BACKGROUND:Pediatric healthcare is critically dependent on the availability of accurate and precise laboratory biomarkers of pediatric disease, and on the availability of reference intervals to allow appropriate clinical interpretation. The development and growth of children profoundly influence normal circulating concentrations of biochemical markers and thus the respective reference intervals. There are currently substantial gaps in our knowledge of the influences of age, sex, and ethnicity on reference intervals. We report a comprehensive covariate-stratified reference interval database established from a healthy, nonhospitalized, and multiethnic pediatric population.
There is a growing trend towards exploring the use of a minimally invasive “liquid biopsy” to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.
BACKGROUND:The practice of personalized medicine has made large strides since the introduction of highthroughput technologies and the vast improvements in computational biotechnology. The personalizedmedicine approach to cancer management holds promise for earlier disease detection, accurate prediction of prognosis, and better treatment options; however, the early experience with personalized medicine has revealed important concerns that need to be addressed before research findings can be translated to the bedside.CONTENT: We discuss several emerging "practical" or "focused" applications of personalized medicine. Molecular testing can have an important positive impact on health and disease management in a number of ways, and the list of specific applications is evolving. This list includes improvements in risk assessment, disease prevention, identification of new diseaserelated mutations, accurate disease classification based on molecular signatures, selection of patients for enrollment in clinical trials, and development of new targeted therapies, especially for metastatic tumors that are refractory to treatment. Several challenges remain to be addressed before genomics information can be applied successfully in the routine clinical management of cancers. Further improvements and investigations are needed in data interpretation, extraction of actionable items, costeffectiveness, how to account for patient heterogeneity and ethnic variation, and how to handle the risk of "incidental findings" in genetic testing.
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