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objective of this application is to evaluate the effects of hypo- and hyperthyroidism on the growth kinetics of human renal cellcancer (RCC) in athymic mice. RCC arises from renal nephron epithelial cells and represents an important clinical neoplasm
with a poor prognosis. Numerous large randomized clinical trials have shown the beneficial effects of (131)iodine-based thyroid
scan with focused (131)iodine treatment (FIT) on this cancer. It is not known whether these effects are related to the therapeutic
activity of (131)iodine or to the general effects of radioiodine on the tumor and the host. Therapy with (131)iodine results in theinduction of apoptosis in treated tumor cells and is associated with decreased proliferation rates and stabilization of tumorgrowth. The molecular mechanisms of these effects are not completely understood. Since RCC is an epithelial tumor, andcatecholamines play an important role in the proliferation of kidney epithelial cells, we hypothesize that catecholamines play animportant role in the pathogenesis of RCC and this tumor is sensitive to both therapeutic and toxic effects of radiation. The firstobjective of this application will be to evaluate the therapeutic effects of hypo- and hyperthyroidism on the growth kinetics ofhuman RCC in athymic mice. The second objective will be to evaluate the biochemical and cellular effects of therapeutic andtoxic levels of radioiodine on murine RCC cells transplanted subcutaneously in athymic mice and cultured in monolayers invitro. The third objective will be to determine if and how catecholamines mediate the effects of radioiodine on RCC. The
effects of radioiodine and catecholamines on the physiological, biochemical, and cellular parameters of tumor growth will beassessed. The results of these studies will increase our understanding of the molecular mechanisms of thyroid hormone andradiation effects on RCC cells and may provide new insights into the pathogenesis and treatment of this malignancy.ability ofHA to avoid re-infectDownload

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