Cell kinetic-directed sequential chemotherapy with cyclophosphamide and adriamycin in T1699 mammary tumors.
Cell kinetic-directed sequential chemotherapy with cyclophosphamide and adriamycin in T1699 mammary tumors.
复制标题
在 T1699 乳腺肿瘤中使用环磷酰胺和阿霉素进行细胞动力学定向序贯化疗。
作者：
P. Braunschweiger;Lewis M. Schiffer
本研究旨在研究阿霉素（5 mg/kg）和环磷酰胺（100 mg/kg）处理T1699小鼠可移植性乳腺肿瘤后，[3 H]脱氧胸苷标记指数、引物依赖性DNA聚合酶标记指数和S-G2转换的变化。用这些药物治疗导致低于正常的肿瘤细胞增殖的时间间隔，如[3 H]脱氧胸苷标记指数，引物依赖性DNA聚合酶标记指数和S-G2转换降低所示。阿霉素治疗后3天和环磷酰胺治疗后6 - 7天观察到恢复，如[3 H]脱氧胸苷标记指数、引物依赖性DNA聚合酶标记指数和S-G2转换增加所示。为了评估有效时间测序的动力学变化的预测性质，设计了序贯联合化疗方案并在T1699荷瘤小鼠中进行了测试。这些研究的结果表明，最有效的化疗方案是那些将药物测序以与单独使用单一药物的细胞动力学恢复相一致的方案。这些有效的测序间隔也被发现是有效的，当用于多部分序贯联合化疗方案。结果表明，药物干扰后细胞动力学参数的变化可以提供潜在有效和无效测序间隔的指示。
The present studies were initiated to investigate the changes [3H]deoxythymidine labeling index, primer-dependent DNA polymerase labeling index, and S-G2 transition after treatment of T1699 transplantable mouse mammary tumors with Adriamycin (5 mg/kg) and cyclophosphamide (100 mg/kg). Treatment with these agents resulted in intervals of subnormal tumor cell proliferation as indicated by decreased [3H]deoxythymidine labeling index, primer-dependent DNA polymerase labeling index, and S-G2 transition. Recovery, as indicated by increases in [3H]deoxythymidine labeling index, primer-dependent DNA polymerase labeling index, and S-G2 transition, was observed three days after Adriamycin treatment and six to seven days after cyclophosphamide treatment. To evaluate the predictive nature of the kinetic changes for effective time sequencing, sequential combination chemotherapy protocols were designed and tested in T1699 tumor-bearing mice. The results from these studies showed that the most effective chemotherapy schedules were those in which the drugs were sequenced to coincide with the cell kinetic recovery from the single agents alone. These effective sequencing intervals were also found to be effective when used in multifraction sequential combination chemotherapy protocols. The results suggest that changes in cell kinetic parameters following drug perturbation can provide indications as to potentially efficacious as well as nonefficacious sequencing intervals.