Differential chemosensitivity of local and metastatic human gastric cancer after orthotopic transplantation of histologically intact tumor tissue in nude mice

We have established a metastatic model of human gastric cancer using orthotopic transplantation of histologically intact tissue in nude mice, and have used this model to evaluate the effects of immunochemotherapy using OK‐432, 5‐fluorouracil (5‐FU) and mitomycin C (MMC) against SC‐I‐NU, a human stomach cancer line. One‐quarter or one‐half maximum tolerated doses (MTDs) of S‐FU or MMC resulted in a significant reduction of stomach tumor growth, while liver metastases were not reduced, possibly due to suppression of natural killer (NK)‐cell activity by both drugs. On the other hand, when combined with OK‐432, half MTDs of 5‐FU and MMC significantly reduced liver metastases, with synergistic reduction of stomach tumor growth, possibly reflecting a rescue of NK‐cell activity by treatment with OK‐432. This metastatic model of human stomach cancer shows that locally growing and metastatic tumors may have different chemosensitivities, and provides the opportunity to test both with various treatment regimens.