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Results for “Biomarker development”

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At least 55 records · Page 3Linked to original sources
PubMed2003

Advances in the development of biomarkers for Alzheimer's disease: from CSF total tau and Abeta(1-42) proteins to phosphorylated tau protein.

Advances have been made to establish biological markers of Alzheimer's disease (AD). Measurement of total tau (t-tau) and beta-amyloid(1-42) (Abeta(1-42)) in the cerebrospinal fluid (CSF) seems useful to discriminate early and incipient AD from age-associated memory-impairment, depression, and some secondary dementias. New immunoassays to detect different phosphorylated tau epitopes (p-tau) have recently been developed. P-tau phosphorylated at threonine 231 (p-tau(231)) showed improvements compared to t-tau in the early detection of AD in subjects with mild cognitive impairment. As p-tau(231) declined during the course of AD, it may have potential to track disease progression. Additionally, p-tau(231) improved differential diagnosis between AD, frontotemporal dementia, and geriatric major depression. P-tau phosphorylated at threonine 181 improved diagnostic accuracy between AD and dementia with Lewy bodies. P-tau phosphorylated at serine 199 demonstrated high discriminative power between AD and non-Alzheimer's dementia. P-tau phosphorylated at serine 306/serine 404 improved differential diagnosis between AD and vascular dementia. A comparative study of the different p-tau epitopes is currently under way. In summary, first clinical multi-center studies suggest that measurement of phosphorylated tau proteins may significantly improve early and differential diagnosis and may come close to fulfilling proposed criteria of a biological marker for AD.

Aged↗
PubMed1995

Biochemical biomarkers in ecotoxicology--some recent developments.

Biochemical biomarkers measure the exposure of organisms to environmental chemicals. They can also provide measures of toxic effect, e.g. where they are based on molecular mechanisms which underly toxicity. Ideally, biomarkers should be sensitive, specific, simple to use and suitable for the assay of material obtained by non-destructive sampling procedures (e.g. of blood). Recently, there has been encouraging progress in the development of several different types of biomarker assays: (1) The measurement of inhibition of serum 'B' esterases to monitor exposure of birds to organophosphorus insecticides. (2) The measurement of DNA damage caused by aromatic hydrocarbons. DNA adduct formation has been studied using the 32P-postlabelling technique. Several other techniques are currently under investigation. (3) The measurement of disturbances to the transthyretin-retinol binding protein complex caused by a metabolite of 3,4,3',4',tetrachlorobiphenyl. (4) The measurement of precursors of clotting proteins in blood following the inhibition of the Vitamin K cycle by anticoagulant rodenticides. Of these examples, the first is only a biomarker of exposure but the remaining three examples are, in principle, biomarkers of toxic effect since they all represent measures of molecular mechanisms which underly toxicity. Biochemical biomarkers have considerable potential for measuring effects of chemicals under field conditions--especially where carefully selected combinations of them are used.

Animals↗
PubMed2006

Cardiovascular proteomics: tools to develop novel biomarkers and potential applications.

Proteomics is the new systems biological approach to the study of proteins and protein variation on a large scale as a result of biological processes and perturbations. The field is undergoing a dramatic transformation, owing to the completion and annotation of the human genome as well as technological advances to study proteins on a large scale. The new science of proteomics can potentially yield novel biomarkers reflecting cardiovascular disease, establish earlier detection strategies, and monitor responses to therapy. Technological advances permit the unprecedented large-scale identification of peptide sequences in a biological sample with mass spectrometry, whereas gel-based techniques provide further refinement on the status of post-translational modification. The application of high throughput protein evaluation with a subset of predefined targets, identified through proteomics, microarray profiling, and pathway analysis in animal models and human tissues, is gaining momentum in research and clinical applications. Proteomic analysis has provided important insights into ischemic heart disease, heart failure, and cardiovascular pathophysiology. The combination of proteomic biomarkers with clinical phenotypes and genetic haplotype information can lead to a more precise diagnosis and therapy on an individual basis--the fundamental premise of "personalized medicine."

Biomarkers↗
PubMed2005

Discovery and development of biomarkers of neurological disease.

The identification of clinically relevant biomarkers for neurological diseases poses unique challenges. These include an historical lack of availability of relevant tissues from the site of pathology, relatively poorly matured techniques for disease diagnosis, the complexity and cellular heterogeneity of the brain, and a clear deficiency of models for functional validation of candidate biomarkers. Here, the unique challenges that neurological disorders introduce to biomarker discovery are described and how modern technological advances in genomics, proteomics and metabolomics are overcoming these obstacles and are driving the discovery of novel biomarkers to improve early diagnosis and therapeutic treatment is discussed.

Animals↗
PubMed2004

Development of biomarkers based on diet-dependent metabolic serotypes: concerns and approaches for cohort and gender issues in serum metabolome studies.

Mathematical models that reflect the effects of dietary restriction (DR) on the sera metabolome may have utility in understanding the mechanisms of DR and in applying this knowledge to human epidemiological studies. Previous studies demonstrated both the feasibility of identifying biomarkers through metabolome analysis and the validity of our approach in independent cohorts of 6-month-old male and female ad libitum fed or DR rats. Cross-cohort studies showed that cohort-specific effects distorted the dataset. The present study extends these observations across the entire sample set, thereby validating our markers independently of specific cohorts. Metabolites originally identified in males were examined in females and vice-versa. DR's effect on the metabolome is partially gender-specific and is modulated by environmental factors. DR reduces inter-gender differences in the metabolome. Univariate statistical methods showed that 56/93 metabolites in the female samples and 39/93 metabolites in the male samples were significantly altered (using our previous cut-off criteria of p < or = 0.2) by DR. The metabolites modulated by DR present a wide spectrum of concentration, redox reactivity and hydrophilicity, suggesting that our serotype is broadly representative of the metabolome and that DR has broad effects on the metabolome. These studies, coupled with those in the preceding and following reports, also highlight the utility for consideration of the metabolome as a network of metabolites using appropriate data analysis approaches. The inter-cohort and inter-gender differences addressed herein suggest potential cautions, and potential approaches, for identification of multivariate biomarker profiles that reflect changes in physiological status, such as a metabolism that predisposes to increased risk of neoplasia.

Animals↗
PubMed2004

Development of biomarkers based on diet-dependent metabolic serotypes: characteristics of component-based models of metabolic serotypes.

Our research seeks to identify a serum profile, or serotype, that reflects the systemic physiologic modifications resultant from dietary restriction (DR), in part such that this knowledge can be applied for biomarker studies. Direct comparison suggests that component-based classification algorithms consistently out-perform distance-based metrics for studies of nutritional modulation of metabolic serotype, but are subject to over-fitting concerns. Intercohort differences in the sera metabolome could partially obscure the effects of DR. Further analysis now shows that implementation of component-based approaches (also called projection methods) optimized for class separation and controlled for over-fitting have >97% accuracy for distinguishing sera from control or DR rats. DR's effect on the metabolome is shown to be robust across cohorts, but differs in males and females (although some metabolites are affected in both). We demonstrate the utility of projection-based methods for both sample and variable diagnostics, including identification of critical metabolites and samples that are atypical with respect to both class and variable models. Inclusion of non-statistically different variables enhances classification models. Variables that contribute to these models are sharply dependent on mathematical processing techniques; some variables that do not contribute under one paradigm are powerful under alternative mathematical paradigms. In practical terms, this information may find purpose in other endeavors, such as mechanistic studies of DR. Application of these approaches confirms the utility of megavariate data analysis techniques for optimal generation of biomarkers based on nutritional modulation of physiological processes.

Animals↗
PubMed2004

Recent developments in biomarkers for the early detection of lung cancer: perspectives based on publications 2003 to present.

PURPOSE OF REVIEW: Given the poor prognosis associated with lung cancer, the ability to diagnose lung cancer in its early stages is considered crucial to achieving decreased lung cancer mortality. Herein, we discuss recent advances in biomarker discovery and evaluation of their potential application in the clinical setting. RECENT FINDINGS: Novel potential biomarkers have been identified via new techniques including cDNA microarray analysis, comparative genomic hybridization, and proteomics. These factors have been evaluated in various validation studies including tissue microarrays, RT-PCR, and assays of bioactivity. The characterization of these potential biomarkers through analysis of pathways that have been associated with neo-plastic transformation may help to identify the precursor lesions that are associated with subsequent progression to invasive carcinoma. In addition, the past year has also produced intriguing results regarding the detection of biomarkers in easily accessible screening specimens such as sputa, serum, and exhaled breath. Recent advances in these aspects of biomarker identification for the early detection of lung cancer are reviewed. SUMMARY: Identification of new candidate biomarkers and improved applications of previously detected biomarkers show great promise for the ultimate establishment of practical lung cancer screening. While recent studies engender optimism for the creation of clinically applicable screening tests, the biomarkers that have been identified need larger, follow-up validational studies and further characterization as to their biologic importance.

Biomarkers, Tumor↗
PubMed1993

Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid: suppressing effects on tumor development and biomarkers expression of colon tumorigenesis.

Our previous study has shown that dietary administration of protocatechuic acid (PCA) acts as potential chemopreventive agent in inhibiting diethylnitrosamine-induced liver carcinogenesis in male F344 rats. The present study was designed to determine the modifying effect of PCA on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats and the effect on intermediate biomarkers, i.e., colonic mucosal ornithine decarboxylase activity and colonic epithelial proliferation, which can be used as effective predictors of colon cancer. Staring at 6 weeks of age, groups of animals were fed the basal diet and experimental diet containing PCA at dose levels of 250, 500, and 1000 ppm. At 7 weeks of age, all animals except the PCA alone group (1000 ppm) and untreated controls were given s.c. injections of AOM at a dose level of 15 mg/kg body weight/week for 3 weeks. PCA at 3 doses was fed during the initiation phase (before 1 week, during, and after 1 week of AOM exposure) or postinitiation phase (for 28 weeks starting 1 week after the last injection of AOM). All animals were then killed at 32 weeks after the start and colonic tumor incidence and multiplicity were determined. Animals intended for cell proliferation study were given injections of bromodeoxyuridine/5-fluoro-2'-deoxyuridine (1 ml/100 g body weight) 1 h prior to be killing. The rate of colonic cell proliferation in the distal portion was assessed by immunohistochemistry using antibromodeoxyuridine and by counting silver-stained nucleolar organizer regions protein. The colonic mucosal ornithine decarboxylase activity was also measured at the termination. The results indicate that dietary PCA administration at 500 and 1000 ppm during the initiation or postinitiation phase significantly inhibited intestinal carcinogenesis induced by AOM as revealed by the reduction of tumor incidence and multiplicity. The data also demonstrate that PCA at 500 ppm and 1000 ppm significantly inhibited bromodeoxyuridine labeling index and also silver-stained nucleolar organizer regions protein number at three doses when animals were fed PCA at the initiation or postinitiation stage. Also, feeding of PCA at 1000 ppm during the initiation and postinitiation phase exerted a pronounced inhibitory effect on the colonic ornithine decarboxylase levels. PCA feeding did not cause any toxicity. These results demonstrate that PCA is a possible new chemopreventive agent for colon carcinogenesis through the suppression of manifestation of intermediate biomarkers induced by AOM, although the precise mechanisms of PCA-induced inhibition during the initiation and postinitiation phases remain to be elucidated.

Adenocarcinoma↗
PubMedDate not supplied

Role of biomarkers in monitoring exposures to chemicals: present position, future prospects.

Biomarkers are becoming increasingly important in toxicology and human health. Many research groups are carrying out studies to develop biomarkers of exposure to chemicals and apply these for human monitoring. There is considerable interest in the use and application of biomarkers to identify the nature and amounts of chemical exposures in occupational and environmental situations. Major research goals are to develop and validate biomarkers that reflect specific exposures and permit the prediction of the risk of disease in individuals and groups. One important objective is to prevent human cancer. This review presents a commentary and consensus views about the major developments on biomarkers for monitoring human exposure to chemicals. A particular emphasis is on monitoring exposures to carcinogens. Significant developments in the areas of new and existing biomarkers, analytical methodologies, validation studies and field trials together with auditing and quality assessment of data are discussed. New developments in the relatively young field of toxicogenomics possibly leading to the identification of individual susceptibility to both cancer and non-cancer endpoints are also considered. The construction and development of reliable databases that integrate information from genomic and proteomic research programmes should offer a promising future for the application of these technologies in the prediction of risks and prevention of diseases related to chemical exposures. Currently adducts of chemicals with macromolecules are important and useful biomarkers especially for certain individual chemicals where there are incidences of occupational exposure. For monitoring exposure to genotoxic compounds protein adducts, such as those formed with haemoglobin, are considered effective biomarkers for determining individual exposure doses of reactive chemicals. For other organic chemicals, the excreted urinary metabolites can also give a useful and complementary indication of exposure for acute exposures. These methods have revealed 'backgrounds' in people not knowingly exposed to chemicals and the sources and significance of these need to be determined, particularly in the context of their contribution to background health risks.

Biomarkers↗
PubMed2005

From traditional biomarkers to transcriptome analysis in drug development.

Traditional biomarkers have played an important role in drug development as well as patient care. A single traditional biomarker or surrogate endpoint is unlikely to either characterize the complete pathophysiology of a complex disease or capture all the therapeutic benefits or potential adverse effects that a drug will have in a diverse patient population. Transciptome analysis, on the other hand, can provide a large-scale survey of gene expression associated with the etiology of a human disease or pharmacological responses to a therapeutic intervention. The quantitative and qualitative readouts can provide increased power to identify novel drug targets or biomarkers indicative of drug safety or efficacy. Transcriptomics has positively impacted drug development and will continue to improve the medicines of the future. Here, we describe the increasingly important roles that traditional biomarkers and transcriptome analysis have played in various phases of drug discovery and development as well as the opportunities and challenges that they present to the pharmaceutical industry.

Biomarkers↗
PubMed2005

Biomarker World Congress 2005.

This report covers some of the many excellent talks, and a selected number of posters, that were presented at this conference. It includes several emerging issues in biomarker development and the question of how biomarker science can drive targeted drug discovery and development and form a scientific basis for personalized medicine. Although relatively small, the meeting provided a good opportunity for business networking, particularly for those involved in the development and regulation of medical diagnostics and biopharmaceuticals.

Animals↗
PubMed2006

Vascular biomarkers and surrogates in cardiovascular disease.

Cardiovascular biomarker research efforts have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. The United States Food and Drug Administration has relied on biomarkers to support clinical applications in many therapeutic fields, including cardiovascular disease. The appropriate application of cardiovascular biomarkers requires an understanding of disease natural history, the mechanism of the intervention, and the characteristics and limitations of the biomarker. Channels of communication among researcher, developer, and regulator must remain open to maximize the success of future biomarker efforts. In 2003, 2004, and 2005, an international panel of cardiovascular biomarker experts convened at the "Cardiovascular Biomarker and Surrogate Endpoints Symposia" held in Bethesda, Md, to discuss the use of biomarkers in the development of improved cardiovascular diagnostics and therapeutics. The information presented in the present report summarizes the authors' perspective distilled from these proceedings.

Atherosclerosis↗
PubMed1995

Analysis of plasma and urinary tea polyphenols in human subjects.

Tea has been shown to inhibit chemically induced tumorigenesis in many animal models, but the effects of tea consumption on human carcinogenesis are not conclusive. In order to develop biomarkers for tea consumption, we developed methods for the analysis of tea polyphenols in human plasma and urine samples using HPLC with the coulochem electrode array detection system. (-)-Epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epicatechin (EC) are the major polyphenols in green tea. Most of the tea polyphenols were in their conjugated forms in the plasma and urine. The samples were incubated with a mixture of beta-glucuronidase and sulfatase to generate the free form of tea polyphenols. After extraction into ethyl acetate and separation by reversed-phase chromatography, EGCG, EGC, and EC were identified on the basis of their retention times and electrochemical characteristics. Due to the high selectivity of the detection mode, interference was minimized. Good quantitative relationships were established for a large concentration range of tea polyphenols. The limits of detection for EGCG, EGC, ECG, and EC were from 0.5 to 1.5 ng/ml of plasma or urine sample. After ingestion of 1.2 g of decaffeinated green tea in warm water, the plasma samples collected at 1 h from 4 human volunteers contained 46-268 ng/ml of EGCG, 82-206 ng/ml of EGC, and 48-80 ng/ml of EC. ECG was not detected in plasma samples. The maximum urinary excretion of EGC and EC occurred at 3-6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

[Biomarkers of Alzheimer's disease].

Recent researches of CSF biomarkers, such as combinations of tau, A beta40, A beta42, are now establishing clinical evidence. These specific biomarkers should be used in clinical practice. To detect incipient AD form MCI and very early AD, these CSF biomarkers are quite useful. Newly developing biomarkers, such as phosphorylated tau and plasma A beta, must be established by large scale prospective study and autopsy-correlations. Thus, the contribution of these biomarkers is desired for diagnosis and clinical practice for Alzheimer's disease.

Alzheimer Disease↗
PubMed1994

Future research needs associated with the assessment of potential human health risks from exposure to toxic ambient air pollutants.

This paper presents key conclusions and future research needs from a Workshop on the Risk Assessment of Urban Air, Emissions, Exposure, Risk Identification, and Quantification, which was held in Stockholm during June 1992 by 41 participants from 13 countries. Research is recommended in the areas of identification and quantification of toxics in source emissions and ambient air, atmospheric transport and chemistry, exposure level assessment, the development of improved in vitro bioassays, biomarker development, the development of more accurate epidemiological methodologies, and risk quantification techniques. Studies are described that will be necessary to assess and reduce the level of uncertainties associated with each step of the risk assessment process. International collaborative research efforts between industry and government organizations are recommended as the most effective way to carry out this research.

Air Pollutants↗
PubMed2026

Progress towards a biotypic biomarker profile for amyotrophic lateral sclerosis-frontotemporal spectrum disorders.

Determining the optimal timing of disease-modifying therapies for neurodegenerative disorders will necessitate identification of when the underlying pathobiological process becomes active, well in advance of the point at which clinical manifestions appear. Phenoconversion, the emergence of clinically manifest syndomes, may be preceded by years to decades of silent pathobiological activity that can only be mapped by an array of biomarkers. ALS and FTD, traditionally identified as distinct clinical syndromes, are increasingly recognized to exist along a spectrum of clinical syndromes with shared genetic risk and shared underlying pathology. This clinicopathological spectrum is underpinned by cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43) as the common neuropathological hallmark. In contrast, the majority of neuropathologically-defined frontotemporal lobar degeneration (FTLD) is associated with alterations in either TDP-43 metabolism (FTLD-TDP) or of the microtubule associated protein tau (FTLD-tau), with a smaller percentage associated with either autosomal dominant genetic mutations or impairments in the ubiquitin proteasome system. As the field of neurodegenerative disorders increasingly shifts towards the frameworks of a pathobiological definition of disease, there is a growing imperative to develop biomarkers that reflect the varied pathobiologies that underly these disorders, and to determine the sensitivity of such biomarkers to detect the presence of these pathobiologies before phenoconversion. To that end, an international workshop was convened in London, Canada in 2025 to review the evidence for existing or evolving biomarkers suitable for (1) the detection of either ALS or FTD pathobiology prior to phenoconversion and/or (2) predict phenoconversion in at risk individuals. Such biomarkers might be conceptualized as "biotypic biomarkers", capturing their ability to describe an underlying pathophysiology whilst being agnostic to the emergent clinical manifestations. Whereas no single biotypic marker is yet able to predict the emergence of ALS, FTD or their intersection, a multimodal approach to developing a biotypic biomarker profile holds promise for the detection of relevant pathobiological processes. The strength of such an approach would be augmented by also addressing issues of resiliency/susceptibility both in terms of genetic risk susceptibility profiles and developing sensitive biomarkers of genomic and cellular aging. By including such nontraditional markers of disease, a more robust picture of not only the degenerative process but also of those factors that might potentially mitigate or drive a heightened probability of disease can be derived.

cryptic exons↗