No abstract

Abstract-Discovery of the common and ubiquitous molecular targets for the disruption of angiogenesis, that are independent of the characteristics of malignant tumors, is desired to develop the more effective antitumor drugs. In this study, we propose that the platelet-derived growth factor receptor-␣ (PDGFR␣)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by fibroblast growth factor-2, is the potent candidate. Using murine limb ischemia as a tumor-free assay system, we demonstrated that p70S6K inhibitor rapamycin (RAPA) targets mesenchymal cells to shut down the sustained expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via silencing of the PDGFR␣-p70S6K pathway. Irrespective of the varied expression profiles of angiogenic factors in each tumor tested, RAPA constantly led the tumors to dormancy and severe ischemia in the time course, even associated with upregulated expression of VEGF from tumors. Because RAPA showed only a minimal effect to hypoxia-related expression of VEGF in culture, these results suggest that RAPA targets the host-vasculature rather than tumor itself in vivo. Thus, our current study indicates that the PDGFR␣-p70S6K pathway is an essential regulator for FGF-2-mediated therapeutic neovascularization, as well as for the host-derived vasculature but not tumors during tumor angiogenesis, via controlling continuity of expression of multiple angiogenic growth factors.

These results demonstrate that low AT-III activity and further decreases in this activity are associated with PVT after splenectomy in cirrhotic patients, and that treatment with AT-III concentrates is likely to prevent the development of PVT in these patients.

With the technical standardization, LS becomes a feasible and safe approach in the setting of liver cirrhosis and portal hypertension.

BackgroundTo evaluate intraocular pressure (IOP) changes in patients undergoing robotic-assisted radical prostatectomy and to evaluate complications from increased IOP.MethodsThirty-one eyes scheduled for robotic prostatectomy were included. Perioperative IOP measurements were performed as follows: prior to induction of anaesthesia while supine and awake (T1); immediately post-induction while supine (T2); every hour from 0 to 5 h while anaesthetised in a steep Trendelenburg position (T3–T8); prior to awakening while supine (T9); and 30 min after awakening while supine (T10). A complete ophthalmic examination including visual acuity and retinal nerve fibre layer thickness (RNFL) was performed at enrolment and 1 month postoperatively.ResultsAverage IOP (mm Hg) for each time point was as follows: T1=18.0, T2=9.8, T3=18.9, T4=21.6, T5=22.5, T6=22.3, T7=24.2, T8=24.0, T9=15.7 and T10=17.9. The proportion of eyes with intraoperative IOP ≧30 mm Hg were as follows: T3=0%, T4=3.23%, T5=9.68%, T6=6.45%, T7=22.22%, and T8=25%. Maximum IOP was 36 mm Hg. Mean visual acuity (logarithm of the minimal angle of resolution) and RNFL showed no statistically significant difference before and after operation and no other ocular complications were found at final examination.ConclusionsWhile IOP increased in a time-dependent fashion in anesthaetised patients undergoing robotic-assisted radical prostatectomy in a steep Trendelenburg position, visual function showed no significant change postoperatively and no complications were seen. Steep Trendelenburg positioning during time-limited procedures appears to pose little or no risk from IOP increases in patients without pre-existing ocular disease.