title: 5-aminosalicylic acid given in the remission stage of colitis suppresses colitis-associated cancer in a mouse colitis model.
abstract: OBJECTIVE
  The risk of colorectal cancer is increased in patients with inflammatory bowel diseases, especially those with ulcerative colitis (UC). Although 5-aminosalicylic acid (5-ASA) is widely used in the treatment of UC to suppress the colitic inflammation, no studies have been conducted to examine the chemopreventive effect of 5-ASA, given in the remission phase of colitis, against colitis-associated cancer using animal models. We therefore investigated the possible inhibition by peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands and 5-ASA of colitis-associated colon carcinogenesis in a mouse model.
  
  
  METHODS
  A dextran sodium sulfate/azoxymethane-induced mouse colon cancer model was used, and the chemopreventive effects of 5-ASA and PPARgamma ligands, given in the remission phase of colitis, against colitis-related colon carcinogenesis, were evaluated.
  
  
  RESULTS
  The number of neoplasms in the mice treated with 5-ASA was significantly lower than that in the control mice. In addition, the size of the neoplasms in treated mice was also significantly smaller than that in the control mice. In contrast, no significant suppression in the number or size of the tumors was observed in the mice treated with PPARgamma ligands. The proliferating cell nuclear antigen-labeling index in the tumor cells of the 5-ASA-treated mice was significantly smaller than that in the control, indicating that 5-ASA reduced tumor cell proliferation.
  
  
  CONCLUSIONS
  Our results revealed that 5-ASA given in the remission phase of colitis significantly suppressed the development of colitis-associated cancer in a mouse model, which indicates the clinical importance of adopting chemopreventive strategies even in UC patients in remission.
authors.affiliation: Gastroenterology Division, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ikeda
authors.forename: Ayako
authors.initials: A
authors.lastname: Tomimoto
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.forename: Toshio
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yonemitsu
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Endo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inamori
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakagama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001835:Body Weight; D003092:Colitis / Q000150:complications* / Q000188:drug therapy*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008024:Ligands; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy*; D047495:PPAR gamma / Q000378:metabolism; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008024:Ligands; D047495:PPAR gamma; D019804:Mesalamine