التفاصيل البيبلوغرافية
| العنوان: |
Sorafenib augments cytotoxic effect of S-1 in vitro and in vivo through TS suppression. |
| المؤلفون: |
Takeuchi, Ario, Shiota, Masaki, Tatsugami, Katsunori, Yokomizo, Akira, Eto, Masatoshi, Inokuchi, Junichi, Kuroiwa, Kentaro, Kiyoshima, Keijiro, Naito, Seiji |
| المصدر: |
Cancer Chemotherapy & Pharmacology; Dec2011, Vol. 68 Issue 6, p1557-1564, 8p |
| مصطلحات موضوعية: |
ANTINEOPLASTIC agents, CANCER treatment, RENAL cell carcinoma, PROTEIN-tyrosine kinases, CYTOKINES, GENE expression, TUMOR growth, DRUG side effects |
| مستخلص: |
Purpose: Sorafenib, a multikinase and tyrosine-kinase inhibitor, has anti-tumor activity in patients with advanced renal cell carcinoma (RCC). Recently, we reported that S-1 was active and well tolerated for the treatment of cytokine-refractory metastatic RCC. Therefore, we hypothesized that S-1 might be a good candidate for combination therapy with molecular targeting agents. In this study, we examined the mechanisms underlying for the synergism between S-1 and Sorafenib for RCC treatment in vitro and in tumor-bearing murine models. Methods: Human RCC cell lines were used for the in vitro cell proliferation assay. ACHN and 786-O tumors were subcutaneously transplanted into NCr-nu/nu-mice. Mice were treated with S-1 and/or Sorafenib, and tumor growth and side effects were monitored. Results: Synergistic anti-proliferative effects of Sorafenib and S-1 were clearly demonstrated in ACHN and 786-O cell lines in vitro due to the suppression of TS and E2F-1 expression. In the NCr-nu/nu model, the synergistic anti-tumor effects of S-1 and Sorafenib were again clearly seen, indicating direct synergistic effects of each drug on tumor growth. Conclusions: Our results demonstrate the synergistic activity of S-1 and Sorafenib and provided the rationale for combination therapy with S-1 and Sorafenib for the treatment of patients with advanced RCC. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
