The use of a cyclooxygenase-2 inhibitor (Nepafenac) in an ocular and metastatic animal model of uveal melanoma.
The expression of cyclooxygenase-2 (COX-2) has been reported as an indicator of poor prognosis in a wide variety of human tumors, including colon, breast and uveal melanoma (UM). COX-2 inhibitors have shown promise in controlling the malignancy of several types of tumors. Previous studies have demonstrated the efficacy of a COX-2 inhibitor on the proliferation rates of human UM cells. The goal of this experiment was to investigate the efficiency of Nepafenac, a topically administered COX-2 inhibitor, in a rabbit model of UM. The animals were divided into two groups of 14 animals for the duration of the 12-week experiment. One animal per group was killed each week to evaluate disease progression and for histopathological studies. The experimental group received drops containing 0.3% Nepafenac solution. Intraocular tumor growth was evaluated weekly by fundoscopic examination and each animal was weighed prior to examination. Blood samples were taken weekly from all rabbits to detect circulating malignant cells (CMCs) throughout the experiment. After the second week of inoculation, the experimental group weighed significantly more than the control group. The control group developed more intraocular tumors and presented with metastases and higher detectable levels of CMCs before the treated group. These results indicate that the topical administration of a COX-2 inhibitor delayed the progression of this malignancy in our animal model. A clinical trail using an anti-COX-2 inhibitor for patients with UM should be considered.
Marshall
Jean-Claude A
JC
The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University Health Center, 3775 University Street, Lyman Duff Building, Room 216, Montreal, Quebec H3A 2B4, Canada. jeanclaude.marshall@gmail.com
Fernandes
Bruno F
BF
Di Cesare
Sebastian
S
Maloney
Shawn C
SC
Logan
Patrick T
PT
Antecka
Emilia
E
Burnier
Miguel N
MN
D000818:Animals; D044482:Benzeneacetamides / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D023421:Models, Animal; D009362:Neoplasm Metastasis; D010648:Phenylacetates / Q000627:therapeutic use*; D011817:Rabbits; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology
D044482:Benzeneacetamides; D052246:Cyclooxygenase 2 Inhibitors; D010648:Phenylacetates; C414203:nepafenac