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 1,081 records · Page 60Linked to original sources
PubMed1997

Tobacco and cancer: approaches using carcinogen biomarkers and chemoprevention.

Tobacco products are the leading cause of avoidable cancer death in the U.S., accounting for approximately 30% of all cancer deaths. While avoidance of tobacco and smoking cessation are clearly the best way to decrease tobacco-related cancer, these approaches have not been uniformly successful. Approximately 25% of the U.S. population over 18 years of age smokes cigarettes, while 6% use smokeless tobacco products; these figures have not changed markedly in recent years. Our approach toward the tobacco and cancer problem is based on an understanding of the carcinogens in tobacco smoke. These carcinogens form the link between nicotine addiction and cancer. In this paper, two strategies for cancer prevention--the development of carcinogen-derived biomarkers and chemopreventive agents--are discussed. Carcinogen-derived biomarkers can provide specific information on individual metabolic activation and detoxification of tobacco carcinogens. This information can be used to assess individual risk for cancer development upon exposure to tobacco products. Chemopreventive agents can be targeted against the important carcinogens in tobacco smoke. Isothiocyanates, strong inhibitors of lung cancer development by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, are discussed as an example of this approach.

Adult↗
PubMed2005

Molecular prostate cancer pathology: current issues and achievements.

Recent developments in the field of molecular techniques have provided new tools that have led to the discovery of many new promising biomarkers for prostate cancer. These biomarkers may be instrumental in the development of new tests that will have a high specificity for the diagnosis and prognosis of prostate cancer. A biomarker is defined as a molecular test that provides additional information to currently available clinical and pathological tests. Biomarkers should be reproducible (both within and between institutes) and have an impact on clinical management. For diagnostic purposes it is important that potential biomarkers are tested in terms of tissue specificity and their discrimination potential between prostate cancer, normal prostate and benign prostatic hyperplasia. The results of (multiple) biomarker-based assays may enhance the specificity of cancer detection. There is an urgent need for molecular prognostic biomarkers for predicting the biological behavior and outcome of cancer.

Antigens, Neoplasm↗
PubMedDate not supplied

Serum levels of the senescence biomarker clusterin/apolipoprotein J increase significantly in diabetes type II and during development of coronary heart disease or at myocardial infarction.

Clusterin/apolipoprotein J (hereafter ApoJ) is a conserved secreted glycoprotein expressed by a wide array of tissues and being implicated in several physiological processes. ApoJ has been shown to associate with both normal in vitro aging, namely replicative senescence, as well as with stress induced premature senescence. In vivo, the protein is up-regulated in many severe physiological disturbances that relate to advanced aging, including accumulation in the artery wall during the development of atherosclerosis. In the current report we have expanded our previous studies that focus in the biological role of ApoJ during aging by addressing two interrelated issues: (a) we have examined the potential ApoJ association with in vivo aging and (b) we have studied whether its accumulation in the artery wall during the development of atherosclerosis is combined with a measurable increase of its serum levels, as well as, whether a similar effect occurs in diseases, such as diabetes type II, known to represent major risk factors of atherosclerosis. By combining a sandwich ELISA assay and immunoblotting analysis we demonstrate a measurable increase of ApoJ serum levels with age in males and provide evidence that, as compared to healthy donors, the serum ApoJ amount increases significantly in diabetic type II patients and in patients suffering from either a developing coronary heart disease, or myocardial infarction. The highest serum ApoJ levels were found during myocardial infarction but no correlation was observed with the number of vessels with documented atherosclerotic damage. In conclusion, this report illustrates that ApoJ accumulation in serum is probably coupled to a generalized stress mediated induction mechanism that is specifically related to certain diseases; moreover these data raise the possibility that elevated ApoJ levels in serum may represent a strong indication of vascular damage.

Analysis of Variance↗
PubMedDate not supplied

Developing a new method for soil pollution monitoring using molecular genetic biomarkers.

Physiological responses to environmental stressors may induce changes in gene expression as part of an organism's homeostatic mechanisms. Thus molecular genetic biomarkers have the potential to be used for monitoring sublethal chemical exposure in ecosystems. This paper describes a methodological assessment of the suitability of a protocol to monitor selected biomarkers. The TaqMan real-time quantitative polymerase chain reaction was used to measure gene transcription in earthworms (Lumbricus rubellus) maintained on control or cadmium- or copper-spiked soil. Changes in the expression of two target genes, that encoding metallothionein isoform 2 (MT-2) and that encoding the mitochondrial large ribosomal subunit (MLRS), were quantified against the internal control gene beta-actin. The protocol used produced reliable and reproducible results. Transcript levels displayed qualitative and quantitative differences in the responses to the two metal ions. MLRS gene levels were unaffected by exposure to cadmium but displayed a response to high levels of copper. Conversely, cadmium greatly induced MT-2 gene expression, but copper only altered transcription of this gene at high exposure concentrations. This study demonstrates that it is now technically feasible to use gene expression as an index of pollution exposure in environmentally relevant organisms.

Adaptation, Physiological↗
PubMed2007

Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling.

Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease that has been linked to altered immune, inflammatory, and angiogenesis responses. A better understanding of these aberrant responses might improve early detection and prognosis of SCCHN and provide novel therapeutic targets. Previous studies examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera. We hypothesized that an expanded panel comprised of multiple cytokines, chemokines, growth factors, and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination. Thus, we evaluated a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple serum biomarkers. Concentrations of 60 cytokines, growth factors, and tumor antigens were measured in the sera of 116 SCCHN patients before treatment (active disease group), 103 patients who were successfully treated (no evidence of disease group), and 117 smoker controls without evidence of cancer. The multimarker panel offering the highest diagnostic power was comprised of 25 biomarkers, including epidermal growth factor, epidermal growth factor receptor, interleukin (IL)-8, tissue plasminogen activator inhibitor-1, alpha-fetoprotein, matrix metalloproteinase-2, matrix metalloproteinase-3, IFN-alpha, IFN-gamma, IFN-inducible protein-10, regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein-1alpha, IL-7, IL-17, IL-1 receptor-alpha, IL-2 receptor, granulocyte colony-stimulating factor, mesothelin, insulin-like growth factor binding protein 1, E-selectin, cytokeratin-19, vascular cell adhesion molecule, and cancer antigen-125. Statistical analysis using an ADE algorithm resulted in a sensitivity of 84.5%, specificity of 98%, and 92% of patients in the active disease group correctly classified from a cross-validation serum set. The data presented show that simultaneous testing using a multiplexed panel of serum biomarkers may present a promising new approach for the early detection of head and neck cancer.

Adult↗
PubMed2001

Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease.

CONTEXT: Several novel risk factors for atherosclerosis have recently been proposed, but few comparative data exist to guide clinical use of these emerging biomarkers. OBJECTIVE: To compare the predictive value of 11 lipid and nonlipid biomarkers as risk factors for development of symptomatic peripheral arterial disease (PAD). DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study using plasma samples collected at baseline from a prospective cohort of 14 916 initially healthy US male physicians aged 40 to 84 years, of whom 140 subsequently developed symptomatic PAD (cases); 140 age- and smoking status-matched men who remained free of vascular disease during an average 9-year follow-up period were randomly selected as controls. MAIN OUTCOME MEASURE: Incident PAD, as determined by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol-HDL-C ratio, triglycerides, homocysteine, C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins (apo) A-I and B-100. RESULTS: In univariate analyses, plasma levels of total cholesterol (P<.001), LDL-C (P =.001), triglycerides (P =.001), apo B-100 (P =.001), fibrinogen (P =.02), CRP (P =.006), and the total cholesterol-HDL-C ratio (P<.001) were all significantly higher at baseline among men who subsequently developed PAD compared with those who did not, while levels of HDL-C (P =.009) and apo A-I (P =.05) were lower. Nonsignificant baseline elevations of lipoprotein(a) (P =.40) and homocysteine (P =.90) were observed. In multivariable analyses, the total cholesterol-HDL-C ratio was the strongest lipid predictor of risk (relative risk [RR] for those in the highest vs lowest quartile, 3.9; 95% confidence interval [CI], 1.7-8.6), while CRP was the strongest nonlipid predictor (RR for the highest vs lowest quartile, 2.8; 95% CI, 1.3-5.9). In assessing joint effects, addition of CRP to standard lipid screening significantly improved risk prediction models based on lipid screening alone (P<.001). CONCLUSIONS: Of 11 atherothrombotic biomarkers assessed at baseline, the total cholesterol-HDL-C ratio and CRP were the strongest independent predictors of development of peripheral arterial disease. C-reactive protein provided additive prognostic information over standard lipid measures.

Adult↗
PubMed2000

Generation of a baculovirus recombinant prostate-specific membrane antigen and its use in the development of a novel protein biochip quantitative immunoassay.

Prostate-specific membrane antigen (PSMA) is a 100-kDa transmembrane glycoprotein identified by the monoclonal antibody 7E11-C5.3 from the human prostate tumor cell line LNCaP. Because of its significant upregulation in androgen refractory and metastatic prostate cancers, PSMA may be a useful prognostic biomarker and a target for developing novel therapeutic strategies. However, the lack of abundant pure PSMA protein and the low efficacy in immunoaffinity isolation from LNCaP cells have hampered the development of clinical assays. In order to obtain a renewable and reliable source of pure antigen, we used the baculovirus/insect cell system to express and purify a recombinant PSMA. A recombinant baculovirus containing a 6x histidine-tagged PSMA gene was generated, from which rPSMA was expressed and purified using cobalt-chelating affinity chromatography. The purity and correct molecular size of rPSMA were demonstrated by gel electrophoresis and mass spectrometry. Glycosidase digestions showed that the oligosaccharides on rPSMA are primarily N-linked high-mannose type. Although the glycosylation is different from the native PSMA, it did not affect the immunoreactivity of rPSMA to antibodies specific for either the intra- or the extracellular domains of PSMA. Finally, the purified rPSMA was successfully used to develop a quantitative PSMA immunoassay using the novel ProteinChip surface-enhanced laser desorption/ionization mass spectrometry technology.

Animals↗
PubMed2006

[Research progress in SELDI-TOF MS and its clinical applications].

Proteinchip profiling is a powerful and innovative proteomic technology for biomarker discovery and diagnostic/prognostic assay development. Based on surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), Ciphergen's proteinchip system offers a single, unified, high-throughput platform for a multitude of proteomic research applications. Proteins are the major functional components of the cell, the study of proteomics provides mankind with a better understanding of disease and life. The remarkable findings in disease biomarkers have shed light to the early diagnosis, monitoring and predicting prognosis of various diseases, especially for cancer. In this article, the development and technology of SELDI-TOF MS are introduced. Some research progress and encouraging research results in oncoproteomics, infectious diseases, neurological diseases and diabetes mellitus using SELDI-TOF MS are also reviewed. The paper is closed by the appraisals on its pros and cons, as well as the future prospective is also expounded.

Animals↗
PubMed2005

The use of biomarkers in surveillance, medical screening, and intervention.

Building on mechanistic information, much of molecular epidemiologic research has focused on validating biomarkers, that is, assessing their ability to accurately indicate exposure, effect, disease, or susceptibility. To be of use in surveillance, medical screening, or interventions, biomarkers must already be validated so that they can be used as outcomes or indicators that can serve a particular function. In surveillance, biomarkers can be used as indicators of hazard, exposure, disease, and population risk. However, to obtain rates for these measures, the population at risk will need to be assessed. In medical screening, biomarkers can serve as early indicators of disease in asymptomatic people. This allows for the identification of those who should receive diagnostic confirmation and early treatment. In intervention (which includes risk assessment and communication, risk management, and various prevention efforts), biomarkers can be used to assess the effectiveness of a prevention or control strategy as well as help determine whether the appropriate individuals are assigned to the correct intervention category. Biomarkers can be used to provide group and individual risk assessments that can be the basis for marshalling resources. Critical for using biomarkers in surveillance, medical screening, and intervention is the justification that the biomarkers can provide information not otherwise accessible by a less expensive and easier-to-obtain source of information, such as medical records, surveys, or vital statistics. The ability to use validated biomarkers in surveillance, medical screening, and intervention will depend on the extent to which a strategy for evidence-based procedures for biomarker knowledge transfer can be developed and implemented. This will require the interaction of researchers and decision-makers to collaborate on public health and medical issues.

Biomarkers↗
PubMedDate not supplied

The role of proteomics in toxicology: identification of biomarkers of toxicity by protein expression analysis.

Proteomics, i.e. the high throughput separation, display and identification of proteins, has the potential to be a powerful tool in drug development. It could increase the predictability of early drug development and identify non-invasive biomarkers of toxicity or efficacy. This review provides an introduction to modern proteomics, with particular reference to applications in toxicology. A literature search was carried out to identify studies in two broad classes: screening/predictive toxicology, and mechanistic toxicology. The strengths and limitations of current methods and the likely impact of techniques in drug development are also considered. Proteomics can increase the speed and sensitivity of toxicological screening by identifying protein markers of toxicity. Proteomics studies have already provided insights into the mechanisms of action of a wide range of substances, from metals to peroxisome proliferators. Current limitations involving speed of throughput are being overcome by increasing automation and the development of new techniques. The isotope-coded affinity tag (ICAT) method appears particularly promising. The application of proteomics to drug development has given rise to the new field of pharmacoproteomics. New associations between proteins and toxicopathological effects are constantly being identified, and major progress is on the horizon as we move into the post-genomic era.

Animals↗
PubMed2007

Design and testing of a disposable microfluidic chemiluminescent immunoassay for disease biomarkers in human serum samples.

This paper presents the development of a plastic microfluidic immunosensor for rapid, reliable and on-the-spot detection of disease biomarkers in human sera. The microfluidic chips were fabricated in cyclic polyolefin by hot-embossing with a silicon master mold. The master itself was made using photolithographic techniques and Deep Reactive Ion Etching (DRIE). As a platform model, serum concentrations of C-reactive protein (CRP), a cardiac and inflammation marker, was measured on-chip using chemiluminescence based immunoassay. The assay results were read via an on-board instant photographic film, and with an imager capable of detecting chemiluminescent signals. The on-board detection module obviates the need for any dedicated bench-top analyzer for reading the immunoassay results, and therefore makes the device self-sufficient for point-of-care diagnostics when simple positive/negative results are sought. The microfluidic chemiluminescence results were compared with standard microplate ELISA analysis to assess the accuracy of the developed microfluidic immunoassay. Screening of CRP in human serum samples showed good correlation with ELISA analysis and the mean difference between the two methods using the Bland and Altman method was -0.079 +/- 0.858 mg/L for hsCRP. With approximate assay times of 25 min, the developed microfluidic immunoassay approach shows great potential for rapid plus sensitive detection of disease markers at the point-of-care.

Biomarkers↗
PubMed2002

[Molecular genetic progression on nasopharyngeal carcinoma].

The aim of this paper was to discuss the molecular genetic events in the development and progression of nasopharyngeal carcinoma (NPC), and the correlation between genetic alterations and clinicopathological changes of NPC. Analyzed by LOH (loss of heterozygosity) and CGH (comparative genomic hybridization) in primary NPC, high frequent allelic losses were observed on chromosomes 1p, 3p, 9p, 9q, 11q, 13q, 14q, 16q, and 19q, and the minimum deletion regions were also localized; there are closely association between LOH on certain deletion regions in NPC and the clinicopathological parameters. In the group of NPC with higher LOH value (FAL), together with higher antibody titers of EBV IgA/VCA and IgA/EA, most of the NPC showed more invasive of primary T stage (T3 + T4), TNM (III + IV stage) and far lymph node metastasis. High frequent chromosomal gain regions were observed on chromosomes 1q, 2q, 3q, 6p, 6q, 7q11.2, 8q, 11q13, 12, 15q, 17q, and 20q, indicating that there may exist oncogenes which are activated on the gain regions in NPC. CGH analysis showed that gains on chromosome 1q, 8q, 18q, and loss on 9p were closely related to advanced stage of NPC. LOH study also showed high frequent LOH on 3p in normal nasopharyngeal epithelium (74%) and dysplasia lesions (75%) from the Southern Chinese, suggesting that LOH at 3p may be an earlier genetic event of NPC tumorigenesis. Linkage analysis indicate that the HLA gene and cytochrome p4502E gene may be susceptibility genes of NPC. New potential susceptibility gene locus has also been localized by this study. cDNA microarray demonstrated differential expression of cell cycle proteins, anti-apoptotic factors, oncogenes/tumor suppressors, growth-enhancing factors of EGR1, tumor-derived growth factor 1, platelet-derived growth factor A chain; differential expression were also observed in different clinical stage NPC. Genetic instabilities (losses and gains) are common molecular events in NPC, and play very important role in the development and progression of NPC. Through LOH, CGH, linkage, and cDNA microarray study, we can find specific biomarkers of NPC, and will support us biomarkers which can be used for earlier diagnosis and prognosis of NPC. More importantly, these biomarkers may be useful in the development of a NPC molecular staging system, which could augment current clinicopathological classification and staging systems.

Chromosome Aberrations↗
PubMedDate not supplied

[Biological markers: utilization in drug development and approval].

The objectives of the reflection on biomarkers are far ahead of the issues of surrogacy, and constitute a major stake for pharmacology: enhancement of the liability of positive or negative screening for candidate drugs, speed-up of development processing, accurate identification of responders to a specific drug, and optimization of drug monitoring. Examples illustrate the situations where biomarkers are useful: diagnosis, prognosis, prediction of therapeutic response, either favourable or unwanted. The advance of pharmacogenetics leaves hope for optimization of drug use through the adaptation of drug choice to an individual profile. Some deficiencies have been identified concerning policies of transfer, evaluation or interdisciplinary validation. The optimization of the use of highest level evidence data, which is possible when appropriate biomarkers and clinical data are systematically collected during all the steps in drug development, the formal modelling of physiological, pathological and pharmacological processes and their assessment through computer simulation, and the simultaneous conduct of pragmatic and cognitive approaches, appear to be the necessary conditions for fulfillment of the objectives defined above.

Biomarkers↗
PubMed2025

Novel Predictive Spatial Biomarker in Non-Small Cell Lung Carcinoma: The Diversity of Niches Unlocking Treatment Sensitivity (DONUTS).

Probabilistic spatial modelling techniques developed on large-scale tumor-immune Atlases (~35M individually mapped cells; 50,000 high power fields) were used to characterize predictive features of treatment-responsive lung cancer. We identified CD8+FoxP3+ cell density as a robust pre-treatment biomarker for outcomes across disease stages and therapy types. In parallel, single-cell RNAseq studies of CD8+FoxP3+ T-cells revealed an activated, early effector phenotype, substantiating an anti-tumor role, and contrasting with CD4+FoxP3+ T-regulatory cells. A spatial biomarker was developed using an empirical probabilistic model to define the immediate cell neighbors or niche surrounding CD8+FoxP3+ cells and proximity to the tumor-stromal boundary. The resultant 'Diversity of Niches Unlocking Treatment Sensitivity (DONUTS)' are more prevalent than the CD8+FoxP3+ cells themselves, mitigating sampling error in small biopsies. Further, the DONUTS only require four markers, are additive to PD-L1, and associate with tertiary lymphoid structure counts. Taken together, the DONUTS represent a next-generation predictive biomarker poised for clinical implementation.

AstroPath↗
PubMed2004

Development and validation of an isotope-dilution electrospray ionization tandem mass spectrometry method with an on-line sample clean-up device for the quantitative analysis of the benzene exposure biomarker S-phenylmercapturic acid in human urine.

An isotope-dilution electrospray ionization tandem mass spectrometry (ESI-MS/MS) method with an on-line sample clean-up device, for the quantitative analysis of human urine for the benzene exposure biomarker S-phenylmercapturic acid (SPMA), was developed and validated. The sample clean-up system was constructed from an autosampler, a reversed-phase C18 trap cartridge, a two-position switching valve, and controlling computer software and hardware. The sample clean-up system was interfaced via 1/20 splitting to the ESI source of a triple-quadrupole mass spectrometer using negative ion mode and multiple reaction monitoring for SPMA and the isotope-labeled internal standard. A strategy was adopted to acquire pooled blank urine matrix and quality control samples spiked with standards. Validated procedures and data on method specificity, detection limits, standard curves, precision and recovery, sample storage stability, and inter-laboratory comparison are presented. The analytical system was fully automated. No tedious manual sample clean-up procedures are required. With the selectivity and the sensitivity provided by ESI-MS/MS detection, the analytical system can be used for high-throughput and accurate determination of SPMA levels in human urine samples, as a biomarker for environmental as well as occupational benzene exposure.

Acetylcysteine↗
PubMed2002

Biomarkers for breast cancer.

Molecular biomarkers for breast cancer are of several types. Risk biomarkers are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, family clustering and inherited germ-line abnormalities. Surrogate endpoint biomarkers are tissue, cellular or molecular alterations that occur between cancer initiation and progression. These biomarkers are utilized as endpoints in short-term chemoprevention trials. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki-67 and proliferating cell nuclear antigen (PCNA); ER and PR overexpression; markers of oncogene overexpression such as c-erbB-2, TGF-a and EGFr; indicators of apoptotic imbalance including overexpression of bcl-2 and an increased bax/bcl-2 ratio; markers of disordered cell signaling such as p53 nuclear protein accumulation; alteration of differentiation signals such as overexpression of c-myc and related proteins; loss of differentiation markers such as TGF-b II receptor and retinoic acid receptor; and alteration of angiogenesis proteins such as VEGF overexpression. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors.

Adult↗