The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Li-Eswt improves hemodynamic parameters thus suggesting neoangiogenesis in patients with vascular erectile dysfunction

Extracorporeal treatment with low intensity shock-wave therapy (LI-ESWT) is a recently introduced non-invasive method which purposes the restoration of the pathophysiological alterations at the base of vasculogenic ED in male patients. The evidence in favour of the neoangiogenic potential of this treatment derived from in vitro studies and on animal models. The purpose of this study, in which the Power Doppler method was applied, is to demonstrate \u2018objectively\u2019 the real efficacy of LI-ESWT at the level of the microcirculation of the corpora cavernosa (neoangiogenesis) in patients affected by vasculogenic ED. Data from this study show, for the first time, that LI-ESWT treatment promotes neovascularisation of the functional arteries in patients affected by vasculogenic ED