Pancreatic Cell News Volume 4.19 | May 21 2013

DIABETES

Limitations of IL-2 and Rapamycin in Immunotherapy of Type 1 Diabetes
Administration of low-dose IL-2 alone or combined with rapamycin (RAPA) prevents hyperglycemia in NOD mice. Researchers studied the effect of higher IL-2 doses as well as low-dose IL-2 and RAPA combination. They showed that despite further boosting regulatory T cells, high doses of IL-2 rapidly precipitated type 1 diabetes in pre-diabetic female and male mice and increased myeloid cells in the pancreas. [Diabetes] Abstract

Genetically Engineered Human Islets Protected from CD8-Mediated Autoimmune Destruction In Vivo
The authors engineered human β cells to express herpesvirus-encoded immune-evasion proteins, “immunevasins.” The capacity of immunevasins to protect β cells from autoreactive T-cell killing was evaluated in vitro and in vivo in humanized mice. [Mol Ther] Abstract

Glucose Regulation of a Cell Cycle Gene Module Is Selectively Lost in Mouse Pancreatic Islets during Aging
Global gene expression was assessed in pancreatic islets from young and aged wild-type and Cdkn2a (Ink4a/Arf)-deficient mice exposed to different glucose concentrations. Gene expression profiling revealed that variations in glucose levels have a widespread and highly dynamic impact on the islet transcriptome. [Diabetologia] Abstract

B Lymphocyte “Original Sin” in the Bone Marrow Enhances Islet Autoreactivity in Type 1 Diabetes-Prone Nonobese Diabetic Mice
Anti-insulin B cells were tracked during development in the polyclonal repertoire of Cg-Tg(Igh-6/Igh-V125)2Jwt/JwtJ mice. Scientists report that an increased proportion of insulin-binding B cells is apparent in nonobese diabetec mice at the earliest point of antigen commitment in the bone marrow. [J Immunol] Abstract

The Orphan Nuclear Receptor Small Heterodimer Partner Negatively Regulates Pancreatic Beta Cell Survival and Hyperglycemia in Multiple Low-Dose Streptozotocin-Induced Type 1 Diabetic Mice
Researchers used small heterodimer partner (SHP) knockout (KO) mice to investigate the role of SHP in multiple low-dose streptozotocin (MLDS)-induced diabetes. SHP KO mice showed significantly lower blood glucose, higher insulin levels, and enhanced glucose tolerance compared with wild type mice after MLDS treatment. Moreover, beta cell mass and pancreatic insulin content were remarkably increased in SHP KO mice. [Int J Biochem Cell B] Abstract

PANCREATIC CANCER

Depletion of RAD17 Sensitizes Pancreatic Cancer Cells to Gemcitabine
A negative selection RNAi screen was performed in cell lines with small hairpin RNA molecules targeting over 10,000 genes. Genes that were found to be synthetically lethal with gemcitabine and whose proteins are acting upstream of checkpoint kinase 1 were characterized in more detail. In particular, the inhibition of RAD17 potentiated gemcitabine cytotoxicity in the pancreatic cancer cell lines BxPC-3, MiaPaca-2 and the primary cell line JoPaca-1 that closely resembles primary tumor tissue. [J Cell Sci] Abstract
 
An Intensified Systemic Trafficking of Bone Marrow-Derived Stem/Progenitor Cells in Patients with Pancreatic Cancer
Investigators comprehensively analyzed systemic trafficking of various populations of bone marrow-derived stem cells (SCs), i.e., mesenchymal, hematopoietic, endothelial stem/progenitor cells, and of recently discovered population of very small embryonic/epiblast-like SCs (VSELs) in pancreatic cancer patients. Higher numbers of circulating VSELs and mesenchymal stem cells were detected in pancreatic cancer patients. [J Cell Mol Med] Abstract | Full Article

Conditionally Replicative Adenoviral Vectors for Imaging the Effect of Chemotherapy on Pancreatic Cancer Cells
Researchers investigated the use of a conditionally replicative adenovirus (CRAd), Ad5/3Cox2CRAd-ΔE3ADP-Luc, for imaging the effects of chemotherapy. CRAd infectivity of pancreatic cancer cells was enhanced by a chimeric Ad5/3 fiber, E1A expression was under the control of the Cox2 promoter, and the luciferase gene was inserted adjacent to the adenovirus death protein (ADP) gene. [Cancer Sci] Abstract

Histological and Prognostic Importance of CD44⁺/CD24⁺/EpCAM⁺ Expression in Clinical Pancreatic Cancer
The authors clarified the characteristics of CD44⁺/CD24⁺/EpCAM⁺ cells in clinical specimens of pancreatic cancer using immunohistochemical assay. CD44⁺/CD24⁺/EpCAM⁺ expression overlapped with poorly differentiated cells and possessed high proliferative potential in clinical pancreatic cancer. [Cancer Sci] Abstract

In Vitro Treatment of Carcinoma Cell Lines with Pancreatic (Pro)Enzymes Suppresses the EMT Programme and Promotes Cell Differentiation
Scientists investigated the in vitro effects of a mixture of two pancreatic pro-enzymes, Chymotrypsinogen and Trypsinogen, and the enzyme Amylase on three human cancer cell lines. After treatment of the three cancer cell lines with different doses of the (pro)enzymes for up to seven days, they observed growth inhibition in a dose-dependent manner. [Cell Oncol] Abstract

REVIEWS

DPP-4 Inhibitors: Multi-Target Drugs, Not Only Anti-Diabetes
The authors provide a systematic and comprehensive review of current researches on the newly-found effect and mechanism of dipeptidyl-peptidase-4 (DPP-4) inhibitors in therapy. [J Diabetes] Abstract

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

Elcelyx Therapeutics Enrolling Phase IIb Trial of NewMet for Type 2 Diabetes
Enrollment of patients with Type 2 diabetes is underway in Elcelyx Therapeutics’ Phase IIb dose-finding clinical trial of product candidate NewMet™, a delayed-release formulation of generic metformin, the foundational treatment for Type 2 diabetes. [Elcelyx Therapeutics, Inc.] Press Release

Oramed Receives FDA Clearance to Initiate Oral Insulin Trials in the U.S.
Oramed Pharmaceuticals Inc. announced that the United States Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug application for ORMD-0801, its oral insulin capsule. [Oramed Pharmaceuticals Inc.] Press Release

Researchers Funded by the Pancreatic Cancer Action Network Leverage $9.15 Million Investment by the Organization into $91 Million in Subsequent Pancreatic Cancer Research Funding
A rigorous analysis of the Pancreatic Cancer Action Network research grants program has shown that the organization’s grant recipients are leveraging their awards to secure impressive subsequent funding, publishing their findings, and enhancing knowledge about the disease. [PR Newswire Association LLC]
Press Release

NIH Saves Lives: Fred Hutchinson Cancer Research Center Calls on Congress to Restore Full NIH Funding
Fred Hutchinson Cancer Research Center called on Congress to support restoring full funding to the National Institutes of Health (NIH), which supports pioneering research that saves lives. Funding was recently cut due to sequestration. [Fred Hutchinson Cancer Research Center]  Press Release

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NEW Frontiers in Stem Cells and Regeneration
September 29 – October 6, 2013
Woods Hole, United States

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

NEW Postdoctoral Position – Tumor Microenvironment & Pancreatic Cancer (INSERMU1068)

PhD Scholarships – Diabetes (Danish Diabetes Academy)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

PhD Positions – Molecular Mechanisms Controlling Acinar Cell Proliferation (University Hospital Zuerich)

PhD Studentship – Obesity and Type 2 Diabetes (German Diabetes Center)

Postdoctoral Researcher (The University of Texas Health Science Center at San Antonio)

Scientist/Specialist – Mitochondrial Function (The Nestlé Institute of Health Sciences)

Postdoctoral Position – Pancreatic Cancer (UT Southwestern Medical Center at Dallas)

Postdoctoral Fellow – Pancreatic Beta Cell Regeneration and Survival (Oklahoma Medical Research Foundation)

Research Associate – Progression and Metastasis of Pancreatic and Breast Cancer (University of North Carolina at Charlotte)

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