Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus

Navtej Singh Buttar, Kenneth Ke Ning Wang, Olga Leontovich, Jay Y. Westcott, Rodney J. Pacifico, Marlys A. Anderson, Krishnawatie K. Krishnadath, Lori S. Lutzke, Lawrence J. Burgart

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Abstract

Background & Aims: Carcinogenesis in Barrett's esophagus (BE) is associated with an increased expression of cyclooxygenase (COX) 2. However, there has been no direct evidence that inhibition of COX-2 prevents cancer in BE. We studied the effect of MF-Tricyclic, a selective COX-2 inhibitor, on the development of BE and adenocarcinoma in a rat model. Methods: Four weeks after esophagojejunostomy, 105 Sprague-Dawley rats were randomized to a chow containing MF-Tricyclic or Sulindac, or a placebo. Ninety-six (92%) rats completed the study and were sacrificed at 28 ± 2 weeks. The animals were assessed for the presence of cancer, tumor volume, BE, degree of inflammation, and COX-2 expression and activity. Results: MF-Tricyclic and Sulindac reduced the relative risk of development of esophageal cancer by 55% (95% confidence interval [CI] = 43%-66%, P < 0.008) and by 79% (95% CI =68%-87%, P < 0.001), respectively, compared with controls. No significant differences were noted in the risk of esophageal cancer between the MF-Tricyclic and the Sulindac group (P = 0.34). The median tumor volume was not significantly different among the 3 groups (P = 0.081). Moderate to severe degree of inflammation was significantly more common (P = 0.005) in the control compared with the MF-Tricyclic and the Sulindac group; however, the prevalence of BE was not significantly different between groups (P = 0.98). Rats in the control group had higher tissue PGE 2 level compared with the MF-Tricyclic and Sulindac groups (P = 0.038). Conclusions: Selective and nonselective COX-2 inhibitors can inhibit inflammation, COX-2 activity, and development of adenocarcinoma induced by reflux. This provides direct evidence that COX-2 inhibitors may have chemopreventive potential in BE.

Original languageEnglish (US)
Pages (from-to)1101-1112
Number of pages12
JournalGastroenterology
Volume122
Issue number4
StatePublished - 2002

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Barrett Esophagus
Sulindac
Cyclooxygenase 2 Inhibitors
Chemoprevention
Adenocarcinoma
Animal Models
Cyclooxygenase 2
Esophageal Neoplasms
Inflammation
Tumor Burden
Confidence Intervals
Prostaglandins E
Sprague Dawley Rats
3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone
Neoplasms
Carcinogenesis
Placebos
Control Groups

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Buttar, N. S., Wang, K. K. N., Leontovich, O., Westcott, J. Y., Pacifico, R. J., Anderson, M. A., ... Burgart, L. J. (2002). Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus. Gastroenterology, 122(4), 1101-1112.

Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus. / Buttar, Navtej Singh; Wang, Kenneth Ke Ning; Leontovich, Olga; Westcott, Jay Y.; Pacifico, Rodney J.; Anderson, Marlys A.; Krishnadath, Krishnawatie K.; Lutzke, Lori S.; Burgart, Lawrence J.

In: Gastroenterology, Vol. 122, No. 4, 2002, p. 1101-1112.

Research output: Contribution to journalArticle

Buttar, NS, Wang, KKN, Leontovich, O, Westcott, JY, Pacifico, RJ, Anderson, MA, Krishnadath, KK, Lutzke, LS & Burgart, LJ 2002, 'Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus', Gastroenterology, vol. 122, no. 4, pp. 1101-1112.
Buttar, Navtej Singh ; Wang, Kenneth Ke Ning ; Leontovich, Olga ; Westcott, Jay Y. ; Pacifico, Rodney J. ; Anderson, Marlys A. ; Krishnadath, Krishnawatie K. ; Lutzke, Lori S. ; Burgart, Lawrence J. / Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus. In: Gastroenterology. 2002 ; Vol. 122, No. 4. pp. 1101-1112.
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title = "Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus",
abstract = "Background & Aims: Carcinogenesis in Barrett's esophagus (BE) is associated with an increased expression of cyclooxygenase (COX) 2. However, there has been no direct evidence that inhibition of COX-2 prevents cancer in BE. We studied the effect of MF-Tricyclic, a selective COX-2 inhibitor, on the development of BE and adenocarcinoma in a rat model. Methods: Four weeks after esophagojejunostomy, 105 Sprague-Dawley rats were randomized to a chow containing MF-Tricyclic or Sulindac, or a placebo. Ninety-six (92{\%}) rats completed the study and were sacrificed at 28 ± 2 weeks. The animals were assessed for the presence of cancer, tumor volume, BE, degree of inflammation, and COX-2 expression and activity. Results: MF-Tricyclic and Sulindac reduced the relative risk of development of esophageal cancer by 55{\%} (95{\%} confidence interval [CI] = 43{\%}-66{\%}, P < 0.008) and by 79{\%} (95{\%} CI =68{\%}-87{\%}, P < 0.001), respectively, compared with controls. No significant differences were noted in the risk of esophageal cancer between the MF-Tricyclic and the Sulindac group (P = 0.34). The median tumor volume was not significantly different among the 3 groups (P = 0.081). Moderate to severe degree of inflammation was significantly more common (P = 0.005) in the control compared with the MF-Tricyclic and the Sulindac group; however, the prevalence of BE was not significantly different between groups (P = 0.98). Rats in the control group had higher tissue PGE 2 level compared with the MF-Tricyclic and Sulindac groups (P = 0.038). Conclusions: Selective and nonselective COX-2 inhibitors can inhibit inflammation, COX-2 activity, and development of adenocarcinoma induced by reflux. This provides direct evidence that COX-2 inhibitors may have chemopreventive potential in BE.",
author = "Buttar, {Navtej Singh} and Wang, {Kenneth Ke Ning} and Olga Leontovich and Westcott, {Jay Y.} and Pacifico, {Rodney J.} and Anderson, {Marlys A.} and Krishnadath, {Krishnawatie K.} and Lutzke, {Lori S.} and Burgart, {Lawrence J.}",
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T1 - Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus

AU - Buttar, Navtej Singh

AU - Wang, Kenneth Ke Ning

AU - Leontovich, Olga

AU - Westcott, Jay Y.

AU - Pacifico, Rodney J.

AU - Anderson, Marlys A.

AU - Krishnadath, Krishnawatie K.

AU - Lutzke, Lori S.

AU - Burgart, Lawrence J.

PY - 2002

Y1 - 2002

N2 - Background & Aims: Carcinogenesis in Barrett's esophagus (BE) is associated with an increased expression of cyclooxygenase (COX) 2. However, there has been no direct evidence that inhibition of COX-2 prevents cancer in BE. We studied the effect of MF-Tricyclic, a selective COX-2 inhibitor, on the development of BE and adenocarcinoma in a rat model. Methods: Four weeks after esophagojejunostomy, 105 Sprague-Dawley rats were randomized to a chow containing MF-Tricyclic or Sulindac, or a placebo. Ninety-six (92%) rats completed the study and were sacrificed at 28 ± 2 weeks. The animals were assessed for the presence of cancer, tumor volume, BE, degree of inflammation, and COX-2 expression and activity. Results: MF-Tricyclic and Sulindac reduced the relative risk of development of esophageal cancer by 55% (95% confidence interval [CI] = 43%-66%, P < 0.008) and by 79% (95% CI =68%-87%, P < 0.001), respectively, compared with controls. No significant differences were noted in the risk of esophageal cancer between the MF-Tricyclic and the Sulindac group (P = 0.34). The median tumor volume was not significantly different among the 3 groups (P = 0.081). Moderate to severe degree of inflammation was significantly more common (P = 0.005) in the control compared with the MF-Tricyclic and the Sulindac group; however, the prevalence of BE was not significantly different between groups (P = 0.98). Rats in the control group had higher tissue PGE 2 level compared with the MF-Tricyclic and Sulindac groups (P = 0.038). Conclusions: Selective and nonselective COX-2 inhibitors can inhibit inflammation, COX-2 activity, and development of adenocarcinoma induced by reflux. This provides direct evidence that COX-2 inhibitors may have chemopreventive potential in BE.

AB - Background & Aims: Carcinogenesis in Barrett's esophagus (BE) is associated with an increased expression of cyclooxygenase (COX) 2. However, there has been no direct evidence that inhibition of COX-2 prevents cancer in BE. We studied the effect of MF-Tricyclic, a selective COX-2 inhibitor, on the development of BE and adenocarcinoma in a rat model. Methods: Four weeks after esophagojejunostomy, 105 Sprague-Dawley rats were randomized to a chow containing MF-Tricyclic or Sulindac, or a placebo. Ninety-six (92%) rats completed the study and were sacrificed at 28 ± 2 weeks. The animals were assessed for the presence of cancer, tumor volume, BE, degree of inflammation, and COX-2 expression and activity. Results: MF-Tricyclic and Sulindac reduced the relative risk of development of esophageal cancer by 55% (95% confidence interval [CI] = 43%-66%, P < 0.008) and by 79% (95% CI =68%-87%, P < 0.001), respectively, compared with controls. No significant differences were noted in the risk of esophageal cancer between the MF-Tricyclic and the Sulindac group (P = 0.34). The median tumor volume was not significantly different among the 3 groups (P = 0.081). Moderate to severe degree of inflammation was significantly more common (P = 0.005) in the control compared with the MF-Tricyclic and the Sulindac group; however, the prevalence of BE was not significantly different between groups (P = 0.98). Rats in the control group had higher tissue PGE 2 level compared with the MF-Tricyclic and Sulindac groups (P = 0.038). Conclusions: Selective and nonselective COX-2 inhibitors can inhibit inflammation, COX-2 activity, and development of adenocarcinoma induced by reflux. This provides direct evidence that COX-2 inhibitors may have chemopreventive potential in BE.

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