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Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice

  • Authors:
    • Mamoru Nukatsuka
    • Hitoshi Saito
    • Fumio Nakagawa
    • Hiroaki  Tsujimoto
    • Kazuki Sakamoto
    • Sayaka Tsukioka
    • Junji  Uchida
    • Mamoru Kiniwa
    • Takashi Kobunai
    • Teiji Takechi
  • View Affiliations / Copyright

    Affiliations: Oncology Medical Affairs Division, Taiho Pharmaceutical Co., Ltd., Tokushima 771-0194, Japan, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., Tokushima 771-0194, Japan, Tsukuba Research Center, Taiho Pharmaceutical Co., Ltd., Okubo Tsukuba-Shi, Ibaraki 300-2611, Japan, Oncology Medical Affairs Division, Taiho Pharmaceutical Co., Ltd., Tokushima 771-0194, Japan, Oncology Medical Affairs Division, Taiho Pharmaceutical Co., Ltd., Tokyo 101-0047, Japan
  • Pages: 755-762
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    Published online on: February 13, 2012
       https://doi.org/10.3892/etm.2012.484
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Abstract

In this study, combination therapies using the oral fluoropyrimidine tegafur-gimeracil-oteracil (S-1) with several targeted agents or antibodies, were evaluated. First, the effects of tyrosine kinase inhibitors (erlotinib hydrochloride, sorafenib tosilate and sunitinib malate) against human non-small cell lung cancer (NSCLC), breast cancer and colorectal cancer were evaluated in vivo. The effects of the combination of S-1 and targeted antibodies (bevacizumab and cetuximab) against human colorectal cancers was also evaluated in vivo. S-1 and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, showed a significant inhibition of growth in human NSCLC (Lu-99 and PC-9 cell lines). The antitumor activity of the combination of S-1 and erlotinib against Lu-99 and PC-9 cancer cell lines was significantly superior to either monotherapy (P<0.05). Combination therapy using the multi-tyrosine kinase inhibitors, sorafenib or sunitinib, with S-1 against breast cancer (MX-1 cell line) and NSCLC (NCI-H460 cell line) was significantly superior to either monotherapy (P<0.01). The combination of the anti‑vascular endothelial growth factor antibody bevacizumab or the anti-EGFR antibody, cetuximab, with S-1 against human colorectal cancer [Col-1, KM20C (bevacizumab) and DLD-1 (cetuximab) cell lines] and a 5-fluorouracil (5-FU)-resistant cell line (KM12C/5-FU) was significantly superior to either monotherapy (p<0.01). In particular, the growth of the Col-1 cells was completely inhibited by the combination of S-1 and bevacizumab. No toxic mortalities and no significant difference in the body weight changes of the animals treated with S-1 combined with the targeted agents or with the monotherapies were observed; therefore, the treatments appeared to be well-tolerated. Our preclinical findings indicate that the combination therapies of S-1 and targeted agents are promising treatment options.
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Copy and paste a formatted citation
Spandidos Publications style
Nukatsuka M, Saito H, Nakagawa F, Tsujimoto H, Sakamoto K, Tsukioka S, Uchida J, Kiniwa M, Kobunai T, Takechi T, Takechi T, et al: Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice. Exp Ther Med 3: 755-762, 2012.
APA
Nukatsuka, M., Saito, H., Nakagawa, F., Tsujimoto, H., Sakamoto, K., Tsukioka, S. ... Takechi, T. (2012). Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice. Experimental and Therapeutic Medicine, 3, 755-762. https://doi.org/10.3892/etm.2012.484
MLA
Nukatsuka, M., Saito, H., Nakagawa, F., Tsujimoto, H., Sakamoto, K., Tsukioka, S., Uchida, J., Kiniwa, M., Kobunai, T., Takechi, T."Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice". Experimental and Therapeutic Medicine 3.5 (2012): 755-762.
Chicago
Nukatsuka, M., Saito, H., Nakagawa, F., Tsujimoto, H., Sakamoto, K., Tsukioka, S., Uchida, J., Kiniwa, M., Kobunai, T., Takechi, T."Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice". Experimental and Therapeutic Medicine 3, no. 5 (2012): 755-762. https://doi.org/10.3892/etm.2012.484
Copy and paste a formatted citation
x
Spandidos Publications style
Nukatsuka M, Saito H, Nakagawa F, Tsujimoto H, Sakamoto K, Tsukioka S, Uchida J, Kiniwa M, Kobunai T, Takechi T, Takechi T, et al: Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice. Exp Ther Med 3: 755-762, 2012.
APA
Nukatsuka, M., Saito, H., Nakagawa, F., Tsujimoto, H., Sakamoto, K., Tsukioka, S. ... Takechi, T. (2012). Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice. Experimental and Therapeutic Medicine, 3, 755-762. https://doi.org/10.3892/etm.2012.484
MLA
Nukatsuka, M., Saito, H., Nakagawa, F., Tsujimoto, H., Sakamoto, K., Tsukioka, S., Uchida, J., Kiniwa, M., Kobunai, T., Takechi, T."Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice". Experimental and Therapeutic Medicine 3.5 (2012): 755-762.
Chicago
Nukatsuka, M., Saito, H., Nakagawa, F., Tsujimoto, H., Sakamoto, K., Tsukioka, S., Uchida, J., Kiniwa, M., Kobunai, T., Takechi, T."Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice". Experimental and Therapeutic Medicine 3, no. 5 (2012): 755-762. https://doi.org/10.3892/etm.2012.484
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