Aaron R H, Elion G B, Colvin O M, Graham M, Keir S, Bigner D D, Friedman H S
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
Cancer Chemother Pharmacol. 1994;35(2):127-31. doi: 10.1007/BF00686634.
We evaluated the antitumor activity of busulfan against a panel of tumor cell lines and xenografts in athymic nude mice derived from childhood high-grade glioma, adult high-grade glioma, ependymoma, and medulloblastoma. Busulfan displayed similar activity against a panel of four medulloblastoma cell lines (D283 Med, Daoy, D341 Med, and D425 Med) and four corresponding sublines with laboratory-generated or clinically acquired resistance to 4-hydroperoxycyclophosphamide [D283 Med (4-HCR), Daoy (4-HCR), D341 Med (4-HCR), and D458 Med] and cross-resistance to melphalan. This is consistent with a nearly total lack of cross-resistance of busulfan to 4-hydroperoxycyclophosphamide. Busulfan was active in the therapy of all but one of the subcutaneous xenografts tested, with growth delays ranging from 14.3 days in D612 EP to 58.4 days in D528 EP. Busulfan produced statistically significant increases in the median survival of mice bearing intracranial D456 MG (66%-90%), D612 EP (18%-33%), and D528 EP (89%) xenografts. These studies suggest that busulfan may be active against medulloblastomas, high-grade gliomas, and ependymomas as well as against cyclophosphamide-resistant neoplasms.
我们评估了白消安对一组肿瘤细胞系以及源自儿童高级别胶质瘤、成人高级别胶质瘤、室管膜瘤和髓母细胞瘤的无胸腺裸鼠异种移植瘤的抗肿瘤活性。白消安对一组四种髓母细胞瘤细胞系（D283 Med、Daoy、D341 Med和D425 Med）以及四种对4-氢过氧环磷酰胺具有实验室诱导或临床获得性耐药性的相应亚系[D283 Med (4-HCR)、Daoy (4-HCR)、D341 Med (4-HCR) 和D458 Med] 显示出相似的活性，并且对美法仑存在交叉耐药性。这与白消安对4-氢过氧环磷酰胺几乎完全缺乏交叉耐药性是一致的。除一个测试的皮下异种移植瘤外，白消安对所有其他异种移植瘤的治疗均有活性，生长延迟范围从D612 EP的14.3天到D528 EP的58.4天。白消安使携带颅内D456 MG（66%-90%）、D612 EP（18%-33%）和D528 EP（89%）异种移植瘤的小鼠的中位生存期有统计学意义的增加。这些研究表明，白消安可能对髓母细胞瘤、高级别胶质瘤和室管膜瘤以及对环磷酰胺耐药的肿瘤有活性。
