山梨医科学雑誌　第22巻4号　071-078(2007)

＜Original Article＞
Chemoradiotherapy with 5-fluorouracil Inhibits the Expression of
Thymidylate Synthase and Dihydropyrimidine Dehydrogenase in
Head and Neck Squamous Cell Carcinoma

Takanobu SHIMADA, Shigetoshi HORIGUCHI, Yoshitaka OKAMOTO,
Zennsei MATSUZAKI, and Keisuke MASUYAMA

Abstract: In order to examine the effect of chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) on thymidylate synthase/dihydropyrimidine dehydrogenase (TS/DPD), the expressions and activities of TS/DPD of the tumors in head and neck squamous cell carcinoma (HNSCC) were examined and evaluated in tumors from the subjects with HNSCC before treatment, in residual tumors after CRT, and in recurrent tumors after a complete response (CR) with CRT. Thirty tissue samples were excised from 26 patients with HNSCC. TS/DPD activities were determined with a tritium release-assay and a radio-enzymatic assay, and the protein contents were evaluated by immunohistochemistry. The mean TS/DPD activities of the residual tumors after CRT were significantly lower than those of the beforetreatment and recurrent tumors. No significant difference was observed between these values in the before-treatment and recurrent tumors. Furthermore, observations obtained from the same subjects with HNSCC before and after CRT demonstrated the TS/DPD enzymatic expressions to be suppressed by CRT with 5-FU; however, they returned to the previous levels when the tumor recurred.These results indicate that 5-FU chemotherapy immediately after CRT may therefore be an effective treatment for residual tumors.

Key words: thymidylate synthase, dihydropyrimidine dehydrogenase, 5-fluorouracil, head and neck squamous cell carcinoma




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