Davol P, Beitz J G, Mohler M, Ying W, Cook J, Lappi D A, Frackelton A R
Department of Medicine, Roger Williams Medical Center, Providence, RI 02908, USA.
Cancer. 1995 Jul 1;76(1):79-85. doi: 10.1002/1097-0142(19950701)76:1<79::aid-cncr2820760111>3.0.co;2-g.
The antitumor activity of the chemical conjugate and recombinant forms of the mitotoxin basic fibroblast growth factor (bFGF) saporin (SAP) and the bFGF receptor-directed immunotoxin 11A8-SAP against human ovarian teratocarcinoma PA-1 was examined in athymic nude mice. Alternative administration schedules to prolong therapeutic efficacy were explored.
Intravenous dosing (0.01-125 micrograms/kg) of chemical conjugate and recombinant bFGF-SAP or 11A8-SAP beginning 5 days after subcutaneous implantation of PA-1 cells was administered by i) weekly injection for 4 weeks, ii) continuous infusion for one week, or iii) daily injection five times a week for 4 weeks.
Weekly injections (31.25 micrograms/kg) of chemical conjugate bFGF-SAP or 11A8-SAP, the latter of which is 25% the molarity of the former, resulted in mean tumor volumes that were, respectively, 35% or 52% of controls (day 30) and 52% or 76% of controls (day 60). Chemical conjugate or recombinant bFGF-SAP administered weekly resulted in mean tumor volumes that were, respectively, 51% or 77% (0.5 microgram/kg) and 42% or 31% (50 micrograms/kg) of controls (day 30). A mean tumor volume of 35% of controls (day 30) and of 49% of controls (day 60) were observed in animals treated by constant infusion of chemical conjugate bFGF-SAP (125 micrograms/kg, total dose). Alternatively, tumors of animals receiving daily injections (125 micrograms/kg, total dose) exhibited a mean volume of 21% of controls (day 30) and prolonged growth inhibition as demonstrated by a mean tumor volume of 22% of controls (day 60).
These studies suggest a therapeutic potential for bFGF-receptor-directed saporin toxins in the treatment of ovarian teratocarcinoma and the importance of frequency of administration in achieving optimal tumor responses.
在无胸腺裸鼠中检测了化学偶联物和重组形式的促有丝分裂毒素碱性成纤维细胞生长因子（bFGF）皂草素（SAP）以及bFGF受体导向免疫毒素11A8 - SAP对人卵巢畸胎瘤PA - 1的抗肿瘤活性。探索了延长治疗效果的替代给药方案。
在皮下植入PA - 1细胞5天后开始静脉给药（0.01 - 125微克/千克）化学偶联物和重组bFGF - SAP或11A8 - SAP，给药方式为：i）每周注射1次，共4周；ii）持续输注1周；或iii）每周5次每日注射，共4周。
每周注射（31.25微克/千克）化学偶联物bFGF - SAP或11A8 - SAP，后者的摩尔浓度是前者的25%，结果显示平均肿瘤体积在第30天分别为对照组的35%或52%，在第60天分别为对照组的52%或76%。每周注射化学偶联物或重组bFGF - SAP，在第30天平均肿瘤体积分别为对照组的51%或77%（0.5微克/千克）以及42%或31%（50微克/千克）。持续输注化学偶联物bFGF - SAP（125微克/千克，总剂量）的动物，在第30天平均肿瘤体积为对照组的35%，在第60天为对照组的49%。另外，每日注射（125微克/千克，总剂量）的动物肿瘤平均体积在第30天为对照组的21%，并且生长抑制延长，在第60天平均肿瘤体积为对照组的22%。
这些研究表明bFGF受体导向的皂草素毒素在治疗卵巢畸胎瘤方面具有治疗潜力，且给药频率对于实现最佳肿瘤反应很重要。
