In vivo combination of misonidazole and the chemotherapeutic agent CCNU.

In vivo combination of misonidazole and the chemotherapeutic agent CCNU.
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米索硝唑和化疗剂 CCNU 的体内组合。

DOI:
10.1038/bjc.1981.57
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发表时间:
1981
影响因子:
8.8
通讯作者:
Siemann,DW
Siemann,DW
中科院分区:
医学1区
文献类型:
--
作者:
Siemann,DW

文献摘要

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肌内生长的KHT肉瘤对化疗剂(1-(2-氯乙基)-3-环己基-1-亚硝基脲(CCNU)单独或同时与化学放射增敏剂米索咪唑(MISO))的反应进行了评估,使用肿瘤生长延迟试验或体内-体外肿瘤切除试验。20 mg/kg环己亚硝脲与0.5或1.0 mg/g MISO联合给药后的中位肿瘤生长延迟时间为19.5和21.5天,而单独使用该剂量的环己亚硝脲为10天。在用20 mg/kg环己亚硝脲加1.0 mg/g MISO处理的RIF-1肿瘤中,观察到MISO对肿瘤反应的增强程度相似(肿瘤生长延迟因子约为2)。KHT肉瘤的克隆原性细胞存活研究表明,MISO以0.25、0.5或1.0 mg/g的剂量与一系列CCNU剂量同时给药,产生的剂量修饰因子(DMF)分别为1.9、2.1和2.4。通过LD 50/7测定法评估的正常组织毒性导致CCNU剂量与0.5和1.0 mg/g MISO组合的DMF为1.2和1.4。因此,在该动物肿瘤模型中,CCNU和MISO的组合似乎导致约1.7倍的潜在增益。
The response of intramuscularly growing KHT sarcomas to the chemotherapeutic agent (1-(2-cloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) alone or simultaneously with the chemical radio-sensitizer misonidazole (MISO) was assessed using either a tumour growth-delay assay or an in vivo-in vitro tumour-excision assay. Median tumour growth delay following the combination of 20 mg/kg CCNU and either 0.5 or 1.0 mg/g MISO was 19.5 and 21.5 days, compared to 10 days for this CCNU dose alone. A similar degree of enhanced tumour response by MISO (factor of approximately 2 in tumour growth delay) was seen in RIF-1 tumours treated with 20 mg/kg CCNU plus 1.0 mg/g MISO. Clonogenic cell-survival studies with KHT sarcomas demonstrated that MISO at doses of 0.25, 0.5 or 1.0 mg/g given simultaneously with a range of CCNU doses produced dose-modifying factors (DMFs) of 1.9, 2.1 and 2.4 respectively. Normal tissue toxicity assessed by an LD50/7 assay led to DMFs of 1.2 and 1.4 for CCNU doses combined with 0.5 and 1.0 mg/g MISO. Thus in this animal tumour model the combination of CCNU and MISO appears to lead to a potential gain by a factor of approximately 1.7.