer (PC) cells identified IL-8 as the most differentially-expressed cytokine. Incubation of gemcitabine-treated PC cells with IL-8 neutralizing antibody diminished its ability to induce growth, migration and invasion of RAW264.7 macrophages, but did not abrogate their M2 polarization. [Sci Rep] Full Article

Multi-Scale Network Model Supported by Proteomics for Analysis of Combined Gemcitabine and Birinapant Effects in Pancreatic Cancer Cells

A multiscale network model was developed to link the signaling pathways of cell cycle regulation, DNA damage response, DNA repair, apoptosis, nuclear factor-kappa β, and mitogen-activated protein kinase-p38 to cell cycle progression, proliferation, and death. [CPT Pharmacometrics Syst Pharmacol] Abstract | Full Article

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Metabolites as Regulators of Insulin Sensitivity and Metabolism

The authors discuss the emerging roles of metabolites in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM). A comprehensive understanding of the metabolic adaptations involved in insulin resistance may enable the identification of novel targets for improving insulin sensitivity and preventing, and treating, T2DM. [Nat Rev Mol Cell Biol] Abstract

Pancreatic Cancer Circulating Tumor Cells: Applications for Personalized Oncology

Investigators describe the use of circulating tumor cells (CTCs) in pancreatic cancer (PC), including isolation methods, the significance of CTC enumeration, and studies examining phenotypic and molecular characteristics of CTCs. They speculate on future directions for PC CTC research such as single-cell analysis and CTC culture. [Expert Rev Mol Diagn] Abstract

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

Icahn Institute Partners in $6.5 Million NIH Award to Advance Precision Medicine and Bioengineering Capabilities

The National Institutes of Health (NIH) have awarded $6.5 million to a consortium that includes the Icahn Institute for Genomics and Multiscale Biology at the Icahn School of Medicine at Mount Sinai, the University of Washington, the University of Connecticut, and the University of Auckland, New Zealand, to establish the Center for Reproducible Biomedical Modeling. [Icahn School of Medicine at Mount Sinai] Press Release

GI Dynamics Announces FDA Approval for EndoBarrier Pivotal Trial

GI Dynamics Inc. announced it has received approval of an investigational device exemption from the U.S. FDA to begin enrollment in a pivotal trial evaluating the safety and efficacy of EndoBarrier in the United States pending Institutional Review Board approval. [GI Dynamics] Press Release

Prometic Receives Rare Pediatric Disease Designation from U.S. FDA for Small Molecule Drug Candidate PBI-4050

Prometic Life Sciences Inc. announced that the U.S. FDA has granted a Rare Pediatric Disease Designation to its small molecule drug candidate, PBI-4050, for the treatment of Alström syndrome. [Prometic Life Sciences Inc.] Press Release

To Lower State Drug Costs, the National Governors Association Is Promoting Several Ideas

As cash-strapped states across America struggle with their drug spending, the National Governors Association has suggested several ways to address the problem, from bulk purchasing and alternative payment plans to the use of metrics for assessing the value of medicines. [STAT News] Editorial

Survey of U.S. Government Scientists Finds Range of Attitudes toward Trump Policies

It’s widely assumed that many U.S. government scientists disagree with President Donald Trump on several of his controversial science appointments, his proposed deep cuts to research, and a spate of executive actions aimed at overturning current government policies to combat climate change. Some have publicly voiced their concerns. But what do the rank-and-file really think of working for this president? [ScienceInsider] Editorial

US Congress Leaves Science Agencies Hanging — Again

Lawmakers in the US Congress are running out of time to pass a budget for the 2019 fiscal year, and have yet to resolve major disagreements over climate-change and environment programs. [Nature News] Editorial

India Cracks Down on Plagiarism at Universities

India has for the first time introduced regulations to detect and punish acts of plagiarism at universities. Punishments for researchers or students caught breaking the rules range from requiring that a manuscript be withdrawn to sacking or expulsion, depending on the extent of the plagiarism. [Nature News] Editorial

Embattled French Health-Agency Chief Withdraws Leadership Bid

The chief of France’s national biomedical-research agency INSERM has said that he will not run for a second term, a decision that ends months of uncertainty about his future at the organization. [Nature News] Editorial

NEW 2018 National Cancer Research Institute (NCRI) Cancer Conference
November 4-6, 2018
Glasgow, United Kingdom

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

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

NEW 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)

Lecturer/ Professor/ Clinical Academic – Diabetes (University of Exeter)

Postdoctoral Research Fellow – Drivers of Pancreatic Cancer Metastasis (The Moffitt Cancer Center)

Postdoctoral Associate – Type 1 Diabetes Research (University of Florida)

Postdoctoral Positions – Immunology of Diabetes (Cochin Institute)

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

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