Yoshida T, Shimizu K, Mogami H, Egawa T, Sakamoto Y
Gan To Kagaku Ryoho. 1987 Jan;14(1):84-90.
A nitrosourea derivative, ACNU (nimustine hydrochloride), is often used in the chemotherapy of brain tumors and shows considerable efficacy, since it crosses the blood-brain barrier (B.B.B.). This drug is also considered to be useful for intrathecal treatment of meningeal gliomatosis (MG) because of its short half-life in the blood or cerebrospinal fluid (CSF) and its strong cytotoxicity for glioma cells. In order to evaluate the efficacy of intrathecal therapy of MG with ACNU, MG models, which were produced by intracisternal inoculation of rat C6 glioma, were treated with intrathecal or intravenous administration of ACNU. When intrathecally administered 1 day or 3 days after tumor inoculation, ACNU (1 mg/kg) significantly prolonged the survival time of MG rats, where ILS was 35.7 to 42.9% and 24.1 to 25.0%, respectively. In MG rats which were treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or intravenously with ACNU (15 mg/kg), ACNU failed to prolong survival time compared with the controls. It might therefore be suggested that intrathecal chemotherapy with a low dose of ACNU is effective in the early stages of MG, in which intravenous treatment with a high dose of ACNU is ineffective.
亚硝基脲衍生物ACNU(盐酸尼莫司汀)常用于脑肿瘤化疗,因其能穿过血脑屏障(BBB),故而疗效显著。由于该药物在血液或脑脊液(CSF)中的半衰期较短,且对胶质瘤细胞具有较强的细胞毒性,所以也被认为可用于鞘内治疗脑膜胶质瘤病(MG)。为评估ACNU鞘内治疗MG的疗效,通过脑池内接种大鼠C6胶质瘤构建MG模型,分别采用鞘内或静脉注射ACNU进行治疗。在肿瘤接种后1天或3天进行鞘内给药时,ACNU(1mg/kg)可显著延长MG大鼠的生存时间,其生命延长率分别为35.7%至42.9%和24.1%至25.0%。在肿瘤接种后5天进行鞘内注射ACNU(1mg/kg)或静脉注射ACNU(15mg/kg)的MG大鼠中,与对照组相比,ACNU未能延长生存时间。因此,可能提示低剂量ACNU鞘内化疗在MG早期有效,而高剂量ACNU静脉治疗无效。