Additive effects of oral fluoropyrimidine derivative S-1 and radiation on human hypopharyngeal cancer xenografts.
CONCLUSIONS
The results presented here provide evidence of the enhancing effect of oral fluoropyrimidine derivative S-1 in concomitant chemoradiotherapy for head and neck cancer and further insights into its biological mechanism.


OBJECTIVE
To investigate the additive effect of S-1 and radiation for human hypopharyngeal cancer.


METHODS
Nude mice bearing hypopharyngeal cancer cells (H891) were used for an in vivo model. S-1 was administered at a volume of 0.01 mg/g body weight per mouse for 14 days, and tumors were irradiated with 2.0 Gy on days 1 and 8. Mice treated with either radiation or S-1 alone were used as controls. The growth of tumors in each group was measured and, after completion of the treatment, a focused DNA array was used to determine mRNA expression levels in the tumors of 132 genes related to 5-fluorouracil (5-FU), radiation or carcinogenesis.


RESULTS
The additive antitumor effect of S-1 and radiation was statistically confirmed on day 14 (p=0.01). DNA array assay showed significant changes in expression of several genes, including DNA repair gene POLD, angiogenesis-related genes bFGF and TP, DNA topoisomerase TOP2A, and nucleoside transporter gene ENT1.
Nakagawa
Takahiro
T
Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Otsuki
Naoki
N
Masai
Yohko
Y
Sasaki
Ryohei
R
Tsukuda
Mamoru
M
Nibu
Ken-Ichi
K
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004338:Drug Combinations; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010094:Oxonic Acid / Q000008:administration & dosage*; D005641:Tegafur / Q000008:administration & dosage*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil