Therapeutic efficacy and apoptosis and necrosis kinetics of doxorubicin compared with cisplatin, combined with whole-body hyperthermia in a rat mammary adenocarcinoma
✍ Scribed by Nobuhiko Toyota; Frederick R. Strebel; L. Clifton Stephens; Hiroyuki Matsuda; Tatuso Oshiro; Gaye N. Jenkins; Joan M. C. Bull
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 299 KB
- Volume
- 76
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
We have compared the therapeutic efficacy as well as the kinetics of treatment-induced apoptosis and necrosis of the maximum tolerated dose (MTD) of doxorubicin (DOX) or cisplatin (CDDP) combined with long-duration, low-temperature whole-body hyperthermia (LL-WBH, at 40.0°C for 6 hr), with the combination of the MTDs of either DOX or CDDP with short-duration, high-temperature WBH (SH-WBH, at 41.5°C for 2 hr), in a rat mammary adenocarcinoma (MTLn3). The MTD of LL-WBH ؉ DOX resulted in increased therapeutic efficacy, compared with the MTD of DOX alone and SH-WBH ؉ DOX. The MTD of LL-WBH ؉ CDDP, however, did not increase therapeutic efficacy, when compared with the MTD of CDDP alone or SH-WBH ؉ CDDP. The MTD of LL-WBH ؉ DOX caused a significant delay in the development of spontaneous axillary lymph node (ALN) metastasis and tended to cause longer mean survival, compared with SH-WBH ؉ DOX. The peak of treatment-induced apoptosis was higher for the MTD of DOX ؉ LL-WBH, compared with SH-WBH ؉ DOX, whereas the apoptosis peak of the MTD of SH-WBH ؉ CDDP was higher than that of LL-WBH ؉ CDDP. The most extensive levels of tumor necrosis appeared to occur earlier with SH-WBH alone and the MTD of SH-WBH ؉ DOX or CDDP than with other groups. Our results suggest that LL-WBH ؉ DOX may be a promising therapy for breast cancer, and the extent of treatmentinduced tumor apoptosis appears to correlate with antitumor response for MTDs of LL-WBH ؉ DOX and SH-WBH ؉ DOX, but not for the MTDs of CDDP with SH-WBH or LL-WBH.