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Title of Journal: Cancer Chemother Pharmacol

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Abbravation: Cancer Chemotherapy and Pharmacology

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Springer-Verlag

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1432-0843

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Sorafenib augments cytotoxic effect of S1 in vitr

Authors: Ario Takeuchi Masaki Shiota Katsunori Tatsugami Akira Yokomizo Masatoshi Eto Junichi Inokuchi Kentaro Kuroiwa Keijiro Kiyoshima Seiji Naito
Publish Date: 2011/05/05
Volume: 68, Issue: 6, Pages: 1557-1564
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Abstract

Sorafenib a multikinase and tyrosinekinase inhibitor has antitumor activity in patients with advanced renal cell carcinoma RCC Recently we reported that S1 was active and well tolerated for the treatment of cytokinerefractory metastatic RCC Therefore we hypothesized that S1 might be a good candidate for combination therapy with molecular targeting agents In this study we examined the mechanisms underlying for the synergism between S1 and Sorafenib for RCC treatment in vitro and in tumorbearing murine modelsSynergistic antiproliferative effects of Sorafenib and S1 were clearly demonstrated in ACHN and 786O cell lines in vitro due to the suppression of TS and E2F1 expression In the NCrnu/nu model the synergistic antitumor effects of S1 and Sorafenib were again clearly seen indicating direct synergistic effects of each drug on tumor growth

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