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10.1186/s13046-016-0411-2 http://scihub22266oqcxt.onion/10.1186/s13046-016-0411-2 C5013589!5013589!27604186     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Exp+Clin+Cancer+Res 2016 ; 35 (1): ä Nephropedia Template TP {{tp|p=27604186|t=2016. Alternative scheduling of pulsatile, high dose sunitinib efficiently suppresses tumor growth |pdf=|usr=}}{{27604186}} gab.com Text Alternative scheduling of pulsatile, high dose sunitinib efficiently suppresses tumor growth JO: J Exp Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=27604186 #FOAvip Background: Increased exposure to multitargeted kinase inhibitor sunitinib is associated with improved outcome, emphasizing the importance of maintaining adequate dosing and drug levels. The currently approved schedule (50 mg daily, four weeks on, two weeks off) precludes further dose-intensification. Recent data suggest that sunitinib, although initially developed as an antiangiogenic agent, has direct antitumor activity. Methods: In this study, we tested whether a chemotherapy-like schedule of pulsatile high dose sunitinib would result in improved antitumor activity. Results: In vitro, a single exposure to 20 ?M sunitinib for 6-9 h resulted in complete inhibition of tumor cell growth and cell death conveyed through activation of caspases and autophagy upregulation. Notably, repeated exposure of tumor cells to pulses of high concentrations of sunitinib did not induce resistance. In vivo, once-weekly treatment with high dose sunitinib of tumors growing on the chorioallantoic membrane (CAM) of the chicken embryo significantly impaired tumor growth by 57 % compared to vehicle, outperforming the daily, standard scheduling. Conclusions: These results prompted the initiation of a phase I clinical trial, where intermittent, high dose sunitinib is being investigated in patients with advanced solid tumors (registration number and date: NCT02058901, 30 September 2013, respectively). The trial is actively recruiting patients and promising preliminary indications of antitumor activity have been observed. Twit Text FOAVip Alternative scheduling of pulsatile, high dose sunitinib efficiently suppresses tumor growth ????J Exp Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=27604186 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27604186 #FOAvip English Wikipedia <ref>{{Cite pmid|27604186}}</ref> Alternative scheduling of pulsatile, high dose sunitinib efficiently suppresses tumor growth #MMPMID27604186 Rovithi M; de Haas RR; Honeywell RJ; Poel D; Peters GJ; Griffioen AW; Verheul HMW J Exp Clin Cancer Res 2016[]; 35 (1): ä PMID27604186show ga Background: Increased exposure to multitargeted kinase inhibitor sunitinib is associated with improved outcome, emphasizing the importance of maintaining adequate dosing and drug levels. The currently approved schedule (50 mg daily, four weeks on, two weeks off) precludes further dose-intensification. Recent data suggest that sunitinib, although initially developed as an antiangiogenic agent, has direct antitumor activity. Methods: In this study, we tested whether a chemotherapy-like schedule of pulsatile high dose sunitinib would result in improved antitumor activity. Results: In vitro, a single exposure to 20 ?M sunitinib for 6-9 h resulted in complete inhibition of tumor cell growth and cell death conveyed through activation of caspases and autophagy upregulation. Notably, repeated exposure of tumor cells to pulses of high concentrations of sunitinib did not induce resistance. In vivo, once-weekly treatment with high dose sunitinib of tumors growing on the chorioallantoic membrane (CAM) of the chicken embryo significantly impaired tumor growth by 57 % compared to vehicle, outperforming the daily, standard scheduling. Conclusions: These results prompted the initiation of a phase I clinical trial, where intermittent, high dose sunitinib is being investigated in patients with advanced solid tumors (registration number and date: NCT02058901, 30 September 2013, respectively). The trial is actively recruiting patients and promising preliminary indications of antitumor activity have been observed. äAlternative scheduling of pulsatile, high dose sunitinib efficiently s(epmc).pdf DeepDyve Pubget Overpricing