IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the development of XXXX in the rat.

@entity10740 @entity32 @entity108 @entity82 @entity7504 @entity5 @entity107 @entity157 @entity3619 @entity5997
Interferon (IFN)-alpha treatment is a common therapy for @entity3619 and contributes to preventing hepatocarcinogenesis. However, it is not clear whether IFN-alpha directly inhibits the clonal expansion of pre-neoplastic hepatocytes. To clarify the mechanism by which IFN-alpha prevents hepatocarcinogenesis, we examined the effect of IFN-alpha in a chemically induced hepatocarcinogenesis model initiated by @entity107 ( @entity108 ) and promoted by @entity5997 ( @entity5997 ) and partial hepatectomy, in which @entity157 ( @entity157 ) arises through pre-neoplastic foci without @entity32 or @entity82 . The protocols of IFN-alpha administration were started simultaneously with chemical initiation and lasted for either 4 or 40 weeks. The pre-neoplastic foci and neoplastic @entity157 were evaluated at 4 or 40 weeks after chemical initiation, respectively. The effects of IFN-alpha were assessed by the expression of @entity5 -related genes and cell cycle-related genes in the pre-neoplastic foci, using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). As a result of IFN-alpha treatment, the numbers and average volume of pre-neoplastic foci were reduced. The proliferating cell nuclear antigen index and the expression of G(1) cyclins were also reduced in the pre-neoplastic foci in the IFN-treated group. The expression of @entity7504 , which is an inhibitor of cyclin-kinase complexes was higher in the foci of the IFN-treated group, while @entity10740 expression was not altered in this group, compared with the control group. IFN-alpha also suppressed the @entity5 development at 40 weeks after initiation. And in the long-term IFN-alpha-treated group, both the @entity5 numbers and average @entity5 size were markedly more reduced than those in the short-term-treated group. Therefore, it was demonstrated that longer treatment with IFN-alpha was more effective, compared with shorter treatment. In conclusion, it was shown that IFN-alpha directly prevented and delayed hepatocarcinogenesis through the suppression of pre-neoplastic cell proliferation and that it may partially depend on @entity7504 induction through a @entity10740 -independent pathway.
