Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biomarker development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed2006

Changes of tumor necrosis factor, surfactant protein A, and phospholipids in bronchoalveolar lavage fluid in the development and progression of coal workers' pneumoconiosis.

OBJECTIVE: To evaluate the alterations of biomarkers in the development and progression of coal workers' pneumoconiosis (CWP). METHODS: The type and number of cells, and the levels of tumor necrosis factor-alpha (TNF-alpha), pulmonary surfactant protein, phospholipids and fibronectin in bronchoalveolar lavage fluid were assayed in 14 health active coal miners, 21 coal miners without CWP and 13 miners with CWP of 0/1 to 1/1. RESULTS: Compared to active coal miners without CWP (8.23 microg/mL), TNF-alpha concentration was gradually decreased when dust exposure was stopped (5.90 microg/mL). Elevated surfactant protein A (SP-A) level and phosphatidylglycerol (PG) to phosphatidylinositol (PI) ratio were found in miners actively exposed to coal dust (6528 ng/mL for SP-A and 10. for PG/PI), and both parameters decreased when CWP progressed from CWP (0/1) (3419 microg/mL for SP-A and 5.9 for PG/PI) to CWP (1/1) (1654 microg/mL for SP-A and 5.5 for PG/PI). CONCLUSION: Biomarkers in bronchoalveolar lavage fluid can be used to screen coal miners at high risk of developing coal workers' pneumoconiosis.

Adult↗
PubMed2006

A cost-effectiveness approach to the qualification and acceptance of biomarkers.

The flow of new medicines to patients depends on the development of new biomarkers and their correct interpretation, yet there are no widely accepted and practically applicable criteria that facilitate adequate biomarker qualification. As a result, case-by-case qualifications are based on subjective assessments that do not lead to optimal decisions for patients, which have contributed to the 'stagnation' in drug productivity identified by the FDA. An alternative is to qualify biomarkers in terms of cost effectiveness using a set of principles that enable the evaluation of biomarkers even with incomplete knowledge. This approach could minimize harm to patients, improve access to medicines and reduce healthcare costs.

Biomarkers↗
PubMed2004

A review of lysosomal membrane stability measured by neutral red retention: is it a workable earthworm biomarker?

The ability of biomarkers to integrate effects of chemicals on biota has lead to increased calls for their application in assessing the status of polluted ecosystems. In tandem there has been an increase in our knowledge of the ecophysiological responses of keystone species to pollutants, which has allowed the development of a number of promising methods. In contrast to the number of biomarker development studies, the number of biomarker validation studies has remained limited. This paper redresses this imbalance by drawing together data from studies that have used the earthworm lysosomal membrane stability response (measured using the neutral red retention assay). This review first gives a short history of the biomarker's development. Second, it sets published applications of the technique against established criteria for a "good" biomarker (i.e., dose-response relationship, sensitivity, ecological relevance, confounding factors, chemical specificity, species differences, time-response relationship, methodological concerns, and overall public/regulator confidence, and acceptance). Discussion of the biomarker's suitability to each criterion is followed by an overall evaluation of its workability for routine soil quality assessment and caveats for its use.

Animals↗
PubMed1996

Molecular biomarkers of occupational lung cancer.

Occupational exposures to certain metals, hydrocarbons and ionizing radiation are associated with increased lung cancer in workers; because these exposures continue, lung cancer remains an important problem in industrialized nations. The gravity of the lung cancer, specifically the low cure rate associated with the disease, has forced researchers to focus efforts at developing biological indicators (biomarkers) of carcinogen exposure and early, reversible effects. This review examines critically the development of these biomarkers for occupational and environmental exposures to polycyclic aromatic hydrocarbons (PAH), a ubiquitous class of lung carcinogens. Biomarkers of several different stages of the carcinogenic process have been proposed. Industrial hygiene and occupational health emphasize exposure and disease prevention. For this reason, biomarkers useful in industrial hygiene practice are those which measure events prior to the initiation phase of carcinogenesis; markers of later events which have a greater positive predictive value may measure irreversible effects and are more appropriate for disease screening and epidemiology. One of the strengths of biological monitoring is that exposures and effects can be measured regardless of route. Data indicates that the dermal route may be a significant pathway for delivery of PAH to the lung. This finding has important ramifications because as airborne exposure limits decrease the relative impact of dermal absorption is increased.

Carcinogens↗
PubMed2003

A parametric empirical Bayes method for cancer screening using longitudinal observations of a biomarker.

A revolution in molecular technology is leading to the discovery of many biomarkers of disease. Monitoring these biomarkers in a population may lead to earlier disease detection, and may prevent death from diseases like cancer that are more curable if found early. For markers whose concentration is associated with disease progression the earliest detection is achieved by monitoring the marker with an algorithm able to detect very small changes. One strategy is to monitor the biomarkers using a longitudinal algorithm that incorporates a subject's screening history into screening decisions. Longitudinal algorithms that have been proposed thus far rely on modeling the behavior of a biomarker from the moment of disease onset until its clinical presentation. Because the data needed to observe the early pre-clinical behavior of the biomarker may take years to accumulate, those algorithms are not appropriate for timely development using new biomarker discoveries. This manuscript presents a computationally simple longitudinal screening algorithm that can be implemented with data that is obtainable in a short period of time. For biomarkers meeting only a few modest assumptions our algorithm uniformly improves the sensitivity compared with simpler screening algorithms but maintains the same specificity. It is unclear what performance advantage more complex methods may have compared with our method, especially when there is doubt about the correct model for describing the behavior of the biomarker early in the disease process. Our method was specifically developed for use in screening for cancer with a new biomarker, but it is appropriate whenever the pre-clinical behavior of the disease and/or biomarker is uncertain.

Algorithms↗
PubMed2006

Bridging the divide: the need for translational informatics.

Translational science promises to deliver real benefit to the pharmaceutical industry, reducing attrition and affording high quality, efficacious medicines. The development and use of biomarkers aims to reduce drug development risks and generate a better understanding of disease. Informatics is an essential component of the translational science toolkit; researchers must be able to work effectively with biomarker data, and the capture and reuse of knowledge is vital for long-term success. An analysis of current data and knowledge management practices in the translational science area is presented.

Humans↗
PubMed2006

Pilot study using SELDI-TOF-MS based proteomic profile for the identification of diagnostic biomarkers of thyroid proliferative diseases.

Biomarkers for thyroid cancer (TCa) lack specificity. To develop TCa specific biomarkers, SELDI-TOF-MS was used to examine the proteomic profile of biopsies obtained from papillary TCa along with adjacent normal tissue. Sixty-three potential biomarkers were categorized by univariate analysis into single biomarker candidates and segregated by multivariate analysis into normal and cancerous groups. Our studies demonstrate the sensitivity and reproducibility of this approach to detect biomarkers for TCa.

Biomarkers, Tumor↗
PubMedDate not supplied

A rapid, sensitive method for the quantitation of N-acetyl-S-(2-hydroxyethyl)-L-cysteine in human urine using isotope-dilution HPLC-MS-MS.

Because of increasing concern about exposure to carcinogens and other toxicants, reliable methods for biological monitoring of potentially exposed populations must be developed. For biological monitoring to be useful, appropriate biomarkers of exposures to xenobiotics must be identified, and sensitive, specific methods for quantifying the targeted biomarker must be developed. We have developed a sensitive and selective method for the analysis of N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA), urinary metabolite of at least three different known human carcinogens (vinyl chloride, ethylene oxide, and ethylene dibromide). The method uses strong anion-exchange solid-phase extraction and isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. Our method is simple and is not labor intensive; the preparation time per sample is less than 10 min. Because urine samples vary in both their concentration and ion strength, intersample variability in HEMA recovery during the extraction is large. To overcome this inherent limitation, we use the isotope-dilution technique, which allows a complete correction for the extraction recovery for each sample. The limit of detection of the method is 0.68 microgram/L in a 1-mL urine sample with a coefficient of variation of 22% (determined by replicate analyses at both 4 and 11 micrograms/L) and an accuracy indistinguishable from 100%. Preliminary analyses of urine from a population with no known overt exposure to the parent toxicants show a frequency of detection of approximately 75%, which indicates that this method has the sensitivity to detect urinary HEMA derived from environmental exposure. We are currently using this method to establish a reference range of background exposure to these toxicants in the U.S. population.

Acetylcysteine↗
PubMed1990

Biomarkers of aging.

This paper summarises a conceptual discussion of some aspects of biomarkers of aging and the logical strategy for developing them. A biomarker of aging is a biological parameter of an organism that either alone or in some multivariate composite will, in the absence of disease, better predict functional capability at some late age than with chronological age. The criteria for putative biomarker measurement and assessment of putative biomarkers are discussed.

Aged↗
PubMed2006

Biomarkers of ovulation, endometrial receptivity, fertilisation, implantation and early pregnancy progression.

Increasing interest in early preconception and periconception exposures and human developmental outcomes has led to studies that monitor subjects from before conception to gestation, birth and childhood. Monitoring ovulation, endometrial receptivity, fertilisation, implantation and gestation requires the non-invasive collection of biological information and samples, and the measurement of biochemical and biological markers (biomarkers) that are associated with the aforementioned physiological events. This paper describes some of the key features of biomarkers needed for epidemiological studies, identifies some existing and potential biomarkers and available measurement devices, and suggests some directions for identification and development of new biomarkers that might be employed in longitudinal studies involving the analysis of female reproductive function and of embryonic development.

Biomarkers↗
PubMed2001

Validation of biomarkers as early predictors of disease.

The development and validation of biomarkers that link environmental exposures to the pathogenesis of human disease is a leading priority in the field of environmental research. The validation of biomarkers as early predictors of clinical disease can enhance health risk assessment and contribute to effective new disease prevention policies in environmental and occupational settings. The process of validating biomarkers involves dealing with a range of characteristics that include the intrinsic qualities of the biomarker, its determinants, and the analytic procedure. We discuss here a three phase approach to validation. The final phase, consisting of longitudinal studies, is reached after the biomarker has been determined to be technically reliable and after the effect of external variables on the association with the outcome has been evaluated. We provide some examples of biomarkers reputed to be early predictors of cancer and cardiovascular disease (CVD). We then present original data to support the potential of DNA adducts to predict cancer and show, through re-evaluation of the Italian database on cytogenetic biomarkers, a lack of association between the frequency of chromosomal aberrations in circulating lymphocytes and CVD mortality rates -- a finding that should not be considered conclusive. In general, whenever a biomarker has been determined to be a valid predictor of disease, it should be used in risk assessment and public health policy.

Biomarkers↗
PubMed2026

Cell-free DNA methylation biomarkers for the early detection and tumor burden monitoring of gastric cancer.

Development of sensitive biomarkers is required to achieve early detection and tumor burden monitoring in gastric cancer (GC). We performed genome-wide methylation sequencing on 78 tissue and 241 plasma samples from 171 GC patients and 114 healthy controls from two independent clinical centers. Differentially methylated regions (DMRs) were screened using paired GC and normal tissues, and refined through cfDNA profiles with LASSO regression to construct a cfDNA-based biomarker, the GCML-score. The GCML-score, consisting of 13 DMRs, demonstrated excellent diagnostic performance (AUC: 0.95/0.99/0.95 overall and 0.96/0.99/0.82 in early GC for training/internal validation/external validation cohorts). In 12 patients receiving neoadjuvant chemotherapy, dynamic changes in GCML-score were consistent with radiological tumor burden, highlighting its monitoring potential. The GCML-score, derived from genome-wide cfDNA methylation profiling, provides a robust tool for early GC detection and real-time tumor burden monitoring, facilitating improved prognosis and personalized therapeutic strategies.

Journal Article↗
PubMed2005

Crypt-restricted loss and decreased protein expression of cytochrome C oxidase subunit I as potential hypothesis-driven biomarkers of colon cancer risk.

There is an increasing demand for the development of intermediate biomarkers to assess colon cancer risk. We previously determined that a live cell bioassay, which assesses apoptosis resistance in the nonneoplastic colonic mucosa, detects approximately 50% of patients with colon cancer. A hypothesis-driven biomarker that reflects apoptosis resistance in routine formalin-fixed, paraffin-embedded tissue would be easier to use. Cytochrome c oxidase is a critical enzyme that controls mitochondrial respiration and is central to apoptosis. We did an immunohistochemical study of cytochrome c oxidase subunit I expression in 46 colonic mucosal samples from 16 patients who had undergone a colonic resection. These included five patients without evidence of colonic neoplasia (three normal and two diverticulitis), three patients with tubulovillous adenomas, and eight patients with colonic adenocarcinomas. Analysis of aberrancies in expression of cytochrome c oxidase subunit I showed that, compared with nonneoplasia, the patients with neoplasia had a higher mean incidence of crypts having decreased expression (1.7 versus 22.8, P = 0.03) and a higher mean incidence having crypt-restricted loss (0.6 versus 3.2, P = 0.06). The percentage with segmented loss was low and was similar in the two groups. Combining these results, the mean % normal (i.e., with none of the three types of abnormality) was 96.7 in nonneoplasia versus only 73.2 in patients with neoplasia (P = 0.02). It should be noted that a defect in cytochrome c oxidase subunit I immunostaining was not detected in all biopsy samples from each patient for whom some abnormality was found, indicating a "patchiness" in the cytochrome c oxidase subunit I field defect. As a result of this "patchiness," the increased variability in the incidence of crypt-restricted loss of cytochrome c oxidase subunit I expression was a statistically significant feature of the neoplasia group. Crypt-restricted loss of cytochrome c oxidase subunit I has not been previously reported in colonic mucosa and is presumably the result of a crypt-restricted stem cell mutation. Decreased cytochrome c oxidase subunit I expression also significantly correlated with apoptosis resistance, a factor known to contribute to carcinogenesis. The results suggest, however, that aberrant cytochrome c oxidase subunit I expression may be a better biomarker than loss of apoptosis competence for increased colon cancer risk.

Adenocarcinoma↗
PubMed2005

Gene overexpression in pancreatic adenocarcinoma: diagnostic and therapeutic implications.

Pancreatic cancer is the deadliest of cancers, and effective diagnostic and therapeutic strategies are lacking. Global gene expression profiling holds promise for improved diagnosis and treatment. Knowledge of the location and timing of gene overexpression and the function of these genes, including their effects on signaling pathways, is important. These data may be used to develop histologic and serum biomarkers as well as to develop immunotherapeutic, molecular targeting, and gene therapy strategies. We have compiled a list of overexpressed genes in pancreatic cancer for which overexpression was confirmed by reverse transcriptase polymerase chain reaction, immunohistochemistry, and/or in situ hybridization following initial identification by global gene expression profiling. The techniques used in the determination of overexpression, problems encountered in global gene expression profiling, and the diagnostic and therapeutic implications of overexpression are discussed. The S100 gene family, mesothelin, prostate stem cell antigen, and 14-3-3 sigma, may have important clinical implications in pancreatic cancer diagnosis and treatment.

14-3-3 Proteins↗
PubMed2004

Biomarkers of ovarian tumours.

Ovarian cancer is one of the most aggressive gynaecological malignancies and most often the high mortality is a direct result of delays in diagnosis. The development of an ovarian cancer-specific biomarker for the early detection of disease has the capacity to improve the dismal survival rate. Currently, there are multiple investigations that are utilising both genomic and proteomic technologies to identify genes, gene products and proteins that may potentially identify diagnostic ovarian cancer biomarkers. Here, we review the studies that are involved in biomarker development for the detection of ovarian cancer.

Biomarkers, Tumor↗
PubMed2003

Development of protein microarray technology to monitor biomarkers of rheumatoid arthritis disease.

Most biological processes are mediated by complex networks of molecular interactions involving proteins. The analysis of protein expression in biological samples is especially important in the identification and monitoring of biomarkers for disease progression and therapeutic endpoints. In this paper, the development of a protein microarray format for multiplexed quantitative analysis of several potential markers for rheumatoid arthritis (RA) is described. Development of a high-performance protein microarray system depends on several key parameters such as surface chemistry, capture agents, immobilization technology, and methods used for signal detection and quantification. Several technical possibilities were investigated and compared: poly-L-lysine versus self-assembled monolayer of octadecyl phosphoric acid ester for surface chemistries; noncontact piezoelectric versus contact printing technology for antibody deposition; CCD camera capture versus fluorescent scanning for image detection; and the concentration of coating antibody. On the basis of reproducibility, signal-to-noise ratio, and sensitivity we have selected self-assembled monolayer, noncontact piezoelectric printer, and high-read-out fluorescence scanning for our microarray format. This format was used to perform multiplexed quantitative analysis of several potential markers of disease progression of rheumatoid arthritis: IL-1beta, IL-6, IL-8, MCP-1, and SAA. Some assays, such as MCP-1, provided a working range that covered physiologically relevant concentrations. Other assays, such as IL-6 and SAA, lacked sensitivity or were too sensitive for measuring biological concentrations, respectively. The results described demonstrate the applicability of protein microarrays to monitor RA markers; however, sandwich assay methodologies need to be further optimized to measure the appropriate biological ranges of these markers on one chip.

Arthritis, Rheumatoid↗
PubMed2002

The path to personalized medicine.

Advances in personalized medicine, or the use of an individual's molecular profile to direct the practice of medicine, have been greatly enabled through human genome research. This research is leading to the identification of a range of molecular markers for predisposition testing, disease screening and prognostic assessment, as well as markers used to predict and monitor drug response. Successful personalized medicine research programs will not only require strategies for developing and validating biomarkers, but also coordinating these efforts with drug discovery and clinical development.

Biomarkers↗
PubMed2002

Biomarkers in cancer screening: a public health perspective.

The last three decades have witnessed a rapid advancement and diffusion of technology in health services. Technological innovations have given health service providers the means to diagnose and treat an increasing number of illnesses, including cancer. In this effort, research on biomarkers for cancer detection and risk assessment has taken a center stage in our effort to reduce cancer deaths. For the first time, scientists have the technologies to decipher and understand these biomarkers and to apply them to earlier cancer detection. By identifying people at high risk of developing cancer, it would be possible to develop intervention efforts on prevention rather than treatment. Once fully developed and validated, then the regular clinical use of biomarkers in early detection and risk assessment will meet nationally recognized health care needs: detection of cancer at its earliest stage. The dramatic rise in health care costs in the past three decades is partly related to the proliferation of new technologies. More recent analysis indicates that technological change, such as new procedures, products and capabilities, is the primary explanation of the historical increase in expenditure. Biomarkers are the new entrants in this competing environment. Biomarkers are considered as a competing, halfway or add-on technology. Technology such as laboratory tests of biomarkers will cost less compared with computed tomography (CT) scans and other radiographs. However, biomarkers for earlier detection and risk assessment have not achieved the level of confidence required for clinical applications. This paper discusses some issues related to biomarker development, validation and quality assurance. Some data on the trends of diagnostic technologies, proteomics and genomics are presented and discussed in terms of the market share. Eventually, the use of biomarkers in health care could reduce cost by providing noninvasive, sensitive and reliable assays at a fraction of the cost of definitive technology, such as CT scan. The National Cancer Institute's Early Detection Research Network (EDRN) has begun an innovative, investigator-initiated project to improve methods for detecting the biomarkers of cancer cells. The EDRN is a consortium of more than 32 institutions to link discovery of biomarkers to the next steps in the process of developing early detection tests. These discoveries will lead to early clinical validation of tests with improved accuracy and reliability.

Biomarkers↗