Volume 5.07 | Feb 25

Pancreatic Cell News 5.07 February 25, 2014
Pancreatic Cell News
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Building a Better Mouse (Model) to Study Pancreatic Cancer
Cancer of the pancreas is usually not detected until it’s too late to cure. But precursor lesions that form in the pancreas and its ducts can signal the disease before it strikes, and when caught early enough, they can be prevented from progressing to become cancer. In a new study, researchers report two breakthroughs in understanding those lesions and their role in pancreatic cancer. [Press release from University of Utah Health Care discussing online prepublication in Nature Cell Biology] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Role of the SIK2-p35-PJA2 Complex in Pancreatic ß-Cell Functional Compensation
Researchers delineate a complex consisting of the AMP-activated protein kinase-related kinase SIK2, the CDK5 activator CDK5R1 and the E3 ligase PJA2 essential for ß-cell functional compensation. [Nat Cell Biol] Abstract

Islet Microenvironment, Modulated by Vascular Endothelial Growth Factor-A Signaling, Promotes ß Cell Regeneration
Researchers transiently increased vascular endothelial growth factor-A (VEGF-A) production by ß cells. VEGF-A induction dramatically increased the number of intra-islet endothelial cell but led to ß cell loss. [Cell Metab] Abstract | Graphical Abstract

Syntaxin 4 Upregulation Increases Efficiency of Insulin Release in Pancreatic Islets from Humans with and without Type 2 Diabetes Mellitus
Human islets from type 2 diabetic and healthy individuals transduced to over-express Syntaxin 4 were examined by perifusion analysis. Streptozotocin-induced diabetic recipient mice transplanted with Syntaxin 4-enriched or normal islets were assessed for rescue of diabetes in vivo. [J Clin Endocrinol Metab] Abstract

IGF-I Stimulates CCN5/WISP2 Gene Expression in Pancreatic ß-Cells, which Promotes Cell Proliferation and Survival against Streptozotocin
To define the role of CCN5 in islet cell biology, scientists stably overexpressed its cDNA in insulinoma MIN6 cells and detected a two-fold increase in the proliferation of MIN6-CCN5 compared to control cells that correlated with significant elevations in the levels of cyclin D1 and the phosphorylation of Akt and Erk2. [Endocrinology] Abstract

High Oxygen Condition Facilitates the Differentiation of Mouse and Human Pluripotent Stem Cells into Pancreatic Progenitors and Insulin-Producing Cells
Researchers tried to establish an effective method for the differentiation of induced pluripotent stem cells into insulin-producing cells by culturing under high oxygen (O2) conditions. They found that a high O2 condition repressed Notch-dependent gene Hes1 expression and increased Ngn3 expression at the stage of pancreatic progenitors. [J Biol Chem] Abstract | Full Article

Calcium Co-Regulates Oxidative Metabolism and ATP-Synthase Dependent Respiration in Pancreatic Beta-Cells
Investigators have studied glucose-induced calcium signaling and energy metabolism, in INS-1E insulinoma cells and human islet beta-cells. [J Biol Chem] Abstract | Full Article

Silencing of the Fibroblast Growth Factor 21 Gene Is an Underlying Cause of Acinar Cell Injury in Mice Lacking MIST1
Researchers examined the regulation and function of fibroblast growth factor 21 in acinar cell injury, specifically in a mouse model of pancreatic injury (Mist1-/-). Mist1-/- mice exhibit acinar cell disorganization, decreased acinar cell communication and exocytosis, and increased sensitivity to cerulein-induced pancreatitis. [Am J Physiol Endocrinol Metab] Abstract


Analysis of the Tumor-Initiating and Metastatic Capacity of PDX1-Positive Cells from the Adult Pancreas
Scientists sought to determine which subsets of pancreatic and duodenal homeobox 1 (PDX1)+ cells may be responsible for tumor growth. Using the Lox-Stop-Lox-KrasG12D genetic mouse model of pancreatic carcinogenesis, they isolated a population of KrasG12D-expressing PDX1+ cells with an inherent capacity to metastasize. [Proc Natl Acad Sci USA] Abstract

Transcriptional Regulation of Fibronectin by p21-Activated Kinase-1 Modulates Pancreatic Tumorigenesis
Scientists analyzed the expression of p21-activated kinase 1 in human pancreatic cancer tissues and found that Pak1 levels are significantly upregulated in pancreatic ductal adenocarcinoma samples as compared with adjacent normals. [Oncogene] Abstract

Anticancer Effects of Gemcitabine Are Enhanced by Co-Administered iRGD Peptide in Murine Pancreatic Cancer Models that Overexpressed Neuropilin-1
Researchers identified a subset of pancreatic cancer models that showed neuropilin-1 overexpression sensitive to internalized-RGD (iRGD) co-administration. [Br J Cancer] Abstract

LSD1 Sustains Pancreatic Cancer Growth via Maintaining HIF1a-Dependent Glycolytic Process
Using in vitro and in vivo models, researchers demonstrated that knock-down of lysine specific demethylase 1 (LSD1) repressed proliferation and tumorigenicity of pancreatic cancer cells. [Cancer Lett] Abstract

Differentiation Doesn't Have to be Difficult - Get Easy, Standardized hPSC Differentiation
Metabolism Addiction in Pancreatic Cancer
Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. [Cell Death Dis] Full Article

Stem Cells for Pancreatic ß-Cell Replacement in Diabetes Mellitus: Actual Perspectives
ß-cell substitution cell therapy, initially pursued by whole pancreatic and isolated islet transplantation, with scarce and limited efficiency, now is looking at the new technologies for cell and molecular therapy for diabetes, based on stem cells. [Curr Opin Organ Transplant] Abstract

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

Cell Line Development Asia 2014
Janssen Initiates CREDENCE Study in Patients with Type 2 Diabetes and Diabetic Nephropathy
Janssen Research & Development, LLC announced the initiation of CREDENCE, a global, multicenter study of INVOKANA® (canagliflozin). This Phase III study is a randomized, double-blind, placebo-controlled, parallel group trial designed to enroll more than 3,700 patients with type 2 diabetes and diabetic nephropathy. [Janssen Research & Development, LLC] Press Release

Encapsulife Receives U.S. Patent Office Notice of Allowance for Living-Cell Bio-Artificial Pancreas Requiring No Immune-Suppression
Encapsulife, Inc. announced the United States Patent and Trademark Office has issued a Notice of Allowance for Encapsulife’s claims in U.S. Patent Application No. 12/989,490. [PR Newswire Association LLC]
Press Release

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NEW International Society for Cellular Therapy (ISCT) 2014
April 23-26, 2014
Paris, France

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW PhD Studentship – Pancreatic Ductal Adenocarcinoma (Institute of Cancer Research)

Postdoctoral Position – Diabetes (Washington University School of Medicine)

Postdoctoral Research Fellow/Associate – Diabetes, Metabolism and Molecular Endocrinology (University of Illinois)

Postdoctoral Positions – Cancer and Diabetes (University of Pennsylvania)

Postdoctoral Fellow – Stem Cell Biology (McEwen Centre for Regenerative Medicine/University Health Network)

Postdoctoral Associate Specialist – Human Pancreatic Stem Cell Research (The Nestlé Institute of Health Sciences)

Postdoctoral Research Scientist – Imaging GTPase Activation in Cancer (Cancer Research UK Beatson Institute in Glasgow)

Postdoctoral Research Scientist – RAC and RAL Signaling Downstream of KRAS Mutation in Pancreatic and Colon Cancer (Cancer Research UK Beatson Institute in Glasgow)

Postdoctoral Fellowship Position – Mechanisms of Action in Obesity and Diabetes Pathogenesis (NIH/NIDDK)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

PhD Student Position – Diabetes and Bone Regeneration (KU Leuven)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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