Side population (SP) cell analysis and sorting have been successfully applied to hepatocellular carcinoma (HCC) cell lines to identify a minor cell population with cancer stem cell properties. However, the molecular mechanisms operating in SP cells remain unclear. The polycomb gene product BMI1 plays a central role in the self-renewal of somatic stem cells in a variety of tissues and organs and seems to be implicated in tumor development. In this study, we determined the critical role of BMI1 in the maintenance of cancer stem cells with the SP phenotype in HCC cell lines. BMI1 was preferentially expressed in SP cells in Huh7 and PLC/PRF/5 HCC cells compared with the corresponding non-SP cells. Lentiviral knockdown of BMI1 considerably decreased the number of SP cells in both Huh7 and PLC/PRF/5 cells. Long-term culture of purified SP cells resulted in a drastic reduction in the SP subpopulation upon the BMI1 knockdown, indicating that BMI1 is required for the self-renewal of SP cells in culture. More importantly, the BMI1 knockdown abolished the tumorinitiating ability of SP cells in nonobese diabetic/severe combined immunodeficiency mice. Derepression of the INK4A and ARF genes that are major targets for BMI1 was not necessarily associated with impaired self-renewal of SP cells caused by BMI1 knockdown. In conclusion, our findings define an important role for BMI1 in the maintenance of tumor-initiating SP cells in HCC. BMI1 might be a novel therapeutic target for the eradication of cancer stem cells in
We should diagnose and treat acute onset AIH patients before they develop into severe and fulminant disease. Performing liver biopsy at the early stage of acute onset AIH, evaluating the biopsy specimens precisely and initiating corticosteroid therapy may be essential for improving the prognosis without liver transplantation.
Rikkunshito increased the plasma acylated ghrelin level in healthy volunteers and normal mice. Additionally, this change was maintained for at least 4 weeks after the end of administration. In mice, Rikkunshito increased the ghrelin mRNA expression level in the stomach.
The early introduction of sufficient doses of corticosteroids and nucleoside analogs could be one option for reversing the potential deterioration of patients with clinically severe, life-threatening exacerbation of chronic hepatitis B.
Heterogeneous hypoattenuation on unenhanced CT was a characteristic CT imaging feature of autoimmune acute liver failure compared with viral ALF. This finding could be one of the tools for diagnosing autoimmune acute liver failure in combination with clinicopathological features.
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