The expression of COX-2 in human choroidal neovascular membranes suggests a possible role for this modulator in age-related macular degeneration pathogenesis. The age-dependent expression observed is novel and warrants further investigation.
During the study period, 10,675 human ophthalmic specimens were received at The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University, Montreal, Canada. Of those, 271 were conjunctival lesions (2.5%), with 101 being classified as melanocytic: 50 (49.5%) nevi, 36 (35.6%) primary acquired melanoses, and 15 (14.9%) melanomas. After exclusion of referred cases, 85 lesions were included in the study: 44 (51.7%) nevi, 33 (38.8%) primary acquired melanoses, and 8 (9.4%) melanomas. The most prevalent location was the bulbar conjunctiva. Conjunctival melanomas were most commonly found in an older age group than primary acquired melanosis or nevi. Conjunctival nevi were subdivided into compound (32.9%), subepithelial (16.4%), and junctional (2.3%). Primary acquired melanosis were further classified into primary acquired melanosis with atypia (8.2%) and primary acquired melanosis without atypia (30.5%). Primary acquired melanoses was the predisposing lesion in 75% of the cases of melanoma. In our sample, referral bias could alter the distribution of conjunctival pigmented lesions, with a shift toward the malignant end.
Imatinib mesylate (IM) is a compound that inhibits both BCR-ABL tyrosine kinase and c-kit receptors. Tyrosine kinases are important in cellular signaling and mediate major cellular processes such as proliferation, differentiation, apoptosis, attachment, and migration. Twenty-six albino rabbits were injected with 1 × 106 human uveal melanoma (UM) cells (92.1) into the suprachoroidal space. Animals were immunosuppressed (cyclosporin A) over the course of the 12-week experiment and divided into two groups (n = 13). The experimental group received IM once daily by gavage while the control group received a placebo. One animal per group was sacrificed every week after the 2nd week. Upon necropsy, organs were harvested for histopathological examination. Cells from the primary tumors were recultured and tested in proliferation and invasion assays. A PCR array was used to investigate the differences in expression of 84 genes related to tumor metastasis. In the treated group, 4 rabbits developed intraocular tumors, with an average largest tumor dimension (LTD) of 2.5 mm and 5 animals reported metastatic disease. Whereas 6 rabbits in the control group developed intraocular tumors, with an average LTD of 5.8 mm and 6 animals reported metastatic disease. The recultured cells from the treated group demonstrated lower proliferation rates and were less invasive (p < 0.001 The PCR array showed differences in expression of genes related to metastasis. Notably, there was 290-fold increase in SERPINB5, a tumor suppressor gene, and a 10-fold higher expression of KISS1, a metastasis suppressor gene, in the treated group. Proangiogenic genes such as VEGFA, PDGFA and PDGFB were downregulated in the treated group. To the best of our knowledge, this is the first report detailing the altered expression of specific genes in UM cells after treatment with IM.
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