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R. D. Braun, K. S. Vistisen; Topical Cromolyn Inhibits the Growth of Human Choroidal Melanoma Xenografts. Invest. Ophthalmol. Vis. Sci. 2008;49(13):62.
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Current treatments of primary choroidal melanoma can negatively affect patient vision, and new effective, vision-sparing therapies for choroidal melanomas are needed. Choroidal melanomas from patients strongly express S100A1, which is a member of the S100 family of calcium-binding proteins. S100A1, S100P, and other S100 proteins are known to interact with the receptor for advanced glycation end products (RAGE), resulting in an increase in cancer cell proliferation and survival. Recently, inhibition of RAGE activation by blocking S100P with the antiallergy drug cromolyn successfully inhibited the growth of human pancreatic tumor xenografts in scid mice. Cromolyn is commercially available for topical application to treat ocular itching. Since it has been shown to bind S100A1, we hypothesize that topical application of this drug could inhibit the growth of choroidal melanoma.
Orthotopic xenografts were grown in 7 eyes by implanting human choroidal melanoma OCM-1 spheroids into the suprachoroidal space of nude, athymic WAG/Nij-rnu/rnu rats. Beginning the day after implantation, all rats received either single drops of 6% cromolyn or artificial tears twice daily (Monday-Friday) for the next 28 days. Four rats received cromolyn, and three rats served as controls and received artificial tears. On Days 7, 14, 21, and 28 after implantation, the rats were anesthetized with ketamine/xylazine, and high-frequency ultrasound was used to measure tumor volume.
OCM-1 spheroids and xenografts expressed high levels of S100A1. On Day 28, tumors in the cromolyn-treated rats were significantly smaller than those in the control rats, 7.9 ± 2.8 mm3 (mean ± SD, n=4) compared to 26.5 ± 8.8 mm3 (n=3), respectively (p=0.009, unpaired t-test).
Topical application of cromolyn was effective at slowing the growth of primary human uveal melanomas when treatment began immediately after implantation. Whether cromolyn can inhibit growth of established tumors remains to be determined.
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