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 |