肝癌の発生・進展とインターフェロンによる制御

抄録

Most early hepatocellular carcinomas (HCCs) are well differentiated, with an ill-defined nodular appearance. When a well-differentiated HCC reaches a size of about 1.5 cm in diameter, less-differentiated cancerous tissues with greater proliferative activity evolve within it. Clonally-related HCC cell lines (HAK-1A and HAK-1B) established from a single HCC nodule with a variety in the histological grade suggest that less-differentiated cancerous tissues develop from clonal dedifferentiation of well-differentiated HCC tissues. Subsequently, moderately to poorly differentiated HCC tissues gradually replace the initial surrounding HCC.
HCC frequently occurs multicentrically whether synchronously or metachronously, defying complete cure by conventional therapies; therefore, chemoprevention of HCC is very important. Interferon (IFN)-α has been used for the treatment of chronic viral liver diseases to eradicate virus. Recently, IFN-α has been shown to possess highly suppressive effects on hepatocellular carcinogenesis. We found that type I IFN preparations inhibit the growth of 13 liver cancer cell lines at various degrees in vitro and in vivo, and the clinical dose of IFN preparations was effective in vivo. The data suggest that IFNs may inhibit the growth of clinically undetectable HCC cells and prevent or delay the development of HCC in patients with chronic viral liver diseases.