1. Cyclooxygenase-2 and gastric carcinogenesis
- Author
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Kirsi Saukkonen, Caj Haglund, Johanna Rintahaka, Bastiaan P. van Rees, J. Jan B. van Lanschot, Anna Sivula, Ari Ristimäki, Marie Christine Rio, G. Johan A. Offerhaus, and Christianne J. Buskens
- Subjects
Pathology ,medicine.medical_treatment ,Gene Expression ,medicine.disease_cause ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Immunology and Allergy ,Mice, Knockout ,0303 health sciences ,Aspirin ,biology ,Stomach ,Anti-Inflammatory Agents, Non-Steroidal ,General Medicine ,3. Good health ,Isoenzymes ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Trefoil Factor-1 ,Adjuvant ,medicine.drug ,Microbiology (medical) ,medicine.medical_specialty ,Adenocarcinoma ,Models, Biological ,Pathology and Forensic Medicine ,03 medical and health sciences ,Stomach Neoplasms ,medicine ,Animals ,Humans ,Cyclooxygenase Inhibitors ,030304 developmental biology ,Cyclooxygenase 2 Inhibitors ,business.industry ,Membrane Proteins ,Cancer ,Prostanoid ,medicine.disease ,digestive system diseases ,chemistry ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,biology.protein ,Celecoxib ,Cancer research ,Cyclooxygenase ,Peptides ,business ,Carcinogenesis - 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.
- Published
- 2003