Blood Test to Predict Radiation Toxicity

血液测试可预测辐射毒性

• 批准号: 8744454
• 负责人: CHANG HEE KIM
• 金额: $ 28万
• 依托单位: DXTERITY DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-12 至 2014-06-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8744454
• 关键词: Bioinformatics; Biological Assay; Biological Markers; Blood; Blood Cells; Blood Tests; Blood specimen; Bone Marrow Transplantation; Cell Line; Clinical; Companions; Data; Diagnostic; Diagnostic tests; Fibroblasts; Gene Expression; Gene Expression Profiling; Genes; Genome; Goals; Laboratories; Literature; Malignant Neoplasms; Measurement; Measures; Multi-Institutional Clinical Trial; Patients; Performance; Peripheral Blood Lymphocyte; Preparation; Process; RNA; RNA purification; Radiation; Radiation Toxicity; Radiation therapy; Risk; Sampling; Symptoms; Technology; Test Result; Testing; Toxicity Tests; Universities; Whole Blood; Whole-Body Irradiation; base; cost effective; design; innovation; irradiation; lymphoblast; lymphoblastoid cell line; prospective; prototype; response; sample collection

DxTerity Diagnostics will develop a rapid, cost-effective prototype assay for measurement of radiation toxicity in blood using its innovative DxDirect technology. The assay will be based on the gene expression response signature of blood cells to radiation exposure ex vivo, and will not require purification of RNA prior to analysis. RNA targets will be selected based on gene expression profiling of normal and radiosensitive lymphoblast cell lines and bioinformatic analysis of prior microarray studies. The assay will used to measure whole blood gene expression responses to ex vivo irradiation in 100 prospective blood samples from radiotherapy patients. Expression results will be correlated with clinical symptoms of radiation toxicity, and the most informative genes for radiation toxicity will be used to design a companion diagnostic test for radiation therapy. The long-term goal is to identify patients prior to therapy who may be at risk of radiotoxicity. This test will be established in DxTerity¿s CLIA-compliant clinical laboratory, optimized and validated prior to transfer of the SOP to the NCI. The resulting test will be the first practical and cost-effective test to reduce complications from the radiotherapeutic treatment of malignancies and can be piloted in larger multi-center clinical trials.

DxTerity Diagnostics 将开发一种快速、经济高效的原型检测方法，利用其创新的 DxDirect 技术测量血液中的辐射毒性。该测定将基于血细胞对离体辐射暴露的基因表达反应特征，并且不需要在分析前纯化RNA。将根据正常和放射敏感淋巴母细胞系的基因表达谱以及先前微阵列研究的生物信息学分析来选择RNA靶标。该检测将用于测量来自放疗患者的 100 份前瞻性血液样本对离体辐射的全血基因表达反应。表达结果将与放射毒性的临床症状相关，并且放射毒性信息最丰富的基因将用于设计放射治疗的伴随诊断测试。长期目标是在治疗前识别可能面临放射毒性风险的患者。该测试将在 DxTerity 符合 CLIA 标准的临床实验室中建立，并在 SOP 转移到 NCI 之前进行优化和验证。由此产生的测试将是第一个实用且具有成本效益的测试，旨在减少恶性肿瘤放射治疗引起的并发症，并且可以在更大规模的多中心临床试验中进行试点。