| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
It has been reported that certain chemotherapeutic agents exhibit the effects to enhance the anti cancer host responses in the patients with malignant diseases. In the present study, we investigated whether Cis-diamminedichloroplatinum (CDDP) and 5-Fluorouracil (5-FU) may induce cytokines and killer cells carrying anti-cancer efficiency in vivo and in vitro. The cultivation of human peripheral blood mononuclear cells (PBMC) derived from healthy donors in the presence of 5-FU (0 to 5.0 μg/ml) or CDDP. (0 to 1.0 μg/ml) resulted in the significant augmentation of natural killer (NK) cell activities as well as generation of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-β, interleukin (IL)-12 and IL-18 that are generally called "Th1-type cytokines"in vitro. All of these activities were almost i completely neutralized by eliminating NK cells by addition of anti-asialo-GMl antibody and complement. In addition, we also investigated cytokine- and killer cell-inducing activities in vitr
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o of these agents on the PBMC derived from oral cancer patients. Both 5-FU and CDDP induced Thl cytokines and killer cells in the PBMC from untreated oral cancer patients as well as from treated, disease-free pateients. These activities were also neutralized by anti-asialo-GMl antibody and complement. In in vivo model, the administration of anti-asialo-GMl antibody significantly shortened the survival time extended by the treatment with CDDP or 5-FU both in human salivary gland tumor-bearing nude mice and in syngeneic Meth-A tumor-bearing BALB/c mice. Furthermore, high levels of Thl cytokines in the sera and of NK-cell activity in the spleen.cells derived from animals given CDDP or 5-FU was detected. Next, we examined Thl cytokines in the sera and killer.cell activity of the PBMC in oral cancer patients treated with CDDP. Both Thl-cytokine 'amounts in the sera and killer-cell activities of the PBMC were significantly increased after CDDP administration.1 These findings suggest that 5-FU and CDDP, chemotherapeutic-agents against cancer, increase anti-cancer immunity mediated by induction of Thl cytokines and killer cell activities in the patients with oral cancer and that NK cells may be qlosely involved in 5-FU- and CDDP-induced anti-cancer immunity. Based on the results from the current study, we will establish the protocol for cancer chemotherapy that can increase anti-cancer host responses in oral cancer parients. Less
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