Increased hepatotoxicity of tumor necrosis factor-related apoptosis-inducing ligand in diseased human liver.

摘要: Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not most normal and has therefore been proposed as a promising antitumor agent. Recent experiments suggested that isolated primary human hepatocytes monkey liver are susceptible to certain TRAIL agonists, raising concerns about the use of cancer treatment. Whether indeed exerts hepatotoxicity vivo how this is influenced by chemotherapeutic drugs or disease completely unknown. Employing different forms recombinant TRAIL, we found cytokine can induce proapoptotic caspase activity hepatocytes. However marked contrast, these preparations induced little no cytotoxicity when incubated with tissue explants fresh healthy liver, an experimental model may more faithfully mimic situation. In only combined histone deacetylase inhibitors. Strikingly, however, alone triggered massive accompanied activation from patients steatosis hepatitis C viral infection. This enhanced sensitivity diseased was associated increased expression receptors up-regulation Bcl-2 proteins. Conclusion: These results suggest clinical trials should be performed great caution chemotherapy administered inflammatory diseases. (HEPATOLOGY 2007.)