Pediatric Cancer Salvia Biorepository

 描述(申请人提供)：唾液中的药物监测与药物基因组学相结合，为监测和研究药物代谢提供了前所未有的机会，因为它与儿童的毒性有关。在儿童癌症中，毒性范围从骨髓抑制到慢性中枢和外周神经缺陷以及心肌病，这些都可能是终生的和进行性的。至少一个导致化疗毒性的因素是无法监测和平衡药物水平与治疗效果和毒性之间的关系。如果SAIV能够被优化为药物监测的基质，那么通过实现更频繁的非侵入性采样，化疗的安全性将会得到改善。为了开发唾液作为最佳的储存库基质，这项研究将优化唾液的收集、稳定、处理、存储和分析方案，从而创建第一个致力于儿童化疗研究的儿童唾液生物储存库。这项研究将分为3个具体目标，包括：(1)精炼收集、稳定、加工和储存未接受阿霉素治疗的儿童唾液中的药物和代谢物分析，(2)对照接受阿霉素治疗的儿童的金标准血液基质验证这些唾液方法，以及(3)利用从冷冻保存的唾液中提取的DNA来确定用于癌症儿童的药物基因组分析的可行性。提高唾液的稳定性将使未来能够研究以家庭为基础的唾液收集用于儿童药物浓度监测的可行性和实用性。因此，我们的总体目标是完善、设计和开发稳定唾液用于药物分析所需的技术和程序，未来的目标是开发家庭药物监测试剂盒，以确保治疗依从性，并建立第一个用于儿童癌症药物监测的唾液生物库。

 DESCRIPTION (provided by applicant): Drug monitoring in saliva combined with pharmacogenomics allows unprecedented opportunity to monitor and investigate drug metabolism as it relates to toxicity in children. In childhood cancers, toxicity ranges from myelosuppression to chronic central and peripheral nervous deficits and cardiomyopathy that can be lifelong and progressive. At least one contributing factor to chemotherapeutic toxicity is the inability to monitor and balance drug levels with therapeutic effects versus toxicity. If saliv could be optimized to as a matrix for drug monitoring, the safety profile of chemotherapy would be improved by enabling more frequent, noninvasive sampling. To develop saliva as an optimal repository matrix, this research will optimize saliva collection, stabilization, processing, storag, and assay protocols thereby creating the first pediatric saliva biorepository dedicated to the study of chemotherapy in children. This research will be segmented into 3 specific aims including: (1) refining collection, stabilization, processing, and storage for drug and metabolite analysis in (spiked) saliva from children not treated with doxorubicin and (2) validating those saliva methods against the gold standard blood matrix in doxorubicin-treated children, and, (3) determining the feasibility of pharmacogenomics analysis in children with cancer using DNA isolated from cryopreserved saliva. Increasing the saliva stability will enable future studies on the feasibility and utility of home-based saliva collection for drug level monitoring in children. Thus, our overall goal is to refine, design, and develop the techniques and procedures needed to stabilize saliva for drug analysis with the future goal of home drug monitoring kit to ensure therapy compliance and to establish the first saliva biorepository for drug monitoring in childhood cancers.