Prevention of human cancer by modulation of chronic inflammatory processes.
Chronic inflammation induced by biological, chemical and physical factors has been associated with increased risk of human cancer at various sites. Inflammation facilitates the initiation of normal cells and their growth and progression to malignancy through production of pro-inflammatory cytokines and diverse reactive oxygen and nitrogen species. These also activate signaling molecules involved in inflammation and carcinogenesis such as nuclear transcription factor (NF-kappaB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Several chemopreventive agents act through inhibition of signaling pathways (e.g. NF-kappaB), inhibition of oxidant-generating enzymes (e.g. iNOS) and mediators of inflammation (e.g. COX-2), scavenging reactive oxygen and nitrogen species, and modulation of xenobiotic-metabolizing enzymes (especially phase II enzyme induction). Some anti-inflammatory drugs have been tested in clinical trials to prevent human cancer at several sites. Better understanding of the molecular mechanisms by which chronic inflammation increases cancer risk will lead to further development of new strategies for cancer prevention at many sites.
Ohshima
Hiroshi
H
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France. ohshima@iarc.fr
Tazawa
Hiroshi
H
Sylla
Bakary S
BS
Sawa
Tomohiro
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000517:prevention & control* / Q000628:therapy; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology
D016588:Anticarcinogenic Agents; D016207:Cytokines; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2