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Biomedical subjects

Steven Skates

Publications and source records attributed to Steven Skates.

5 recordsLinked to original sources
PubMed2006

Proteomic-based discovery and characterization of glycosylated eosinophil-derived neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine.

PURPOSE: The objective was to identify and characterize low molecular weight proteins/peptides in urine and their posttranslational modifications that might be used as a screening tool for ovarian cancer. EXPERIMENTAL DESIGN: Urine samples collected preoperatively from postmenopausal women with ovarian cancer and benign conditions and from nonsurgical controls were analyzed by surface-enhanced laser desorption/ionization mass spectrometry and two-dimensional gel electrophoresis. Selected proteins from mass profiles were purified by chromatography and followed by liquid chromatography-tandem mass spectrometry sequence analysis. Specific antibodies were generated for further characterization, including immunoprecipitation and glycosylation. Quantitative and semiquantitative ELISAs were developed for preliminary validation in patients of 128 ovarian cancer, 52 benign conditions, 44 other cancers, and 188 healthy controls. RESULTS: A protein (m/z approximately 17,400) with higher peak intensities in cancer patients than in benign conditions and controls was identified and subsequently defined as eosinophil-derived neurotoxin (EDN). A glycosylated form of EDN was specifically elevated in ovarian cancer patients. A cluster of COOH-terminal osteopontin was identified from two-dimensional gels of urine from cancer patients. Modified forms EDN and osteopontin fragments were elevated in early-stage ovarian cancers and a combination of both resulted to 93% specificity and 72% sensitivity. CONCLUSIONS: Specific elevated posttranslationally modified urinary EDN and osteopontin COOH-terminal fragments in ovarian cancer might lead to potential noninvasive screening tests for early diagnosis. Urine with less complexity than serum and relatively high thermodynamic stability of peptides or metabolites is a promising study medium for discovery of the novel biomarkers which may present in many non-urinary tract neoplastic diseases.

Adenocarcinoma, Clear Cell↗
PubMed2006

Evaluating markers for the early detection of cancer: overview of study designs and methods.

BACKGROUND: The field of cancer biomarker development has been evolving rapidly. New developments both in the biologic and statistical realms are providing increasing opportunities for evaluation of markers for both early detection and diagnosis of cancer. PURPOSE: To review the major conceptual and methodological issues in cancer biomarker evaluation, with an emphasis on recent developments in statistical methods together with practical recommendations. METHODS: We organized this review by type of study: preliminary performance, retrospective performance, prospective performance and cancer screening evaluation. RESULTS: For each type of study, we discuss methodologic issues, provide examples and discuss strengths and limitations. CONCLUSION: Preliminary performance studies are useful for quickly winnowing down the number of candidate markers; however their results may not apply to the ultimate target population, asymptomatic subjects. If stored specimens from cohort studies with clinical cancer endpoints are available, retrospective studies provide a quick and valid way to evaluate performance of the markers or changes in the markers prior to the onset of clinical symptoms. Prospective studies have a restricted role because they require large sample sizes, and, if the endpoint is cancer on biopsy, there may be bias due to overdiagnosis. Cancer screening studies require very large sample sizes and long follow-up, but are necessary for evaluating the marker as a trigger of early intervention.

Biomarkers, Tumor↗
PubMed2004

Molecular markers for early detection of renal carcinoma: investigative approach.

Molecular markers for renal cell carcinoma could guide early detection of localized disease in defined populations at high risk for the disease or early disease recurrence after nephrectomy for renal cell carcinoma. In addition, sensitive and specific markers may provide surrogate end points for clinical trials of treatment and/or disease prevention. Powerful techniques of genomic and proteomic analysis of human renal carcinoma cell lines, tumor samples, and biological fluids, such as plasma and urine, obtained from patients with renal cell carcinoma, are likely to identify candidate markers. Careful selection among early candidate markers and further testing in independent patient populations are required for marker validation.

Algorithms↗
PubMed2002

Modeling and optimization in early detection programs with a single exam.

The choice of timing of screening examinations is an important element in determining the efficacy of strategies for the early detection of occult disease. In this article, we describe a flexible decision-making framework for the design of early detection programs, and we investigate the choice of timing when each individual in the screening program is examined only once. We focus on the theoretical relation between the optimal examination time and the distributions of sojourn times in health-related states. Specifically, we derive closed-form solutions of the optimal age using two specifications of utility functions, discuss the effects of natural history and utility specifications on the optimal solution, and present an application to early detection of colorectal cancer by once-only sigmoidoscopy or colonoscopy.

Age Factors↗