Molecular biological analysis of a development and progression of hepatocellular carcinoma to establish a rational treatment for it

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Our experimental goal are (1) molecular biological analysis of development and progression of hepatocellular carcinoma (HCC) and (2) establishment of a molecular biological diagnostic method to differentiate multicentric development from intrahepatic metastasis of HCC.As differentiated diagnosis of multiple HCC,integration pattern of hepatitis B viral DNA (HBvDNA) in the tumor was availabel, that is in case of multicentric HCC,integration pattern of HBvDNA is different in each tumor. But, HCC patients with HB viral infection were less than 30% in Japan. So, analysis of mutation pattern of p53 supressor oncogene of other HCC specific oncogene should be available from now. While as analysis of development and progression of HCC in human was difficult, because we could not get such a case as in early stage or in precancerous lesion from human cases. So, within this term, we developed an experimental HCC model in mice induced by DirDirect Deep Black Extra (DDB-Ex), a pigment of the Benzidine. Histologically the tumors in this mode were very similar to those of human HCC,that is the tumor is nodular and histologically grow in cords of variable thickness which is same as the human trabecular pattern HCC.In molecular biological study no mutations in the p53 supressor gene were found out but 65% mutations in the Ha-ras oncogene and 12% of mutations in Ki-ras oncogene were detected in this model. The HCC in mice induced by DDB-Ex share the pathological and molecular biological character with human HCC and is available for studying the development and progression of humanHCC.