The effect of neoadjuvant therapy on the 5-fluorouracil metabolic and relative enzymes of oral squamous cell carcinoma.
To assess the effect of neoadjuvant therapy using tegafur/uracil (UFT) and radiation therapy on the 5-fluorouracil (5-FU) metabolic and relative enzymes, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in oral squamous cell carcinoma (OSCC), we examined the mRNA expression and immunohistochemical staining status of these enzymes using 17 surgical specimens. Seven patients did not receive any neoadjuvant therapy and 10 were treated with UFT and local irradiation therapy. Our result showed that the mRNA expression of these enzymes in neoadjuvant group was not significantly different from that of non-treated group using real-time quantitative PCR. To confirm the protein expression, we also carried out immunohistological staining of TS and DPD two key enzymes in the 5-FU metabolism, using the same specimens. Immunohistological staining status did not correspond to the results of mRNA analysis completely, though no significant difference between the groups was observed. Furthermore, no significant relationship between the UFT administration period and mRNA expression of the 5-FU metabolic enzymes was observed in neoadjuvant therapy group and also the distribution of the enzyme mRNA expression levels was similar to that of non-treated group. The results suggested that the neoadjuvant therapy of OSCC might not affect the expression status of 5-FU metabolic and relative enzymes in surgical tumor samples and the tumor tissues might serve as a useful specimen source to analyze the expression status of the 5-FU metabolic and relative enzymes and to determine the prospective efficiency of 5-FU-based adjuvant chemotherapy.
Yamashita
Tomomi
T
Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. yamatomo@gifu-u.ac.jp
Toida
Makoto
M
Kato
Keizo
K
Long
Nguyen Khanh
NK
Miyazaki
Yasuo
Y
Asaka
Yuichiro
Y
Hatakeyama
Daijiro
D
Yonemoto
Kazuhiro
K
Makita
Hiroki
H
Kato
Yukihiro
Y
Shibata
Toshiyuki
T
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000032:analysis / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy*; D020360:Neoadjuvant Therapy; D009962:Orotate Phosphoribosyltransferase / Q000032:analysis / Q000235:genetics; D005641:Tegafur / Q000008:administration & dosage; D013939:Thymidine Phosphorylase / Q000032:analysis / Q000235:genetics; D013940:Thymidylate Synthase / Q000032:analysis / Q000235:genetics; D014498:Uracil / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil