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J.Jpn. Surg. Soc.. 86(3): 258-265, 1985
Original article
CORRELATION BETWEEN ANTI-TUMOR EFFECT AND DELAYED HYPERSENSITIVITY INDUCED BY TOPICALLY APPLIED OK-432 WITH HISTOLOGICAL FINDINGS
Delayed hypersensitivity (DH) against OK-432 was induced in BALB/c mice by injecting 2 KE of OK-432 with Freund’s incomplete adjuvant into foot pads.
One week after presensitization with OK-432, 2×10
5 cells of Meth A tumor were implanted subcutaneously in all mice, followed by intratumoral injection of 1 KE of OK-432 five times every other day starting at 7th day in experimental group. Tumor growth was significantly inhibited in the OK-432 presensitized group comparing to non-sensitized group. In experimental groups marked inhibition was observed in mice which were injected with OK-432 intratumorally 2 to 3 weeks after presensitization. This effect correlated well with delayed hypersensitivity against OK-432.
Histological changes after intratumoral injection of OK-432 were examined in order to analyse the mechanism of this effect. The main finding of OK-432 injected specimen by H.E. staining were degeneration of tumor cells and infiltration of inflammatory cells. These changes were stronger in OK-432 presensitized mice. By β-D-galactosidase staining accumulation of macrophages was found both inside the tumor and the surrounding tissue, and these macrophages increased in OK-432 presensitized mice. Immunoperoxidase staining with antiasialo GMI anti-serum was also perfomed. Greater number of activate macrophages were observed to accumulate in the specimen of OK-432 presensitized mice than that of control mice.
Some T cells were observed only around tumor tissues and not in the tumor of both presensitized and unsensitized mice. These results suggest that the activated macrophages play a major role in the augmentation of antitumor effect by presensitization with OK-432.
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