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International Journal of Hyperthermia 2007-Nov

Antitumor effect of whole body hyperthermia with alpha-galactosylceramide in a subcutaneous tumor model of colon cancer.

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Takeshi Hattori
Satoshi Kokura
Toshimitsu Okuda
Tetsuya Okayama
Tomohisa Takagi
Osamu Handa
Yuji Naito
Norimasa Yoshida
Toshikazu Yoshikawa

キーワード

概要

OBJECTIVE

Whole body hyperthermia (WBH) has been used clinically as an adjunct to radio- and chemotherapy in patients with various cancers. Recently, it has been reported that an activation of the immune system has recently been reported as a possible contributor to the therapeutic effects of WBH. Conversely, the glycolipid alpha-galactosylceramide (alpha-GalCer) is recognized by natural killer (NK) T cells together with the monomorphic MHC-like antigen, CD1d, in mice and humans. This study investigated the antitumor effects of WBH combined with alpha-GalCer in a mouse subcutaneous tumor model of colon cancer.

METHODS

Colon26 cells were inoculated subcutaneously into male BALB/c mice to establish subcutaneous tumor. Colon26-bearing mice were treated with WBH using far infrared rays three times/week. Rectal temperature was maintained for 60 min at 41 degrees C. In some experimental groups, alpha-GalCer was intraperitoneally injected before WBH. We investigated the therapeutic effects of WBH, alpha-GalCer and combined therapy.

RESULTS

(1) Compared with controls, WBH alone resulted in significant inhibition of tumor growth. (2) No inhibitory effect on tumor growth was seen with alpha-GalCer. (3) The combination of WBH and alpha-GalCer showed significant inhibition of tumor growth and prolongation of survival. (4) Serum IFN-gamma increased after 3 h and returned to basal levels by 24 h after alpha-GalCer administration. (5) CTL activity was enhanced following combination therapy with WBH and alpha-GalCer.

CONCLUSIONS

WBH showed antitumor effects in a mouse subcutaneous tumor model of colon cancer. Addition of alpha-GalCer increased the efficacy of WBH, probably via enhancement of immune response.

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