Characterization of cyclooxygenase-2 (COX-2) during tumorigenesis in human epithelial cancers: evidence for potential clinical utility of COX-2 inhibitors in epithelial cancers

Increased prostaglandins (PGs) are associated with many inflammatory pathophysiological conditions; and are synthesized from arachidonic acid by either of 2 enzymes, cyclooxygenase-1 (COX-1) or -2 (COX-2). Recent epidemiologic, expression, and pharmacologic studies suggest COX-2 derived metabolites...

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Published in:Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2002-01, Vol.66 (1), p.13-18
Main Authors: Koki, A.T., Khan, N.K., Woerner, B.M., Seibert, K., Harmon, J.L., Dannenberg, A.J., Soslow, R.A., Masferrer, J.L.
Format: Article
Language:English
Subjects:
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - pharmacology
Cyclooxygenase Inhibitors - therapeutic use
Disease Models, Animal
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Isoenzymes - antagonists & inhibitors
Isoenzymes - genetics
Isoenzymes - metabolism
Membrane Proteins
Neoplasms, Glandular and Epithelial - drug therapy
Neoplasms, Glandular and Epithelial - enzymology
Neoplasms, Glandular and Epithelial - prevention & control
Prostaglandin-Endoperoxide Synthases - genetics
Prostaglandin-Endoperoxide Synthases - metabolism
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Summary:Increased prostaglandins (PGs) are associated with many inflammatory pathophysiological conditions; and are synthesized from arachidonic acid by either of 2 enzymes, cyclooxygenase-1 (COX-1) or -2 (COX-2). Recent epidemiologic, expression, and pharmacologic studies suggest COX-2 derived metabolites also play a functional role in the maintenance of tumor viability, growth and metastasis. Archival and/or prospectively collected human tissues were prepared for immunohistochemistry, and representative cases assayed via Western blot, RT-PCR, or TAQman analysis. Consistent overexpression of COX-2 was observed in a broad range of premalignant, malignant, and metastatic human epithelial cancers. COX-2 was detected in ca. 85% of the hyperproliferating, dysplastic, and neoplastic epithelial cells, and in the existing and angiogenic vasculature within and adjacent to hyperplastic/neoplastic lesions. These data collectively imply COX-2 may play an important role during premalignant hyperproliferation, as well as the later stages of invasive carcinoma and metastasis in various human epithelial cancers.
ISSN:0952-3278
1532-2823
DOI:10.1054/plef.2001.0335