Khoo S K, Hurst T, Webb M J
Aust N Z J Obstet Gynaecol. 1985 Aug;25(3):215-20. doi: 10.1111/j.1479-828x.1985.tb00647.x.
There is a need for a predictive test which will assist in the selection of an effective cytotoxic drug and thereby, provide a means of avoiding unnecessary drug-induced toxicity and tumour resistance. In the present study, the viable fraction of the tumour cell suspension from ovarian cancer was used as targets for the effect of the drug, cisplatin, in a 3-hour in vitro assay. DNA synthesis was measured by the incorporation of 3H-thymidine as an index of proliferative activity and RNA synthesis by the incorporation of 3H-uridine as an index of protein metabolism. There was a good correlation between cell activity as determined by the uptake of thymidine and uridine. The degree of drug inhibition was variable over the spectrum of tumour histologic types; thymidine uptake was significantly inhibited by cisplatin in 53% of serous cystadenocarcinomas, and uridine uptake in 21% of tumours. A clear difference in drug effect was observed between those patients who showed clinical response and those who did not. These results support the value of this assay as an indicator of drug sensitivity of the tumour.
需要一种预测性测试,以协助选择有效的细胞毒性药物,从而提供一种避免不必要的药物诱导毒性和肿瘤耐药性的方法。在本研究中,在一项3小时的体外试验中,来自卵巢癌的肿瘤细胞悬液的存活分数被用作药物顺铂作用的靶标。通过掺入³H-胸腺嘧啶核苷来测量DNA合成,作为增殖活性的指标;通过掺入³H-尿苷来测量RNA合成,作为蛋白质代谢的指标。通过胸腺嘧啶核苷和尿苷摄取所确定的细胞活性之间存在良好的相关性。药物抑制程度在肿瘤组织学类型范围内是可变的;顺铂在53%的浆液性囊腺癌中显著抑制胸腺嘧啶核苷摄取,在21%的肿瘤中抑制尿苷摄取。在有临床反应的患者和无临床反应的患者之间观察到明显的药物效应差异。这些结果支持了该试验作为肿瘤药物敏感性指标的价值。