Pancreatic ductal adenocarcinoma (PDAC) is usually detected late in the disease process. Clinical work-up through imaging and tissue biopsies is often complex and expensive due to a paucity of reliable biomarkers. Here, we used an advanced multiplexed plasmonic assay to analyze circulating, tumor-derived extracellular vesicles (tEV) in over 100 clinical populations. Using EV based protein marker profiling, we identified a signature of 5 markers (PDACEV signature) for PDAC detection. In our prospective cohort, the accuracy for the PDACEV signature was 84% (95% confidence interval, CI: 69–93%), but only 63–72% for single marker screening. GPC1 alone had a sensitivity of 82% (CI: 60–95%) and a specificity of 52% (CI: 30–74%) while the PDACEV signature showed a sensitivity of 86% (CI: 65–97%) and a specificity of 81% (CI: 58–95%). We show that the PDACEV signature of tEV offered higher sensitivity, specificity, and accuracy than existing serum (CA 19-9) or single tEV marker analyses. This approach should enhance the diagnosis of pancreatic cancer.

This review is intended to stress again the great potential, as yet not fully realized, for B(12)-based therapeutics, tumor imaging and oral drug delivery. This review discusses recent reports that demonstrate that the issues noted above can be overcome and need not be seen as negating the great potential of B(12) in the drug delivery field.

Epigenetic modifiers are an emerging class of anti-tumor drugs, potent in multiple cancer contexts. Their effect on spontaneously developing autoimmune diseases has been little explored. We report that a short treatment with I-BET151, a small-molecule inhibitor of a family of bromodomain-containing transcriptional regulators, irreversibly suppressed development of type-1 diabetes in NOD mice. The inhibitor could prevent or clear insulitis, but had minimal influence on the transcriptomes of infiltrating and circulating T cells. Rather, it induced pancreatic macrophages to adopt an anti-inflammatory phenotype, impacting the NF-κB pathway in particular. I-BET151 also elicited regeneration of islet β-cells, inducing proliferation and expression of genes encoding transcription factors key to β-cell differentiation/function. The effect on β cells did not require T cell infiltration of the islets. Thus, treatment with I-BET151 achieves a ‘combination therapy’ currently advocated by many diabetes investigators, operating by a novel mechanism that coincidentally dampens islet inflammation and enhances β-cell regeneration.DOI: http://dx.doi.org/10.7554/eLife.04631.001