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PubMed2005

A homocysteine metabolism-related dietary pattern and the risk of coronary heart disease in two independent German study populations.

A biomarker profile of high folate and vitamin B-12 and low plasma homocysteine concentrations reduces the risk of coronary heart disease (CHD) and may be linked to diet. The objectives of the present study were to identify a food pattern related to these biomarkers and to examine its association with CHD risk. Dietary patterns related to biomarker plasma concentrations were constructed from data obtained in the Coronary Risk Factors for Atherosclerosis in Women (CORA) Study (200 cases; 255 controls) using the reduced rank regression statistical method. Risks for CHD with relation to the identified pattern were estimated in the CORA study and in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study with 157 cases of incident myocardial infarction among 26,795 participants. In these 2 German study populations, whole-grain bread, fresh fruit, olive oil, mushrooms, cruciferous vegetables, wine, and nuts contributed the most positively and fried potatoes the most negatively to a dietary pattern that was directly associated with both plasma folate and vitamin B-12 concentrations, but inversely with plasma homocysteine. Multivariate-adjusted relative risks for CHD across increasing quintiles of the food pattern score were 1.0, 0.55, 0.52, 0.58, 0.39 (P for trend = 0.05) in the case-control sample and 1.0, 0.95, 0.75, 0.56, 0.72 (P for trend = 0.041) in the prospective study. The combination of a high intake of whole-grain bread, fresh fruit, olive oil, mushrooms, cruciferous vegetables, wine, and nuts with a low intake of fried potatoes was associated with a favorable biomarker profile of homocysteine metabolism and reduced risk of CHD.

Aged↗
PubMed2005

Inter-relationships between DNA damage, ascorbic acid and glycaemic control in Type 2 diabetes mellitus.

AIMS: The onset of complications in Type 2 diabetes mellitus (DM) patients cannot be predicted in individuals. Evidence suggests a link between complications and hyperglycaemia, oxidative stress and antioxidants, but causality is unclear. This study investigated baseline (entry) fasting plasma ascorbic acid, lymphocytic DNA damage and glycaemic control in Type 2 DM as part of a long-term study, the aim of which is to explore a biomarker profiling approach to identify and improve outcome in high-risk subjects. METHODS: A cross-sectional study, in which DNA damage, glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and ascorbic acid (AA) were measured on fasting blood samples collected from 427 Type 2 DM subjects. RESULTS: DNA damage was significantly (P < 0.0001) and directly correlated to both FPG (r = 0.540) and HbA(1c) (r = 0.282), and was significantly (P < 0.0001), independently and inversely correlated to plasma AA (r = -0.449). In those subjects with both poor glycaemic control and low AA (< 48 microm, the overall mean value for the study group), DNA damage was significantly (P < 0.005) higher compared with those subjects with a similar degree of hyperglycaemia but with AA above the mean. CONCLUSIONS: The novel finding of a significant inverse relationship between plasma AA and DNA damage in Type 2 DM indicates that poorly controlled diabetic subjects might benefit from increased dietary vitamin C. The data also have important implications for biomarker profiling to identify those subjects who might benefit most from intensive therapy. Longer-term follow-up is underway.

Ascorbic Acid↗
PubMed2006

Sample preparation for serum/plasma profiling and biomarker identification by mass spectrometry.

In this article, we present an overview of the different strategies for sample preparation for identification by mass spectrometry (MS) of biomarkers from serum and/or plasma. We consider the effects of the variables involved in sample collection, handling and storage, and describe different approaches for removal of high abundance proteins and serum/plasma fractionation. We review the advantages and disadvantages of such techniques as centrifugal ultrafiltration, different formats for solid phase extraction, organic solvent extraction, gel and capillary electrophoresis, and liquid chromatography. We also discuss a variety of current proteomic methods and their main applications for biomarker-related studies.

Analytic Sample Preparation Methods↗
PubMed2003

Biomarkers of human cutaneous squamous cell carcinoma from tissues and cell lines identified by DNA microarrays and qRT-PCR.

Squamous cell carcinoma (SCC) is the second most common form of skin cancer in Caucasians. Here we report on the identification of biomarkers of human cutaneous SCC cell lines in vitro and tissue samples in vivo using DermArray and PharmArray DNA microarrays, consisting of ca. 7400 unique human cDNAs. Differentially expressed genes were identified in two facial skin SCC cell lines (SCC 12 and SCC 13) compared to normal keratinocytes, and three cutaneous SCC tissue samples compared to normal skin. Quantitative validations of up- and down-regulated biomarkers were performed by qRT-PCR on 23 biomarker genes for the cell lines and 20 biomarker genes for the tumor tissues. In addition, three oral SCC cell lines were also included in the qRT-PCR validations for comparison, and the biomarker profiles were highly similar between the cutaneous and the oral SCC cell lines for all 23 biomarkers examined. The expression profiles for a variety of non-cutaneous SCC types, such as head-and-neck, oral, and lung, have been previously published. This report is the first to describe biomarkers for cutaneous SCC in two contexts, in vitro and in vivo. Although there was minimal overlap between the two different contexts using DNA microarrays, five genes were found common to both the cell lines and tissues, namely fibronectin 1, annexin A5, glyceraldehyde 3-phosphate dehydrogenase, zinc-finger protein 254, and huntingtin-associated protein interacting protein. Some of our previously published biomarkers of normal keratinocytes were down-regulated in SCC, suggestive of the dedifferentiated status of the transformed cells. While recent reports have identified some of the same genes as SCC biomarkers, for instance in head-and-neck cancer, thereby validating our approach, we have identified some novel biomarkers for cutaneous disease. These biomarker lists may be useful in molecular diagnostics of non-melanoma skin cancer, and a subset of the biomarkers might serve as suitable targets for drug discovery efforts of therapies for SCC.

Biomarkers, Tumor↗
PubMed2025

CancerTrialMatch: a computational resource for the management of biomarker-based clinical trials at a community cancer center.

MOTIVATION: The widespread implementation of next-generation sequencing in cancer care has enabled routine use of molecular and biomarker profiling. At our cancer center, as with many others, biomarker-based clinical trials are increasingly available to oncologists as potential treatment options via molecular tumor boards. To better support this effort, we developed CancerTrialMatch, a systematic approach to capture structured clinical trial data and match patients to trials based on their disease characteristics and sequencing profiles. RESULTS: CancerTrialMatch is an open-source application designed to streamline clinical trial curation and patient trial matching, while also enabling an institution's curated trial portfolio to be distributed across the institution for easy access to providers, care teams and researchers. It facilitates curating, updating, and searching for trials through a semi-automated interface built using R Shiny, MongoDB, and Docker. While much of the trial data is retrieved via the clinicaltrials.gov Application Programming Interface, certain items like biomarkers and disease subtypes are entered manually. The user inputs disease type using the OncoTree classification, and provides relevant biomarker details, such as mutations, copy numbers, fusions, and other disease-specific markers. This resource reduces the time required for institutional trial management and helps to identify potential clinical trials for patients, ultimately supporting larger clinical trial enrollment and enhancing the clinical application of precision oncology. AVAILABILITY AND IMPLEMENTATION: CancerTrialMatch was implemented and tested on Windows 11 (64-bit, 32 GB RAM) using WSL2 with Ubuntu 22.04. Docker 27.0.3 and Docker Compose 2.28.1 were used to build images and containers. Users can build it by cloning the repo and following the README instructions and supplemental file (cancertrialmatchsupplemental.pdf) . The source code and example data are available in GitHub and Figshare at https://github.com/AveraSD/CancerTrialMatch and 10.6084/m9.figshare.28447367 respectively.

Humans↗
PubMed2005

Discriminatory proteomic biomarker analysis identifies free hemoglobin in the cerebrospinal fluid of women with severe preeclampsia.

OBJECTIVE: Preeclampsia is an idiopathic multisystem disorder specific to human pregnancy. This study used proteomic analysis of cerebrospinal fluid (CSF) to identify protein biomarkers characteristic of preeclampsia and related to its severity. STUDY DESIGN: CSF was collected from women diagnosed clinically with severe preeclampsia (sPE: n = 7), mild preeclampsia (mPE: n = 8), and normotensive controls (CRL: n = 8). Samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy. A discriminative proteomic biomarker profile was extracted by applying Mass Restricted analysis, and a Preeclampsia Proteomic Biomarker (PPB) score developed based on the presence or absence of four discriminatory protein peaks in individual CSF SELDI tracings. In-gel tryptic digests, Western blot analysis, on-chip immunoassays, ELISA, and spectral analysis were used to identify the biomarkers composing the PPB score. RESULTS: PPB score distinguished patients with a clinical diagnosis of sPE from mPE and CRLs. (PPB median [range]: sPE: 4 [0-4] vs mPE: 1 [0-1] vs CRL: 0 [0-0]; P < 0.001). PPB scores were unaffected by parity, magnesium seizure prophylaxis, CSF leukocyte counts, and total protein content. Proteomic identification techniques matched the discriminatory protein peaks to the alpha- and beta-hemoglobin chains. ELISA confirmed that women diagnosed clinically with sPE had significantly higher CSF hemoglobin concentrations than women with mPE or CRL (median [range]: sPE: 6.6 [0.0-10.3] microg/mL vs mPE: 0 [0-1.3] microg/mL vs CRL: 0 [0-0] microg/mL; P < 0.001). CONCLUSION: Proteomic analysis of CSF can accurately distinguish sPE from both mPE and CRL. Patients with sPE have nanomolar amounts of free hemoglobin in their CSF. Further studies are needed to confirm these observations and determine their physiologic implications.

Biomarkers↗
PubMed2006

Biomarkers in cardiovascular disease: integrating pathophysiology into clinical practice.

Biomarkers play an important role in the diagnosis, prognostic assessment, and management of patients with suspected acute coronary syndromes (ACS). Specific biomarkers identify different components of the pathophysiology of ACS: troponins are prototype markers of myocyte necrosis, natriuretic peptides reflect neurohormonal activation and hemodynamic stress, soluble CD40 ligand is an indicator of platelet activation, and C-reactive protein, myeloperoxidase, and monocyte chemoattractant protein-1 reflect various inflammatory processes. When combined, multiple biomarkers reflecting different pathophysiologic processes appear to enhance risk stratification, as compared with using individual markers alone. Advances in proteomic technology promise to identify additional novel biomarkers that facilitate diagnosis, risk stratification, and selection of therapies in ACS. In the future, it is hoped that multiple biomarker panels will form the basis of an individualized approach to the treatment of ACS, in which therapy is tailored to individual biomarker profiles.

Biomarkers↗
PubMed2003

NMR-based metabolomics: a powerful approach for characterizing the effects of environmental stressors on organism health.

It is important to assess the chronic effects of chemical, physical, and biological stressors on organisms in the environment. Appropriate methods must enable rapid, inexpensive, and multibiomarker analyses of organism health. Here we investigate withering syndrome in red abalone (Haliotis rufescens), an important wild and farmed shellfish species along the Pacific coast, using a metabolomic approach that combines the metabolic profiling capabilities of nuclear magnetic resonance spectroscopy (NMR) with pattern recognition methods. Foot muscle, digestive gland, and hemolymph samples were collected from healthy, stunted, and diseased abalone, and the extracts were analyzed by NMR. Following spectral preprocessing, principal components analyses of the metabolite profiles were conducted. Our results confirm that NMR-based metabolomics can successfully distinguish the biochemical profiles of the three groups of animals, in every type of tissue or biofluid studied. Furthermore, this discovery-based approach successfully identified novel metabolic biomarker profiles associated with withering syndrome. The application of these methods for investigating other environmental stressors is discussed, as are the advantages of NMR-based metabolomics for biomonitoring, particularly in conjunction with gene and protein expression profiling.

Animals↗
PubMed2003

Aliphatic hydrocarbons and polycyclic aromatic hydrocarbons (PAHs) in sediments collected from the 110 mile hole and along a transect from 58 degrees 58.32'N 1 degree 10.38'W to the inner Moray Firth, Scotland.

Sediments were collected from the 110 mile hole and along a transect from 58 degrees 58.32' N 1 degree 10.38' W to the UK National Marine Monitoring (NMMP) site in the inner Moray Firth, for determination of hydrocarbon concentration and composition. Total PAH concentrations (2- to 6-ring PAHs, parent and branched) were highest at NMMP site 95 and at the associated end of the transect in the inner Moray Firth. PAHs in this area were of predominately pyrolytic origin and could be attributed to urban and industrial activities. The majority of sediments collected in the middle section of the transect had low total PAH concentrations (< 100 ng g(-1) dry weight). The high proportion of naphthalenes and alkylated PAHs in this area suggested a predominately petrogenic input. The GC-FID aliphatic hydrocarbon profiles showed that the majority of sediments, including those in the inner Firth, had a limited petrogenic input. This was supported by the geochemical biomarker profiles, which contained triterpanes typical of Middle Eastern crude oil. Principal component analysis was used to investigate spatial trends in the PAH distributions and demonstrated that there were differences between areas. The NMMP site 95 and transect start and middle sediments were well separated. PCA further confirmed that sediments from the NMMP site 95, the 110 mile hole and the inner Moray Firth (south west) end of the transect contained PAHs from predominately pyrolytic sources, whereas sediments from the north east end (start) and the middle of the transect were typified by a greater petrogenic component.

Environmental Monitoring↗
PubMed2005

The distribution and composition of hydrocarbons in sediments from the Fladen Ground, North Sea, an area of oil production.

The distribution and composition of hydrocarbons in sediment from the Fladen Ground oilfield in the northern North Sea have been investigated. The total PAH concentrations (2- to 6-ring parent and alkylated PAHs, including the 16 US EPA PAHs) in sediments were relatively low (<100 microg kg(-1) dry weight). The PAH, the Forties crude and diesel oil equivalent concentrations were generally higher in sediment of fine grain size and higher organic carbon concentration. PAH distributions and concentration ratios indicated a predominantly pyrolytic input, being dominated by the heavier, more persistent, 5- and 6-ring compounds, and with a high proportion of parent PAHs. The n-alkane profiles of a number of the sediments contained small, high boiling point, UCMs, indicative of weathered oil arising from a limited petrogenic input. The geochemical biomarker profiles of the sediments that contained UCMs showed a small bisnorhopane peak and a high proportion of norhopane relative to hopane, indicating that there was contamination from both Middle Eastern and North Sea oils. Therefore contamination was not directly as a result of oil exploration activity in the area. The most likely source of petrogenic contamination was from general shipping activity.

Environmental Monitoring↗
PubMed2005

Combinatorial biomarkers: From early toxicology assays to patient population profiling.

Advanced biomarkers for improved prediction and monitoring of disease and toxicology mechanisms are needed to control the high clinical failure rates among new compounds. Along with other uses, biomarkers are currently used in the industry to screen for toxic side effects of drug candidates and to identify appropriate patient populations. The use of combinatorial biomarkers is a first step towards an effective systems biology approach to drug development. In combination with high content screening, and in particular a novel, high content in situ proteomic technology, combinatorial biomarkers will strongly support the knowledge-based decision-making process by providing crucial information on functional biology.

Animals↗
PubMed2000

Comparative polymerase chain reaction analysis of c-myc amplification on archival breast fine-needle aspiration materials.

The oncogene c-myc is a key regulator of cell cycle progression (from G1 to S phase). The amplification of c-myc can either induce cell proliferation or apoptosis. As a part of our ongoing effort to develop methods for multiple tumor marker analysis, this study was carried out to determine whether biomarkers such as c-myc amplification could be analyzed on genetic materials collected from archival fine-needle aspiration (FNA) smears. A novel comparative PCR analysis was used to analyze c-myc amplification semiquantitatively. Genomic DNA was prepared using cells obtained from archival FNA materials that had undergone quantitative fluorescence image analysis (QFIA) for other biomarkers. Of the 72 cases selected from 1995 for this study, 53 had an adequate amount of DNA for analysis. A novel comparative PCR analysis was used to analyze c-myc amplification quantitatively. For each batch of experiments, DNA from the high c-myc expressing cells, HL-60, and DNA from the low expressing cells, K562, were served as positive and negative controls, respectively. c-myc amplification was observed in 16 (94.1%) of 17 malignant lesions, 5 (41.7%) of 12 proliferative breast diseases with nuclear atypia, and 4 (16.7%) of 24 other benign lesions (fibroadenoma or fibrocystic disease). The overall difference of c-myc expression among these groups was highly significant by chi2 analysis (P = 0.0002). We conclude that multiple phenotypic markers and genotypic markers may be combined in a risk assessment biomarker profile on small FNA samples that can be obtained on multiple occasions relatively noninvasively from the patient. The results of this study suggest that c-myc amplification may be a biomarker of breast cancer risk. However, additional large, prospective studies are needed to confirm the current observation.

Adult↗
PubMed2004

Quantitative profiling of plasma peptides in asthmatic mice using liquid chromatography and mass spectrometry.

Asthma is increasing in prevalence worldwide as a result of factors associated with a Western lifestyle. However, simple and reliable diagnostic and prognostic markers are yet to be found. In an attempt to identify protein biomarker profiles among small molecular weight ranges, we employed an approach combining liquid chromatography with mass spectrometry, instead of two-dimensional gel electrophoresis (2-DE), which has previously been used to analyze protein expression patterns. Here we described its application to compare plasma peptides from control and chronic asthma mice. Peptides were quantitatively profiled as a multidimensional peptide mass fingerprint by a combination of reverse-phase high-performance liquid chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. They were identified by peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry. In this study, we quantitatively identified the fragment f of complement 3 (C3f), which is important in inflammation. C3f was significantly higher in controls than chronic asthma mice. Our strategy allowed the detection and identification of different plasma peptides between control and chronic asthma mice on a proteomic scale. Therefore, these results suggest that native small peptides detected by non-2-DE techniques may be useful and specific biomarkers of disease.

Animals↗
PubMed2004

Biomarkers of Alzheimer disease in plasma.

Plasma and serum biochemical markers proposed for Alzheimer disease (AD) are based on pathophysiologic processes such as amyloid plaque formation [amyloid beta-protein (A beta), A beta autoantibodies, platelet amyloid precursor protein (APP) isoforms], inflammation (cytokines), oxidative stress (vitamin E, isoprostanes), lipid metabolism (apolipoprotein E, 24S-hydroxycholesterol), and vascular disease [homocysteine, lipoprotein (a)]. Most proteins or metabolites evaluated in plasma or serum thus far are, at best, biological correlates of AD: levels are statistically different in AD versus controls in some cohorts, but they lack sensitivity or specificity for diagnosis or for tracking response to therapy. Approaches combining panels of existing biomarkers or surveying the range of proteins in plasma (proteomics) show promise for discovering biomarker profiles that are characteristic of AD, yet distinct from nondemented patients or patients with other forms of dementia.

Alzheimer Disease↗
PubMed2000

Urinalysis to exclude and monitor nephrotoxicity.

A large number of compounds, which are in common usage in industry and medicine, are potentially nephrotoxic. Renal damage and disease resulting from toxic exposure is progressive and will, if unarrested, culminate in irreversible renal disease. There is, therefore, a need to develop a battery of tests with which to monitor and characterise the nephrotoxic cascade. A European-wide study compared biomarker profiles of adult male workers who were exposed to heavy metals or solvents. It became apparent that the urinary profiles varied with the nature of the toxin, reflecting the functional region of the kidney affected and also the severity of the damage. Children are a particularly vulnerable group and the investigation of range of biomarkers indicated that they were indeed susceptible to nephrotoxic pollutants in their environment. It is proposed that a small cohort of tests should be used to monitor the early (pre-clinical stages) of renal damage or dysfunction; these can be supplemented if necessary by additional specific tests. In the future better information on at-risk populations and genetic information will enable the determination of individual susceptibility to be assessed more precisely.

Adult↗
PubMed2006

Nutrition and food science go genomic.

The wealth of genomic information and high-throughput profiling technologies are now being exploited by scientists in the disciplines of nutrition and food science. Diet and food components are prime environmental factors that affect the genome, transcriptome, proteome and metabolome, and this life-long interaction defines the health or disease state of an individual. For the first time the interaction of foods, and individual food constituents, with the biological systems can be defined on a molecular basis. Profiling technologies are used in basic-science applications for identifying the mode of action of foods or particular ingredients, and are similarly taken into the science-driven development of foods with a defined biofunctionality. Biomarker profiles and patterns derived from genomics applications in humans should guide nutrition and food science in developing evidence-based dietary recommendations and health-promoting foods.

Food↗
PubMedDate not supplied

Evaluation of heat shock protein 70 as a biomarker of environmental stress in Fucus serratus and Lemna minor.

Heat shock proteins (Hsps) are known to be induced in response to short-term stress. The present study aimed to evaluate the potential of Hsp70 as a biomarker of stress produced by increased temperature, osmotic pressure, and exposure to cadmium and sodium chloride in marine macroalgae and fresh water plant species. An indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) was developed with a working range of 0.025-10 microg ml(-1) using a monoclonal antibody raised against purified Hsp70 of Phaseolus aureus (mung bean). Fucus serratus (toothed wrack), Chondrus crispus (Stackhouse or Carrageen moss), Ulva lactuca (sea lettuce) and Lemna minor (common duckweed) sample extracts were stressed for up to 24 h and then tested in the IC-ELISA. The presence of Hsp70 and cross-reactivity of the monoclonal antibody was confirmed by Western blot. The heat shock response was confirmed in each species using a 2-h 42 degrees C treatment. Following heat shock, Hsp70 concentrations increased to a peak at 2 h (F. serratus) or 4 h (L. minor), after which concentrations decreased. Osmotic and cadmium stresses also resulted in elevated Hsp70 concentrations in samples of F. serratus and L. minor when compared with unstressed controls. In both, osmotic and metal stress, the production of Hsp70 increased to a maximum and subsequently decreased as the stressor levels increased. Results suggest that Hsp70 IC-ELISA could potentially be applied to the detection of stress in these aquatic species, although it would probably be most effective when used in conjunction with other measurements to provide a stressor-specific biomarker profile or fingerprint.

Antibodies, Monoclonal↗