Independent activation of CREB3L2 by glucose fills a regulatory gap in mouse β-cells by co-ordinating insulin biosynthesis with secretory granule formation.

Objective: Although individual steps have been characterized, there is little understanding of the overall process whereby glucose co-ordinates the biosynthesis of insulin with its export out of the endoplasmic reticulum (ER) and incorporation into insulin secretory granules (ISGs). Here we investigate a role for the transcription factor CREB3L2 in this context.

Methods: MIN6 cells and mouse islets were analysed by immunoblotting after treatment with glucose, fatty acids, thapsigargin and various inhibitors.

Precision medicine and phosphoproteomics for the identification of novel targeted therapeutic avenues in sarcomas.

Rapid advances in genomic technologies have enabled in-depth interrogation of cancer genomes, revealing novel and unexpected therapeutic targets in many cancer types. Identifying actionable dependencies in the diverse and heterogeneous group of sarcomas, particularly those that occur in children or adolescents and young adults (AYAs), remains especially challenging. These patients rarely harbor actionable genomic aberrations, no targeted agent is approved, and outcomes have remained poor for the past decades.

CD30 and ALK combination therapy has high therapeutic potency in RANBP2-ALK-rearranged epithelioid inflammatory myofibroblastic sarcoma.

Background: Epithelioid inflammatory myofibroblastic sarcoma (eIMS) is characterised by perinuclear ALK localisation, CD30 expression and early relapse despite crizotinib treatment. We aimed to identify therapies to prevent and/or treat ALK inhibitor resistance.

Methods: Malignant ascites, from an eIMS patient at diagnosis and following multiple relapses, were used to generate matched diagnosis and relapse xenografts.

Potentiating the cellular targeting and anti-tumor activity of Dp44mT via binding to human serum albumin: two saturable mechanisms of Dp44mT uptake by cells.

Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) demonstrates potent anti-cancer activity. We previously demonstrated that 14C-Dp44mT enters and targets cells through a carrier/receptor-mediated uptake process. Despite structural similarity, 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT) and pyridoxal isonicotinoyl hydrazone (PIH) enter cells via passive diffusion.