Correlations between thymidylate synthase expression and chemosensitivity to 5-fluorouracil, cell proliferation and clinical outcome in head and neck squamous cell carcinoma.
BACKGROUND
5-Fluorouracil (5-FU) is a widely used drug in head and neck squamous cell carcinoma (HNSCC). Thymidylate synthase (TS), which is the target enzyme of 5-FU, has been demonstrated to be a key regulatory enzyme. In this study, we examined whether TS expression is correlated with chemosensitivity to 5-FU, cell proliferation and clinical outcome in HNSCC.


METHODS
An antisense TS cDNA was constitutively expressed in the HNSCC cell line. The effects of TS expression on in vitro cell growth and 5-FU cytotoxicity were examined. We also evaluated the association between TS expression and cell proliferation in surgical specimens, and prognosis in HNSCC patients.


RESULTS
Antisense TS transfection increases the cytotoxicity of 5-FU and inhibits cell proliferation in HNSCC cells in vitro. Immunohistochemical expression of TS may have prognostic value in patients with HNSCC.


CONCLUSIONS
These results indicate that TS expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy.
Yasumatsu
Ryuji
R
Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. yasuryuj@qent.med.kyushu-u.ac.jp
Nakashima
Torahiko
T
Uryu
Hideoki
H
Ayada
Toranoshin
T
Wakasaki
Takahiro
T
Kogo
Ryunosuke
R
Masuda
Muneyuki
M
Fukushima
Masakazu
M
Komune
Shizuo
S
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil