Fujimoto S, Shrestha R D, Ohta M, Igarashi K, Miyazaki M, Endoh F, Shimura T, Takahashi O, Kawata S, Kurihara M
Gan To Kagaku Ryoho. 1986 Oct;13(10):3016-20.
Antitumor therapy using the polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), combined with ACNU was studied in human gastric cancer xenotransplanted into nude mice. DFMO 1,000 mg/kg (in two divided doses) and MGBG 50 mg/kg were given i.p. for 6 successive days from the time when the xenotransplanted tumor weighed about 100 mg, and ACNU 20 mg/kg was given i.p. every other day from the same time. Antitumor efficacy was assessed by the time course of tumor weight as well as of DNA biosynthesis and polyamine levels in tumor tissue. Tumor weight was estimated using Battelle's Columbus Institute protocol and DNA biosynthesis was assayed biochemically by 3H-TdR injection at a prescribed interval after termination of therapy. Furthermore, tumoral polyamine levels were assayed by HPLC. This three-drug regimen showed a favorable antitumor effect, compared to those of the other two therapies with DFMO plus MGBG as well as ACNU only. These data suggest that this combined regimen may have a synergistic efficacy judging from the action mechanisms of these three drugs.
在移植到裸鼠体内的人胃癌模型中，研究了使用多胺抗代谢物α-二氟甲基鸟氨酸（DFMO）和甲基乙二醛双脒腙（MGBG）联合阿糖胞苷（ACNU）进行抗肿瘤治疗的效果。从异种移植肿瘤重量约为100mg时起，连续6天腹腔注射DFMO 1000mg/kg（分两次给药）和MGBG 50mg/kg，同时从同一时间起每隔一天腹腔注射ACNU 20mg/kg。通过肿瘤重量的时间进程以及肿瘤组织中DNA生物合成和多胺水平来评估抗肿瘤疗效。使用巴特尔哥伦布研究所的方案估算肿瘤重量，并在治疗终止后的规定间隔通过注射3H-TdR进行生化分析以测定DNA生物合成。此外，通过高效液相色谱法测定肿瘤多胺水平。与DFMO加MGBG以及仅使用ACNU的其他两种治疗方法相比，这种三联疗法显示出良好的抗肿瘤效果。从这三种药物的作用机制判断，这些数据表明这种联合方案可能具有协同疗效。
