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 5-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.
Furukawa
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Watanabe
M
M
Kuo
T H
TH
Kitajima
M
M
Hoffman
R M
RM
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002452:Cell Count; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000556:secondary* / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000008:administration & dosage; D009368:Neoplasm Transplantation; D010844:Picibanil / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013274:Stomach Neoplasms / Q000556:secondary* / Q000628:therapy*; D014183:Transplantation, Heterologous
D010844:Picibanil; D016685:Mitomycin; D005472:Fluorouracil