title: Therapeutic effect of nimesulide on colorectal carcinogenesis in experimental murine ulcerative colitis.
abstract: BACKGROUND
  Patients with ulcerative colitis (UC) exhibit an increased risk for the development of cancer of the colon and rectum. Cyclooxygenase (COX)-2 inhibitors are known to suppress sporadic colorectal cancer, but it is unknown whether selective COX-2 inhibitors exhibit a preventive effect in UC-associated neoplasia. This study investigated the preventive effect of nimesulide, a selective COX-2 inhibitor, on colorectal carcinogenesis in an experimental model of murine UC.
  
  
  METHODS
  Chronic colitis was induced in mice by administration of four cycles of dextran sulfate sodium (DSS) (each cycle: 5% DSS for 7 days and then distilled water for 14 days). The mice were killed 120 days after the completion of the fourth cycle. The mice were divided into the following five groups: group A served as a disease control; group B received a diet mixed with 400 p.p.m. of nimesulide during the whole period; group C received nimesulide during the four cycles of DSS administration (active phase); group D received nimesulide for 120 days from the end of the fourth cycle (remission phase); group E received no agents including DSS and served as a normal control.
  
  
  RESULTS
  The incidence of dysplasia and/or cancer was 28%, 15%, 11.8%, 6.7% and 0% in groups A-E, respectively. In group D, nimesulide significantly suppressed the occurrence of dysplasia and/or cancer (P < 0.05). Strong COX-2 expression was detected by immunohistochemistry in cancer and dysplastic lesions while diffusely weak COX-2 expression was also found in the residual colon (i.e. lesion-free colon). The mucosal concentration of prostaglandin E(2) was significantly lower in groups B and D than in group A.
  
  
  CONCLUSIONS
  The administration of the selective COX-2 inhibitor nimesulide (especially during the remission phase) exerts a suppressive effect on the development of dysplasia and/or cancer in a murine model of DSS-induced colitis. These findings may have relevance to long-standing UC in humans.
authors: Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan.
authors: Takuya
authors: T
authors: Inoue
authors: Mitsuyuki
authors: M
authors: Murano
authors: Yosuke
authors: Y
authors: Abe
authors: Eijiro
authors: E
authors: Morita
authors: Naoko
authors: N
authors: Murano
authors: Shingo
authors: S
authors: Yasumoto
authors: Ken
authors: K
authors: Toshina
authors: Takashi
authors: T
authors: Nishikawa
authors: Kentaro
authors: K
authors: Maemura
authors: Ichiro
authors: I
authors: Hirata
authors: Ken-ichi
authors: K
authors: Katsu
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D015232:Dinoprostone; C012655:nimesulide