Kakeji Y, Teicher B A
Dana-Farber Cancer Institute, Boston, MA 021150, USA.
Invest New Drugs. 1997;15(1):39-48. doi: 10.1023/a:1005718628223.
TNP-740, minocycline, suramin and genistein have demonstrated antiangiogenic activity in various experimental systems. The effect of these agents alone and in two agent combinations on the number of intratumoral vessels and response to cytotoxic anticancer therapies was assessed in animals bearing the Lewis lung carcinoma. Treatment with each of the antiangiogenic agents alone and in two agent combinations decreased the number of intratumoral vessels visualized by CD31 or Factor VIII staining to 30% to 50% of the number in the untreated control tumors. In general, the antiangiogenic agents are more effective adjuvants to cytotoxic therapies when used as two agent combinations than as single agents. The most effective antiangiogenic combinations were: TNP-470/minocycline > TNP-470/genistein > TNP-470/suramin. The increases in the response of the primary tumor to cyclophosphamide, adriamycin, CDDP, BCNU, x-rays or 5-fluorouracil and the lung metastases occur to about the same level with the addition of antiangiogenic agents to the therapies. With the treatment combination TNP-470/minocycline/cyclophosphamide 40% of the animals were cured. The results of these studies indicate that antiangiogenic agents can be very useful additions to treatment regimens for solid tumors.
TNP - 740、米诺环素、苏拉明和染料木黄酮在各种实验系统中均已显示出抗血管生成活性。在携带Lewis肺癌的动物中，评估了这些药物单独使用以及两种药物联合使用对肿瘤内血管数量和细胞毒性抗癌治疗反应的影响。单独使用每种抗血管生成药物以及两种药物联合使用，均可使通过CD31或因子VIII染色显示的肿瘤内血管数量减少至未治疗对照肿瘤中血管数量的30%至50%。一般来说，抗血管生成药物作为两种药物联合使用时，作为细胞毒性疗法的佐剂比单独使用时更有效。最有效的抗血管生成组合为：TNP - 470/米诺环素＞TNP - 470/染料木黄酮＞TNP - 470/苏拉明。在治疗中添加抗血管生成药物后，原发肿瘤对环磷酰胺、阿霉素、顺铂、卡氮芥、X射线或5 - 氟尿嘧啶的反应增加以及肺转移的发生率达到大致相同的水平。使用TNP - 470/米诺环素/环磷酰胺联合治疗时，40%的动物被治愈。这些研究结果表明，抗血管生成药物可非常有效地添加到实体瘤的治疗方案中。
