RADIOPROTECTANT AND TUMORICIDAL EFFECTS OF SELENIUM

描述(申请人提供)：儿童骨和软组织恶性肿瘤患者的放射治疗可能会在治疗后导致一系列不良的骨科临床结果，包括生长障碍、病理性骨折和角度畸形。然而，放射治疗仍然是许多软组织肉瘤的重要辅助治疗方法，是尤文骨肉瘤手术的替代方案。为进一步减少辐射的负面影响所作的努力侧重于使用化学放射防护剂。这项工作建议进一步探索天然矿物硒作为放射防护剂和杀瘤剂在儿科患者中的治疗潜力。硒的杀瘤和辐射防护作用将在一种新的体外细胞培养模型中进行评估，该模型使用了可能受放射治疗影响最大的骨髓/骨髓细胞谱。不同的功能分析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影响。体外结果将得到体内研究的证实，在体内研究中，将向在放射治疗前用TC-71尤文氏肉瘤细胞攻击的动物注射硒。力学测试、骨密度测量、肢体生长差异的放射测量以及肿瘤生长和死亡的定量组织学将被用来确定硒作为体内辐射防护剂和肿瘤杀伤剂的整体有效性。

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.