DIABETES Ku70 Functions in Addition to Nonhomologous End Joining in Pancreatic Beta-Cells: A Connection to Beta-Catenin Regulation To further delineate the function of nonhomologous end joining (NHEJ), researchers analyzed mice deficient for another key NHEJ factor, Ku70, to discover the effect of cellular responses to DNA damage in pancreatic β-cells on cellular proliferation and glucose homeostasis. Analysis of Ku70-/- pancreatic β-cells revealed an accumulation of DNA damage and activation of p53-dependent cellular senescence. [Diabetes] Abstract Identification of ATP Synthase as a Lipid Peroxide Protein Adduct in Pancreatic Islets from Humans with and without Type 2 Diabetes Mellitus Oxidative stress has been proposed as a mechanism for impaired β-cell function in type 2 diabetes. Lipid peroxides caused by reactive oxygen species are damaging to body tissues. The authors report that lipid peroxide-protein adducts occur in β-cells in the nondiabetic state and in diabetes. [J Clin Endocr Metab] Abstract Neurogenin3 Cooperates with Foxa2 to Autoactivate Its Own Expression Scientists showed that the broadly expressed endodermal forkhead factors Foxa1 and Foxa2 can cooperate synergistically to amplify Neurogenin3 autoregulation in vitro. However, only Foxa2 colocalizes with Neurogenin3 in pancreatic progenitors, thus indicating a primary role for this factor in regulating Neurogenin3 expression in vivo. [J Biol Chem] Abstract Exendin-4 Protects Hypoxic Islets from Oxidative Stress and Improves Islet Transplantation Outcome Investigators report that exendin-4 enhanced Akt phosphorylation of β-cells and insulin released from them. It even augmented insulin secretion from islets cultivated at hypoxic conditions. [Endocrinology] Abstract Role of BMP Signaling in Pancreatic Progenitor Differentiation from Human Embryonic Stem Cells Scientists report that human embryonic stem cells were differentiated into PDX1 positive pancreatic progenitor stage following their established protocol with few modifications, and then the progenitor cells were passaged in a defined proliferation medium. [Stem Cells Rev] Abstract PANCREATIC CANCER MAZ-Binding G4-Decoy with Locked Nucleic Acid and Twisted Intercalating Nucleic Acid Modifications Suppresses KRAS in Pancreatic Cancer Cells and Delays Tumor Growth in Mice Investigators report that myc-associated zinc-finger (MAZ) activates KRAS transcription. To knockdown oncogenic KRAS in pancreatic cancer cells, they designed oligonucleotides that mimicked one of the G-quadruplexes formed by nuclease-hypersensitive element (G4-decoys). [Nucleic Acids Res] Full Article Dormant Cancer Cells Contribute to Residual Disease in a Model of Reversible Pancreatic Cancer To experimentally address whether c-Myc is essential for the growth and survival of cancer cells, researchers developed a novel mouse model that allows a temporally and spatially controlled expression of this oncogene in pancreatic progenitors and derived lineages of the exocrine pancreas. [Cancer Res] Abstract Alkaline Phosphatase Alkaline Phosphatase Placental-Like 2 Is a Novel Pancreatic Carcinoma-Associated Protein To identify novel pancreatic cancer biomarkers that can facilitate early diagnosis and also help in the development of effective therapeutics, scientists developed RNA aptamers targeting pancreatic cancer by cell-systematic evolution of ligands by exponential enrichment approach. [Cancer Res] Abstract Targeting miR-21 for the Therapy of Pancreatic Cancer Researchers demonstrated that lentiviral vectors-transduced human pancreatic ductal adenocarcinoma (PDA) efficiently downregulated microRNA-21 (miR-21) expression, both in vitro and in vivo. Consequently, cell proliferation was strongly inhibited and PDA-derived cell lines died by apoptosis through the mitochondrial pathway. [Mol Ther] Abstract The Differentiation of Pancreatic Tumor-Initiating Cells by Vitronectin Can Be Blocked by Cilengitide Scientists used a sphere formation assay to enrich putative tumor-initiating cells (TICs) and used human serum as a driver of differentiation. They demonstrated that by using specific blocking reagents that they can inhibit the differentiation process and maintain TIC-associated markers and genes. [Pancreas] Abstract |