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人髓母细胞瘤化学敏感性的体外与体内相关性

In vitro versus in vivo correlations of chemosensitivity of human medulloblastoma.

作者信息

Friedman H S, Schold S C, Muhlbaier L H, Bjornsson T D, Bigner D D

出版信息

Cancer Res. 1984 Nov;44(11):5145-9.

PMID:6488174
Abstract

An in vitro clonogenic assay was used to test the chemosensitivity of the human medulloblastoma cell line TE-671. Dose-response relationships for reduction in colony formation were generated for cyclophosphamide, vincristine, Adriamycin, 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC 409962), and 1,4-cyclohexadiene-1,4-dicarbamic acid, 2,5-bis(1-aziridinyl)-3,6-dioxo-diethylester (NSC 182986); and the in vitro drug dose at which there is a 75% reduction in the number of colonies in comparison to controls (ID75S) were derived from these data. Methotrexate produced no colony reduction at any dose tested up to 1000 micrograms/ml. The in vitro results were compared to growth delays in s.c. TE-671 xenografts in athymic mice treated with the same agents. Agents with an ID75 less than assumed in vivo plasma drug concentrations were all active in vivo, whereas two of the three agents with an ID75 greater than assumed in vivo plasma drug concentrations demonstrated no in vivo activity. These results suggest that for these agents, the relationship between the ID75 of the drug and its in vivo concentration allows in vitro clonogenic assay results to agree with in vivo growth delay responses.

摘要

采用体外克隆形成试验检测人髓母细胞瘤细胞系TE - 671的化学敏感性。针对环磷酰胺、长春新碱、阿霉素、1,3 - 双(2 - 氯乙基)-1 - 亚硝基脲(NSC 409962)和1,4 - 环己二烯 - 1,4 - 二氨基甲酸 - 2,5 - 双(1 - 氮丙啶基)-3,6 - 二氧代 - 二乙酯(NSC 182986),生成了集落形成减少的剂量 - 反应关系;并根据这些数据得出与对照相比集落数量减少75%时的体外药物剂量(ID75S)。甲氨蝶呤在高达1000微克/毫升的任何测试剂量下均未导致集落减少。将体外结果与用相同药物处理的无胸腺小鼠体内TE - 671异种移植瘤的生长延迟情况进行比较。ID75低于假定体内血浆药物浓度的药物在体内均有活性,而ID75高于假定体内血浆药物浓度的三种药物中有两种在体内无活性。这些结果表明,对于这些药物,药物的ID75与其体内浓度之间的关系使得体外克隆形成试验结果与体内生长延迟反应一致。

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