Experimental Chemotherapy

Correlations between Thymidylate Synthase Expression and Chemosensitivity to 5-Fluorouracil, Cell Proliferation and Clinical Outcome in Head and Neck Squamous Cell Carcinoma
Ryuji Yasumatsu^a, Torahiko Nakashima^a, Hideoki Uryu^a, Toranoshin Ayada^a, Takahiro Wakasaki^a, Ryunosuke Kogo^a, Muneyuki Masuda^a, Masakazu Fukushima^b, Shizuo Komune<sup>a

a</sup>Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, and
^bCancer Research Laboratory, Taiho Pharmaceutical Co. Ltd., Saitama, Japan

Address of Corresponding Author

Chemotherapy 2009;55:36-41 (DOI: 10.1159/000175465)

  Key Words

• Cell proliferation
• 5-Fluorouracil
• Head-neck squamous cell carcinoma
• Thymidylate synthase

  Abstract

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 cellsin 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.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Ryuji Yasumatsu, MD
Department of Otorhinolaryngology, Graduate School of Medical Sciences
Kyushu University, 3-1-1 Maidashi, Higashi-ku
Fukuoka 812-8582 (Japan)
Tel. +81 92 642 5668, Fax +81 92 642 5685, E-Mail yasuryuj@qent.med.kyushu-u.ac.jp

  Article Information

Received: June 9, 2008
Accepted after revision: September 23, 2008
Published online: November 21, 2008
Number of Print Pages : 6
Number of Figures : 5, Number of Tables : 1, Number of References : 26