Temporal treatment with interferon-beta prevents hepatocellular carcinoma in hepatitis B virus X gene transgenic mice
| Autor: | Yutaka Aoyagi, Yo-hei Aoki, Shogo Ohkoshi, Yasunobu Matsuda, Satoshi Yamagiwa, Masaaki Takamura, Masahiko Yano, Kenta Suzuki, Kazuhide Yamazaki, Ken Toba, So Kurita |
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| Rok vydání: | 2007 |
| Předmět: |
Genetically modified mouse
Mice Transgenic medicine.disease_cause Virus S Phase Mice Liver Neoplasms Experimental Orthohepadnavirus Interferon medicine Animals Humans Viral Regulatory and Accessory Proteins Cells Cultured Hepatitis B virus Hepatology biology DNA Interferon-beta biology.organism_classification medicine.disease digestive system diseases STAT1 Transcription Factor Hepadnaviridae Apoptosis Hepatocellular carcinoma Immunology Hepatocytes Trans-Activators medicine.drug Signal Transduction |
| Zdroj: | Journal of hepatology. 48(2) |
| ISSN: | 0168-8278 |
| Popis: | The preventive effect of interferon (IFN) against hepatocellular carcinoma (HCC) has been confirmed clinically. We sought to determine whether the temporal administration of IFN-beta prevents hepatocarcinogenesis in a mouse model where HCC develops without necroinflammation.Hepatocarcinogenic mice that are transgenic for the hepatitis B virus X gene (HBx-Tg) were treated with IFN-beta or saline (control) for three months, from 3 to 6 months of age, and the incidence of HCC was determined at 18 months of age. The effects of IFN-beta on DNA synthesis and apoptosis were tested.The incidence of HCC was significantly lower in the IFN-beta-treated mice than the controls (0 vs. 50%, P0.01). Inhibition of DNA synthesis in hepatocytes by IFN-beta was observed in the livers of HBx-Tg, without any significant induction of apoptosis. Although the treatment of IFN-beta was temporal, the number of hepatocytes with DNA synthesis remained lower 3 and 12 months later in life.Temporal administration of IFN-beta has a significant preventive effect on the occurrence of HCC in a mouse model where HCC develops without inflammation. The mechanisms are the inhibition of DNA synthesis and cell cycle progression of hepatocytes. |
| Databáze: | OpenAIRE |
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