This proposal describes continuing studies related to the etiology, pathogenesis, pathobiology and treatment of ocular melanomas and retinoblastomas. The major portion of these studies will utilize human ocular melanoma and retinoblastoma grown in culture. Experiments with these cell lines will be performed in vitro and in nude mice. The following objectives are proposed for the next 5 years: (1) Characterization of ocular melanoma and retinoblastoma cell lines by (a) detemrining their in vitro growth characteristics and requirements; (b) examining their morphology by use of light microscopy, TEM and SEM (c) karyotyping of established ocular melanoma cell lines by the use of sensitive new banding methods. (2) Establishment of an in vivo model for cultured ocular melanoma cell lines and new retinoblastoma lines by growing them in nude mice. (3) Determination of the effectiveness of various treatments on ocular melanoma using both in vitro and in vivo assay systems. The treatment methods to be tested include x-irradiation and cytotoxic drugs. (4) Evaluation of the effect of retinoids and vitamin D on melanoma and retinoblastoma in vitro and in vivo using nude mice. (5) Study of nuclear magnetic resonance (NMR) spectra of melanoma and retinoblastoma. When human tumor cells are removed from the patient, dispersed and grown in tissue culture and in nude mice, it is uncertain how the biological behavior of the tumor cells and their response to treatment modalities are altered. NMR study of the metabolic processes of tumor cells in vitro, in the nude mouse, in tissue freshly removed from the enucleated eye, and in the eye will be carried out to compare and test the validity of extrapolating from in vitro and nude mouse models to the human situation. NMR studies to be conducted include proton, 31-P and 13-C spectroscopy to yield T1 and T2 relaxation times, intracellular pH in different phases of tumor study, and responses to glucose uptake. This work will provide insights into the pathobiology of the two major primary ocular tumors. The tissue culture studies will determine a broad spectrum of morphologic and physiologic characteristics. Using this information, a nude mouse model will be developed to simulate the human condition. Subsequent treatment studies will provide information needed for rational and improved methods of therapy. To achieve these goals, a large number of areas of investigation have been chosen and the help of experts in these disciplines enlisted. The information gained from these investigations will allow for the development of a cohesive model of the pathogenesis and treatment of these blinding and lethal diseases.
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| Burris, Christopher K H; Raven, Meisha L; Rodriguez, Maria E et al. (2017) Bilateral Primary Mucinous Carcinoma of the Eyelid. Ophthal Plast Reconstr Surg 33:S72-S73 |
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| van Ginkel, Paul R; Yang, William; Marcet, Marcus M et al. (2007) 1 alpha-Hydroxyvitamin D2 inhibits growth of human neuroblastoma. J Neurooncol 85:255-62 |
| Albert, Daniel M; Scheef, Elizabeth A; Wang, Shoujian et al. (2007) Calcitriol is a potent inhibitor of retinal neovascularization. Invest Ophthalmol Vis Sci 48:2327-34 |
| Tolleson, William H; Doss, Jason C; Latendresse, John et al. (2005) Spontaneous uveal amelanotic melanoma in transgenic Tyr-RAS+ Ink4a/Arf-/- mice. Arch Ophthalmol 123:1088-94 |
| Albert, Daniel M; Kumar, Amit; Strugnell, Stephen A et al. (2004) Effectiveness of 1alpha-hydroxyvitamin D2 in inhibiting tumor growth in a murine transgenic pigmented ocular tumor model. Arch Ophthalmol 122:1365-9 |
| Albert, Daniel M; Kumar, Amit; Strugnell, Stephen A et al. (2004) Effectiveness of vitamin D analogues in treating large tumors and during prolonged use in murine retinoblastoma models. Arch Ophthalmol 122:1357-62 |
| Cullinan, Amy E; Lindstrom, Mary J; Sabet, Sina et al. (2004) Evaluation of the antitumor effects of Herpes simplex virus lacking ribonucleotide reductase in a murine retinoblastoma model. Curr Eye Res 29:167-72 |
| Audo, Isabelle; Darjatmoko, Soesiawati R; Schlamp, Cassandra L et al. (2003) Vitamin D analogues increase p53, p21, and apoptosis in a xenograft model of human retinoblastoma. Invest Ophthalmol Vis Sci 44:4192-9 |
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