Changes in circulating microRNA levels associated with prostate cancer

BACKGROUND: The aim of this study was to investigate the hypothesis that changes in circulating microRNAs (miRs) represent potentially useful biomarkers for the diagnosis, staging and prediction of outcome in prostate cancer. METHODS: Real-time polymerase chain reaction analysis of 742 miRs was performed using plasma-derived circulating microvesicles of 78 prostate cancer patients and 28 normal control individuals to identify differentially quantified miRs. RESULTS: A total of 12 miRs were differentially quantified in prostate cancer patients compared with controls, including 9 in patients without metastases. In all, 11 miRs were present in significantly greater amounts in prostate cancer patients with metastases compared with those without metastases. The association of miR-141 and miR-375 with metastatic prostate cancer was confirmed using serum-derived exosomes and microvesicles in a separate cohort of patients with recurrent or non-recurrent disease following radical prostatectomy. An analysis of five selected miRs in urine samples found that miR-107 and miR-574-3p were quantified at significantly higher concentrations in the urine of men with prostate cancer compared with controls. CONCLUSION: These observations suggest that changes in miR concentration in prostate cancer patients may be identified by analysing various body fluids. Moreover, circulating miRs may be used to diagnose and stage prostate cance

Editorial Approaches to Wittgenstein’s Nachlass: Towards a Historical Appreciation

Building on the unpublished correspondence between Ludwig Wittgenstein's literary executors Rush Rhees, Elizabeth Anscombe and Georg Henrik von Wright, this paper sketches the historical development of different editorial approaches to Wittgenstein's Nachlass. Using the metaphor of a ladder, it is possible to distinguish seven significant “rungs” or “steps” in the history of editing Wittgenstein's writings. The paper focuses particularly on the first four rungs, elucidating how Rhees, Anscombe and von Wright developed different editorial approaches that resulted in significant differences in their editions. The paper sheds light on how these editorial differences are grounded in the editors' divergent understandings of their task. It is suggested that future research may investigate the development of editorial approaches to Wittgenstein's Nachlass as a human story of philosophical inheritance