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IL-12 is considered to be one of the most important cytokines in anti-cancer therapy. We have demonstrated that substances derived from Basidiomycetes, such as active hexose-correlated compound (AHCC) and PSK induce the production of IL-12. In this study, the MHC dependency of IL-12 production induced by various mycelial extracts, PSK, AHCC and IL-X, was examined. During tumor-bearing, higher serum IL-12 levels were observed in H-2a and H-2b mice as compared to H-2d mice. Concerning the effect of genetic background of mice on response to mycelial extracts, AHCC administration enhanced the serum IL-12 level in H-2b mice but not in H-2d mice, while PSK administration increased the serum IL-12 level in H-2d mice but not in H-2b mice. IL-X, components derived from the same Basidiomycetes, also enhanced the serum IL-12 level in H-2b mice in the early stage of tumor like AHCC, and maintained serum IL-12 at a level higher than the normal value accompanying tumor growth, whereas AHCC did not restore the lowered serum IL-12 level accompanying tumor growth. These results showed that AHCC or IL-X is effective in a genetically Th1-dominant individual whereas PSK is effective in a genetically Th2-dominant individual or Th2-dominant status in advanced cancer patients. So we propose that the suitable combinations of various mycelial extracts may be effective methods of endogenous IL-12 induction for cancer patients of all stages, which is important as a cancer therapy that is relatively free from adverse reactions and which emphasizes the QOL in individual patients.

The influence of intratumor administration of OK-432 on the tumor-selective antitumor effect of 5'-DFUR was studied in 49 patients with advanced gastric cancer. The patients were divided into 4 groups that received oral 5'-DFUR, intratumor OK-432, oral 5'-DFUR plus intratumor and intracutaneous OK-432, or no therapy before operation. Using surgical specimens, the PyNPase activity and 5-FU content were measured, and the localization of PyNPase was determined immunohistologically. The results were as follows: 1) 5'-DFUR therapy decreased intratumor PyNPase activity whereas administration of OK-432 increased it. 2) PyNPase activity was higher in cancer tissue than in normal tissue for all groups. 3) The 5-FU content of cancer tissue was higher in patients receiving OK-432 plus 5'-DFUR than in patients receiving 5'-DFUR alone. 4) In the resected tumors, PyNPase was mainly localized in the cancer cells of some patients and in the stromal cells of others. Thus, the localization of PyNPase showed two major patterns.

Lentinan was administered for gastric cancer in order to determine what type of changes would occur as a consequence. In an experimental study, the intraperitoneal administration of lentinan on cancerous tissues caused a marked development of reticular fibers, along with an enhanced interstitial response. Findings which support the relationship between a marked development of reticular fibers and an anti-tumor effect, were also obtained. Furthermore, lentinan was administered for human gastric cancer to evaluate whether or not an increase in interstitial response would be observed. As a result, reticular fibers developed in tumor sites with a resultant fragmentation of cancer cell nests. Many T lymphocytes infiltrated cancer sites where the lentinan was administered. These findings suggest that the intratumor administration of lentinan enhanced an interstitial response and also activated an anti-tumor immune response in the human gastric cancer tissues.