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Responsiveness of Human Gastric Tumors Implanted in Nude Mice to Clinically Equivalent Doses of Various Antitumor Agents

To reproduce clinical effects of various antitumor agents in the human tumor/nude mouse model, we investigated the responsiveness of 11 lines of human gastric tumor xenografts to doses of the agents pharmacokinetically equivalent to the respective clinical doses, which we designated the “rational do...

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Detalles Bibliográficos
Autores principales: Inaba, Makoto, Tashiro, Tazuko, Kkobayashi, Tomowo, Sakurai, Yoshio, Maruo, Koji, Ohnishi, Yasuyuki, Ueyama, Yoshito, Nomura, Tatsuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1988
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5917506/
https://www.ncbi.nlm.nih.gov/pubmed/3133340
http://dx.doi.org/10.1111/j.1349-7006.1988.tb01621.x
Descripción
Sumario:To reproduce clinical effects of various antitumor agents in the human tumor/nude mouse model, we investigated the responsiveness of 11 lines of human gastric tumor xenografts to doses of the agents pharmacokinetically equivalent to the respective clinical doses, which we designated the “rational dose” (RD). We found that the response rates to mitomycin C, 3‐[(4‐amino‐2‐methyl‐5‐pyrimidinyl]methyl‐1‐[2‐chloroethyl]‐1‐nitrosourea (ACNU), adriamycin, 5‐fluorouracil were 18%, and that to vinblastine was 30%; on the other hand, those to vincristine, methotrexate, and cyclophosphamide were poor. In contrast, in our previous study using the maximum tolerated doses, response rates to mitomycin C, ACNU, and vinblastine were as high as 64–82%, and those to adriamycin and 5‐fluorouracil were 18%. When these results were compared with the clinical response rates of gastric tumors, as a whole, the results with RD's exhibited much better coincidence with the clinical data in terms of relative therapeutic potency, indicating the validity of the use of clinically equivalent doses instead of maximum tolerated doses in the human tumor model.