Nishihara E, Nagayama Y, Narimatsu M, Namba H, Watanabe M, Niwa M, Yamashita S
Department of Nature Medicine, Nagasaki University School of Medicine, Japan.
Anticancer Res. 1998 May-Jun;18(3A):1521-5.
To develop a suitable suicide gene/prodrug therapy for the treatment of thyroid carcinomas, the relative therapeutic efficacy of four different suicide gene/prodrug combinations was compared in thyroid carcinomas in vitro. Herpes simplex virus thymidine kinase and ganciclovir (HSV-TK/GCV), Escherichia coli cytosine deaminase and 5-fluorocytosine (CD/5FC), E coli nitroreductase and CB1954 (NTR/CB1954), and human deoxycytidine kinase and cytosine arabinoside (dCK/AraC) were employed. The suicide genes were transduced into two thyroid carcinoma cell lines with retroviral vectors in which all the suicide genes were under the control of the same promoter. When the relative efficacy of four suicide gene/prodrugs was compared with therapeutic index and degree of bystander effect, we found a clear dissociation between these two parameters. Thus, HSV-TKIGCV demonstrated the widest therapeutic index, while CD/5FC and NTR/CB1954 showed the stronger bystander effect than HSV-TK/GCV. dCK/AraC had little efficacy. Advantages and limitations of each suicide gene/prodrug combinations are discussed.
为开发一种适用于治疗甲状腺癌的自杀基因/前药疗法，在体外甲状腺癌模型中比较了四种不同自杀基因/前药组合的相对治疗效果。使用了单纯疱疹病毒胸苷激酶和更昔洛韦（HSV-TK/GCV）、大肠杆菌胞嘧啶脱氨酶和5-氟胞嘧啶（CD/5FC）、大肠杆菌硝基还原酶和CB1954（NTR/CB1954）以及人脱氧胞苷激酶和阿糖胞苷（dCK/AraC）。通过逆转录病毒载体将自杀基因导入两种甲状腺癌细胞系，所有自杀基因均受同一启动子控制。当比较四种自杀基因/前药的相对疗效与治疗指数及旁观者效应程度时，发现这两个参数之间存在明显差异。因此，HSV-TK/GCV表现出最宽的治疗指数，而CD/5FC和NTR/CB1954的旁观者效应比HSV-TK/GCV更强。dCK/AraC几乎没有疗效。讨论了每种自杀基因/前药组合的优缺点。
