| First Author | Udd L | Year | 2004 |
| Journal | Gastroenterology | Volume | 127 |
| Issue | 4 | Pages | 1030-7 |
| PubMed ID | 15480979 | Mgi Jnum | J:93361 |
| Mgi Id | MGI:3056942 | Doi | 10.1053/j.gastro.2004.07.059 |
| Citation | Udd L, et al. (2004) Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2. Gastroenterology 127(4):1030-7 |
| abstractText | Background & Aims: Peutz-Jeghers syndrome (PJS) is typically manifested as severe gastrointestinal polyposis. Polyps in PJS patients and in Lkb1 +/- mice that model PJS polyposis are frequently characterized by elevated cyclooxygenase-2 (COX-2). This study was designed to determine whether COX-2 inhibition would reduce tumor burden in Lkb1 +/- mice or Peutz-Jeghers patients. Methods: Genetic interactions between Cox-2 and Lkb1 in polyp formation were analyzed in mice with combined deficiencies in these genes. Pharmacologic inhibition of COX-2 was achieved by supplementing the diet of Lkb1 +/- mice with 1500 ppm celecoxib between 3.5-10 and 6.5-10 months. In PJS patients, COX-2 was inhibited with a daily dose of 2 x 200 mg celecoxib for 6 months. Results: Total polyp burden in Lkb1 +/- mice was significantly reduced in a Cox-2 +/- (53%) and in a Cox-2 -/- (54%) background. Celecoxib treatment initiating before polyposis (3.5-10 months) led to a dramatic reduction in tumor burden (86%) and was associated with decreased vascularity of the polyps. Late treatment (6.5-10 months) also led to a significant reduction in large polyps. In a pilot clinical study, a subset of PJS patients (2/6) responded favorably to celecoxib with reduced gastric polyposis. Conclusions: These data establish a role for COX-2 in promoting Peutz-Jeghers polyposis and suggest that COX-2 chemoprevention may prove beneficial in the treatment of PJS. |
