Radiation therapy in pediatric patients with bone and soft-tissue malignancies may result in a wide range of adverse clinical orthopedic outcomes following treatment, including the impairment of growth, pathologic fracture, and angular deformity. Radiation therapy, however, remains an important adjuvant therapy in many soft tissue sarcomas and is an alternative to surgery in Ewing's sarcoma of bone. Efforts to further reduce the negative effects of irradiation have focused on the use of chemoradioprotectants. This work proposes to further explore the therapeutic potential of the naturally occurring mineral selenium as a radioprotectant and a tumoricidal agent in pediatric patients. The tumoricidal and radioprotective effects of selenium will be assessed in a novel in-vitro cell culture model that employs a spectrum of bone/bone marrow cells likely to be most affected by radiation therapy. Various functional assays will be combined with measures of apoptosis to determine the individual effects on particular cell types in vitro. In vitro results will then be corroborated with in vivo studies in which selenium will be administered to animals that have been challenged with TC-71 Ewing's sarcoma tumor cells prior to radiation therapy. Mechanical testing, bone mineral density measurements, radiographic measure of limb growth disparity, and quantitative histology of tumor growth and death will be used to determine the overall effectiveness of selenium as a radioprotectant and tumoricidal agent in vivo. ? ?
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