Boven E, Nauta M M, Schluper H M, Elferink F, van der Vijgh W J, Pinedo H M
Eur J Cancer Clin Oncol. 1985 Oct;21(10):1253-60. doi: 10.1016/0277-5379(85)90023-9.
Five TNO platinum compounds were evaluated for antitumor activities in two human ovarian carcinoma tumor lines grown in nude mice. The most active drug, TNO-38, was investigated in five additional lines with a known range of sensitivity to cisplatin. None of the new compounds showed superior activity to cisplatin. The slightly lower activity of TNO-38 as compared to the parent compound was reproducible in all tumor lines. Besides the similarity in the antitumor activity, a remarkable correspondence in platinum distribution and retention at 24 hr of TNO-38 and cisplatin could be observed. Chromatographic analysis of the compounds in their injection fluids showed single peaks for TNO-26 and TNO-38. The degradation products of the latter drugs may have affected their activity and toxicity. These human ovarian cancer xenografts may offer a reliable screening model for selection of a cisplatin analog with a higher therapeutic index or without cross-resistance for treatment in ovarian cancer.
对五种TNO铂化合物在裸鼠体内生长的两个人类卵巢癌肿瘤系中进行了抗肿瘤活性评估。最具活性的药物TNO - 38，在另外五个对顺铂敏感性已知的肿瘤系中进行了研究。没有一种新化合物显示出比顺铂更优越的活性。与母体化合物相比，TNO - 38活性略低，这在所有肿瘤系中均可重现。除了抗肿瘤活性相似外，还可观察到TNO - 38和顺铂在24小时时铂分布和保留情况有显著对应关系。对其注射液中的化合物进行色谱分析显示，TNO - 26和TNO - 38为单峰。后一种药物的降解产物可能影响了它们的活性和毒性。这些人卵巢癌异种移植瘤可能为选择具有更高治疗指数或无交叉耐药性的顺铂类似物用于卵巢癌治疗提供一个可靠的筛选模型。
