RADIOPROTECTANT AND TUMORICIDAL EFFECTS OF SELENIUM

描述（由申请方提供）：骨和软组织恶性肿瘤儿科患者的放射治疗可能导致治疗后广泛的不良临床骨科结局，包括生长障碍、病理性骨折和成角畸形。然而，放射治疗仍然是许多软组织肉瘤的重要辅助治疗，并且是骨尤文氏肉瘤手术的替代治疗。进一步减少辐射的负面影响的努力集中在化学放射防护剂的使用。这项工作提出了进一步探索的治疗潜力，天然存在的矿物质硒作为一种辐射防护剂和杀肿瘤剂在儿科患者。将在一种新型体外细胞培养模型中评估硒的杀肿瘤和辐射防护作用，该模型采用可能受放射治疗影响最大的骨/骨髓细胞谱。各种功能测定将与细胞凋亡的测量相结合，以确定体外对特定细胞类型的个体效应。然后将用体内研究证实体外结果，在体内研究中，将硒给予在放射治疗前用TC-71尤文氏肉瘤肿瘤细胞攻击的动物。将使用机械测试、骨矿物质密度测量、肢体生长差异的放射学测量以及肿瘤生长和死亡的定量组织学来确定硒作为体内辐射防护剂和杀肿瘤剂的总体有效性。

DESCRIPTION (provided by applicant): 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.