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K. D. Godeiro, E. Antecka, J. C. Marshal, S. Maloney, M. N. Burnier, Jr.; The Role of NF-B and Bortezomib in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):64.
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Uveal melanoma (UM) is the most common primary intra-ocular malignancy in adults. Despite the high accuracy of clinical diagnosis and advances in local treatment, more than 40% of UM patients will develop metastases that ultimately lead to death. It has been previously shown by our laboratory that the nuclear factor-kappa B (NF-ΚB), a transcription factor related to carcinogenesis, is highly expressed in UM specimens . Bortezomib is a NF-ΚB inhibitor, which received accelerated FDA approval to treat multiple myeloma patients refractory to previous therapies. Although the role of NF-ΚB in protecting skin melanoma cells from apoptosis and the effects of bortezomib in skin melanoma have received considerable interest recently, the role of NF-ΚB and bortezomib in UM has not yet been studied.
Four human UM cell lines and one human transformed uveal melanocyte cell line were assayed for proliferative ability under conditions of increasing concentrations of bortezomib.
All UM cell lines exposed to bortezomib disclosed a very statistically significant decreased proliferation rate when compared to the control group.
The results of this study demonstrated that NF-ΚB is highly expressed in UM and that bortezomib treatment effectively decreases the proliferation rate of human UM cell lines. Recent advances in the development of drugs that down-regulate NF-ΚB signalling may therefore provide potential adjuvant modalities to conventional therapies in UM.
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