SUMMARY
Uveal melanoma (UM) is the most common cancer in adult eyes. Approximately eighty percent of UMs harbor somatic activating mutations in GNAQ or GNA11 (encodes Gq or G11 respectively). Herein, we show in both cell culture and human tumors that cancer-associated Gq/11 mutants activate YAP, a major effector of the Hippo tumor suppressor pathway that is also regulated by G-protein coupled receptor (GPCR) signaling. YAP mediates the oncogenic activity of mutant Gq/11 in UM development, and the YAP inhibitor verteporfin blocks tumor growth of UM cells containing Gq/11 mutations. This study reveals an essential role of the Hippo-YAP pathway in Gq/11-induced tumorigenesis and suggests YAP as a potential drug target for UM patients carrying mutations in GNAQ or GNA11.
Intravitreal bevacizumab did not appear toxic to the retina in albino rabbits at a concentration of 2.5 mg. Intravitreally injected bevacizumab should be evaluated for efficacy in choroidal neovascularization and macular edema.
Aim: To evaluate the effect of topically administered bevacizumab (Avastin) on experimental corneal neovascularisation in rats. Methods: Silver nitrate sticks (75% silver nitrate, 25% potassium nitrate) were used to perform chemical cauterisation on the corneas of 16 eyes from 16 male Long Evans rats. For the following 7 days, the 10 eyes in the treatment group were instilled with bevacizumab 4 mg/ml drops twice daily, whereas the 6 eyes in the control group received placebo (normal saline drops twice daily). Digital photographs of the cornea were analysed to determine the area of cornea covered by neovascularisation as a percentage of the total corneal area. Results: In the bevacizumab-treated eyes, neovascularisation covered, on average, 38.2% (15.5%) (mean (SD)) of the corneal surface compared with 63.5% (5.0%) in the control group (p,0.02, Mann-Whitney U test). Conclusion: Topically administered bevacizumab (Avastin) at a concentration of 4 mg/ml limits corneal neovascularisation following chemical injury in the male Long Evans rat model.
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