Improvement of human tumor xenograft-mouse model as a preclinical evaluation system of new drugs discovered and developed by the novel strategy against cancer

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In the recent strategy for treatment of cancer disease, concepts such as inhibition of oncogene activity, control of invasion and metastasis of cancer cells were attentioned as a novel target.To apply human tumor xenograft (HTX) model to the evaluation of new drugs which are discovered by those concepts, we improved host mouse and procedures of implantation of HTX.We also analyzed gene expression related to progress of carcinogenecity and malignancy of neoplasm.We established double mutant mice for athymic nude (nu) and severe combined immune deficient (scid) genes.This allowed us that human skin was implanted more efficiently in the mice than in nude mouse.We first developed human skin grafted-mice using these double mutant mice, then HTX was implanted into the human skin.The tumor grew in the skin, and moreover focused in the liver of host mice.We established HTX-mouse model which overexpressed c-erbB-2/HER2 gene, and evaluated monoclonal antibody against C-ErbB-2/HER2 products.We analyzed expression of isoforms of vascular endothelial growth factor (EGER) gene in the HTXs, and found that expression of VEGF 189 in tumor tissue was related to xenotransplantability to SCID mice.