Kammertoens T, Gelbmann W, Karle P, Alton K, Saller R, Salmons B, Günzburg W H, Uckert W
Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
Cancer Gene Ther. 2000 Apr;7(4):629-36. doi: 10.1038/sj.cgt.7700139.
The success of chemotherapeutic intervention is limited because the necessary high local drug doses cannot be achieved without systemic toxicity. Application of suicide genes (SGs) and direct conversion of prodrugs (PDs) to toxic metabolites in situ by SGs may enhance the efficacy of chemotherapy. To evaluate this strategy in two murine breast cancer models, TS/A and GR, we injected cellulose sulfate capsules harboring cat kidney cells expressing the SGs cytosine deaminase and cytochrome P450 2B1 (CYP2B1) intratumorally. The PDs 5-fluorocytosine and ifosfamide were administered in 3-day intervals. The effect of in situ chemotherapy with each PD alone and the combination was analyzed over a period of 100 days. The results reveal that for TS/A tumors, the antitumoral effect mediated by CYP2B1 is more efficient than that of cytosine deaminase, whereas for GR tumors, both systems worked equally well. Furthermore, we find additive toxicity using both SG/PD systems for both TS/A and GR tumors.
化疗干预的成功受到限制，因为在不产生全身毒性的情况下无法达到所需的高局部药物剂量。应用自杀基因（SGs）以及通过SGs将前体药物（PDs）原位直接转化为有毒代谢物可能会提高化疗效果。为了在两种小鼠乳腺癌模型TS/A和GR中评估该策略，我们将携带表达SGs胞嘧啶脱氨酶和细胞色素P450 2B1（CYP2B1）的猫肾细胞的硫酸纤维素胶囊瘤内注射。每隔3天给予PDs 5-氟胞嘧啶和异环磷酰胺。在100天的时间内分析了单独使用每种PD以及联合使用时原位化疗的效果。结果显示，对于TS/A肿瘤，CYP2B1介导的抗肿瘤作用比胞嘧啶脱氨酶更有效，而对于GR肿瘤，两种系统的效果相同。此外，我们发现对于TS/A和GR肿瘤，使用两种SG/PD系统均具有累加毒性。
