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Association of right-sided tumors with high thymidine phosphorylase gene expression levels and the response to oral uracil and tegafur/leucovorin chemotherapy among patients with colorectal cancer

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Abstract

Purpose

To identify useful predictive factors for the response to 5-fluorouracil (5-FU)/leucovorin (LV) and oral uracil and tegafur (UFT)/LV chemotherapy among patients with colorectal cancer, we investigated the association between the gene expression levels of pyrimidine and folate metabolism-related enzymes in colorectal cancer (CRC) tissues and the response to UFT/LV neoadjuvant chemotherapy.

Methods

The subjects were 76 CRC patients who were scheduled to undergo surgery. UFT (300 mg/m2/day) and LV (75 mg/body/day) were administered for 2 weeks before surgery. Biopsy samples were endoscopically obtained before drug administration. The gene expression levels of 14 genes in the biopsy samples were quantitatively evaluated using a real-time polymerase chain reaction (RT-PCR) assay.

Results

Fifteen patients (19.7 %) with marked pathological regression were judged to be responders. Thymidine phosphorylase (TP) gene expression levels among the responders were significantly higher than those among the non-responders. Right-sided tumors with high TP gene expression levels were associated with a significantly higher response rate to UFT/LV chemotherapy than left-sided tumors.

Conclusions

TP gene expression levels in primary CRC tissues and the primary tumor site may be useful predictors of the efficacy of oral UFT/LV chemotherapy.

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Conflict of interest

S. Sadahiro, T. Suzuki, A. Tanaka, and K. Okada have reported no potential conflicts of interest. H. Nagase and J. Uchida are employees of Taiho Pharmaceutical Co., Ltd.

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Authors and Affiliations

  1. Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya Isehara, Kanagawa, 259-1193, Japan

    Sotaro Sadahiro, Toshiyuki Suzuki, Akira Tanaka & Kazutake Okada

  2. Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2 Ebisuno Hiraishi, Kawauchi-cho, Tokushima, 771-0194, Japan

    Hideki Nagase & Junji Uchida

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  1. Sotaro Sadahiro
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  2. Toshiyuki Suzuki
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  3. Akira Tanaka
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Correspondence to Sotaro Sadahiro.

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Sadahiro, S., Suzuki, T., Tanaka, A. et al. Association of right-sided tumors with high thymidine phosphorylase gene expression levels and the response to oral uracil and tegafur/leucovorin chemotherapy among patients with colorectal cancer. Cancer Chemother Pharmacol 70, 285–291 (2012). https://doi.org/10.1007/s00280-012-1909-8

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