Fujimoto S, Igarashi K, Shrestha R D, Ohta M, Miyazaki M, Endoh F, Shimura T, Sugasawa H, Takahashi O, Kawata S
Gan To Kagaku Ryoho. 1986 Jan;13(1):60-4.
Hyperthermic treatment using ACNU combined with a thermosensitizing drug, methylglyoxal-bis-guanylhydrazone (MGBG), was studied in human gastric cancer xenotransplanted into nude mice. In order to increase the intra-cellular MGBG content, intraperitoneal injection of alpha-difluoromethylornithine(DFMO) 1000 mg/kg was performed twice with an interval of 6 hours and 50 mg/kg of MGBG was given at the time of the second administration of DFMO. After 6 hours of MGBG administration, ACNU 20 mg/kg was given intraperitoneally and, subsequently a 23-minute hyperthermia was carried out in a water bath at 43.5 degrees C. After 48 hours a second hyperthermia was performed by the same method. Tumor weight was estimated using Battelle's Columbus Institute protocol and the inoculated tumors, which were extirpated 60 minutes after 3H-thymidine injection at a prescribed interval after cessation of hyperthermia, were assayed biochemically for the determination of DNA biosynthesis. In mice given ACNU, DFMO, MGBG plus heat, considerably superior results were obtained. Although the DFMO plus MGBG group was inferior in antitumor activity to the ACNU only or heat only group, the DFMO, MGBG plus heat group showed much the same antitumor effects, compared to the ACNU plus heat group. These data suggest that the thermosensitizing efficacy of MGBG may be applicable for clinical use.
在移植到裸鼠体内的人胃癌模型中，研究了使用阿糖胞苷（ACNU）联合热敏药物甲基乙二醛双脒腙（MGBG）进行热疗的效果。为了增加细胞内MGBG的含量，腹腔注射1000mg/kg的α-二氟甲基鸟氨酸（DFMO），间隔6小时注射两次，在第二次注射DFMO时给予50mg/kg的MGBG。给予MGBG 6小时后，腹腔注射20mg/kg的ACNU，随后在43.5℃的水浴中进行23分钟的热疗。48小时后，用相同方法进行第二次热疗。使用巴特尔哥伦布研究所的方案估计肿瘤重量，并对热疗停止后在规定间隔时间注射3H-胸腺嘧啶核苷60分钟后切除的接种肿瘤进行生化分析，以测定DNA生物合成。在给予ACNU、DFMO、MGBG加加热的小鼠中，获得了相当优异的结果。虽然DFMO加MGBG组的抗肿瘤活性低于单独使用ACNU组或单独加热组，但与ACNU加热组相比，DFMO、MGBG加加热组显示出大致相同的抗肿瘤效果。这些数据表明，MGBG的热敏增效作用可能适用于临床应用。
