Riondel J, Jacrot M, Fessi H, Puisieux F
Laboratoire de Physiologie et Pharmacologie I, Faculté de Pharmacie de Grenoble, La Tronche, France.
In Vivo. 1992 Jan-Feb;6(1):23-7.
Free taxol and liposome-encapsulated taxol were compared for their antitumoral activities on two human brain tumors serially grafted into female athymic mice in the scapular region. In the first experiment, a human glioblastoma (15th and 16th passages) was studied. In the second experiment, a fast growing human gliosarcoma (19th passage) was used. Free taxol and liposomal taxol were administered intraperitoneally, at the same dose; 12.5 mg/kg (i.e. 1/15 of the evaluated LD 50 value). In the first experiment, the treatment was performed for four consecutive days, with four courses separated by three rest periods of three days in between. Both free taxol and encapsulated taxol produced a statistically significant delay in tumor growth, and at the end of the experiment some total tumor regressions were obtained. However, liposomes were observed to be more effective in their action on the two consecutive passages of the glioblastoma, giving a marked increase of the number of total tumor regressions. In the second experiment another schedule of treatment was chosen because of the fast growth pattern of the xenografted human gliosarcoma: free taxol and liposome-encapsulated taxol were administered for five consecutive days and three courses of treatment were performed with two rest periods of two days. The two forms of taxol had a significant inhibitory effect on gliosarcoma tumor growth; as before encapsulation in liposomes was found to increase the anti-tumoral activity of taxol, although, in this case no tumor regression was observed.
对游离紫杉醇和脂质体包裹的紫杉醇在两种连续移植到雌性无胸腺小鼠肩胛区的人脑肿瘤上的抗肿瘤活性进行了比较。在第一个实验中,研究了一株人胶质母细胞瘤(第15和16代)。在第二个实验中,使用了一株快速生长的人胶质肉瘤(第19代)。游离紫杉醇和脂质体紫杉醇以相同剂量腹腔注射;12.5mg/kg(即评估的LD50值的1/15)。在第一个实验中,连续四天进行治疗,四个疗程之间间隔三天休息期。游离紫杉醇和包裹的紫杉醇均使肿瘤生长出现统计学上显著的延迟,并且在实验结束时获得了一些肿瘤完全消退。然而,观察到脂质体对胶质母细胞瘤的连续两代的作用更有效,使肿瘤完全消退的数量显著增加。在第二个实验中,由于异种移植的人胶质肉瘤生长迅速,选择了另一种治疗方案:游离紫杉醇和脂质体包裹的紫杉醇连续五天给药,进行三个疗程的治疗,中间有两个两天的休息期。两种形式的紫杉醇对胶质肉瘤肿瘤生长均有显著抑制作用;如前所述,脂质体包裹被发现可增强紫杉醇的抗肿瘤活性,尽管在这种情况下未观察到肿瘤消退。