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The prostate-specific antigen test has been a major factor in increasing awareness and better patient management of prostate cancer (PCA), but its lack of specificity limits its use in diagnosis and makes for poor early detection of PCA. The objective of our studies is to identify better biomarkers for early detection of PCA using protein profiling(More)
With recent advances in mass spectrometry techniques, it is now possible to investigate proteins over a wide range of molecular weights in small biological specimens. This advance has generated data-analytic challenges in proteomics, similar to those created by microarray technologies in genetics, namely, discovery of 'signature' protein profiles specific(More)
Discovery of "signature" protein profiles that distinguish disease states (eg, malignant, benign, and normal) is a key step towards translating recent advancements in proteomic technologies into clinical utilities. Protein data generated from mass spectrometers are, however, large in size and have complex features due to complexities in both biological(More)
BACKGROUND Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. METHODS We sequenced exons 18-21 of the EGFR(More)
BACKGROUND The occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived populations, overweight and obesity are established causes of diabetes. The shape of the association of overweight and obesity with diabetes risk and its overall impact(More)
Research methods for biomarker evaluation lag behind those for evaluating therapeutic treatments. Although a phased approach to development of biomarkers exists and guidelines are available for reporting study results, a coherent and comprehensive set of guidelines for study design has not been delineated. We describe a nested case-control study design that(More)
BACKGROUND Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer. METHODS Two sequential(More)
There are two popular statistical approaches to biomarker evaluation. One models the risk of disease (or disease outcome) with, for example, logistic regression. A marker is considered useful if it has a strong effect on risk. The second evaluates classification performance by use of measures such as sensitivity, specificity, predictive values, and receiver(More)
BACKGROUND The epidermal growth factor receptor (EGFR) gene is the prototype member of the type I receptor tyrosine kinase (TK) family and plays a pivotal role in cell proliferation and differentiation. There are three well described polymorphisms that are associated with increased protein production in experimental systems: a polymorphic dinucleotide(More)
BACKGROUND The free prostate-specific antigen (PSA) isoform, [-2]proPSA, has been shown to be associated with prostate cancer. The study objective was to characterize the clinical utility of serum [-2]proPSA for prostate cancer detection and assess its association with aggressive disease. METHODS From among 669 subjects in a prospective prostate cancer(More)