Dual stromal targeting sensitizes pancreatic adenocarcinoma for anti-PD-1 therapy

Background and AimsThe stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms.MethodsA murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-PD-1 antibody …

Continue reading Dual stromal targeting sensitizes pancreatic adenocarcinoma for anti-PD-1 therapy

Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation

Pancreatic islet transplantation can cure diabetes but requires accessible, high-quality islets in sufficient quantities. Cryopreservation could solve islet supply chain challenges by enabling quality-controlled banking and pooling of donor islets. Unfortunately, cryopreservation has not succeeded in this objective, as it must simultaneously provide high recovery, viability, function and scalability. Here, we achieve this goal in …

Continue reading Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation

Changes in #metabolic syndrome status are associated with altered risk of #pancreatic cancer: A nationwide cohort study

Background & AimsMetabolic syndrome (MetS) is reversible; however, the effect of changes in MetS status on pancreatic cancer risk is unknown. We aimed to investigate the effects of changes and persistence in MetS status on pancreatic cancer risk. MethodsThis nationwide cohort study included 8,203,492 adults without cancer who underwent two consecutive biennial health screenings provided …

Continue reading Changes in #metabolic syndrome status are associated with altered risk of #pancreatic cancer: A nationwide cohort study

NOX4 links metabolic regulation in #pancreatic #cancer to endoplasmic reticulum redox vulnerability and dependence on PRDX4

There is an urgent need to identify vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). PDAC cells acquire metabolic changes that augment NADPH production and cytosolic redox homeostasis. Here, we show that high NADPH levels drive activity of NADPH oxidase 4 (NOX4) expressed in the endoplasmic reticulum (ER) membrane. NOX4 produces H2O2 metabolized by peroxiredoxin 4 (PRDX4) …

Continue reading NOX4 links metabolic regulation in #pancreatic #cancer to endoplasmic reticulum redox vulnerability and dependence on PRDX4

#Glucagon blockade restores functional β-cell mass in type 1 #diabetic mice and enhances function of human islets

Both type 1 and type 2 diabetes are associated with reduced β-cell mass or function, resulting from decreased proliferation and increased apoptosis. Understanding the signals governing β-cell survival and regeneration is critical for developing strategies to maintain healthy populations of these cells in individuals. Both forms of diabetes are associated with hyperglucagonemia and an increased …

Continue reading #Glucagon blockade restores functional β-cell mass in type 1 #diabetic mice and enhances function of human islets