摘要
目的 以人肾母细胞瘤裸鼠异种移植瘤模型 ,研究 5 氟胞嘧啶 (5 FC)作为原药对表达胞嘧啶脱氨酶 (CD)的肾母细胞瘤治疗 (以下简称CD/ 5 FC)的作用。方法 1例低分化肾母细胞瘤组织 ,移植于无胸腺BALB/c裸鼠 ,经连续传代 ,建立了人肾母细胞瘤异种移植瘤模型。以腺病毒为载体 ,分别建立CD基因 (Ad/CMV CD)和lac基因 (Ad/CMV lac)的表达载体。瘤内注射基因表达载体 ,使基因转导入肿瘤细胞。用RT PCR检测转导基因在瘤细胞内的表达。腹腔注射 5 FC ,5 0 0mg·kg-1·d-1,连续 10d ,观察移植瘤生长情况。结果 经 5 FC治疗的小鼠 ,表达lac基因的移植瘤生长情况与未转导基因的移植瘤并无两样 ;表达CD基因的移植瘤生长则受到显著抑制。根据接种肿瘤后 8周的肿瘤重量 ,5 FC治疗对CD基因转导的移植瘤生长抑制率为 6 5 %。病理检查可见瘤细胞坏死 ,细胞器出现空泡。结论 在瘤内转导CD基因的基础上施以 5 FC治疗 ,对人肾母细胞瘤裸鼠移植瘤有明显疗效。
Objective To study the effect of 5 fluorocytosine (5 FC) as prodrug in the treatment of Wilms′ tumor xenografts transduced with cytosine deaminase (CD) gene.Methods An in vivo model of a poorly differentiated Wilms′ tumor transplanted in nude mice was established. Expression adenoviral vector of CD gene (Ad/CMV CD) or lac gene (Ad/CMV lac) was transduced to the tumor xenografts by intratumoral injections. Expression of the transduced genes were confirmed by RT PCR. Mice with Wilms′ tumor xenograft were treated with 5 FC (500 mg·kg -1 ·d -1 ×10d). Tumor growth was monitored.Results The growth of tumor xenografts transduced with lac gene grew as quick as the untransduced ones. In contrast, the growth of the tumor xenografts transduced with CD gene was significantly inhibited as compared to untransduced and lac gene transduced xenografts. The average rate of inhibition was 65% according to the tumor weight at 8 wk. Cell necrosis was observed in the CD gene transduced tumors. Conclusion Intratumoral cytosine deaminase gene transduction followed by systemic 5 fluorocytosine is effective in the treatment of Wilms′ tumor. Subject
出处
《中华肿瘤杂志》
CSCD
北大核心
2000年第2期113-115,共3页
Chinese Journal of Oncology
基金
国家自然科学基金!资助项目 (39570 72 4 )
关键词
肾母细胞瘤
药物疗法
氟胞嘧啶
胞嘧啶脱氨酶
Wilms' tumor/drug therapy
5 fluorocytosine
Cytosine deaminase
CD gene
