Toyota N, Strebel F R, Stephens L C, Rowe W, Matsuda H, Oshiro T, Jenkins G N, Bull J M
First Department of Surgery, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.
Oncol Rep. 1998 Sep-Oct;5(5):1231-6. doi: 10.3892/or.5.5.1231.
We investigated the correlation between antitumor efficacy and kinetics of tumor and normal tissue apoptosis when cis-diamminedichloroplatinum (II) (CDDP) was combined with two different durations of whole body hyperthermia [SH-WBH, at 41.5 degrees C for 1 h (1 h WBH) or 2 h (2 h WBH)]. Rats bearing a mammary adenocarcinoma (MTLn3) were treated with 1 or 2 h WBH CDDP and then assessed for tumor growth delay (TGD). A separate study examined the amount of induced apoptosis in tumor and normal tissue (thymus and ileum) over 96 h following the same treatments. 1 h WBH + CDDP increased the TGD to 10.5+/-0.5 days, which was not statistically different from the TGD of 12.3+/-0.5 days obtained with 2 h WBH + CDDP. The area under the curve (AUC) of percentage tumor apoptosis for 1 h WBH + CDDP was 50% of that of 2 h WBH + CDDP. The AUC of percentage thymus apoptosis for 1 h WBH + CDDP was 25% of that of 2 h WBH + CDDP, and the AUC of the score of ileal apoptosis for 1 h WBH + CDDP was 81% of that of 2 h WBH + CDDP. These data indicate that while 1 h WBH + CDDP induced less tumor apoptosis than 2 h WBH + CDDP, antitumor activity was enhanced to a similar degree by both 1 h and 2 h WBH + CDDP, and since 1 h WBH + CDDP caused less normal tissue apoptosis than 2 h WBH + CDDP, a 1 h duration of WBH + CDDP may be a therapy that is both, as effective as, and safer than a 2 h duration of WBH + CDDP.
我们研究了顺二氯二氨铂（II）（CDDP）与两种不同时长的全身热疗[短时间全身热疗（SH-WBH），41.5摄氏度持续1小时（1小时WBH）或2小时（2小时WBH）]联合使用时，抗肿瘤疗效与肿瘤及正常组织凋亡动力学之间的相关性。对患有乳腺腺癌（MTLn3）的大鼠进行1小时或2小时WBH联合CDDP治疗，然后评估肿瘤生长延迟（TGD）。另一项研究检测了相同治疗后96小时内肿瘤和正常组织（胸腺和回肠）中诱导凋亡的量。1小时WBH + CDDP使TGD增加至10.5±0.5天，这与2小时WBH + CDDP获得的12.3±0.5天的TGD在统计学上无差异。1小时WBH + CDDP的肿瘤凋亡百分比曲线下面积（AUC）是2小时WBH + CDDP的50%。1小时WBH + CDDP的胸腺凋亡百分比AUC是2小时WBH + CDDP的25%，1小时WBH + CDDP的回肠凋亡评分AUC是2小时WBH + CDDP的81%。这些数据表明，虽然1小时WBH + CDDP诱导的肿瘤凋亡比2小时WBH + CDDP少，但1小时和2小时WBH + CDDP增强抗肿瘤活性的程度相似，并且由于1小时WBH + CDDP引起的正常组织凋亡比2小时WBH + CDDP少，1小时时长的WBH + CDDP可能是一种与2小时时长的WBH + CDDP一样有效且更安全的治疗方法。
