Additive effects of oral fluoropyrimidine derivative S-1 and radiation on human hypopharyngeal cancer xenografts
Additive effects of oral fluoropyrimidine derivative S-1 and radiation on human hypopharyngeal cancer xenografts
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DOI：
10.1080/00016480701784999
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发表时间：
2008-01-01
影响因子：
1.4
通讯作者：
Nibu, Ken-Ichi
中科院分区：
文献类型：
--
作者：
Nakagawa, Takahiro;Otsuki, Naoki;Nibu, Ken-Ichi
结论。本研究结果为口服氟嘧啶类化合物S-1在头颈部肿瘤同期放化疗中的增效作用提供了证据，并进一步揭示了其生物学机制。目标。目的：探讨S-1与放射治疗对人下咽癌的相加作用。材料和方法。以荷下咽癌细胞(H891)的裸鼠为动物模型。S 1号按0.01 mg/g体重剂量连续给药14d，第1、8天给予2.0Gy射线照射肿瘤，并设单纯照射组和单纯照射组小鼠为对照组。观察各组肿瘤生长情况，用聚焦DNA芯片检测与5-氟尿嘧啶(5-FU)、放射或致癌相关的132个基因在肿瘤中的表达水平。结果。在第14天，S-1与放射治疗相加的抗肿瘤作用被统计学证实(p=0.01)。DNA阵列分析显示，DNA修复基因pold、血管生成相关基因bFGF和TP、DNA拓扑异构酶TOP2A和核苷转运蛋白基因ENT1的表达发生了显著变化。
Conclusion. 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. Materials and 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.