Cyclooxygenase-2 and gastric carcinogenesis

Kirsi Saukkonen, Johanna Rintahaka, Anna Sivula, Christianne J. Buskens, Bastiaan P. Van Rees, Marie Christine Rio, Caj Haglund, J. Jan B Van Lanschot, G. Johan A Offerhaus, Ari Ristimäki

Research output: Contribution to journalArticle

Abstract

Epidemiological studies have shown that the use of nonsteroid anti-inflammatory drugs (NSAIDs) is associated with reduced risk of gastric cancer. The best-known target of NSAIDs is the cyclooxygenase (Cox) enzyme. Two Cox genes have been cloned, of which Cox-2 has been connected with gastric carcinogenesis. Expression of Cox-2 is elevated in gastric adenocarcinomas, which correlates with several clinicopathological parameters, including depth of invasion and lymph node metastasis. This suggests that Cox-2-derived prostanoids promote aggressive behavior of adenocarcinomas of the stomach. Cox-2 expression is especially prominent in intestinal-type gastric carcinoma and it is already present in dysplastic precursor lesions of this disease, which suggests that Cox-2 contributes to gastric carcinogenesis already at the preinvasive stage. Our most recent data show that Cox-2 is expressed in gastric adenomas of trefoil factor 1 deficient mice. Treatment of these mice with a Cox-2 selective inhibitor, celecoxib, reduced the size of the adenomas. Taken together these data support efforts to initiate clinical studies to investigate the effect of Cox-2 inhibitors as chemotherapeutic agents and as adjuvant treatment modalities against gastric neoplasias.

Original languageEnglish (US)
Pages (from-to)915-925
Number of pages11
JournalAPMIS
Volume111
Issue number10
DOIs
StatePublished - Oct 2003
Externally publishedYes

Keywords

  • Aspirin
  • Cancer
  • Prostaglandin
  • Prostanoid
  • Stomach

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Microbiology (medical)
  • Immunology

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  • Cite this

    Saukkonen, K., Rintahaka, J., Sivula, A., Buskens, C. J., Van Rees, B. P., Rio, M. C., Haglund, C., Van Lanschot, J. J. B., Offerhaus, G. J. A., & Ristimäki, A. (2003). Cyclooxygenase-2 and gastric carcinogenesis. APMIS, 111(10), 915-925. https://doi.org/10.1034/j.1600-0463.2003.1111001.x