Cyclooxygenase-2 and gastric carcinogenesis.
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.
Saukkonen
Kirsi
K
Department of Pathology, Helsinki University, Central Hospital, Helsinki, Finland.
Rintahaka
Johanna
J
Sivula
Anna
A
Buskens
Christianne J
CJ
Van Rees
Bastiaan P
BP
Rio
Marie-Christine
MC
Haglund
Caj
C
Van Lanschot
J Jan B
JJ
Offerhaus
G Johan A
GJ
Ristimaki
Ari
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010455:Peptides / Q000172:deficiency / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000071163:Trefoil Factor-1
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010455:Peptides; C472724:Tff1 protein, mouse; D000071163:Trefoil Factor-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases