title: The effect of neoadjuvant therapy on the 5-fluorouracil metabolic and relative enzymes of oral squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. yamatomo@gifu-u.ac.jp
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Makoto
authors.initials: M
authors.lastname: Toida
authors.forename: Keizo
authors.initials: K
authors.lastname: Kato
authors.forename: Nguyen Khanh
authors.initials: NK
authors.lastname: Long
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Asaka
authors.forename: Daijiro
authors.initials: D
authors.lastname: Hatakeyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yonemoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Makita
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shibata
mesh_terms: 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
chemical_list: D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil