RADIOPROTECTANT AND TUMORICIDAL EFFECTS OF SELENIUM

描述（由申请人提供）：对患有骨和软组织恶性肿瘤的儿科患者进行放射治疗可能导致治疗后各种不良的临床骨科结果，包括生长损害、病理性骨折和角畸形。然而，放射治疗仍然是许多软组织肉瘤的重要辅助治疗，也是骨尤文氏肉瘤手术的替代治疗方法。进一步减少辐照负面影响的努力集中在使用化学放射保护剂上。本研究旨在进一步探索天然矿物质硒作为放射保护剂和杀瘤剂在儿科患者中的治疗潜力。硒的肿瘤杀伤和辐射保护作用将在一种新的体外细胞培养模型中进行评估，该模型采用了可能受放射治疗影响最大的骨/骨髓细胞谱。各种功能分析将与细胞凋亡的测量相结合，以确定在体外对特定细胞类型的个体影响。体外实验结果随后将与体内研究相证实，体内研究将在放射治疗前给TC-71尤因氏肉瘤肿瘤细胞攻击的动物施用硒。机械测试、骨密度测量、肢体生长差异的x线测量以及肿瘤生长和死亡的定量组织学将用于确定硒作为体内放射保护剂和杀瘤剂的总体有效性。

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.