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S Dithmar, H Yang, J Freeman, HE Grossniklaus; Analysis of Angiostatin Activity and Angiostatin Treatment in a Murine Model for Metastatic Ocular Melanoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1120.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To analyse the angiostatin activity of B16-LS9 melanoma cells and to perform an experimental trial for the effect of angiostatin (given after enucleation) on metastases and micrometastases in a murine uveal melanoma model. Methods:Angiostatin activity of B16-LS9 melanoma cells was analysed using tritiated thymidine as an indirect marker for angiostatin production. Bovine vascular endothelial cells (EJG) served as a negative control. B16-LS9 tissue culture melanoma cells were inoculated into the posterior compartment of two groups of C57BL/6 mice. The inoculated eyes were enucleated at 7 days and the mice were sacrificed at 21 days post-inoculation with number of metastases and micrometastases determined from the necropsy using standard techniques. Group 1 (n=22) was the control group, group 2 (n=24) was the treatment group. The groups were given daily SC injections of 50µl of PBS (group 1) or human recombinant angiostatin (0.6µg/µl)(group 2) for 14 days starting day 1 post-enucleation. Results:B16-LS9 melanoma cells produce angiostatin (1.27% for B16-LS9 cells, -2.63% for EJG cells). Pulmonary metastases were detected in 3/22 (14%) and 2/24 (12,5%) of groups 1 and 2, respectively. Avascular hepatic micrometastases appeared in 12/22 (55%) and 8/24 (33%) of groups 1 and 2, respectively. Conclusion:Experimental studies have shown that recombinant angiostatin inhibits angiogenesis and metastatic cancer. The removal of an angiostatin producing primary tumor (enucleation) might support the development of metastases due to the lack of angiostatin production. This experimental study supports the hypothesis that angiostatin treatment can decrease the metastatic rate.
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