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S. Bakalian, J. C. Marshall, D. Faingold, S. Maloney, C. Edelstein, M. N. Burnier, Jr.; The Effect of a Topical COX-2 Inhibitor on the Expression of a Metastasis Suppressor Gene NM23 in an Experimental Model of Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5232.
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The expression of cyclooxygenase-2 (COX-2) has been reported in a wide variety of human tumors as an indicator of poor prognosis.COX-2 inhibitors have shown promise in controlling the malignant characteristics of several types of tumors. Previous work has demonstrated that a COX-2 inhibitor (Nepafenac) has delayed the progression of uveal melanoma as well as the development of metastatic disease in an immunosuppressed rabbit model. The aim of this study is to investigate the expression levels of nm23-H1 in the intraocular tumors from Nepafenac treated and non-treated animals.
The animals were divided into two groups of 14 animals each. The control group received drops that contained only the vehicle, while the experimental group received drops containing 0.3% Nepafenac solution. Each group was given two drops, twice daily. The duration of the experiment was 12 week. Twenty-eight cases of paraffin-embedded specimens of uveal melanomas of treated and non-treated experimental rabbits were immuno-stained with nm23-H1 monoclonal antibody using the standard ABC technique. The immuno-staining was evaluated in semi-quantitative fashion based on their extent and intensity. Moreover, the expression levels of m-RNA of nm23-H1 was assessed in 5 human uveal melanoma cell lines (92.1, OCM-1, SP6.5, MKT-BR, and UW-1) before and after treatment with Amfenac the active metabolite of Nepafenac using quantitative Real Time PCR.
All intraocular tumors showed varying degrees of immuno-expression of the metastasis suppressor gene nm23-H1. The immuno-expression of nm23-H1 was significantly stronger in the primary tumor of all treated group as compared to the primary tumors of the non-treated group. In addition, all of the five treated human uveal melanoma cell lines had significantly higher expression levels of nm23-H1 following treatment with a COX-2 inhibitor (p<0.05).
To the best of our knowledge this is the first study to show that the inhibition of COX-2 causes an up regulation of a metastasis suppressor gene. Therefore anti-COX-2 topical medication might be helpful as an adjuvant therapy for patients with uveal melanoma. Further studies detailing the pathway of this up regulation are underway.
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