Prevention of hepatocellular carcinoma development associated with chronic hepatitis by anti-fas ligand antibody therapy.
A persistent immune response to hepatitis viruses is a well-recognized risk factor for hepatocellular carcinoma. However, the molecular and cellular basis for the procarcinogenic potential of the immune response is not well defined. Here, using a unique animal model of chronic hepatitis that induces hepatocellular carcinogenesis, we demonstrate that neutralization of the activity of Fas ligand prevented hepatocyte apoptosis, proliferation, liver inflammation, and the eventual development of hepatocellular carcinoma. The results indicate that Fas ligand is involved not only in direct hepatocyte killing but also in the process of inflammation and hepatocellular carcinogenesis in chronic hepatitis. This is the first demonstration that amelioration of chronic inflammation by some treatment actually caused reduction of cancer development.
Nakamoto
Yasunari
Y
Department of Gastroenterology, Graduate School of Medicine. Center for the Development of Molecular Target Drugs, Cancer Research Institute, Kanazawa University, Ishikawa 920-0934, Japan.
Kaneko
Shuichi
S
Fan
Hong
H
Momoi
Takashi
T
Tsutsui
Hiroko
H
Nakanishi
Kenji
K
Kobayashi
Kenichi
K
Suda
Takashi
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications*; D022781:Hepatocytes / Q000166:cytology; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000150:complications / Q000276:immunology / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006514:Hepatitis B Surface Antigens; D008562:Membrane Glycoproteins