Pediatric Cancer Salvia Biorepository

 描述（由申请方提供）：唾液中的药物监测与药物基因组学相结合，为监测和研究与儿童毒性相关的药物代谢提供了前所未有的机会。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可能是终身和渐进性的心肌病。化疗毒性的至少一个促成因素是不能监测和平衡药物水平与治疗效果与毒性。如果saliv可以作为药物监测的基质进行优化，化疗的安全性将通过更频繁的非侵入性采样来改善。为了将唾液开发为最佳储存库基质，这项研究将优化唾液收集、稳定、处理、储存和测定方案，从而创建第一个专门用于儿童化疗研究的儿科唾液生物储存库。这项研究将分为三个具体目标，包括：（1）改进收集、稳定化、处理和储存，以用于来自未用阿霉素治疗的儿童的（掺入的）唾液中的药物和代谢物分析，和（2）针对阿霉素治疗的儿童中的金标准血液基质验证那些唾液方法，以及，（3）确定从冷冻保存的唾液中提取的DNA用于癌症儿童药物基因组学分析的可行性。增加唾液稳定性将使未来的研究的可行性和实用性的家庭为基础的唾液收集的药物水平监测儿童。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，未来的目标是家庭药物监测试剂盒，以确保治疗依从性，并建立第一个唾液生物储存库用于儿童癌症的药物监测。

 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.