Pancreatic Cell News Volume 7.22 | Jun 7 2016

TOP STORY

Novel Imaging Model Helps Reveal New Therapeutic Target for Pancreatic Cancer

Pancreatic ductal adenocarcinoma, the most common of pancreatic cancers, is extraordinarily lethal, with a 5-year survival rate of just 6 percent. Chemotherapy treatments are poorly effective, in part due to a high degree of drug-resistance to currently used regimens. Researchers describe an innovative new model that not only allowed them to track drug resistance in vivo, but also revealed a new therapeutic target, which early testing suggests could provide a strategy to arrest pancreatic cancer growth. [Press release from the University of California at San Diego discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

The MDM2–p53–Pyruvate Carboxylase Signaling Axis Couples Mitochondrial Metabolism to Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells

Scientists showed that the activation of p53 in β-cells, by genetic deletion or pharmacological inhibition of its negative regulator MDM2, impairs glucose-stimulated insulin secretion, leading to glucose intolerance in mice. [Nat Commun] Full Article

Developmental Programming of Polycystic Ovary Syndrome: Prenatal Androgens Establish Pancreatic Islet α/β Cell Ratio and Subsequent Insulin Secretion

Via ultrasound guidance researchers applied steroids directly to ovine fetuses at day (d)62 and d82 of gestation, and examined fetal and postnatal pancreatic structure and function. Of three classes of steroid agonists applied, only androgens caused altered pancreatic development. [Sci Rep] Full Article

Deteriorated High-Fat Diet-Induced Diabetes Caused by Pancreatic β-Cell-Specific Overexpression of Reg3β Gene in Mice

In their previous study, the authors reported that Reg3β overexpression did not increase islet growth but prevented streptozotocin-induced islet damage by inducing specific genes. In order to explore its role in type 2 diabetes, they established high-fat diet-induced obesity and diabetes in RIP-I/Reg3β mice. [Endocrine] Abstract

Mechanisms of Doxorubicin Toxicity in Pancreatic β-Cells

Using the rat β-cell line INS-1 832/13 and isolated mouse pancreatic islets, researchers investigated the effect of the chemotherapeutic drug doxorubicin on pancreatic β-cell survival and function. [Toxicol Sci] Abstract

PANCREATIC CANCER

CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma

Researchers showed that CXCR2 signaling in the myeloid compartment can promote pancreatic tumorigenesis and is required for pancreatic cancer metastasis, making it an excellent therapeutic target. [Cancer Cell] Full Article | Graphical Abstract

Ex Vivo Testing of Patient-Derived Xenografts Mirrors the Clinical Outcome of Patients with Pancreatic Ductal Adenocarcinoma

Translation of the pancreatic ductal adenocarcinoma model into a method for practical personalized cancer treatment is prevented by the intense resources and time necessary to generate and test each tumorgraft. The authors aimed to develop a high-throughput ex vivo drug testing approach that can be used for personalized cancer treatment design. [Clin Cancer Res] Abstract

Resolution of Novel Pancreatic Ductal Adenocarcinoma Subtypes by Global Phosphotyrosine Profiling

Investigators used immunoaffinity-coupled high-resolution mass spectrometry to characterize global tyrosine phosphorylation patterns across two large panels of human pancreatic ductal adenocarcinoma cell lines: the ATCC series and TKCC series. [Mol Cell Proteomics] Abstract | Full Article

Hexokinase 2 Promotes Tumor Growth and Metastasis by Regulating Lactate Production in Pancreatic Cancer

Stable knockdown of hexokinase 2 (HK2) decreased primary tumor growth in cell line xenografts and decreased incidence of lung metastasis after tail vein injection. Gene expression analysis of tumors with decreased HK2 expression showed alterations in VEGF-A signaling, a pathway important for angiogenesis and metastasis, consistent with a requirement of HK2 in promoting metastasis. [Oncotarget] Full Article

Continuous Exposure of Pancreatic Cancer Cells to Dietary Bioactive Agents Does Not Induce Drug Resistance unlike Chemotherapy

The repeated treatment of cancer cells with chemo- or radiotherapy induces therapy resistance, but it was previously unknown whether the same effect occurs upon continuous exposure of cancer cells to diet-derived chemopreventive agents. Scientists elucidated this interesting question in pancreatic ductal adenocarcinoma, which is a highly aggressive cancer entity with a marked resistance toward gemcitabine and other cytotoxic drugs. [Cell Death Dis] Full Article

Closing In On Mass Production of Mature Human Beta Cells

Human pluripotent stem cell differentiation protocols based on mimicking developmental pathways are getting close to generating fully fledged pancreatic endocrine cells, including insulin-producing beta cells. However, challenges remain in identifying pathways to trigger the attainment of robust glucose responsiveness that occurs postnatally in beta cells. [Cell Stem Cell] Full Article

Towards a New Classification of Gastroenteropancreatic Neuroendocrine Neoplasms

Researchers’ molecular understanding of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains insufficient to inform on patient prognosis or selection for treatments, and the WHO classification continues to form the basis for management of this disease. Nevertheless, their increasing understanding of the molecular genetics and biology of GEP-NENs has begun to expose flaws in the WHO classification. [Nat Rev Clin Oncol] Abstract

MicroRNA in Pancreatic Cancer

The authors summarize the microRNA (miRNA) profiles of normal pancreatic tissue and cancer tissue of patients with pancreatic ductal adenocarcinoma (PDAC) and characterize the expression of miRNAs associated with tumor progression. Further, they highlight the target genes and signaling pathways of miRNAs that are aberrantly expressed in PDACs. [J Hum Genet] Abstract

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

Janssen Expands Body of Evidence for INVOKANA^® (Canagliflozin) with 18 New Data Presentations

Janssen Research & Development, LLC announced that 18 presentations on INVOKANA^® will be featured. [Press release from Janssen Research & Development, LLC discussing research to be presented at the 2016 American Diabetes Association’s 76^th Scientific Sessions, New Orleans] Press Release

Halozyme Presents Stage One Efficacy and Safety Analysis of Phase II Clinical Study in Metastatic Pancreatic Cancer Patients Treated with PEGPH20

Halozyme Therapeutics, Inc. announced results from a final analysis of 135 metastatic pancreatic cancer patients who were treated in Stage One of HALO 109-202, a Phase II clinical study of its investigational new drug PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine as compared to ABRAXANE and gemcitabine alone. [Halozyme Therapeutics, Inc.] Press Release

MabVax Therapeutics Expands Patient Enrollment in Phase I Trial for Treatment of Pancreatic Cancer to Memorial Sloan Kettering Cancer Center

MabVax Therapeutics Holdings, Inc. announces the initiation of patient enrollment at Memorial Sloan Kettering Cancer Center in the Phase I clinical trial evaluating its leading clinical development product MVT-5873 (HuMab-5B1) as a therapeutic treatment for patients with locally advanced or metastatic adenocarcinoma of the pancreas or other CA19-9 positive malignancies. [MabVax Therapeutics Holdings, Inc.] Press Release

NEW 7^th International Conference on Stem Cells and Cancer (ICSCC-2016): Proliferation, Differentiation and Apoptosis
October 21-23, 2016
Goa, India

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

NEW Postdoctoral Fellow – Cell Processes in Pancreatic Cells (University of Copenhagen)

Postdoctoral Researcher (Katholieke Universiteit Leuven)

Postdoctoral Researcher – Pathophysiology of Adipose Tissue in Obesity and Type 2 Diabetes (Università degli Studi di Bari Aldo Moro)

PhD Studentship – Molecular and Translational Aspects of Pancreatic Cancer (German Cancer Research Center)

Research Associate – Pancreatic Cancer Pharmacology (University of Cambridge)

Postdoctoral Fellow – Quantitative Hepato-Pancreatic MR Imaging (Inserm)

Postdoctoral Fellow – Diabetes Mellitus and Metabolic Syndrome (Northwestern University)

Associate Senior Lecturer – Medical Cell Biology or Physiology (Uppsala University)

Postdoctoral Fellow – Type 2 Diabetes and Insulin Resistance (King Abdullah University of Science and Technology)

PhD Studentship – Type 2 Diabetes and Insulin Resistance (King Abdullah University of Science and Technology)

Postdoctoral Fellow(s) – Pancreatic Islet Biology (Vanderbilt University Medical Center)

Postdoctoral Fellow – Somatic Stem Cell Biology of Liver/Pancreas (The Swiss Federal Institute of Technology in Zurich)

Postdoctoral Fellow – Pancreas Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Diabetic Peripheral Neuropathy (University of North Dakota)

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