Pancreatic Cell News Volume 7.03 | Jan 26 2016

SerpinB1 Promotes Pancreatic β Cell Proliferation
Using proteomics the authors showed that serpinB1, a protease inhibitor, which is abundant in the hepatocyte secretome and sera derived from liver insulin receptor knockout mice, is the liver-derived secretory protein that regulates β cell proliferation in humans, mice, and zebrafish. [Cell Metab] Abstract | Graphical Abstract

Inhibition of hIAPP Amyloid Aggregation and Pancreatic β-Cell Toxicity by OH-Terminated PAMAM Dendrimer
Scientists showed that generation-3 OH-terminated poly(amidoamine) dendrimer, a polymeric nanoparticle, can effectively halt the aggregation of human islet amyloid polypeptide (hIAPP, or amylin) and shut down hIAPP toxicity in pancreatic MIN6 and NIT-1 cells as well as in mouse islets. [Small] Abstract

Inhibition of the MAP3 Kinase Tpl2 Protects Rodent and Human β-Cells from Apoptosis and Dysfunction Induced by Cytokines and Enhances Anti-Inflammatory Actions of Exendin-4
Scientists demonstrated that tumor progression locus 2 (Tpl2) is expressed in INS-1E β-cells, mouse and human islets, is activated and upregulated by cytokines and mediates ERK1/2, JNK and p38 activation. Tpl2 inhibition protects β-cells, mouse and human islets from cytokine-induced apoptosis and preserves glucose-induced insulin secretion in mouse and human islets exposed to cytokines. [Cell Death Dis] Full Article

PANCREATIC CANCER

Functional Annotation of Rare Gene Aberration Drivers of Pancreatic Cancer
Investigators describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumor driver screens. They apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma. [Nat Commun] Full Article

A Novel Association of Neuropilin-1 and MUC1 in Pancreatic Ductal Adenocarcinoma: Role in Induction of VEGF Signaling and Angiogenesis
Expression of tumor-associated MUC1 (tMUC1) positively correlated with neuropilin-1 levels in human and mouse pancreatic ductal adenocarcinoma (PDA). Further, tMUC1^hi PDA cells secreted high levels of vascular endothelial growth factor (VEGF) and expressed high levels of VEGF receptor 2 (VEGFR2) and its phosphorylated forms as compared with tMUC1^low/null PDA. [Oncogene] Abstract

Metabolic Reprogramming of Pancreatic Cancer Mediated by CDK4/6 Inhibition Elicits Unique Vulnerabilities
CDK4/6 inhibition stimulated glycolytic and oxidative metabolism and was associated with an increase in mTORC1 activity. MTOR and MEK inhibitors potently cooperate with CDK4/6 inhibition in eliciting cell-cycle exit. However, MTOR inhibition fully suppressed metabolism and yielded apoptosis and suppression of tumor growth in xenograft models. [Cell Rep] Full Article | Graphical Abstract | Press Release

β2-Adrenergic Receptor Signaling Promotes Pancreatic Ductal Adenocarcinoma (PDAC) Progression through Activating PCBP2-dependent C-myc Expression
Researchers identified poly(rC)-binding protein 2 (PCBP2) as a novel binding partner for β2-adrenergic receptor (β2-AR) using immunoprecipitation-mass spectrometry (IP-MS) approach. The association between β2-AR and PCBP2 was verified using reciprocal immunoprecipitation. Additionally, they found significant interaction and co-localization of the two proteins in the presence of β2-AR agonist in Panc-1 and Bxpc3 pancreatic ductal adenocarcinoma cells. [Cancer Lett] Abstract

Nimbolide Inhibits Pancreatic Cancer Growth and Metastasis through ROS-Mediated Apoptosis and Inhibition of Epithelial-to-Mesenchymal Transition
Scientists assessed the anticancer properties of nimbolide against pancreatic cancer. Data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells. [Sci Rep] Full Article

Pancreatic Cancer: Current Research and Future Directions
The aim of this review is to describe the latest discoveries and advancements in pancreatic cancer research and to discuss future directions. [Biochim Biophys Acta] Abstract

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

Phase I Trial Data for Cornerstone Pharmaceuticals’ CPI-613 in Combination with Modified Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin (mFOLFIRINOX) in Metastatic Pancreatic Adenocarcinoma to Be Presented at the Annual Gastrointestinal Cancers Symposium
Cornerstone Pharmaceuticals, Inc., announced that data from the Phase I clinical trial evaluating CPI-613 in combination with modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) to treat metastatic pancreatic adenocarcinoma will be presented. [Press release from Cornerstone Pharmaceuticals, Inc discussing research presented at the Annual Gastrointestinal Cancers Symposium, San Francisco] Press Release

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C. Ronald Kahn, M.D., is Awarded the Prestigious Wolf Prize in Medicine for Groundbreaking Research in Insulin Signaling
The Wolf Foundation announced that it has awarded the Wolf Prize in Medicine to C. Ronald Kahn, M.D., Chief Academic Officer and Senior Investigator at Joslin Diabetes Center and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. [Joslin Diabetes Center] Press Release

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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

Post-Doc Fellowship – Computational Analysis Pancreas (Karolinska Institutet)

Post-Doc Fellowship/PhD Studentship – Cancer Metastasis (The University of Helsinki)

Post-Doc Fellowship (The Leibniz Institute for Plasma Science and Technology)

Post-Doc Researcher – Drug Discovery in Cancer/Diabetes (D. E. Shaw Research)

Post-Doc Fellowship – Diabetes Research (Sanford Research/University of South Dakota)

Faculty Position – Biomedical Metabolomics & Metabolism (University of Ottawa)

Post-Doc Researcher – Pancreatic Cancer (The Walter and Eliza Hall Institute of Medical Research)

Visiting Scientist – Diabetes (Danish Diabetes Academy)

Post-Doc Researcher – Type 1 Diabetes (University of Turku)

Post-Doc Researcher – Functional Genomics of Obesity (Inserm)

MD/PhD Researcher – Biomedical Sciences (Hannover Medical School)

PhD Studentship – Cancer Biology (University of Salzburg)

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