Female C3H/He mice aged 10 weeks with transplanted MM46 tumor were used in an investigation of the timing of administration of immunomodulators, such as PSK (a protein-bound polysaccharide prepared from Coriolus versicolor), OK-432 (streptococcal preparation), bestatin (inhibitor of aminopeptidase B) combined with two fractionated local irradiation with the total dose of 3,000 rad. The daily dose of 250 mg/kg of PSK, 1.0 KE/mouse of OK-432, or 300 μg/mouse of bestatin were injected intraperitoneally for 4 consecutive days before or after irradiation. The antitumor effect was evaluated by the changes of tumor volume and survival curves. When PSK or OK-432 was administered after irradiation, tumor growth was decreased and 60-day survival rate and survival curve were significantly elongated compared with the control group and the group to which PSK or OK-432 were administered before irradiation (p < 0.025, p < 0.05, respectively). As for bestatin, no remarkable difference was observed irrespective of the timing of administration. These results suggested that some immunomodulators show different antitumor activity depending on the combined timing relative to radiotherapy.

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