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Venezia, Italy

D'Incalci M.,IRCCS
Future Oncology | Year: 2013

Trabectedin is a tetrahydroisoquinoline molecule that binds to the N2 of guanine in the minor groove, causing DNA damage and affecting transcription regulation in a promoter- and gene-specific manner. The antitumor activity of trabectedin appears to be not only related to its direct effects on cancer cells, but also on the tumor microenvironment. In cancer cells, the drug induces cell cycle arrest and cell death that is not dependent on p53 status, and it is increased dramatically in cells deficient in homologous recombination (e.g., cells with mutations of BRCA1/2). Trabectedin also has potent immunomodulatory effects, being selectively cytotoxic against monocytes and tumor-associated macrophages. In addition, it inhibits production of proinflammatory and angiogenic mediators, which induces changes in the tumor microenvironment and contributes to its antitumor activity. The opportunity to combine direct cytotoxic activity with a capacity to favorably modify the tumor microenvironment, using either single-agent or combination therapy, is an especially appealing therapeutic option for a diverse range of cancers. © 2013 Future Medicine Ltd. Source

Mancia G.,IRCCS | Mancia G.,University of Milan Bicocca | Grassi G.,University of Milan Bicocca
Circulation Research | Year: 2014

Physiological studies have long documented the key role played by the autonomic nervous system in modulating cardiovascular functions and in controlling blood pressure values, both at rest and in response to environmental stimuli. Experimental and clinical investigations have tested the hypothesis that the origin, progression, and outcome of human hypertension are related to dysfunctional autonomic cardiovascular control and especially to abnormal activation of the sympathetic division. Here, we review the recent literature on the adrenergic and vagal abnormalities that have been reported in essential hypertension, with emphasis on their role as promoters and as amplifiers of the high blood pressure state. We also discuss the possible mechanisms underlying these abnormalities and their importance in the development and progression of the structural and functional cardiovascular damage that characterizes hypertension. Finally, we examine the modifications of sympathetic and vagal cardiovascular influences induced by current nonpharmacological and pharmacological interventions aimed at correcting elevations in blood pressure and restoring the normotensive state. © 2014 American Heart Association, Inc. Source

Cappelletti P.,IRCCS
Rivista Italiana della Medicina di Laboratorio | Year: 2013

Summary: The Editorial summarizes some critical points of the economic theory of innovation, from its definition and general characteristics to sources, generation models, diffusion and cycle of life. In Medicine, the epitome of innovation theory is Translational Medicine. Its interpretative models (T models and process models) and generation, synthesis and diffusion of evidence (Evidence-based Medicine, Comparative Effectiveness Research and Health Technology Assessment) are briefly revised. The goals and methodology of Knowledge Translation, a tool for overcoming the barriers to spread of innovation and evidence, are described, with attention to the criticism derived from the concept of "wisdom translation". In conclusion, two examples of innovation in Laboratory Medicine (biomarkers cycle of life; instrumental miniaturization and information technology) are examined to highlight the indissoluble integration of innovation, evidence generation and synthesis, knowledge translation and clinical diagnostic in Laboratory Medicine. © 2013 Springer-Verlag Italia. Parole chiave: InnovazioneEvidence-based medicineComparative effectiveness researchHealth technology assessmentKnowledge translationMedicina di Laboratorio. Source

Di Donato M.,University of Florence | Castelvecchio S.,IRCCS | Menicanti L.,IRCCS
European Journal of Heart Failure | Year: 2010

Aims A left ventricular end-systolic volume (LVESV) ≥60 mL/m 2 has been shown to be associated with increased cardiac mortality after a reperfused myocardial infarction (MI). The reduction in LVESV following surgical ventricular reconstruction (SVR) is reported to be between 19 and 50 but its impact on prognosis is not well-established. The aim of this study was therefore to assess the impact on survival of a residual LVESV index (LVESVI) of ≥ or <60 mL/m 2 following SVR.Methods and resultsAll patients undergoing SVR at our Centre between July 2001 and March 2009 were eligible to be included in this study if they had a preoperative LVESVI of ≥60 mL/m 2 and an LVESVI measurement performed at discharge (7-10 days after surgery). Two hundred and sixteen patients (aged 64 ± 9 years, 33 women) satisfied these criteria. Coronary artery bypass graft was performed in 197 patients (91.2) and mitral repair in 63 patients (29). Left ventricular ESVI had decreased by 41 at discharge in the overall population. Patients were grouped according to the residual LVESVI at discharge as follows: Group 1, LVESVI ≥ 60 mL/m 2 (n = 71), and Group 2, LVESVI < 60 mL/m 2 (n = 145). In both groups, LVESVI decreased significantly with respect to baseline, by 29 in Group 1 and by 47 in Group 2. At multivariate analysis, the presence of a non-Q-wave MI and a preoperative internal diastolic diameter of 65 mm were the strongest predictors of a residual post-operative LVESVI of ≥60 mL/m 2. Risk of all-cause death was significantly higher in Group 1. Post-operative LVESVI of ≥60 mL/m 2 was an independent predictor of mortality at follow-up [Exp(B) = 10.7, CI: 2.67-42.9, P = 0.001].ConclusionOur findings confirm the role of LVESVI in predicting survival following SVR; the lack of additional improvement in survival with SVR observed in the STICH trial might be due to the inadequate volume reduction (-19). © The Author 2010. Source

The increasing use of nanomaterials incorporated into consumer products leads to the need for developing approaches to establish "quantitative structure-activity relationships" (QSARs) for various nanomaterials. However, the molecular structure as rule is not available for nanomaterials at least in its classic meaning. An possible alternative of classic QSAR (based on the molecular structure) is the using of data on physicochemical features of TiO2 nanoparticles. The damage to cellular membranes (unitsL-1) by means of various TiO2 nanoparticles is examined as the endpoint. © 2013 Elsevier Ltd. Source

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