May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
The Effect of a COX-2 Inhibitor on Circulating Malignant Cells in an Ocular Melanoma Animal Model
Author Affiliations & Notes
  • S. Di Cesare
    Ocular Pathology, McGill University, Montreal, Quebec, Canada
  • J.-C. Marshall
    Ocular Pathology, McGill University, Montreal, Quebec, Canada
  • S. Maloney
    Ocular Pathology, McGill University, Montreal, Quebec, Canada
  • P. Logan
    Ocular Pathology, McGill University, Montreal, Quebec, Canada
  • B. F. Fernandes
    Ocular Pathology, McGill University, Montreal, Quebec, Canada
  • M. N. Burnier, Jr.
    Ocular Pathology, McGill University, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships S. Di Cesare, None; J. Marshall, None; S. Maloney, None; P. Logan, None; B.F. Fernandes, None; M.N. Burnier, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5253. doi:
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      S. Di Cesare, J.-C. Marshall, S. Maloney, P. Logan, B. F. Fernandes, M. N. Burnier, Jr.; The Effect of a COX-2 Inhibitor on Circulating Malignant Cells in an Ocular Melanoma Animal Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5253.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: The expression of cyclooxygenase-2 (COX-2) has been reported in a wide variety of human tumours, including colon, breast and uveal melanoma (UM) as an indicator of poor prognosis. COX-2 inhibitors have shown promise in controlling some of the malignant characteristics of several tumour types. We aim to investigate the effect of Nepafenac, a COX-2 inhibitor, on circulating malignant cells (CMC’s) in an immunosuppressed rabbit model of human UM.

Methods:: Twenty-eight albino rabbits were injected with 1x106 human UM cells (92.1) in the suprachoroidal space of the eye. Animals were immunosuppressed using cyclosporine A throughout the 12 week long experiment. The animals were randomly divided into two groups of 14 animals each. The control group received drops that contained only the vehicle. The experimental group received drops containing 0.3% Nepafenac solution. Each group was given two drops, twice daily. Peripheral blood samples were obtained weekly from each rabbit and at the moment of euthenasia by cardiac puncture. Samples were processed for RNA using the RiboPure blood kit (Ambion, Austin, Texas, USA). The presence of circulating malignant cells was determined by quantitative real-time PCR, performed using QuantiTect® one step SYBR Green PCR method (Qiagen, Mississauga, Ontario, Canada). A Chromo4 thermocycler (MJ Research) was used for all experiments and all results were analyzed using the GeneEx software. QuantiTect® primer assay pair (Qiagen) for Melan-A was used in order to ascertain the presence of CMC’s, and the housekeeper gene ß-actin was used for purposes of normalization.

Results:: Circulating malignant cells were detected in all rabbits in both groups during at least one time point. On average, the presence of CMC’s in the control group was seen one week post-surgery and remained positive at varying levels throughout the experiment. Conversely, detection of CMC’s in the treated group (0.3% Nepafenac solution) was not seen until week 3 of the experiment. There also appears to be an average 10-fold decrease in mRNA expression for Melan-A in the treated group.

Conclusions:: The results indicate that a COX-2 inhibitor (Nepafenac) has an effect on the human UM CMC’s in this immunosuppressed rabbit model. The use of this inhibitor has delayed the progression of CMC detection as well as the overall mRNA expression level of Melan-A in the treated group. We hypothesize that this may be due to an overall decrease in total amount of CMC’s present in the treated rabbit group. A clinical trail using an anti-COX-2 inhibitor for patients with UM should be considered.

Keywords: oncology • melanoma • pathobiology 
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