ABSTRACT
Purpose: Uveal melanoma, although a rare form of cancer, is the most common primary malignancy of the eye in adults. Nuclear factor-kapaB (NF-kapaB) is a transcription factor that transactivates genes involved in the regulation of cell growth, apoptosis, angiogenesis, and metastasis, but the molecular mechanisms that negatively regulate NF-kapaB activation are not fully understood. NF-kapaB can also be activated by DNA damage pathway through NEMO protein. Therefore, the objective of this study is to elucidate the role of NEMO/IKKgamma protein in uveal melanoma patients. Methods: Seventy-five formalin-fixed paraffin-embedded prospective tissues of uveal melanoma were included in the present study. These cases were reviewed and investigated for the expression of NEMO/IKKgamma protein by immunohistochemistry and validated by western blotting along with the qRT-PCR for mRNA expression. Expression levels were correlated with the clinicopathological parameters and patients outcome. Results: Immunohistochemistry showed cytoplasmic expression of NEMO/IKKgamma expression in only 22 out of 75 (29.33%) cases. This result was confirmed by western blotting, and correlated well with the immunohistochemical expression of NEMO/IKKgamma protein (48 kDa). In addition, downregulation of this gene was found in 87.93% of the cases when compared with the normal tissues. On statistical analysis, loss of NEMO/IKKgamma protein was correlated with neovascularization, high mitotic count, and presence of vascular loop (p < 0.05). There was less overall survival rate with low expression of NEMO/IKKgamma protein in patients with uveal melanoma. Conclusion: This was the first study suggesting the relevant role of NEMO/IKKgamma protein, and highlights the prognostic significance with outcome in uveal melanoma patients. This protein might be used as a screening biomarker in these patients after large-scale validation and translational studies
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Subject(s)
Humans , Uveal Neoplasms/genetics , Melanoma/genetics , NF-kappa B/genetics , Receptor Activator of Nuclear Factor-kappa B/genetics , Uveal Neoplasms/pathology , Melanoma/pathology , Genetic Markers/genetics , Immunohistochemistry/methods , Translational Research, BiomedicalSubject(s)
Buffaloes/embryology , Embryo, Mammalian/drug effects , Guanidines/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide/metabolism , Nitroprusside/pharmacology , Animals , Embryo Culture Techniques/veterinary , Embryonic Development/drug effects , Female , Fertilization in Vitro/veterinary , Nitric Oxide Synthase/metabolismABSTRACT
Quenching of neutral red (NR; neutral form of the dye) fluorescence by a number of aromatic amines has been investigated in acetonitrile solutions. The bimolecular quenching constants (kq) obtained from steady-state and time-resolved measurements for a particular donor-acceptor pair are seen to be the same within experimental error. Correlation of the changes in the kq values with the oxidation potentials of the donors (amines) indicates that electron transfer (ET) is the mechanism operative in the present systems. Direct evidence for ET has been obtained from picosecond transient absorption studies on a suitable amine-NR pair. Experimentally determined kq values are seen to correlate well with the free energy changes (delta G0) for the ET reactions, within the frame-work of the Marcus outer sphere ET theroy. From the correlation between the experimentally determined and theoretically calculated kq values, it appears that solvent reorganization plays a major role in governing ET dynamics in the systems investigated.
