RADIOPROTECTANT AND TUMORICIDAL EFFECTS OF SELENIUM

硒的辐射防护和抗肿瘤作用

• 批准号: 6954252
• 负责人: Bryan Samuel Margulies
• 金额: $ 3.82万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2006-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954252
• 关键词: Ewing' s tumor; alternative medicine; antineoplastics; apoptosis; athymic mouse; bone density; bone development; clinical research; combination chemotherapy; cytotoxicity; dosage; histology; human subject; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; nonhuman therapy evaluation; pediatric neoplasm /cancer; photon absorptiometry; predoctoral investigator; radioprotective agents; selenium; therapy adverse effect; therapy design /development; tissue /cell culture

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.

描述（由申请人提供）：患有骨和软组织恶性肿瘤的儿科患者的放射治疗可能会导致治疗后出现多种不良的临床骨科结果，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，并且是尤文氏骨肉瘤手术的替代疗法。进一步减少辐射负面影响的努力集中在化学放射防护剂的使用上。这项工作旨在进一步探索天然存在的矿物质硒作为儿科患者的辐射防护剂和杀肿瘤剂的治疗潜力。硒的杀肿瘤和放射防护作用将在一种新型体外细胞培养模型中进行评估，该模型采用可能受放射治疗影响最大的一系列骨/骨髓细胞。各种功能测定将与细胞凋亡测量相结合，以确定体外对特定细胞类型的个体影响。然后，体外结果将与体内研究得到证实，体内研究将在放射治疗前对经过 TC-71 尤文氏肉瘤肿瘤细胞攻击的动物施用硒。机械测试、骨矿物质密度测量、肢体生长差异的放射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辐射防护剂和杀肿瘤剂的总体有效性。