Radiation Dose-Dependent Interventions

辐射剂量依赖性干预措施

• 批准号: 7025565
• 负责人: GEORGE Earl GEORGES
• 金额: $ 448.54万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-31 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7025565
• 关键词: clinical research; cooperative study; radiation dosage; radiation recovery; radiobiology

The primary goal of this Center for Medical Countermeasures against Radiation (CMCR) is to develop dosimetry and medical products that will allow for dose-appropriate interventions that mitigate the effects of radiation exposure. We propose to integrate three different approaches for dosimetry development: optical, proteomics, and mRNA detection to create an accurate 'user-friendly' biodosimeter. Dose-appropriate interventions will be developed using cytokine and cell-based therapies in the clinically relevant dog model. Project 1 will assess changes in exposed skin using non-invasive optical imaging and spectroscopy as a means to accurately measure radiation exposure. Project 2 will test if radiation induced changes in the proteome (plasma, peripheral blood lymphocytes or urine) can serve as a clinical biomarker of exposure. Project 3 will develop dosimetry assays for plasma and peripheral blood that quantitate radiation induced gene expression using real-time polymerase chain reaction (RT/PCR). The complementary and integrated dosimetry methods will be studied in dogs exposed to varying doses of total body irradiation (TBI) and validated in patients undergoing radiation therapy. Three additional projects focus on the development of cytokine and cell based therapies. For dogs exposed to 4 to 7 Gray (Gy) TBI, Project 4 will ask if an "off the shelf cryopreserved, universal donor cell product of ex vivo expanded myeloid progenitors can support granulocyte production until the endogenous hematopoietic system recovers. For dogs exposed to 7 to 10 Gy, Project 5 will optimize donor engraftment and rapid neutrophil recovery using major histocompatibility complex (MHC)-mismatched umbilical cord blood (UCB), thousands of units of which are already cryopreserved. Project 6 will evaluate an alternative source of stem cells by developing methods to improve the safety and effectiveness of delayed MHC- mismatched adult stem transplantation. Three scientific cores, Radiation Dosimetry, Canine Resource, and Cell Therapy are proposed to support all 6 research/ development projects. An Administrative Core will provide scientific and budgetary oversight. It will also administer both an Educational and Pilot Project Core. Using the well-established canine model, the results from which can be extrapolated to humans, this CMCR will develop biodosimetry and cell based therapies that make it possible to provide dose appropriate interventions to victims of a nuclear terrorist attack.

该辐射医学对策中心 (CMCR) 的主要目标是开发剂量测定和医疗产品，以便采取适当剂量的干预措施，减轻辐射暴露的影响。我们建议整合三种不同的剂量测定开发方法：光学、蛋白质组学和 mRNA 检测，以创建精确的“用户友好”生物剂量计。将在临床相关的狗模型中使用细胞因子和细胞疗法开发剂量适当的干预措施。项目 1 将使用非侵入性光学成像和光谱学作为准确测量辐射暴露的手段来评估暴露皮肤的变化。项目 2 将测试辐射引起的蛋白质组（血浆、外周血淋巴细胞或尿液）变化是否可以作为暴露的临床生物标志物。项目 3 将开发血浆和外周血的剂量测定方法，使用实时聚合酶链反应 (RT/PCR) 定量辐射诱导的基因表达。补充和综合剂量测定方法将在暴露于不同剂量全身照射（TBI）的狗中进行研究，并在接受放射治疗的患者中进行验证。另外三个项目专注于细胞因子和细胞疗法的开发。对于暴露于 4 至 7 戈瑞 (Gy) TBI 的狗，项目 4 将询问“现成的冷冻保存的、体外扩增的骨髓祖细胞的通用供体细胞产品是否可以支持粒细胞生成，直到内源性造血系统恢复。” 7 至 10 Gy，项目 5 将利用主要组织相容性复合体 (MHC) 不匹配来优化供体植入和快速中性粒细胞恢复脐带血 (UCB) 已冷冻保存数千单位，项目 6 将通过开发提高 MHC 不匹配成人干移植的安全性和有效性的方法来评估干细胞的替代来源。三个科学核心：辐射剂量测定。 、犬类资源和细胞治疗计划将支持所有 6 个研究/开发项目，并将提供科学和预算监督。该 CMCR 将开发生物剂量测定法和基于细胞的疗法，从而能够为核恐怖袭击的受害者提供适当剂量的干预措施。