Ocular metastasis of murine melanoma.
Item
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Title
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Ocular metastasis of murine melanoma.
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Identifier
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AAI9000701
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identifier
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9000701
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Creator
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Harning, Ronald.
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Contributor
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Adviser: Jeanne Szalay
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Date
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1989
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, General
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Abstract
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The metastasis of murine ocular melanoma is characterized using the in vivo derived B16F10 melanoma cell line in C57BL/6J mice. Intraocular tumor readily metastasizes to the lungs and 100% of the animals die with extensive pulmonary metastasis 5-6 weeks post inoculation. In contrast, when cells passaged 5 times in tissue culture are inoculated intracamerally (ic), a marked decrease in the frequency and extent of metastasis, and an increase in survival is seen.;The efficacy of a new therapeutic immunomodulator, Linomide, is demonstrated against metastases from both ocular and flank tumors. Linomide was shown to significantly reduce metastases from either ocular or flank tumors when administered at a dosage of 160 mg/kg/day to mice. The combined treatment of Linomide and enucleation significantly reduced the number of pulmonary metastases, decreased the incidence of metastasis to the lung and lymph nodes, increased survival, and resulted in an apparent cure rate of 31%.;The role of natural killer (NK) cells in the regulation of metastasis of ocular tumors was also explored using animals with either depleted or enhanced NK activity. In C57BL/6J beige mice, with low NK activity, metastasis to the lungs was increased and survival decreased. In normal mice bearing intraocular tumors, treatment with PK136, an anti-NK cell monoclonal antibody, resulted in a significant increase in pulmonary metastases and an altered pattern of metastasis. Metastases were observed in spleen, liver, and adrenals.;In other experiments, the effect of a combined treatment protocol on metastasis and survival of tumor bearing mice was explored. In unenucleated mice, treatment with Linomide and cyclophosphamide (Cy) resulted in a significant reduction of pulmonary and lymph node metastases, and an increase in survival but no cures. The combined treatment of Linomide, Cy, and enucleation resulted in an apparent cure rate of 22%, a significant reduction of pulmonary and lymph node metastases, and an increase in survival.;Treatment protocols to reduce macrophage and T-cell activity in tumor-bearing mice were also utilized in this study and no effect on metastasis or survival was seen. In summary, the above work demonstrates the importance of the NK cell as a primary effector cell for the control of metastasis from in vivo derived B16F10 melanoma in this model of murine ocular melanoma.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
