Background: Leptin is a pleiotropic hormone whose mitogenic and angiogenic activity has been implicated in the development and progression of several malignancies, including brain tumors. In human brain cancer, especially in glioblastoma multiforme (GBM), leptin and its receptor (ObR) are overexpressed relative to normal tissue. Until present, the potential of intratumoral leptin to exert proangiogenic effects on endothelial cells has not been addressed. Using in vitro models, we investigated if GBM can express leptin, if leptin can affect angiogenic and mitogenic potential of endothelial cells, and if its action can be inhibited with specific ObR antagonists. Leptin effects were compared with that induced by the best-characterized angiogenic regulator, VEGF.

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The aim of this study was to evaluate the role of metabolic parameters analyzed at baseline and at interim FDG‐PET in predicting disease outcome in unresectable MPM patients receiving pemetrexed‐based chemotherapy. A consecutive series of MPM patients treated between February 2004 and July 2013 with first‐line pemetrexed‐based chemotherapy, and evaluated by FDG‐PET and CT scan at baseline and after two cycles of chemotherapy, was reviewed. Best CT scan response was assessed according to modified RECIST criteria. Progression‐free survival (PFS) and overall survival (OS) were correlated with FDG‐PET parameters, such as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and percentage changes in SUVmax (∆SUV) and TLG (∆TLG). Overall, 142 patients were enrolled; 77 (54%) received talc pleurodesis before chemotherapy. Baseline SUVmax and TLG showed a statistically significant correlation with PFS and OS (P < 0.05) in both group of patients (treated and untreated with pleurodesis). In 65 patients not receiving pleurodesis, SUVmax reduction ≥25% (∆SUV ≥ 25%) and TLG reduction ≥30% (∆TLG ≥ 30%) were significantly associated with longer PFS (P < 0.05). Patients showing both ∆SUV ≥ 25% and ∆TLG ≥ 30% responses had a significant reduction in the risk of disease progression (HR:0.31, P < 0.001) and death (HR:0.52, P = 0.044). Neither ∆SUV nor ∆TLG showed similar association with survival outcomes in patients treated with pleurodesis. Our study confirmed the prognostic role of baseline FDG‐PET in a large series of MPM patients treated with first‐line pemetrexed‐based chemotherapy. Moreover, use of ∆SUV ≥ 25% and ∆TLG ≥ 30% as cut‐off values to define early metabolic response supported the role of FDG‐PET in predicting disease outcome and treatment response in patients not receiving pleurodesis.