Crowell, Pamela L.Schmidt, C. MaxYip-Schneider, Michele T.Savage, Jesse J.Hertzler II, Dean A.Cummings, William O.2021-02-042021-02-042006-06Crowell, P. L., Schmidt, C. M., Yip-Schneider, M. T., Savage, J. J., Hertzler II, D. A., & Cummings, W. O. (2006). Cyclooxygenase-2 expression in hamster and human pancreatic neoplasia. Neoplasia, 8(6), 437-445.https://hdl.handle.net/1805/25145Cyclooxygenase-2 (COX-2) has been implicated in the development of gastrointestinal malignancies. The aim of the present study was to determine COX-2 expression/activity throughout stages of experimental and human pancreatic neoplasia. COX-2 immunohistochemistry was performed in pancreata of hamsters subjected to the carcinogen N-nitrosobis-(2-oxopropyl)amine (BOP) and in human pancreatic tumors. COX-2 activity was determined by prostaglandin E2 assay in tumor versus matched normal pancreatic tissues. The activity of the COX inhibitor sulindac was tested in the PC-1 hamster pancreatic cancer model. COX-2 expression was elevated in all pancreatic intraepithelial neoplasias (PanINs) and adenocarcinomas. In BOP-treated hamsters, there were significant progressive elevations in COX-2 expression throughout pancreatic tumorigenesis. In human samples, peak COX-2 expression occurred in PanIN2 lesions and remained moderately elevated in PanIN3 and adenocarcinoma tissues. COX-2 activity was significantly elevated in hamster and human pancreatic cancers compared to pair-matched normal pancreas. Furthermore, hamster pancreatic tumor engraftment/formation in the PC-1 hamster pancreatic cancer model was reduced 4.9-fold by oral administration of sulindac. Increased COX-2 expression is an early event in pancreatic carcinogeneses. The BOP-induced hamster carcinogenesis model is a representative model used to study the role of COX-2 in well-differentiated pancreatic tumorigenesis. COX inhibitors may have a role in preventing tumor engraftment/formation.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalPancreatic neoplasmsPanINCOX-2chemical carcinogenesisArticle