The effect of a topical COX-2 inhibitor on the expression of C-Met in a rabbit model of uveal melanoma
Bibliographic record
Abstract
2313 Purpose: Expression of C-Met was significantly associated with melanoma specific mortality in uveal melanoma patients. On the other hand, the expression of cyclooxygenase-2 (COX-2) has been reported as an indicator of poor prognosis in a wide variety of tumors including uveal melanoma. 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 a rabbit model. The aim of this study is to investigate the immunostaining levels of C-Met in the intraocular tumors of non-treated and Nepafenac treated animals. In addition, evaluate the expression levels of C-Met mRNA in non-treated and treated human uveal melanoma cell lines. Methods: 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 non-treated and treated rabbits were immuno-stained with C-Met monoclonal antibody using the standard ABC technique. The immunostaining was evaluated in semi-quantitative fashion based on their extent and intensity. The expression levels of C-Met mRNA were assessed in five 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. Results: All intraocular tumors showed varying degrees of immunostaining for C-Met. The immunostaining was cytoplasmic in all samples. The intensity of immunostaining was significantly higher in the primary tumors of all non-treated group of rabbits as apposed to the primary tumors of all treated group. All five human uveal melanoma cell lines expressed different amounts of C-Met mRNA. The expression levels of C-Met mRNA were always higher in non-treated cell lines compared to treated cell lines. There was up to four-fold decrease in the expression levels of C-Met mRNA after treatment with Amfenac. Conclusion: This is the first study to show that the inhibition of COX-2 causes a down regulation of C-Met in uveal melanoma. Therefore, anti-COX-2 topical medication might be a useful strategy for an adjuvant therapy in uveal melanoma patients. Further studies detailing the pathway of this down regulation are underway.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".