Evaluation of Apoptosis Biomarkers that Determine the Chemosensitivity of Hepatocellular Carcinoma and Early Identification of Non-Responders to Anticancer Therapy
The goal of this project is to investigate the molecular mechanisms of treatment failure in HCC and to identify novel treatment strategies that restore HCC apoptosis sensitivity. Since there is a lack of appropriate methods for closely monitoring the chemotherapy response, we have established novel bioassays for the detection of apoptosis/necrosis in serum samples. These biomarkers provide for the first time, an excellent non-invasive tool to detect chemotherapy-induced apoptosis/necrosis in HCC patients. This approach will allow for the early identification of non-responding HCC patients who might benefit from alternative anticancer therapies.
List of relevant publications
- Volkmann X, Anstaett M, Hadem J, Stiefel P, Bahr MJ, Lehner F, Manns MP, Schulze-Osthoff K, Bantel H (2008) Caspase activation is associated with spontaneous recovery from acute liver failure. Hepatology 40:1624-33.
- Volkmann X, Fischer U, Bahr MJ, Lehner F, MacFarlane M, Cohen GM, Manns MP, Schulze-Osthoff K, Bantel H (2007) Increased hepatotoxicity of TRAIL in diseased human liver. Hepatology 46:1498-508. Editorial by Malhi H (2007) TRAILs and tribulation. Hepatology 46:1320-22.
- Volkmann X, Cornberg M, Wedemeyer H, Lehner F, Manns MP, Schulze-Osthoff K, Bantel H (2006) Caspase activation is required for antiviral treatment response in chronic hepatitis C virus infection. Hepatology 43:1311-16.
- Seidel N, Volkmann X, Laenger F, Flemming P, Manns MP, Schulze-Osthoff K, Bantel H (2005) The extent of liver steatosis in chronic hepatitis C virus infection is mirrored by caspase activity in serum. Hepatology 42:113-20.
- Bantel H, Lügering A, Heidemann J, Volkmann X, Poremba C, Strassburg CP, Manns MP, Schulze-Osthoff K (2004) Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury. Hepatology 40:1078-1087. Editorial by Feldstein AE and Gores GJ (2004) An apoptosis biomarker goes to HCV clinic. Hepatology 40:1044-45. Comment by Foster GR (2005) Apoptotic cell death: the caspase-cleavage “gold rush”. The Lancet 365:1293-94.
- Bantel H, Essmann F, Totzke G, Engels IH, Sinha B, Schulze-Osthoff K, Jänicke RU (2004) Staphylococcus aureus alpha-toxin-induced cell death: predominant necrosis despite apoptotic caspase activation. Cell Death Differ 10:1260-72.
- Bantel H, Lügering A, Poremba C, Lügering N, Domschke W, Schulze-Osthoff K (2001) Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infection. Hepatology 34:758-67. Comment by Hahn YS, Soguero C, Cruise M (2001) Towards a reliable parameter of liver damage in hepatitis C: TUNEL versus caspase activation. Hepatology 34:840-41.
- Bantel H, Ruck P, Gregor M, Schulze-Osthoff K (2001) Detection of elevated caspase activation and early apoptosis in liver diseases. Eur J Cell Biol 80:230-39.
- Bantel H, Sinha B, Schulze-Osthoff K, Jänicke RU (2001) Alpha-toxin is a mediator of staphylococcus aureus-induced cell death and activates caspases via the intrinsic death pathway independently of death receptor signaling. J Cell Biol 155:637-47.
- Bantel H, Engels IH, Voelter W, Schulze-Osthoff K, Wesselborg S (1999) Mistletoe lectin activates caspase8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. Cancer Res 59:2083-90.