Cancer Biomarker Discovery: Lectin-Based Strategies Targeting Glycoproteins

Directory of Open Access Journals (Sweden)

David Clark

2012-01-01

Full Text Available Biomarker discovery can identify molecular markers in various cancers that can be used for detection, screening, diagnosis, and monitoring of disease progression. Lectin-affinity is a technique that can be used for the enrichment of glycoproteins from a complex sample, facilitating the discovery of novel cancer biomarkers associated with a disease state.

Metabolism and Biomarkers of Heterocyclic Aromatic Amines in Molecular Epidemiology Studies: Lessons Learned from Aromatic Amines

Science.gov (United States)

2011-01-01

Aromatic amines and heterocyclic aromatic amines (HAAs) are structurally related classes of carcinogens that are formed during the combustion of tobacco or during the high-temperature cooking of meats. Both classes of procarcinogens undergo metabolic activation by N-hydroxylation of the exocyclic amine group, to produce a common proposed intermediate, the arylnitrenium ion, which is the critical metabolite implicated in toxicity and DNA damage. However, the biochemistry and chemical properties of these compounds are distinct and different biomarkers of aromatic amines and HAAs have been developed for human biomonitoring studies. Hemoglobin adducts have been extensively used as biomarkers to monitor occupational and environmental exposures to a number of aromatic amines; however, HAAs do not form hemoglobin adducts at appreciable levels and other biomarkers have been sought. A number of epidemiologic studies that have investigated dietary consumption of well-done meat in relation to various tumor sites reported a positive association between cancer risk and well-done meat consumption, although some studies have shown no associations between well-done meat and cancer risk. A major limiting factor in most epidemiological studies is the uncertainty in quantitative estimates of chronic exposure to HAAs and, thus, the association of HAAs formed in cooked meat and cancer risk has been difficult to establish. There is a critical need to establish long-term biomarkers of HAAs that can be implemented in molecular epidemioIogy studies. In this review article, we highlight and contrast the biochemistry of several prototypical carcinogenic aromatic amines and HAAs to which humans are chronically exposed. The biochemical properties and the impact of polymorphisms of the major xenobiotic-metabolizing enzymes on the biological effects of these chemicals are examined. Lastly, the analytical approaches that have been successfully employed to biomonitor aromatic amines and HAAs, and

Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

Directory of Open Access Journals (Sweden)

Warut Tulalamba

2012-01-01

Full Text Available Nasopharyngeal carcinoma (NPC is an uncommon cancer, which has a distinctive ethnic and geographic distribution. Etiology of NPC is considered to be related with a complex interaction of environmental and genetic factors as well as Epstein-Barr virus infection. Since NPC is located in the silent painless area, the disease is usually therefore diagnosed at the advanced stages; hence early detection of NPC is difficult. Furthermore, understanding in molecular pathogenesis is still lacking, pondering the identification of effective prognostic and diagnostic biomarkers. Dysregulation of signaling molecules in intracellular signal transduction, which regulate cell proliferation, apoptosis, and adhesion, underlines the basis of NPC pathogenesis. In this paper, the molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression. The important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.

Prognostic clinical and molecular biomarkers of renal disease in type 2 diabetes

DEFF Research Database (Denmark)

Pena, Michelle J; de Zeeuw, Dick; Mischak, Harald

2015-01-01

biomarkers address the predictive performance of novel biomarker panels in addition to the classical panel in type 2 diabetes. However, the prospective studies conducted so far have small sample sizes, are insufficiently powered and lack external validation. Adequately sized validation studies of multiple......Diabetic kidney disease occurs in ∼ 25-40% of patients with type 2 diabetes. Given the high risk of progressive renal function loss and end-stage renal disease, early identification of patients with a renal risk is important. Novel biomarkers may aid in improving renal risk stratification...... and metabolomics biomarkers. We focus on multiple biomarker panels since the molecular processes of renal disease progression in type 2 diabetes are heterogeneous, rendering it unlikely that a single biomarker significantly adds to clinical risk prediction. A limited number of prospective studies of multiple...

Molecular and phenotypic biomarkers of aging [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Xian Xia

2017-06-01

Full Text Available Individuals of the same age may not age at the same rate. Quantitative biomarkers of aging are valuable tools to measure physiological age, assess the extent of ‘healthy aging’, and potentially predict health span and life span for an individual. Given the complex nature of the aging process, the biomarkers of aging are multilayered and multifaceted. Here, we review the phenotypic and molecular biomarkers of aging. Identifying and using biomarkers of aging to improve human health, prevent age-associated diseases, and extend healthy life span are now facilitated by the fast-growing capacity of multilevel cross-sectional and longitudinal data acquisition, storage, and analysis, particularly for data related to general human populations. Combined with artificial intelligence and machine learning techniques, reliable panels of biomarkers of aging will have tremendous potential to improve human health in aging societies.

Multiplexed mass spectrometry monitoring of biomarker candidates for osteoarthritis.

Science.gov (United States)

Fernández-Puente, Patricia; Calamia, Valentina; González-Rodríguez, Lucía; Lourido, Lucía; Camacho-Encina, María; Oreiro, Natividad; Ruiz-Romero, Cristina; Blanco, Francisco J

2017-01-30

The methods currently available for the diagnosis and monitoring of osteoarthritis (OA) are very limited and lack sensitivity. Being the most prevalent rheumatic disease, one of the most disabling pathologies worldwide and currently untreatable, there is a considerable interest pointed in the verification of specific biological markers for improving its diagnosis and disease progression studies. Considering the remarkable development of targeted proteomics methodologies in the frame of the Human Proteome Project, the aim of this work was to develop and apply a MRM-based method for the multiplexed analysis of a panel of 6 biomarker candidates for OA encoded by the Chromosome 16, and another 8 proteins identified in previous shotgun studies as related with this pathology, in specimens derived from the human joint and serum. The method, targeting 35 different peptides, was applied to samples from human articular chondrocytes, healthy and osteoarthritic cartilage, synovial fluid and serum. Subsequently, a verification analysis of the biomarker value of these proteins was performed by single point measurements on a set of 116 serum samples, leading to the identification of increased amounts of Haptoglobin and von Willebrand Factor in OA patients. Altogether, the present work provides a tool for the multiplexed monitoring of 14 biomarker candidates for OA, and verifies for the first time the increased amount of two of these circulating markers in patients diagnosed with this disease. We have developed an MRM method for the identification and relative quantification of a panel of 14 protein biomarker candidates for osteoarthritis. This method has been applied to analyze human articular chondrocytes, articular cartilage, synovial fluid, and finally a collection of 116 serum samples from healthy controls and patients suffering different degrees of osteoarthritis, in order to verify the biomarker usefulness of the candidates. HPT and VWF were validated as increased in OA

Molecular Biomarkers in the Clinical Management of Prostate Cancer.

Science.gov (United States)

Udager, Aaron M; Tomlins, Scott A

2018-01-08

Prostate cancer, one of the most common noncutaneous malignancies in men, is a heterogeneous disease with variable clinical outcome. Although the majority of patients harbor indolent tumors that are essentially cured by local therapy, subsets of patients present with aggressive disease or recur/progress after primary treatment. With this in mind, modern clinical approaches to prostate cancer emphasize the need to reduce overdiagnosis and overtreatment via personalized medicine. Advances in our understanding of prostate cancer pathogenesis, coupled with recent technologic innovations, have facilitated the development and validation of numerous molecular biomarkers, representing a range of macromolecules assayed from a variety of patient sample types, to help guide the clinical management of prostate cancer, including early detection, diagnosis, prognostication, and targeted therapeutic selection. Herein, we review the current state of the art regarding prostate cancer molecular biomarkers, emphasizing those with demonstrated utility in clinical practice. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

A Selected Reaction Monitoring Mass Spectrometry Protocol for Validation of Proteomic Biomarker Candidates in Studies of Psychiatric Disorders.

Science.gov (United States)

Reis-de-Oliveira, Guilherme; Garcia, Sheila; Guest, Paul C; Cassoli, Juliana S; Martins-de-Souza, Daniel

2017-01-01

Most biomarker candidates arising from proteomic studies of psychiatric disorders have not progressed for use in clinical studies due to insufficient validation steps. Here we describe a selective reaction monitoring mass spectrometry (SRM-MS) approach that could be used as a follow-up validation tool of proteins identified in blood serum or plasma. This protocol specifically covers the stages of peptide selection and optimization. The increasing application of SRM-MS should enable fast, sensitive, and robust methods with the potential for use in clinical studies involving sampling of serum or plasma. Understanding the molecular mechanisms and identifying potential biomarkers for risk assessment, diagnosis, prognosis, and prediction of drug response goes toward the implementation of translational medicine strategies for improved treatment of patients with psychiatric disorders and other debilitating diseases.

Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance

Science.gov (United States)

Gonzalez de Castro, D; Clarke, P A; Al-Lazikani, B; Workman, P

2013-01-01

The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution. PMID:23361103

Wearable and flexible electronics for continuous molecular monitoring.

Science.gov (United States)

Yang, Yiran; Gao, Wei

2018-04-03

Wearable biosensors have received tremendous attention over the past decade owing to their great potential in predictive analytics and treatment toward personalized medicine. Flexible electronics could serve as an ideal platform for personalized wearable devices because of their unique properties such as light weight, low cost, high flexibility and great conformability. Unlike most reported flexible sensors that mainly track physical activities and vital signs, the new generation of wearable and flexible chemical sensors enables real-time, continuous and fast detection of accessible biomarkers from the human body, and allows for the collection of large-scale information about the individual's dynamic health status at the molecular level. In this article, we review and highlight recent advances in wearable and flexible sensors toward continuous and non-invasive molecular analysis in sweat, tears, saliva, interstitial fluid, blood, wound exudate as well as exhaled breath. The flexible platforms, sensing mechanisms, and device and system configurations employed for continuous monitoring are summarized. We also discuss the key challenges and opportunities of the wearable and flexible chemical sensors that lie ahead.

Clinical librarian support for rapid review of clinical utility of cancer molecular biomarkers.

Science.gov (United States)

Geng, Yimin; Fowler, Clara S; Fulton, Stephanie

2015-01-01

The clinical librarian used a restricted literature searching and quality-filtering approach to provide relevant clinical evidence for the use of cancer molecular biomarkers by institutional policy makers and clinicians in the rapid review process. The librarian-provided evidence was compared with the cited references in the institutional molecular biomarker algorithm. The overall incorporation rate of the librarian-provided references into the algorithm was above 80%. This study suggests the usefulness of clinical librarian expertise for clinical practice. The searching and filtering methods for high-level evidence can be adopted by information professionals who are involved in the rapid literature review.

Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers.

Science.gov (United States)

Wu, Hua-Hsi; Lin, Wen-chang; Tsai, Kuo-Wang

2014-01-23

Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

Science.gov (United States)

Aerts, Johannes M F G; Kallemeijn, Wouter W; Wegdam, Wouter; Joao Ferraz, Maria; van Breemen, Marielle J; Dekker, Nick; Kramer, Gertjan; Poorthuis, Ben J; Groener, Johanna E M; Cox-Brinkman, Josanne; Rombach, Saskia M; Hollak, Carla E M; Linthorst, Gabor E; Witte, Martin D; Gold, Henrik; van der Marel, Gijs A; Overkleeft, Herman S; Boot, Rolf G

2011-06-01

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, recently developed chemical tools allowing specific visualization of enzymatically active lysosomal glucocerebrosidase are described. Such probes, coined inhibodies, offer entirely new possibilities for more sophisticated molecular diagnosis, enzyme replacement therapy monitoring, and fundamental research.

Parallel in vivo monitoring of pH in gill capillaries and muscles of fishes using microencapsulated biomarkers

Directory of Open Access Journals (Sweden)

Ekaterina Borvinskaya

2017-05-01

Full Text Available Tracking physiological parameters in different organs within the same organism simultaneously and in real time can provide an outstanding representation of the organism's physiological status. The state-of-the-art technique of using encapsulated fluorescent molecular probes (microencapsulated biomarkers is a unique tool that can serve as a platform for the development of new methods to obtain in vivo physiological measurements and is applicable to a broad range of organisms. Here, we describe a novel technique to monitor the pH of blood inside the gill capillaries and interstitial fluid of muscles by using microencapsulated biomarkers in a zebrafish model. The functionality of the proposed technique is shown by the identification of acidification under anesthesia-induced coma and after death. The pH in muscles reacts to hypoxia faster than that in the gill bloodstream, which makes both parameters applicable as markers of either local or bodily reactions.

Integration of gene expression, clinical, and demographic information in relation to asthma status to identify biomarkers associated with subtypes of childhood asthma

Science.gov (United States)

Advances in biomarker development have improved our ability to detect early changes at the molecular, cellular, and pre-clinical level that are often predictive of adverse health outcomes. Biomarkers for monitoring the underlying molecular mechanisms of disease are of increasing...

Impact of biomarker development on drug safety assessment

International Nuclear Information System (INIS)

Marrer, Estelle; Dieterle, Frank

2010-01-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

Common Subcluster Mining in Microarray Data for Molecular Biomarker Discovery.

Science.gov (United States)

Sadhu, Arnab; Bhattacharyya, Balaram

2017-10-11

Molecular biomarkers can be potential facilitators for detection of cancer at early stage which is otherwise difficult through conventional biomarkers. Gene expression data from microarray experiments on both normal and diseased cell samples provide enormous scope to explore genetic relations of disease using computational techniques. Varied patterns of expressions of thousands of genes at different cell conditions along with inherent experimental error make the task of isolating disease related genes challenging. In this paper, we present a data mining method, common subcluster mining (CSM), to discover highly perturbed genes under diseased condition from differential expression patterns. The method builds heap through superposing near centroid clusters from gene expression data of normal samples and extracts its core part. It, thus, isolates genes exhibiting the most stable state across normal samples and constitute a reference set for each centroid. It performs the same operation on datasets from corresponding diseased samples and isolates the genes showing drastic changes in their expression patterns. The method thus finds the disease-sensitive genesets when applied to datasets of lung cancer, prostrate cancer, pancreatic cancer, breast cancer, leukemia and pulmonary arterial hypertension. In majority of the cases, few new genes are found over and above some previously reported ones. Genes with distinct deviations in diseased samples are prospective candidates for molecular biomarkers of the respective disease.

A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification

Directory of Open Access Journals (Sweden)

Amin Manik A

2006-10-01

Full Text Available Abstract Background In spite of the recognized diagnostic potential of biomarkers, the quest for squelching noise and wringing in information from a given set of biomarkers continues. Here, we suggest a statistical algorithm that – assuming each molecular biomarker to be a diagnostic test – enriches the diagnostic performance of an optimized set of independent biomarkers employing established statistical techniques. We validated the proposed algorithm using several simulation datasets in addition to four publicly available real datasets that compared i subjects having cancer with those without; ii subjects with two different cancers; iii subjects with two different types of one cancer; and iv subjects with same cancer resulting in differential time to metastasis. Results Our algorithm comprises of three steps: estimating the area under the receiver operating characteristic curve for each biomarker, identifying a subset of biomarkers using linear regression and combining the chosen biomarkers using linear discriminant function analysis. Combining these established statistical methods that are available in most statistical packages, we observed that the diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the real datasets used in the study. These estimates were comparable to or better than the ones previously reported using alternative methods. In a synthetic dataset, we also observed that all the biomarkers chosen by our algorithm were indeed truly differentially expressed. Conclusion The proposed algorithm can be used for accurate diagnosis in the setting of dichotomous classification of disease states.

Design of tumor biomarker-monitoring trials: a proposal by the European Group on Tumor Markers

NARCIS (Netherlands)

Sölétormos, György; Duffy, Michael J.; Hayes, Daniel F.; Sturgeon, Catharine M.; Barak, Vivian; Bossuyt, Patrick M.; Diamandis, Eleftherios P.; Gion, Massimo; Hyltoft-Petersen, Per; Lamerz, Rolf M.; Nielsen, Dorte L.; Sibley, Paul; Tholander, Bengt; Tuxen, Malgorzata K.; Bonfrer, Johannes M. G.

2013-01-01

A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such

COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry.

Directory of Open Access Journals (Sweden)

Janice M Leung

Full Text Available Acute exacerbations of chronic obstructive pulmonary disease (AECOPD result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD.We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72. Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate 1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel was then tested in two independent AECOPD cohorts (Cohort B, n = 37, and Cohort C, n = 109 using leave-pair-out cross-validation methods.Five proteins were identified distinguishing AECOPD and convalescent states in Cohort A. Biomarker scores derived from this model were significantly higher during AECOPD than in the convalescent state in the discovery cohort (p<0.001. The receiver operating characteristic cross-validation area under the curve (CV-AUC statistic was 0.73 in Cohort A, while in the replication cohorts the CV-AUC was 0.77 for Cohort B and 0.79 for Cohort C.A panel of five biomarkers shows promise in distinguishing AECOPD from convalescence and may provide the basis for a clinical blood test to diagnose AECOPD. Further validation in larger cohorts is necessary for future clinical translation.

A network-based biomarker approach for molecular investigation and diagnosis of lung cancer

Directory of Open Access Journals (Sweden)

Chen Bor-Sen

2011-01-01

Full Text Available Abstract Background Lung cancer is the leading cause of cancer deaths worldwide. Many studies have investigated the carcinogenic process and identified the biomarkers for signature classification. However, based on the research dedicated to this field, there is no highly sensitive network-based method for carcinogenesis characterization and diagnosis from the systems perspective. Methods In this study, a systems biology approach integrating microarray gene expression profiles and protein-protein interaction information was proposed to develop a network-based biomarker for molecular investigation into the network mechanism of lung carcinogenesis and diagnosis of lung cancer. The network-based biomarker consists of two protein association networks constructed for cancer samples and non-cancer samples. Results Based on the network-based biomarker, a total of 40 significant proteins in lung carcinogenesis were identified with carcinogenesis relevance values (CRVs. In addition, the network-based biomarker, acting as the screening test, proved to be effective in diagnosing smokers with signs of lung cancer. Conclusions A network-based biomarker using constructed protein association networks is a useful tool to highlight the pathways and mechanisms of the lung carcinogenic process and, more importantly, provides potential therapeutic targets to combat cancer.

MALDI-TOF mass spectrometry analysis of small molecular weight compounds (under 10 KDa) as biomarkers of rat hearts undergoing arecoline challenge.

Science.gov (United States)

Chen, Tung-Sheng; Chang, Mu-Hsin; Kuo, Wei-Wen; Lin, Yueh-Min; Yeh, Yu-Lan; Day, Cecilia Hsuan; Lin, Chien-Chung; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang

2013-04-01

Statistical and clinical reports indicate that betel nut chewing is strongly associated with progression of oral cancer because some ingredients in betel nuts are potential cancer promoters, especially arecoline. Early diagnosis for cancer biomarkers is the best strategy for prevention of cancer progression. Several methods are suggested for investigating cancer biomarkers. Among these methods, gel-based proteomics approach is the most powerful and recommended tool for investigating biomarkers due to its high-throughput. However, this proteomics approach is not suitable for screening biomarkers with molecular weight under 10 KDa because of the characteristics of gel electrophoresis. This study investigated biomarkers with molecular weight under 10 KDa in rats with arecoline challenge. The centrifuging vials with membrane (10 KDa molecular weight cut-off) played a crucial role in this study. After centrifuging, the filtrate (containing compounds with molecular weight under 10 KDa) was collected and spotted on a sample plate for MALDI-TOF mass spectrometry analysis. Compared to control, three extra peaks (m/z values were 1553.1611, 1668.2097 and 1740.1832, respectively) were found in sera and two extra peaks were found in heart tissue samples (408.9719 and 524.9961, respectively). These small compounds should play important roles and may be potential biomarker candidates in rats with arecoline. This study successfully reports a mass-based method for investigating biomarker candidates with small molecular weight in different types of sample (including serum and tissue). In addition, this reported method is more time-efficient (1 working day) than gel-based proteomics approach (5~7 working days).

Molecular profiling of childhood cancer: Biomarkers and novel therapies.

Science.gov (United States)

Saletta, Federica; Wadham, Carol; Ziegler, David S; Marshall, Glenn M; Haber, Michelle; McCowage, Geoffrey; Norris, Murray D; Byrne, Jennifer A

2014-06-01

Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

Exposure assessment of process-related contaminants in food by biomarker monitoring.

Science.gov (United States)

Rietjens, Ivonne M C M; Dussort, P; Günther, Helmut; Hanlon, Paul; Honda, Hiroshi; Mally, Angela; O'Hagan, Sue; Scholz, Gabriele; Seidel, Albrecht; Swenberg, James; Teeguarden, Justin; Eisenbrand, Gerhard

2018-01-01

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario's and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment.

Accurate Quantification of Cardiovascular Biomarkers in Serum Using Protein Standard Absolute Quantification (PSAQ™) and Selected Reaction Monitoring*

Science.gov (United States)

Huillet, Céline; Adrait, Annie; Lebert, Dorothée; Picard, Guillaume; Trauchessec, Mathieu; Louwagie, Mathilde; Dupuis, Alain; Hittinger, Luc; Ghaleh, Bijan; Le Corvoisier, Philippe; Jaquinod, Michel; Garin, Jérôme; Bruley, Christophe; Brun, Virginie

2012-01-01

Development of new biomarkers needs to be significantly accelerated to improve diagnostic, prognostic, and toxicity monitoring as well as therapeutic follow-up. Biomarker evaluation is the main bottleneck in this development process. Selected Reaction Monitoring (SRM) combined with stable isotope dilution has emerged as a promising option to speed this step, particularly because of its multiplexing capacities. However, analytical variabilities because of upstream sample handling or incomplete trypsin digestion still need to be resolved. In 2007, we developed the PSAQ™ method (Protein Standard Absolute Quantification), which uses full-length isotope-labeled protein standards to quantify target proteins. In the present study we used clinically validated cardiovascular biomarkers (LDH-B, CKMB, myoglobin, and troponin I) to demonstrate that the combination of PSAQ and SRM (PSAQ-SRM) allows highly accurate biomarker quantification in serum samples. A multiplex PSAQ-SRM assay was used to quantify these biomarkers in clinical samples from myocardial infarction patients. Good correlation between PSAQ-SRM and ELISA assay results was found and demonstrated the consistency between these analytical approaches. Thus, PSAQ-SRM has the capacity to improve both accuracy and reproducibility in protein analysis. This will be a major contribution to efficient biomarker development strategies. PMID:22080464

Lipid Biomarkers and Molecular Carbon Isotopes for Elucidating Carbon Cycling Pathways in Hydrothermal Vents

Science.gov (United States)

Zhang, C. L.; Dai, J.; Campbell, B.; Cary, C.; Sun, M.

2003-12-01

Increasing molecular evidence suggests that hydrothermal vents in mid-ocean ridges harbor large populations of free-living bacteria, particularly the epsilon Proteobacteria. However, pathways for carbon metabolism by these bacteria are poorly known. We are addressing this question by analyzing the lipid biomarkers and their isotope signatures in environments where the epsilon Proteobacteria are likely predominant. Solid materials were collected from hydrothermal vents in the East Pacific Rise and at the Guaymas Basin in the Gulf of California. Fatty acids extracted from these samples are dominated by 16:0 (27-41%), 18:0 (16-48%), 18:1 (11-42%), 16:1 (7-12%), and 14:0 (5-28%). In addition, 15:0 and anteiso-15:0 are significantly present (2-3%) in samples from the Guaymas Basin. The isotopic compositions of these fatty acids range from -15.0\\permil to -33.1\\permil with the most positive values occurring only in monounsaturated fatty acids (16:1 and 18:1). We are currently unable to assign these biomarkers to any of the epsilon Proteobacteria because biomarkers are poorly known for these organisms isolated from the vents. However, no polyunsaturated fatty acids were detected in these samples, which are consistent with the absence of vent animals at the sampling sites. Signature biomarkers of 20:1 and cy21:0, which are characteristic of the thermophilic chemolithoautotrophs such as Aquificales, are also absent in these samples. These results imply that the deeply branched Aquificales species do not constitute the major microbial community in these vent environments. The large range of molecular isotopic compositions suggests that these lipids are synthesized from various carbon sources with different isotopic compositions or through different biosynthetic pathways, or both. We are currently measuring the isotopic compositions of the total organic carbon in the bulk samples and will determine the fractionations between lipid biomarkers and the total organic carbon

Toward Precision Medicine: A Cancer Molecular Subtyping Nano-Strategy for RNA Biomarkers in Tumor and Urine.

Science.gov (United States)

Koo, Kevin M; Wee, Eugene J H; Mainwaring, Paul N; Wang, Yuling; Trau, Matt

2016-12-01

Cancer is a heterogeneous disease which manifests as different molecular subtypes due to the complex nature of tumor initiation, progression, and metastasis. The concept of precision medicine aims to exploit this cancer heterogeneity by incorporating diagnostic technology to characterize each cancer patient's molecular subtype for tailored treatments. To characterize cancer molecular subtypes accurately, a suite of multiplexed bioassays have currently been developed to detect multiple oncogenic biomarkers. Despite the reliability of current multiplexed detection techniques, novel strategies are still needed to resolve limitations such as long assay time, complex protocols, and difficulty in interpreting broad overlapping spectral peaks of conventional fluorescence readouts. Herein a rapid (80 min) multiplexed platform strategy for subtyping prostate cancer tumor and urine samples based on their RNA biomarker profiles is presented. This is achieved by combining rapid multiplexed isothermal reverse transcription-recombinase polymerase amplification (RT-RPA) of target RNA biomarkers with surface-enhanced Raman spectroscopy (SERS) nanotags for "one-pot" readout. This is the first translational application of a RT-RPA/SERS-based platform for multiplexed cancer biomarker detection to address a clinical need. With excellent sensitivity of 200 zmol (100 copies) and specificity, we believed that this platform methodology could be a useful tool for rapid multiplexed subtyping of cancers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biomarkers as drug development tools: discovery, validation, qualification and use.

Science.gov (United States)

Kraus, Virginia B

2018-06-01

The 21st Century Cures Act, approved in the USA in December 2016, has encouraged the establishment of the national Precision Medicine Initiative and the augmentation of efforts to address disease prevention, diagnosis and treatment on the basis of a molecular understanding of disease. The Act adopts into law the formal process, developed by the FDA, of qualification of drug development tools, including biomarkers and clinical outcome assessments, to increase the efficiency of clinical trials and encourage an era of molecular medicine. The FDA and European Medicines Agency (EMA) have developed similar processes for the qualification of biomarkers intended for use as companion diagnostics or for development and regulatory approval of a drug or therapeutic. Biomarkers that are used exclusively for the diagnosis, monitoring or stratification of patients in clinical trials are not subject to regulatory approval, although their qualification can facilitate the conduct of a trial. In this Review, the salient features of biomarker discovery, analytical validation, clinical qualification and utilization are described in order to provide an understanding of the process of biomarker development and, through this understanding, convey an appreciation of their potential advantages and limitations.

Monitoring Progression of Amyotrophic Lateral Sclerosis Using Ultrasound Morpho-Textural Muscle Biomarkers: A Pilot Study.

Science.gov (United States)

Martínez-Payá, Jacinto J; Ríos-Díaz, José; Medina-Mirapeix, Francesc; Vázquez-Costa, Juan F; Del Baño-Aledo, María Elena

2018-01-01

The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation. In regard to textural parameters, muscle heterogeneity tended to increase as a result of the neoformation of non-contractile tissue through denervation. Considering some limitations of the study, the quantitative muscle ultrasound biomarkers evaluated showed a promising ability to monitor patients affected by ALS. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Biomarkers of HIV-associated Cancer

OpenAIRE

Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd

2014-01-01

Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of can...

Aberrantly methylated DNA as a biomarker in breast cancer

DEFF Research Database (Denmark)

Kristiansen, Søren; Jørgensen, Lars Mønster; Guldberg, Per

2013-01-01

hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients...... occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients...... as a versatile biomarker tool for screening, diagnosis, prognosis and monitoring of breast cancer. Standardization of methods and biomarker panels will be required to fully exploit this clinical potential....

CURRENT APPROACHES TO THE LABORATORY DIAGNOSIS OF RHEUMATIC DISEASES: ROLE OF MOLECULAR AND CELLULAR BIOMARKERS

Directory of Open Access Journals (Sweden)

E. N. Aleksandrova

2016-01-01

Full Text Available Laboratory medicine in the early 21st century has achieved advances due to the development and prompt practical introduction of innovative molecular cell technologies, which have assisted in increasing the diagnostic sensitivity and specificity of laboratory tests and in substantially expanding the spectrum of study biomarkers in rheumatology. High-technology automated analytical systems using both classical uniplex methods for immunochemical analysis (indirect immunofluorescence test, enzyme immunoassay, immunoblotting, immunodot assay, immunonephelometry, chemiluminescence immunoassay, and radioimmunoassay and multiplex diagnostic platforms based on DNA, RNA, protein and cellular microchips, polymerase chain reaction, flow cytometry, and mass spectrometry have been used in the past decade to determine biomarkers of rheumatic diseases (RD in blood, synovial fluid, urine, biopsy specimens of the synovial membrane, kidney, and other affected tissues.Present-day generation of molecular and cellular biomarkers (autoantibodies, acute-phase inflammatory proteins, cytokines, chemokines, vascular endothelial activation markers, immunoglobulins, complement components, lymphocyte subpopulations, osseous and cartilaginous tissue metabolic products, intracellular signaling molecules, proteases, and genetic, epigenetic, and transcriptomic markers is an important tool for prevention, early diagnosis, assessment of disease activity, progression rate, clinical laboratory subtypes of RD, prediction of the efficiency of therapy and the risk of adverse events during treatment. Deciphering of the key pathogenetic mechanisms of RD could identify the molecular and cellular biomarkers that might be used as therapeutic targets. Biologicals (monoclonal antibodies and hybrid protein molecules that selectively inhibit proinflammatory cytokines and membrane molecules mediating the pathological activation of immunocompetent cells are successfully used to treat RD today

Protein biomarker discovery and fast monitoring for the identification and detection of Anisakids by parallel reaction monitoring (PRM) mass spectrometry.

Science.gov (United States)

Carrera, Mónica; Gallardo, José M; Pascual, Santiago; González, Ángel F; Medina, Isabel

2016-06-16

Anisakids are fish-borne parasites that are responsible for a large number of human infections and allergic reactions around the world. World health organizations and food safety authorities aim to control and prevent this emerging health problem. In the present work, a new method for the fast monitoring of these parasites is described. The strategy is divided in three steps: (i) purification of thermostable proteins from fish-borne parasites (Anisakids), (ii) in-solution HIFU trypsin digestion and (iii) monitoring of several peptide markers by parallel reaction monitoring (PRM) mass spectrometry. This methodology allows the fast detection of Anisakids in Biomarker Discovery and the Fast Monitoring for the identification and detection of Anisakids in fishery products. The strategy is based on the purification of thermostable proteins, the use of accelerated in-solution trypsin digestions under an ultrasonic field provided by High-Intensity Focused Ultrasound (HIFU) and the monitoring of several peptide biomarkers by Parallel Reaction Monitoring (PRM) Mass Spectrometry in a linear ion trap mass spectrometer. The workflow allows the unequivocal detection of Anisakids, in <2h. The present strategy constitutes the fastest method for Anisakids detection, whose application in the food quality control area, could provide to the authorities an effective and rapid method to guarantee the safety to the consumers. Copyright © 2016 Elsevier B.V. All rights reserved.

Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

Directory of Open Access Journals (Sweden)

Debasish Paul

2013-01-01

Full Text Available Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches.

Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

Science.gov (United States)

Paul, Debasish; Kumar, Avinash; Gajbhiye, Akshada; Santra, Manas K.; Srikanth, Rapole

2013-01-01

Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA) were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches. PMID:23586059

Anchoring novel molecular biomarker responses to traditional responses in fish exposed to environmental contamination

International Nuclear Information System (INIS)

Nogueira, Patricia; Pacheco, Mario; Lourdes Pereira, M.; Mendo, Sonia; Rotchell, Jeanette M.

2010-01-01

The responses of Dicentrarchus labrax and Liza aurata to aquatic pollution were assessed in a contaminated coastal lagoon, using both traditional and novel biomarkers combined. DNA damage, assessed by comet assay, was higher in both fish species from the contaminated sites, whereas levels of cytochrome P450 1A1 gene expression were not significantly altered. The liver histopathological analysis also revealed significant lesions in fish from contaminated sites. Alterations in ras and xpf genes were analysed and additional pollutant-responsive genes were identified. While no alterations were found in ras gene, a downregulation of xpf gene was observed in D. labrax from a contaminated site. Suppression subtractive hybridization applied to D. labrax collected at a contaminated site, revealed altered expression in genes involved in energy metabolism, immune system activity and antioxidant response. The approach and results reported herein demonstrate the utility of anchoring traditional biomarker responses alongside novel biomarker responses. - Novel molecular biomarkers of aquatic environmental contamination in fish.

Biomarkers for monitoring intestinal health in poultry: present status and future perspectives.

Science.gov (United States)

Ducatelle, Richard; Goossens, Evy; De Meyer, Fien; Eeckhaut, Venessa; Antonissen, Gunther; Haesebrouck, Freddy; Van Immerseel, Filip

2018-05-08

Intestinal health is determined by host (immunity, mucosal barrier), nutritional, microbial and environmental factors. Deficiencies in intestinal health are associated with shifts in the composition of the intestinal microbiome (dysbiosis), leakage of the mucosal barrier and/or inflammation. Since the ban on growth promoting antimicrobials in animal feed, these dysbiosis-related problems have become a major issue, especially in intensive animal farming. The economical and animal welfare consequences are considerable. Consequently, there is a need for continuous monitoring of the intestinal health status, particularly in intensively reared animals, where the intestinal function is often pushed to the limit. In the current review, the recent advances in the field of intestinal health biomarkers, both in human and veterinary medicine are discussed, trying to identify present and future markers of intestinal health in poultry. The most promising new biomarkers will be stable molecules ending up in the feces and litter that can be quantified, preferably using rapid and simple pen-side tests. It is unlikely, however, that a single biomarker will be sufficient to follow up all aspects of intestinal health. Combinations of multiple biomarkers and/or metabarcoding, metagenomic, metatranscriptomic, metaproteomic and metabolomic approaches will be the way to go in the future. Candidate biomarkers currently are being investigated by many research groups, but the validation will be a major challenge, due to the complexity of intestinal health in the field.

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Science.gov (United States)

Tahara, Hideaki; Sato, Marimo; Thurin, Magdalena; Wang, Ena; Butterfield, Lisa H; Disis, Mary L; Fox, Bernard A; Lee, Peter P; Khleif, Samir N; Wigginton, Jon M; Ambs, Stefan; Akutsu, Yasunori; Chaussabel, Damien; Doki, Yuichiro; Eremin, Oleg; Fridman, Wolf Hervé; Hirohashi, Yoshihiko; Imai, Kohzoh; Jacobson, James; Jinushi, Masahisa; Kanamoto, Akira; Kashani-Sabet, Mohammed; Kato, Kazunori; Kawakami, Yutaka; Kirkwood, John M; Kleen, Thomas O; Lehmann, Paul V; Liotta, Lance; Lotze, Michael T; Maio, Michele; Malyguine, Anatoli; Masucci, Giuseppe; Matsubara, Hisahiro; Mayrand-Chung, Shawmarie; Nakamura, Kiminori; Nishikawa, Hiroyoshi; Palucka, A Karolina; Petricoin, Emanuel F; Pos, Zoltan; Ribas, Antoni; Rivoltini, Licia; Sato, Noriyuki; Shiku, Hiroshi; Slingluff, Craig L; Streicher, Howard; Stroncek, David F; Takeuchi, Hiroya; Toyota, Minoru; Wada, Hisashi; Wu, Xifeng; Wulfkuhle, Julia; Yaguchi, Tomonori; Zeskind, Benjamin; Zhao, Yingdong; Zocca, Mai-Britt; Marincola, Francesco M

2009-01-01

might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions. PMID:19534815

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Directory of Open Access Journals (Sweden)

Rivoltini Licia

2009-06-01

were recognized that might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions.

PET imaging biomarkers in head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Differding, Sarah; Gregoire, Vincent [Universite Catholique de Louvain, St-Luc University Hospital, Department of Radiation Oncology, and Center for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Experimentale et Clinique (IREC), Brussels (Belgium); Hanin, Francois-Xavier [Universite Catholique de Louvain, St-Luc University Hospital, Department of Nuclear Medicine, and Center for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Experimentale et Clinique (IREC), Brussels (Belgium)

2015-04-01

In locally advanced head and neck squamous cell carcinoma (HNSCC), the role of imaging becomes more and more critical in the management process. In this framework, molecular imaging techniques such as PET allow noninvasive assessment of a range of tumour biomarkers such as metabolism, hypoxia and proliferation, which can serve different purposes. First, in a pretreatment setting they can influence therapy selection strategies and target delineation for radiation therapy. Second, their predictive and/or prognostic value could help enhance the therapeutic ratio in the management of HNSCC. Third, treatment modification can be performed through the generation of a molecular-based heterogeneous dose distribution with dose escalation to the most resistant parts of the tumour, a concept known as dose painting. Fourth, they are increasingly becoming a tool for monitoring response to therapy. In this review, PET imaging biomarkers used in the routine management of HNSCC or under investigation are discussed. (orig.)

Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma

Energy Technology Data Exchange (ETDEWEB)

Lopci, Egesta [Humanitas Clinical and Research Hospital, Nuclear Medicine, Humanitas Cancer Center, Rozzano, MI (Italy); Riva, Marco; Raneri, Fabio; Pessina, Federico [Humanitas Clinical and Research Hospital, Neurosurgery, Rozzano, Milan (Italy); Olivari, Laura; Rossi, Marco; Alfieri, Tommaso [Universita degli Studi di Milano, Milan (Italy); Soffietti, Riccardo; Ruda, Roberta [University and City of Health and Science Hospital, Neuro-Oncology, Turin (Italy); Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine, Genova (Italy); Bizzi, Alberto [Fondazione IRCCS Istituto Neurologico Carlo Besta, Neuroradiology, Milan (Italy); Navarria, Pierina; Ascolese, Anna Maria [Humanitas Clinical and Research Hospital, Radiosurgery and Radiotherapy, Rozzano, Milan (Italy); Fernandes, Bethania [Humanitas Clinical and Research Hospital, Pathology, Rozzano, Milan (Italy); Grimaldi, Marco [Humanitas Clinical and Research Hospital, Medical Oncology, Rozzano, Milan (Italy); Simonelli, Matteo; Zucali, Paolo Andrea [Humanitas Clinical and Research Hospital, Radiology Department, Rozzano, Milan (Italy); Scorsetti, Marta [Humanitas Clinical and Research Hospital, Pathology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Bello, Lorenzo [Humanitas Clinical and Research Hospital, Neurosurgery, Rozzano, Milan (Italy); Universita degli Studi di Milano, Milan (Italy); Chiti, Arturo [Humanitas Clinical and Research Hospital, Nuclear Medicine, Humanitas Cancer Center, Rozzano, MI (Italy); Humanitas University, Rozzano, Milan (Italy)

2017-07-15

We evaluated the relationship between {sup 11}C-methionine PET ({sup 11}C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative {sup 11}C-METH PET were analysed. Semiquantitative evaluation of the {sup 11}C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). In all patients, the tumour was identified on {sup 11}C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. {sup 11}C-METH PET parameters are significantly correlated with histological grade and IDH1

Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

Science.gov (United States)

Papadakis, G; Friedt, J M; Eck, M; Rabus, D; Jobst, G; Gizeli, E

2017-09-01

The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

Science.gov (United States)

Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-01-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (PM. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. PMID:24903276

Evaluation of neopterin as a biomarker for the monitoring of Gaucher disease patients.

Science.gov (United States)

Drugan, Cristina; Drugan, Tudor C; Miron, Nicolae; Grigorescu-Sido, Paula; Naşcu, Ioana; Cătană, Cristina

2016-07-01

Biomarker research is an important area of investigation in Gaucher disease, caused by an inherited deficiency of a lysosomal enzyme, glucocerebrosidase. We evaluated the usefulness of neopterin, as a novel biomarker reflecting chronic inflammation and immune system activation in Gaucher disease and analysed its evolution in response to enzyme replacement therapy (ERT). Circulating plasma neopterin levels in 31 patients with non-neuronopathic Gaucher disease were measured before and after the onset of ERT and were compared with those of 18 healthy controls. Plasma chitotriosidase activity was also monitored, as a reference biomarker, against which we evaluated the evolution of neopterin. Neopterin levels were significantly increased in treatment-naïve patients (mean 11.90 ± 5.82 nM) compared with controls (6.63 ± 5.59 nM, Mann-Whitney U test P = 0.001), but returned to normal levels (6.92 ± 4.66 nM) following ERT. Investigating the diagnostic value of neopterin by receiver operating characteristic analysis, we found a cut-off value of 7.613 nM that corresponds to an area under the curve of 0.780 and indicates a good discrimination capacity, with a sensitivity of 0.774 and a specificity of 0.778. Our results suggest that measurement of circulating neopterin may be considered as a novel test for the confirmation of diagnosis and monitoring of the efficacy of therapeutic intervention in Gaucher disease. Plasma neopterin levels reflect the global accumulation and activation of Gaucher cells and the extent of chronic immune activation in this disorder. Neopterin may be an alternative storage cell biomarker in Gaucher disease, especially in chitotriosidase-deficient patients.

Aberrantly methylated DNA as a biomarker in breast cancer.

Science.gov (United States)

Kristiansen, Søren; Jørgensen, Lars M; Guldberg, Per; Sölétormos, György

2013-01-01

Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients into subgroups based on DNA biomarkers may improve prognosis. Serial monitoring of DNA-methylation markers in blood during treatment may be useful, particularly when the cancer burden is below the detection level for standard imaging techniques. Overall, aberrant DNA methylation has a great potential as a versatile biomarker tool for screening, diagnosis, prognosis and monitoring of breast cancer. Standardization of methods and biomarker panels will be required to fully exploit this clinical potential.

Advances in Biomarkers in Critical Ill Polytrauma Patients.

Science.gov (United States)

Papurica, Marius; Rogobete, Alexandru F; Sandesc, Dorel; Dumache, Raluca; Cradigati, Carmen A; Sarandan, Mirela; Nartita, Radu; Popovici, Sonia E; Bedreag, Ovidiu H

2016-01-01

The complexity of the cases of critically ill polytrauma patients is given by both the primary, as well as the secondary, post-traumatic injuries. The severe injuries of organ systems, the major biochemical and physiological disequilibrium, and the molecular chaos lead to a high rate of morbidity and mortality in this type of patient. The 'gold goal' in the intensive therapy of such patients resides in the continuous evaluation and monitoring of their clinical status. Moreover, optimizing the therapy based on the expression of certain biomarkers with high specificity and sensitivity is extremely important because of the clinical course of the critically ill polytrauma patient. In this paper we wish to summarize the recent studies of biomarkers useful for the intensive care unit (ICU) physician. For this study the available literature on specific databases such as PubMed and Scopus was thoroughly analyzed. Each article was carefully reviewed and useful information for this study extracted. The keywords used to select the relevant articles were "sepsis biomarker", "traumatic brain injury biomarker" "spinal cord injury biomarker", "inflammation biomarker", "microRNAs biomarker", "trauma biomarker", and "critically ill patients". For this study to be carried out 556 original type articles were analyzed, as well as case reports and reviews. For this review, 89 articles with relevant topics for the present paper were selected. The critically ill polytrauma patient, because of the clinical complexity the case presents with, needs a series of evaluations and specific monitoring. Recent studies show a series of either tissue-specific or circulating biomarkers that are useful in the clinical status evaluation of these patients. The biomarkers existing today, with regard to the critically ill polytrauma patient, can bring a significant contribution to increasing the survival rate, by adapting the therapy according to their expressions. Nevertheless, the necessity remains to

Biomarkers and Molecular Analysis to Improve Bloodstream Infection Diagnostics in an Emergency Care Unit

Science.gov (United States)

Loonen, Anne J. M.; de Jager, Cornelis P. C.; Tosserams, Janna; Kusters, Ron; Hilbink, Mirrian; Wever, Peter C.; van den Brule, Adriaan J. C.

2014-01-01

Molecular pathogen detection from blood is still expensive and the exact clinical value remains to be determined. The use of biomarkers may assist in preselecting patients for immediate molecular testing besides blood culture. In this study, 140 patients with ≥ 2 SIRS criteria and clinical signs of infection presenting at the emergency department of our hospital were included. C-reactive protein (CRP), neutrophil-lymphocyte count ratio (NLCR), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels were determined. One ml EDTA blood was obtained and selective pathogen DNA isolation was performed with MolYsis (Molzym). DNA samples were analysed for the presence of pathogens, using both the MagicPlex Sepsis Test (Seegene) and SepsiTest (Molzym), and results were compared to blood cultures. Fifteen patients had to be excluded from the study, leaving 125 patients for further analysis. Of the 125 patient samples analysed, 27 presented with positive blood cultures of which 7 were considered to be contaminants. suPAR, PCT, and NLCR values were significantly higher in patients with positive blood cultures compared to patients without (p molecular assays perform poorly when one ml whole blood is used from emergency care unit patients. NLCR is a cheap, fast, easy to determine, and rapidly available biomarker, and therefore seems most promising in differentiating BSI from non-BSI patients for subsequent pathogen identification using molecular diagnostics. PMID:24475269

Binding sites for luminescent amyloid biomarkers from non-biased molecular dynamics simulations.

Science.gov (United States)

König, Carolin; Skånberg, Robin; Hotz, Ingrid; Ynnerman, Anders; Norman, Patrick; Linares, Mathieu

2018-03-25

A very stable binding site for the interaction between a pentameric oligothiophene and an amyloid-β(1-42) fibril has been identified by means of non-biased molecular dynamics simulations. In this site, the probe is locked in an all-trans conformation with a Coulombic binding energy of 1200 kJ mol -1 due to the interactions between the anionic carboxyl groups of the probe and the cationic ε-amino groups in the lysine side chain. Upon binding, the conformationally restricted probes show a pronounced increase in molecular planarity. This is in line with the observed changes in luminescence properties that serve as the foundation for their use as biomarkers.

Potential of Mass Spectrometry in Developing Clinical Laboratory Biomarkers of Nonvolatiles in Exhaled Breath.

Science.gov (United States)

Beck, Olof; Olin, Anna-Carin; Mirgorodskaya, Ekaterina

2016-01-01

Exhaled breath contains nonvolatile substances that are part of aerosol particles of submicrometer size. These particles are formed and exhaled as a result of normal breathing and contain material from distal airways of the respiratory system. Exhaled breath can be used to monitor biomarkers of both endogenous and exogenous origin and constitutes an attractive specimen for medical investigations. This review summarizes the present status regarding potential biomarkers of nonvolatile compounds in exhaled breath. The field of exhaled breath condensate is briefly reviewed, together with more recent work on more selective collection procedures for exhaled particles. The relation of these particles to the surfactant in the terminal parts of the respiratory system is described. The literature on potential endogenous low molecular weight compounds as well as protein biomarkers is reviewed. The possibility to measure exposure to therapeutic and abused drugs is demonstrated. Finally, the potential future role and importance of mass spectrometry is discussed. Nonvolatile compounds exit the lung as aerosol particles that can be sampled easily and selectively. The clinical applications of potential biomarkers in exhaled breath comprise diagnosis of disease, monitoring of disease progress, monitoring of drug therapy, and toxicological investigations. © 2015 American Association for Clinical Chemistry.

In situ monitoring of molecular changes during cell differentiation processes in marine macroalgae through mass spectrometric imaging.

Science.gov (United States)

Kessler, Ralf W; Crecelius, Anna C; Schubert, Ulrich S; Wichard, Thomas

2017-08-01

Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was employed to discriminate between cell differentiation processes in macroalgae. One of the key developmental processes in the algal life cycle is the production of germ cells (gametes and zoids). The gametogenesis of the marine green macroalga Ulva mutabilis (Chlorophyta) was monitored by metabolomic snapshots of the surface, when blade cells differentiate synchronously into gametangia and giving rise to gametes. To establish MSI for macroalgae, dimethylsulfoniopropionate (DMSP), a known algal osmolyte, was determined. MSI of the surface of U. mutabilis followed by chemometric data analysis revealed dynamic metabolomic changes during cell differentiation. DMSP and a total of 55 specific molecular biomarkers, which could be assigned to important stages of the gametogenesis, were detected. Our research contributes to the understanding of molecular mechanisms underlying macroalgal cell differentiation. Graphical abstract Molecular changes during cell differentiation of the marine macroalga Ulva were visualized by matrix assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI).

Improving Blood Monitoring of Enzymes as Biomarkers of Risk from Anticholinergic Pesticides and Chemical Warfare Agents

National Research Council Canada - National Science Library

Wilson, Barry W

2006-01-01

Blood biomarkers are an important way to monitor exposure to anticholinergic pesticides and chemical warfare agents and to establish whether some personnel are at greater risk than others from exposure...

Improving Blood Monitoring of Enzymes as Biomarkers of Risk from Anticholinergic Pesticides and Chemical Warfare Agents

National Research Council Canada - National Science Library

Wilson, Barry W

2005-01-01

Blood biomarkers are an important way to monitor exposure to anticholinergic pesticides and chemical warfare agents and to establish whether some personnel are at greater risk than others from exposure...

A Network Biology Approach to Discover the Molecular Biomarker Associated with Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Liwei Zhuang

2014-01-01

Full Text Available In recent years, high throughput technologies such as microarray platform have provided a new avenue for hepatocellular carcinoma (HCC investigation. Traditionally, gene sets enrichment analysis of survival related genes is commonly used to reveal the underlying functional mechanisms. However, this approach usually produces too many candidate genes and cannot discover detailed signaling transduction cascades, which greatly limits their clinical application such as biomarker development. In this study, we have proposed a network biology approach to discover novel biomarkers from multidimensional omics data. This approach effectively combines clinical survival data with topological characteristics of human protein interaction networks and patients expression profiling data. It can produce novel network based biomarkers together with biological understanding of molecular mechanism. We have analyzed eighty HCC expression profiling arrays and identified that extracellular matrix and programmed cell death are the main themes related to HCC progression. Compared with traditional enrichment analysis, this approach can provide concrete and testable hypothesis on functional mechanism. Furthermore, the identified subnetworks can potentially be used as suitable targets for therapeutic intervention in HCC.

A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease

DEFF Research Database (Denmark)

Brinkmalm, Gunnar; Sjödin, Simon; Simonsen, Anja Hviid

2018-01-01

SCOPE: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). EXPERIMENTAL DESIGN: Thirteen proteins were selected based on their association with neurode......SCOPE: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). EXPERIMENTAL DESIGN: Thirteen proteins were selected based on their association...... with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and two to three peptides per protein were quantified using stable isotope-labeled peptide standards. RESULTS: Coefficients of variation were generally below 15%. Clinical...

Effects of cadmium on olfactory mediated behaviors and molecular biomarkers in coho salmon (Oncorhynchus kisutch)

Energy Technology Data Exchange (ETDEWEB)

Williams, Chase R.; Gallagher, Evan P., E-mail: evang3@u.washington.edu

2013-09-15

Highlights: •Low Cd exposures elicited significant olfactory mediated behavioral changes independent of histological injury. •The olfactory behavioral deficits persisted following a 16-day depuration. •Olfactory molecular biomarkers expression was strongly linked to injury to the olfactory epithelium. •Cd induced a strong antioxidant response in the coho salmon olfactory system. •Results suggest a sensitivity of salmonids to waterborne Cd. -- Abstract: The olfactory system of salmonids is sensitive to the adverse effects of metals such as copper and cadmium. In the current study, we analyzed olfactory-mediated alarm responses, epithelial injury and recovery, and a suite of olfactory molecular biomarkers encoding genes critical in maintaining olfactory function in juvenile coho salmon receiving acute exposures to cadmium (Cd). The molecular biomarkers analyzed included four G-protein coupled receptors (GPCRs) representing the two major classes of odorant receptors (salmon olfactory receptor sorb and vomeronasal receptors svra, svrb, and gpr27), as well as markers of neurite outgrowth (nrn1) and antioxidant responses to metals, including heme oxygenase 1 (hmox1), and peroxiredoxin 1 (prdx1). Coho received acute (8–168 h) exposures to 3.7 ppb and 347 ppb Cd, and a subset of fish was analyzed following a 16-day depuration. Coho exposed to 347 ppb Cd over 48 h exhibited a reduction in freeze responses, and an extensive loss of olfaction accompanied by histological injury to the olfactory epithelium. The olfactory injury in coho exposed to 347 ppb Cd was accompanied at the gene level by significant decreases in expression of the olfactory GPCRs and increased expression of hmox1. Persistent behavioral deficits, histological injury and altered expression of a subset of olfactory biomarkers were still evident in Cd-exposed coho following a 16-day depuration in clean water. Exposure to 3.7 ppb Cd also resulted in reduced freeze responses and histological changes

Remote in vivo stress assessment of aquatic animals with microencapsulated biomarkers for environmental monitoring

Science.gov (United States)

Gurkov, Anton; Shchapova, Ekaterina; Bedulina, Daria; Baduev, Boris; Borvinskaya, Ekaterina; Meglinski, Igor; Timofeyev, Maxim

2016-11-01

Remote in vivo scanning of physiological parameters is a major trend in the development of new tools for the fields of medicine and animal physiology. For this purpose, a variety of implantable optical micro- and nanosensors have been designed for potential medical applications. At the same time, the important area of environmental sciences has been neglected in the development of techniques for remote physiological measurements. In the field of environmental monitoring and related research, there is a constant demand for new effective and quick techniques for the stress assessment of aquatic animals, and the development of proper methods for remote physiological measurements in vivo may significantly increase the precision and throughput of analyses in this field. In the present study, we apply pH-sensitive microencapsulated biomarkers to remotely monitor the pH of haemolymph in vivo in endemic amphipods from Lake Baikal, and we compare the suitability of this technique for stress assessment with that of common biochemical methods. For the first time, we demonstrate the possibility of remotely detecting a change in a physiological parameter in an aquatic organism under ecologically relevant stressful conditions and show the applicability of techniques using microencapsulated biomarkers for remote physiological measurements in environmental monitoring.

Interactive effects of nutrition, reproductive state and pollution on molecular stress responses of mussels, Mytilus galloprovincialis Lamarck, 1819.

Science.gov (United States)

González-Fernández, Carmen; Albentosa, Marina; Sokolova, Inna

2017-10-01

Marine bivalves including mussels Mytilus galloprovincialis are commonly used as sentinels for pollution monitoring and ecosystem health assessment in the coastal zones. Use of biomarkers to assess the pollution effects assumes that the effects of pollutants on the biomarkers exceed the natural background variability; yet this assumption has rarely been tested. We exposed mussels at different reproductive stages and nutritive states to two concentrations of a polycyclic aromatic hydrocarbon (fluoranthene, 3 and 60 μg L -1 ) for three weeks. Expression levels of the molecular biomarkers related to the detoxification and general stress response [cytochrome P450 oxidase (CYP450), glutathione S-transferases (GST-α; GST-S1; GST-S2), the multixenobiotic resistance protein P-glycoprotein (PgP), metallothioneins (MT10 and MT20), heat shock proteins (HSP22, HSP70-2; HSP70-3; HSP70-4), as well as mRNA expression of two reproduction-related genes, vitellogenin (Vitel) and vitelline coat lysin M7 (VCLM7)] were measured. The mussels' nutrition and reproductive state affected the baseline mRNA levels of molecular biomarkers and modulated the transcriptional responses of biomarker genes to the pollutant exposure. Thus, mussel physiological state could act as a confounding factor in the evaluation of the response of pollution through molecular biomarkers. The biomarker baseline levels must be determined across a range of physiological states to enable the use of biomarkers in monitoring programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

WE-H-207A-09: Theoretical Limits to Molecular Biomarker Detection Using Magnetic Nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Weaver, J [Dartmouth-Hitchcock Medical Center, Lebanon, NH (United States); Geisel School of Medicine, Dartmouth College, Hanover, NH (United States)

2016-06-15

Purpose: Estimate the limits of molecular biomarker detection using magnetic nanoparticle methods like in vivo ELISA. Methods: Magnetic nanoparticles in an alternating magnetic field produce a magnetization that can be detected at exceedingly low levels because the signal at the harmonic frequencies is uniquely produced by the nanoparticles. Because the magnetization can also be used to characterize the nanoparticle rotational freedom, the bound state can be found. If the nanoparticles are coated with molecules that bind the desired biomarker, the rotational freedom reflects the biomarker concentration. The irreducible noise limit is the thermal noise or Johnson noise of the tissue and the contrast that can be measured must be larger than that limit. The contrast produced is a function of the applied field and depends strongly on nanoparticle volume. We have estimated the contrast using a Langevin function of a single composite variable to approximate the full stochastic Langevin equation for nanoparticle dynamics. Results: The thermal noise for a bandwidth reasonable for spectroscopy suggests mid zeptomolar (10–21) to low attomolar (10–18) concentrations can be measured in a volume that is 10cm in scale. The suggested sensitivity is far below the physiologically concentrations of almost all critical biomarkers including cytokines (picomolar), hormones (nanomolar) and heat shock proteins. Conclusion: The sensitivity of in vivo ELISA concentration measurements should be sufficient to measure physiological concentrations of critical biomarkers like cytokines in vivo. Further the sensitivity should be sufficient to measure concentrations of other biomarkers that are six to eight orders of magnitude lower in concentration than immune signaling molecules like cytokines. NIH - 1U54CA151662-01 Department of Radiology.

Biomarkers in molecular epidemiology study of oral squamous cell carcinoma in the era of precision medicine

Directory of Open Access Journals (Sweden)

Qing-Hao Zhu

2017-01-01

Full Text Available Oral cancer, which occurs in the mouth, lips, and tongue, is a multifactorial disease whose etiology involves environment, genetic, and epigenetic factors. Tobacco use and alcohol consumption are regarded as the primary risk factors for oral squamous cell carcinoma (OSCC, and betel use, other chemicals, radiation, environmental, and genetics are reported as relevant risk factors for oral carcinogenesis. The human papillomavirus infection is an independent risk factor. Traditional epidemiology studies have revealed that environmental carcinogens are risk factors for OSCC. Molecular epidemiology studies have revealed that the susceptibility to OSCC is influenced by both environmental and genetic risk factors. However, the details and mechanisms of risk factors involved in OSCC are unclear. Advanced methods and techniques used in human genome studies provide great opportunities for researchers to explore and identify (a the details of such risk factors and (b genetic susceptibility involved in OSCC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era into the era of genome-wide association study. In the era of precision medicine, molecular epidemiology studies should focus on biomarkers for cancer genomics and their potential utility in clinical practice. Here, we briefly reviewed several molecular epidemiology studies of OSCC, focusing on biomarkers as valuable utility in risk assessment, clinical screening, diagnosis, and prognosis prediction of OSCC in the era of precision medicine.

Chronic myelogenous leukemia: molecular monitoring in clinical practice

Directory of Open Access Journals (Sweden)

N. R. Ryabchikova

2013-01-01

Full Text Available Use of tyrosine kinase inhibitor imatinib has led to significant progress in chronic myeloid leukemia (CML treatment. To date, genetic monitoring is a mandatory attribute of therapy with tyrosine kinase inhibitors. The purpose of this study was to access the imatinib therapy efficacy in CML patients using complete molecular genetic monitoring by standard cytogenetics, realtime polymerase chain reaction and mutational analysis. Correlation between cytogenetic and molecular response was shown. Heterogeneity of molecular response in each patient group was revealed by expression of BCR-ABL. Kinase domain mutations were detected in 32 % of CML patients resistant to imatinib.

LABORATORY BIOMARKERS FOR ANKYLOSING SPONDYLITIS

Directory of Open Access Journals (Sweden)

E. N. Aleksandrova

2017-01-01

Full Text Available Ankylosing spondylitis (AS is a chronic inflammatory disease from a group of spondyloarthritis (SpA, which is characterized by lesions of the sacroiliac joints and spine with the common involvement of entheses and peripheral joints in the pathological process. Advances in modern laboratory medicine have contributed to a substantial expansion of the range of pathogenetic, diagnostic, and prognostic biomarkers of AS. As of now, there are key pathogenetic biomarkers of AS (therapeutic targets, which include tumor necrosis factor-α (TNF-α, interleukin 17 (IL-17, and IL-23. Among the laboratory diagnostic and prognostic biomarkers, HLA-B27 and C-reactive protein are of the greatest value in clinical practice; the former for the early diagnosis of the disease and the latter for the assessment of disease activity, the risk of radiographic progression and the efficiency of therapy. Anti-CD74 antibodies are a new biomarker that has high sensitivity and specificity values in diagnosing axial SpA at an early stage. A number of laboratory biomarkers, including calprotectin, matrix metalloproteinase-3 (MMP-3, vascular endothelial growth factor, Dickkopf-1 (Dkk-1, and C-terminal telopeptide of type II collagen (CTX II do not well reflect disease activity, but may predict progressive structural changes in the spine and sacroiliac joints in AS. Blood calprotectin level monitoring allows the effective prediction of a response to therapy with TNF inhibitors and anti-IL-17А monoclonal antibodies. The prospects for the laboratory diagnosis of AS are associated with the clinical validation of candidate biomarkers during large-scale prospective cohort studies and with a search for new proteomic, transcriptomic and genomic markers, by using innovative molecular and cellular technologies.

Radiation exposure assessment using cytological and molecular biomarkers

Energy Technology Data Exchange (ETDEWEB)

Blakely, W.F

2001-07-01

Chromosome aberration analysis is the conventional means of assessing radiation exposure. The Armed Forces Radiobiological Research Institute recently established an alternative method to measure radiation-induced chromosome aberrations in interphase cells. The method uses commercially available chemical agents to induce premature chromosome condensation in 'resting' G{sub 0} human peripheral blood lymphocytes. Then specific whole-chromosome DNA probes are used with fluorescence in situ hybridisation to detect aberrant cells rapidly over a broad dose range. In new research, the real-time fluorogenic 5'-nuclease, or TaqMan{sup TM}, polymerase chain reaction assay is being used to identify radiation-responsive molecular biomarkers, including gene expression targets and DNA mutations. The goal is to establish rapid, precise, high-throughput assay systems that are practical in a variety of radiation exposure scenarios. The new methodologies that have a number of other applications, together with diagnostic software now in development, could improve the United States military's emergency response capability and medical readiness. (author)

Multiple reaction monitoring assay based on conventional liquid chromatography and electrospray ionization for simultaneous monitoring of multiple cerebrospinal fluid biomarker candidates for Alzheimer's disease.

Science.gov (United States)

Choi, Yong Seok; Lee, Kelvin H

2016-03-01

Alzheimer's disease (AD) is the most common type of dementia, but early and accurate diagnosis remains challenging. Previously, a panel of cerebrospinal fluid (CSF) biomarker candidates distinguishing AD and non-AD CSF accurately (>90 %) was reported. Furthermore, a multiple reaction monitoring (MRM) assay based on nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) was developed to help validate putative AD CSF biomarker candidates including proteins from the panel. Despite the good performance of the MRM assay, wide acceptance may be challenging because of limited availability of nLC-MS/MS systems in laboratories. Thus, here, a new MRM assay based on conventional LC-MS/MS is presented. This method monitors 16 peptides representing 16 (of 23) biomarker candidates that belonged to the previous AD CSF panel. A 30-times more concentrated sample than the sample used for the previous study was loaded onto a high capacity trap column, and all 16 MRM transitions showed good linearity (average R(2) = 0.966), intra-day reproducibility (average coefficient of variance (CV) = 4.78 %), and inter-day reproducibility (average CV = 9.85 %). The present method has several advantages such as a shorter analysis time, no possibility of target variability, and no need for an internal standard.

The future: biomarkers, biosensors, neuroinformatics, and e-neuropsychiatry.

Science.gov (United States)

Lowe, Christopher R

2011-01-01

The emergence of molecular biomarkers for psychological, psychiatric, and neurodegenerative disorders is beginning to change current diagnostic paradigms for this debilitating family of mental illnesses. The development of new genomic, proteomic, and metabolomic tools has created the prospect of sensitive and specific biochemical tests to replace traditional pen-and-paper questionnaires. In the future, the realization of biosensor technologies, point-of-care testing, and the fusion of clinical biomarker data, electroencephalogram, and MRI data with the patient's past medical history, biopatterns, and prognosis may create personalized bioprofiles or fingerprints for brain disorders. Further, the application of mobile communications technology and grid computing to support data-, computation- and knowledge-based tasks will assist disease prediction, diagnosis, prognosis, and compliance monitoring. It is anticipated that, ultimately, mobile devices could become the next generation of personalized pharmacies. Copyright © 2011 Elsevier Inc. All rights reserved.

In vitro anticoagulation monitoring of low-molecular-weight heparin

Institute of Scientific and Technical Information of China (English)

WANG Jian-qi; SHI Xu-bo; YANG Jin-gang; HU Da-yi

2009-01-01

Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxapadn, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.Methods Atotal of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r= 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU,diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin.The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-Ila activities.

Materiomics for Oral Disease Diagnostics and Personal Health Monitoring: Designer Biomaterials for the Next Generation Biomarkers

Science.gov (United States)

Zhang, Wenjun; Wang, Ming L.; Khalili, Sammy

2016-01-01

Abstract We live in exciting times for a new generation of biomarkers being enabled by advances in the design and use of biomaterials for medical and clinical applications, from nano- to macro-materials, and protein to tissue. Key challenges arise, however, due to both scientific complexity and compatibility of the interface of biology and engineered materials. The linking of mechanisms across scales by using a materials science approach to provide structure–process–property relations characterizes the emerging field of ‘materiomics,’ which offers enormous promise to provide the hitherto missing tools for biomaterial development for clinical diagnostics and the next generation biomarker applications towards personal health monitoring. Put in other words, the emerging field of materiomics represents an essentially systematic approach to the investigation of biological material systems, integrating natural functions and processes with traditional materials science perspectives. Here we outline how materiomics provides a game-changing technology platform for disruptive innovation in biomaterial science to enable the design of tailored and functional biomaterials—particularly, the design and screening of DNA aptamers for targeting biomarkers related to oral diseases and oral health monitoring. Rigorous and complementary computational modeling and experimental techniques will provide an efficient means to develop new clinical technologies in silico, greatly accelerating the translation of materiomics-driven oral health diagnostics from concept to practice in the clinic. PMID:26760957

Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

International Nuclear Information System (INIS)

Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés

2017-01-01

Highlights: • Arsenic early induces MAPK pathway in R. arenarum embryos and larvae. • The MAPKs MEK-ERK in turn upregulate the transcription factors c-FOS and c-JUN. • SOD, CAT and GST would be affected by ROS at synthesis and degradation level. • Low As levels inducing molecular biomarkers have high probabilities of exceedence. • Molecular biomarkers are most adequate to ascertain As impact in R. arenarum. - Abstract: Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15 mg L"–"1. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of

Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

Energy Technology Data Exchange (ETDEWEB)

Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés, E-mail: a.venturino@conicet.gov.ar

2017-05-15

Highlights: • Arsenic early induces MAPK pathway in R. arenarum embryos and larvae. • The MAPKs MEK-ERK in turn upregulate the transcription factors c-FOS and c-JUN. • SOD, CAT and GST would be affected by ROS at synthesis and degradation level. • Low As levels inducing molecular biomarkers have high probabilities of exceedence. • Molecular biomarkers are most adequate to ascertain As impact in R. arenarum. - Abstract: Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15 mg L{sup –1}. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of

Current and future molecular diagnostics in non-small-cell lung cancer.

Science.gov (United States)

Li, Chun Man; Chu, Wing Ying; Wong, Di Lun; Tsang, Hin Fung; Tsui, Nancy Bo Yin; Chan, Charles Ming Lok; Xue, Vivian Wei Wen; Siu, Parco Ming Fai; Yung, Benjamin Yat Ming; Chan, Lawrence Wing Chi; Wong, Sze Chuen Cesar

2015-01-01

The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored.

Preparation, Characterization, and UV Irradiation of Mars Soil Analogues Under Simulated Martian Conditions to Support Detection of Molecular Biomarkers

Science.gov (United States)

Fornaro, T.; Brucato, J. R.; ten Kate, I. L.; Siljeström, S.; Steele, A.; Cody, G. D.; Hazen, R. M.

2018-04-01

We present laboratory activities of preparation, characterization, and UV irradiation processing of Mars soil analogues, which are key to support both in situ exploration and sample return missions devoted to detection of molecular biomarkers on Mars.

Biology and Biomarkers for Wound Healing

Science.gov (United States)

Lindley, Linsey E.; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

2016-01-01

Background As the population grows older, the incidence and prevalence of conditions which lead to a predisposition for poor wound healing also increases. Ultimately, this increase in non-healing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has, and will continue to be the leading pathway to the discovery of therapeutic targets as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of non-healing patients for whom biomarker-guided approaches may aid in healing. Methods A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Results Currently, biomarkers are being identified using biomaterials sourced locally, from human wounds and/or systemically using systematic high-throughput “omics” modalities (genomic, proteomic, lipidomic, metabolomic analysis). In this review we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum including those measured in tissue specimens e.g. β-catenin and c-myc, wound fluid e.g. MMP’s and interleukins, swabs e.g. wound microbiota and serum e.g. procalcitonin and MMP’s. Conclusions Identification of numerous potential biomarkers utilizing different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity, and consistent implementation of these biomarkers as well as an emphasis on efficacious follow-up therapeutics is necessary for transition of this technology to clinically feasible point-of-care applications. PMID:27556760

Biomarker Identification Using Text Mining

Directory of Open Access Journals (Sweden)

Hui Li

2012-01-01

Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

Network-based identification of biomarkers coexpressed with multiple pathways.

Science.gov (United States)

Guo, Nancy Lan; Wan, Ying-Wooi

2014-01-01

Unraveling complex molecular interactions and networks and incorporating clinical information in modeling will present a paradigm shift in molecular medicine. Embedding biological relevance via modeling molecular networks and pathways has become increasingly important for biomarker identification in cancer susceptibility and metastasis studies. Here, we give a comprehensive overview of computational methods used for biomarker identification, and provide a performance comparison of several network models used in studies of cancer susceptibility, disease progression, and prognostication. Specifically, we evaluated implication networks, Boolean networks, Bayesian networks, and Pearson's correlation networks in constructing gene coexpression networks for identifying lung cancer diagnostic and prognostic biomarkers. The results show that implication networks, implemented in Genet package, identified sets of biomarkers that generated an accurate prediction of lung cancer risk and metastases; meanwhile, implication networks revealed more biologically relevant molecular interactions than Boolean networks, Bayesian networks, and Pearson's correlation networks when evaluated with MSigDB database.

The use of biomarkers as integrative tools for transitional water bodies monitoring in the Water Framework Directive context - A holistic approach in Minho river transitional waters.

Science.gov (United States)

Capela, R; Raimundo, J; Santos, M M; Caetano, M; Micaelo, C; Vale, C; Guimarães, L; Reis-Henriques, M A

2016-01-01

The Water Framework Directive (WFD) provides an important legislative opportunity to promote and implement an integrated approach for the protection of inland surface waters, transitional waters, coastal waters and groundwaters. The transitional waters constitute a central piece as they are usually under high environmental pressure and by their inherent characteristics present monitoring challenges. Integrating water quality monitoring with biological monitoring can increase the cost-effectiveness of monitoring efforts. One way of doing this is with biomarkers, which effectively integrate physical-chemical status and biological quality elements, dealing holistically with adverse consequences on the health of water bodies. The new Marine Strategy Framework Directive (MSFD) already incorporates the biomarker approach. Given the recent activities of OSPAR and HELCOM to harmonize existing monitoring guidelines between MSFD and WFD the use of similar methodologies should be fostered. To illustrate the potential of the biomarker approach, juveniles of flounder (Platichthys flesus) were used to evaluate the quality of the Minho river-estuary water bodies. The use of juveniles instead of adults eliminates several confounding factors such changes on the biological responses associated with reproduction. Here, a panel of well-established biomarkers, EROD, AChE, SOD, CAT, GST, LPO, ENA and FACs (1-Hydroxyrene) were selected and measured along with a gradient of different physical conditions, and integrated with trace elements characterization on both biota and sediments. In general, a clear profile along the water bodies was found, with low seasonal and spatial variation, consistent with a low impacted area. Overall, the results support the use of both the battery of biomarkers and the use of juvenile flounders in the monitoring of the water quality status within the WFD. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmacogenomic Biomarkers

Directory of Open Access Journals (Sweden)

Sandra C. Kirkwood

2002-01-01

Full Text Available Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

Bio-monitoring of mycotoxin exposure in Cameroon using a urinary multi-biomarker approach.

Science.gov (United States)

Abia, Wilfred A; Warth, Benedikt; Sulyok, Michael; Krska, Rudolf; Tchana, Angele; Njobeh, Patrick B; Turner, Paul C; Kouanfack, Charles; Eyongetah, Mbu; Dutton, Mike; Moundipa, Paul F

2013-12-01

Bio-monitoring of human exposure to mycotoxin has mostly been limited to a few individually measured mycotoxin biomarkers. This study aimed to determine the frequency and level of exposure to multiple mycotoxins in human urine from Cameroonian adults. 175 Urine samples (83% from HIV-positive individuals) and food frequency questionnaire responses were collected from consenting Cameroonians, and analyzed for 15 mycotoxins and relevant metabolites using LC-ESI-MS/MS. In total, eleven analytes were detected individually or in combinations in 110/175 (63%) samples including the biomarkers aflatoxin M1, fumonisin B1, ochratoxin A and total deoxynivalenol. Additionally, important mycotoxins and metabolites thereof, such as fumonisin B2, nivalenol and zearalenone, were determined, some for the first time in urine following dietary exposures. Multi-mycotoxin contamination was common with one HIV-positive individual exposed to five mycotoxins, a severe case of co-exposure that has never been reported in adults before. For the first time in Africa or elsewhere, this study quantified eleven mycotoxin biomarkers and bio-measures in urine from adults. For several mycotoxins estimates indicate that the tolerable daily intake is being exceeded in this study population. Given that many mycotoxins adversely affect the immune system, future studies will examine whether combinations of mycotoxins negatively impact Cameroonian population particularly immune-suppressed individuals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genomic Biomarkers for Personalized Medicine: Development and Validation in Clinical Studies

Directory of Open Access Journals (Sweden)

Shigeyuki Matsui

2013-01-01

Full Text Available The establishment of high-throughput technologies has brought substantial advances to our understanding of the biology of many diseases at the molecular level and increasing expectations on the development of innovative molecularly targeted treatments and molecular biomarkers or diagnostic tests in the context of clinical studies. In this review article, we position the two critical statistical analyses of high-dimensional genomic data, gene screening and prediction, in the framework of development and validation of genomic biomarkers or signatures, through taking into consideration the possible different strategies for developing genomic signatures. A wide variety of biomarker-based clinical trial designs to assess clinical utility of a biomarker or a new treatment with a companion biomarker are also discussed.

PET imaging-based phenotyping as a predictive biomarker of response to tyrosine kinase inhibitor therapy in non-small cell lung cancer: Are we there yet?

Energy Technology Data Exchange (ETDEWEB)

Gerbaudo, Victor H.; Kim, Chun K. [Div. of Nuclear Medicine and Molecular Imaging, Dept. of Radiology,Brigham and Women' s Hospital and Harvard Medical School, Boston (United States)

2017-03-15

The increased understanding of the molecular pathology of different malignancies, especially lung cancer, has directed investigational efforts to center on the identification of different molecular targets and on the development of targeted therapies against these targets. A good representative is the epidermal growth factor receptor (EGFR); a major driver of non-small cell lung cancer tumorigenesis. Today, tumor growth inhibition is possible after treating lung tumors expressing somatic mutations of the EGFR gene with tyrosine kinase inhibitors (TKI). This opened the doors to biomarker-directed precision or personalized treatments for lung cancer patients. The success of these targeted anticancer therapies depends in part on being able to identify biomarkers and their patho-molecular make-up in order to select patients that could respond to specific therapeutic agents. While the identification of reliable biomarkers is crucial to predict response to treatment before it begins, it is also essential to be able to monitor treatment early during therapy to avoid the toxicity and morbidity of futile treatment in non-responding patients. In this context, we share our perspective on the role of PET imaging-based phenotyping in the personalized care of lung cancer patients to non-invasively direct and monitor the treatment efficacy of TKIs in clinical practice.

Identification of a 5-protein biomarker molecular signature for predicting Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Martín Gómez Ravetti

Full Text Available BACKGROUND: Alzheimer's disease (AD is a progressive brain disease with a huge cost to human lives. The impact of the disease is also a growing concern for the governments of developing countries, in particular due to the increasingly high number of elderly citizens at risk. Alzheimer's is the most common form of dementia, a common term for memory loss and other cognitive impairments. There is no current cure for AD, but there are drug and non-drug based approaches for its treatment. In general the drug-treatments are directed at slowing the progression of symptoms. They have proved to be effective in a large group of patients but success is directly correlated with identifying the disease carriers at its early stages. This justifies the need for timely and accurate forms of diagnosis via molecular means. We report here a 5-protein biomarker molecular signature that achieves, on average, a 96% total accuracy in predicting clinical AD. The signature is composed of the abundances of IL-1alpha, IL-3, EGF, TNF-alpha and G-CSF. METHODOLOGY/PRINCIPAL FINDINGS: Our results are based on a recent molecular dataset that has attracted worldwide attention. Our paper illustrates that improved results can be obtained with the abundance of only five proteins. Our methodology consisted of the application of an integrative data analysis method. This four step process included: a abundance quantization, b feature selection, c literature analysis, d selection of a classifier algorithm which is independent of the feature selection process. These steps were performed without using any sample of the test datasets. For the first two steps, we used the application of Fayyad and Irani's discretization algorithm for selection and quantization, which in turn creates an instance of the (alpha-beta-k-Feature Set problem; a numerical solution of this problem led to the selection of only 10 proteins. CONCLUSIONS/SIGNIFICANCE: the previous study has provided an extremely

Detection of molecular biomarkers as a diagnostic tool in the planning and progression of orthodontic treatment

Directory of Open Access Journals (Sweden)

Aditi Gaur

2017-01-01

Full Text Available Orthodontic treatment focuses on providing patient care at the appropriate timing to utilize the growth potential for best results. It involves growth modification of the craniofacial region along with alveolar bone remodeling during tooth movement. The dynamic process of bone metabolism involves the release of biochemical mediators in the circulation. These molecules are indicative of the bone remodeling activity of osteoblastic deposition and osteoclastic resorption. Such biomarkers when detectable in the systemic circulation highlight the skeletal maturity of orthodontic patients and when detected locally as, in gingival crevicular fluid (GCF and saliva, indicate the progression of orthodontically induced alveolar bone remodeling. Assessment of molecular biomarkers of bone remodeling in the body fluids would aid the clinicians in planning orthodontic treatment at the ideal timing and evaluating the advent of the treatment.

Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

Science.gov (United States)

Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

2015-01-01

Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

Urinary high molecular weight matrix metalloproteinases as non-invasive biomarker for detection of bladder cancer

OpenAIRE

Mohammed, Mohammed A; Seleim, Manar F; Abdalla, Mohga S; Sharada, Hayat M; Abdel Wahab, Abdel Hady A

2013-01-01

Background Matrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis. Over-expression of different MMPs in tumor tissues can disturb the homeostasis and increase the level of various body fluids. Many MMPs including high molecular weights (HMWs) were detected in the urine of prostate and bladder cancer patients. Our aim here is to assess the usefulness of HMW MMPs as non invasive biomarkers in bilharzial bladder cancer in Egyptian patients. Methods The activ...

Identification of cancer protein biomarkers using proteomic techniques

Energy Technology Data Exchange (ETDEWEB)

Mor, Gil G.; Ward, David C.; Bray-Ward, Patricia

2016-10-18

The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

[A surveillance study on CRISPR/Cas molecular biomarker in Escherichia coli].

Science.gov (United States)

Liang, W J; Zhang, R G; Duan, G C; Hong, L J; Zhang, B; Xi, Y L; Yang, H Y; Chen, S Y; Lou, T Y; Zhao, Y X

2016-08-10

A new method related to molecular biomarker with CRISPR/Cas (clustered regularly interspaced short palindromic repeats-cas) in Escherichia (E.) coli was developed and used for surveillance programs. CRISPR/Cas sequence that containing 135 strains with complete sequence and 203 strains with whole genome shotgun sequence of E. coli in GenBank by BLAST and 361 strains of E. coli (including 38 strains of E. coli O157∶H7) in laboratory were identified by PCR and analyzed with the CRISPR Finder. Spacers were compared with DANMAN and the phylogenetic trees of cas gene were constructed under Clustal Ⅹ and Mega 5.1. With new perspective, a descriptive method was developed targeting on the position of CRISPR/cas in E. coli. The CRISPR1 was detected in 77.04%, 100.00% and 75.62% and the CRISPR2 was detected in 74.81%, 100.00% and 92.24% and the CRISPR3 and CRISPR4 were detected in 11.85%, 0 and 1.39% for 135 strains with complete sequence, 203 strains with whole genome shotgun sequence and 361 strains in the laboratory, respectively. One strain downloaded in GenBank with whole genome sequencing and 2 strains in the our laboratory were identified that containing four CRISPR locus. The other E. coli strain was with insertion sequence in downstream of the non-cas CRISPR1. The unique CRISPR was found in 8 strains of O55∶H7, in 180 strains of O157∶H7, in 8 strains of O157∶HNM, in 40 strains of O104∶H4, in 4 strains of O145∶H28, in all the 699 E. coli strains. The phylogenetic tree could be divided into two groups-cas with type I-E or type I-F. CRISPR/Cas might be used as a valuable molecular biomarker in epidemiological surveillance studies to identify the high virulent strains or new strains of E. coli. Phage night be related to the missing or obtaining of spacers.

WONOEP appraisal: Biomarkers of epilepsy-associated comorbidities.

Science.gov (United States)

Ravizza, Teresa; Onat, Filiz Y; Brooks-Kayal, Amy R; Depaulis, Antoine; Galanopoulou, Aristea S; Mazarati, Andrey; Numis, Adam L; Sankar, Raman; Friedman, Alon

2017-03-01

Neurologic and psychiatric comorbidities are common in patients with epilepsy. Diagnostic, predictive, and pharmacodynamic biomarkers of such comorbidities do not exist. They may share pathogenetic mechanisms with epileptogenesis/ictogenesis, and as such are an unmet clinical need. The objectives of the subgroup on biomarkers of comorbidities at the XIII Workshop on the Neurobiology of Epilepsy (WONOEP) were to present the state-of-the-art recent research findings in the field that highlighting potential biomarkers for comorbidities in epilepsy. We review recent progress in the field, including molecular, imaging, and genetic biomarkers of comorbidities as discussed during the WONOEP meeting on August 31-September 4, 2015, in Heybeliada Island (Istanbul, Turkey). We further highlight new directions and concepts from studies on comorbidities and potential new biomarkers for the prediction, diagnosis, and treatment of epilepsy-associated comorbidities. The activation of various molecular signaling pathways such as the "Janus Kinase/Signal Transducer and Activator of Transcription," "mammalian Target of Rapamycin," and oxidative stress have been shown to correlate with the presence and severity of subsequent cognitive abnormalities. Furthermore, dysfunction in serotonergic transmission, hyperactivity of the hypothalamic-pituitary-adrenocortical axis, the role of the inflammatory cytokines, and the contributions of genetic factors have all recently been regarded as relevant for understanding epilepsy-associated depression and cognitive deficits. Recent evidence supports the utility of imaging studies as potential biomarkers. The role of such biomarker may be far beyond the diagnosis of comorbidities, as accumulating clinical data indicate that comorbidities can predict epilepsy outcomes. Future research is required to reveal whether molecular changes in specific signaling pathways or advanced imaging techniques could be detected in the clinical settings and correlate

Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions

Directory of Open Access Journals (Sweden)

Radu M. Nanau

2015-06-01

Full Text Available Background: The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. Methods: A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010–2015. The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Findings: Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions.

Science.gov (United States)

Nanau, Radu M; Neuman, Manuela G

2015-06-29

The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010-2015). The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

Science.gov (United States)

Palumbo, Barbara; Buresta, Tommaso; Nuvoli, Susanna; Spanu, Angela; Schillaci, Orazio; Fravolini, Mario Luca; Palumbo, Isabella

2014-01-01

Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed. PMID:24897023

Biomarkers to Monitor Gluten-Free Diet Compliance in Celiac Patients

Directory of Open Access Journals (Sweden)

María de Lourdes Moreno

2017-01-01

Full Text Available Gluten-free diet (GFD is the only treatment for celiac disease (CD. There is a general consensus that strict GFD adherence in CD patients leads to full clinical and histological remission accompanied by improvement in quality of life and reduced long-term complications. Despite the importance of monitoring the GFD, there are no clear guidelines for assessing the outcome or for exploring its adherence. Available methods are insufficiently accurate to identify occasional gluten exposure that may cause intestinal mucosal damage. Serological tests are highly sensitive and specific for diagnosis, but do not predict recovery and are not useful for follow-up. The use of serial endoscopies, it is invasive and impractical for frequent monitoring, and dietary interview can be subjective. Therefore, the detection of gluten immunogenic peptides (GIP in feces and urine have been proposed as new non-invasive biomarkers to detect gluten intake and verify GFD compliance in CD patients. These simple immunoassays in human samples could overcome some key unresolved scientific and clinical problems in CD management. It is a significant advance that opens up new possibilities for the clinicians to evaluate the CD treatment, GFD compliance, and improvement in the quality of life of CD patients.

Biomarkers for personalized oncology: recent advances and future challenges.

Science.gov (United States)

Kalia, Madhu

2015-03-01

Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and

The inflammatory cytokines: molecular biomarkers for major depressive disorder?

Science.gov (United States)

Martin, Charlotte; Tansey, Katherine E; Schalkwyk, Leonard C; Powell, Timothy R

2015-01-01

Cytokines are pleotropic cell signaling proteins that, in addition to their role as inflammatory mediators, also affect neurotransmitter systems, brain functionality and mood. Here we explore the potential utility of cytokine biomarkers for major depressive disorder. Specifically, we explore how genetic, transcriptomic and proteomic information relating to the cytokines might act as biomarkers, aiding clinical diagnosis and treatment selection processes. We advise future studies to investigate whether cytokine biomarkers might differentiate major depressive disorder patients from other patient groups with overlapping clinical characteristics. Furthermore, we invite future pharmacogenetic studies to investigate whether early antidepressant-induced changes to cytokine mRNA or protein levels precede behavioral changes and act as longer-term predictors of clinical antidepressant response.

Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging.

Science.gov (United States)

Fan, Quli; Cheng, Kai; Hu, Xiang; Ma, Xiaowei; Zhang, Ruiping; Yang, Min; Lu, Xiaomei; Xing, Lei; Huang, Wei; Gambhir, Sanjiv Sam; Cheng, Zhen

2014-10-29

Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated αvβ3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. The multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation.

Convergence of biomarkers, bioinformatics and nanotechnology for individualized cancer treatment

Science.gov (United States)

Phan, John H.; Moffitt, Richard A.; Stokes, Todd H.; Liu, Jian; Young, Andrew N.; Nie, Shuming; Wang, May D.

2013-01-01

Recent advances in biomarker discovery, biocomputing, and nanotechnology have raised new opportunities for the emerging field of personalized medicine in which disease detection, diagnosis, and therapy are tailored to each individual’s molecular profile, and also for predictive medicine that uses genetic/molecular information to predict disease development, progression, and clinical outcome. Here we discuss advanced biocomputing tools for cancer biomarker discovery and multiplexed nanoparticle probes for cancer biomarker profiling, together with prospects and challenges in correlating biomolecular signatures with clinical outcome. This bio-nano-info convergence holds great promise for molecular diagnosis and individualized therapy of cancer and other human diseases. PMID:19409634

Telomere Length – a New Biomarker in Medicine

Directory of Open Access Journals (Sweden)

Agnieszka Kozłowska

2015-12-01

Full Text Available A number of xenobiotics in the environment and workplace influences on our health and life. Biomarkers are tools for measuring such exposures and their effects in the organism. Nowadays, telomere length, epigenetic changes, mutations and changes in gene expression pattern have become new molecular biomarkers. Telomeres play the role of molecular clock, which influences on expectancy of cell life and thus aging, the formation of damages, development diseases and carcinogenesis. The telomere length depends on mechanisms of replication and the activity of telomerase. Telomere length is currently used as a biomarker of susceptibility and/or exposure. This paper describes the role of telomere length as a biomarker of aging cells, oxidative stress, a marker of many diseases including cancer, and as a marker of environmental and occupational exposure.

A novel immunotherapy of Brucellosis in cows monitored non invasively through a specific biomarker.

Directory of Open Access Journals (Sweden)

Hari Mohan Saxena

2018-04-01

Full Text Available Brucellosis is an important zoonotic disease causing huge economic losses worldwide. Currently no effective immunotherapy for Brucellosis or any biomarker to monitor the efficacy of therapy is available. Treatment is ineffective and animals remain carrier lifelong. S19 and RB51 are live attenuated vaccine strains of Brucella abortus. However, S19 induces only antibody, ineffective for intracellular pathogen. RB51 induces cell mediated immunity (CMI but it is Rifampicin resistant. Both organisms are secreted in milk and can infect humans and cause abortions in animals. Phage lysed bacteria (lysates retain maximum immunogenicity as opposed to killing by heat or chemicals. We report here the successful immunotherapy of bovine Brucellosis by phage lysates of RB51 (RL and S19 (SL. The SL induced strong antibody response and RL stimulated CMI. In vitro restimulation of leukocytes from RL immunized cattle induced interferon gamma production. A single subcutaneous dose of 2 ml of cocktail lysate (both RL and SL, eliminated live virulent Brucella from Brucellosis affected cattle with plasma level of Brucella specific 223 bp amplicon undetectable by RT-PCR and blood negative for live Brucella by culture in 3 months post-immunization. This is the first report on minimally invasive monitoring of the efficacy of antibacterial therapy employing plasma RNA specific for live bacteria as a biomarker as well as on the use of RB51 phage lysate for successful immunotherapy of Brucellosis in cattle.

[Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

Science.gov (United States)

Shevchenko, V E; Arnotskaia, N E; Ogorodnikova, E V; Davydov, M M; Ibraev, M A; Turkin, I N; Davydov, M I

2014-01-01

Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

Extracellular vesicle RNAs reflect placenta dysfunction and are a biomarker source for preterm labour.

Science.gov (United States)

Fallen, Shannon; Baxter, David; Wu, Xiaogang; Kim, Taek-Kyun; Shynlova, Oksana; Lee, Min Young; Scherler, Kelsey; Lye, Stephen; Hood, Leroy; Wang, Kai

2018-05-01

Preterm birth (PTB) can lead to lifelong complications and challenges. Identifying and monitoring molecular signals in easily accessible biological samples that can diagnose or predict the risk of preterm labour (PTL) in pregnant women will reduce or prevent PTBs. A number of studies identified putative biomarkers for PTL including protein, miRNA and hormones from various body fluids. However, biomarkers identified from these studies usually lack consistency and reproducibility. Extracellular vesicles (EVs) in circulation have gained significant interest in recent years as these vesicles may be involved in cell-cell communication. We have used an improved small RNA library construction protocol and a newly developed size exclusion chromatography (SEC)-based EV purification method to gain a comprehensive view of circulating RNA in plasma and its distribution by analysing RNAs in whole plasma and EV-associated and EV-depleted plasma. We identified a number of miRNAs in EVs that can be used as biomarkers for PTL, and these miRNAs may reflect the pathological changes of the placenta during the development of PTL. To our knowledge, this is the first study to report a comprehensive picture of circulating RNA, including RNA in whole plasma, EV and EV-depleted plasma, in PTL and reveal the usefulness of EV-associated RNAs in disease diagnosis. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

Directory of Open Access Journals (Sweden)

Barbara Palumbo

2014-06-01

Full Text Available Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI is discussed.

In Vivo Fluorescence Lifetime Imaging Monitors Binding of Specific Probes to Cancer Biomarkers

Science.gov (United States)

Ardeshirpour, Yasaman; Chernomordik, Victor; Zielinski, Rafal; Capala, Jacek; Griffiths, Gary; Vasalatiy, Olga; Smirnov, Aleksandr V.; Knutson, Jay R.; Lyakhov, Ilya; Achilefu, Samuel; Gandjbakhche, Amir; Hassan, Moinuddin

2012-01-01

One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the “image and treat” concept, especially for early evaluation of the efficacy of the therapy. PMID:22384092

In vivo fluorescence lifetime imaging monitors binding of specific probes to cancer biomarkers.

Directory of Open Access Journals (Sweden)

Yasaman Ardeshirpour

Full Text Available One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the "image and treat" concept, especially for early evaluation of the efficacy of the therapy.

Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas.

Science.gov (United States)

Kuboki, Yuko; Shimizu, Kyoko; Hatori, Takashi; Yamamoto, Masakazu; Shibata, Noriyuki; Shiratori, Keiko; Furukawa, Toru

2015-03-01

We aimed to identify molecular biomarkers for assessing the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN). We retrospectively investigated molecular aberrations and their associations with clinicopathological features in 172 IPMNs. GNAS and KRAS mutations were detected in 48% and 56% of IPMNs, respectively. No mutations of EGFR, PIK3CA GNAO1, GNAQ, or GNAI2 were observed. Significant associations were observed between IPMN morphological types and GNAS mutations, KRAS mutations, the expression of phosphorylated MAPK (pMAPK), AKT, and phosphorylated AKT (pAKT), nuclear accumulation of β-catenin, SMAD4 loss, and TP53 overexpression; histological grades and the expression of EGFR, pMAPK, AKT, and pAKT, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression; invasive phenotypes and KRAS mutations, the nuclear β-catenin, and SMAD4 loss; and prognosis and SMAD4 loss and TP53 overexpression. Multivariate analysis to compare prognostic impacts of multiple molecular features revealed that TP53 overexpression was an independent prognostic factor (P = 0.030; hazard ratio, 5.533). These results indicate that mutations in GNAS and KRAS, the expression of EGFR and pMAPK, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression may be relevant for assessing the clinical course of IPMN, including its progression into different morphological types, invasion, and prognosis.

Meeting Report--NASA Radiation Biomarker Workshop

Energy Technology Data Exchange (ETDEWEB)

Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.

2008-05-01

A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

OpenAIRE

Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-01-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P

Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

International Nuclear Information System (INIS)

Bradshaw, Tyler J.; Bowen, Stephen R.; Deveau, Michael A.; Kubicek, Lyndsay; White, Pamela; Bentzen, Søren M.; Chappell, Richard J.; Forrest, Lisa J.; Jeraj, Robert

2015-01-01

Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV max ; SUV mean ) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R 2 . Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV mean (P=.018), and midtreatment FLT SUV max (P=.006). Large decreases in FLT SUV mean from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV max (P=.022) in combination with large FLT response from

Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

Energy Technology Data Exchange (ETDEWEB)

Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

2015-03-15

Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

Modern molecular biomarkers of head and neck cancer. Part I. Epigenetic diagnostics and prognostics: Systematic review.

Science.gov (United States)

Juodzbalys, Gintaras; Kasradze, David; Cicciù, Marco; Sudeikis, Aurimas; Banys, Laurynas; Galindo-Moreno, Pablo; Guobis, Zygimantas

2016-01-01

Nearly half of the head and neck cancer cases are diagnosed in late stages. Traditional screening modalities have many disadvantages. The aim of the present article was to review the scientific literature about novel head and neck cancer diagnostics - epigenetic biomarkers. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in English language published from 2004 to 2015. A total of thirty three relevant studies were included in the review. Fifteen of them concerned DNA methylation alterations, nine evaluation of abundancies in histone expressions and nine miRNA expression changes in HNC. Considerable number of epigenetic biomarkers have been identified in both tumor tissue and salivary samples. Genes with best diagnostic effectiveness rates and further studying prospects were: TIMP3, DCC, DAPK, CDH1, CCNA1, AIM1, MGMT, HIC1, PAX1, PAX5, ZIC4, p16, EDNRB, KIF1A, MINT31, CD44, RARβ , ECAD. Individual histone and miRNA alterations tend to be hnc specific. Prognostic values of separate biomarkers are ambiguous. No established standards for molecular assay of head and neck cancer was found in order to elude the paradoxical results and discrepancies in separate trials.

CURRENT APPROACHES FOR RESEARCH OF MULTIPLE SCLEROSIS BIOMARKERS

Directory of Open Access Journals (Sweden)

Kolyada T.I

2016-12-01

severity, progression, pathogenetic type and treatment efficacy are based on transcriptomics, proteomics and metabolomics technologies. Transcriptomics includes genome-wide research of RNA sequences based on the results obtained with comparative genomic hybridization on biochips, massive parallel RNA sequencing, and measuring the amount of mRNA by real-time PCR. This technology is actively used in studies of gene expression profile of peripheral blood mononuclear cells from MS patients aimed at identifying molecular markers of disease status suitable for clinical use. Proteomics is a large-scale expression and protein distribution studies in patients with MS based on the results obtained via microarray and mass spectrometry, liquid and gas chromatography methods. In recent years, a growing number of MS proteomic studies using 2DE-MS method (two-dimensional electrophoresis coupled with mass spectrometry. Metabolomics studies of low-molecular-weight metabolic profiles based on the results obtained by mass spectrometry, liquid and gas chromatography, nuclear magnetic resonance. However, unlike other «-omics»-technologies, in metabolomics microarray-techniques are not used. Conclusion. Search, verification and clinical application of biomarkers for multiple sclerosis are one of the most challenging medical and biological problems. Its solution requires an interdisciplinary approach, organization of large-scale research and engagement of new research methods. In recent years, a significant amount of data received allowed to reveal hundreds of candidate biomarkers. Some of these biomarkers have significant potential for the monitoring of disease activity and assessment of therapy efficiency. However, the verification is required for a widespread clinical application; it implies further large-scale studies in different countries. The development of personalized medicine in Ukraine, the application of its principles to the management of multiple sclerosis patients, along with

Prognostic biomarkers in osteoarthritis

Science.gov (United States)

Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

2013-01-01

Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

A selection of reference genes and early-warning mRNA biomarkers for environmental monitoring using Mytilus spp. as sentinel species.

Science.gov (United States)

Lacroix, C; Coquillé, V; Guyomarch, J; Auffret, M; Moraga, D

2014-09-15

mRNA biomarkers are promising tools for environmental health assessment and reference genes are needed to perform relevant qPCR analyses in tissue samples of sentinel species. In the present study, potential reference genes and mRNA biomarkers were tested in the gills and digestive glands of native and caged mussels (Mytilus spp.) exposed to harbor pollution. Results highlighted the difficulty to find stable reference genes in wild, non-model species and suggested the use of normalization indices instead of single genes as they exhibit a higher stability. Several target genes were found differentially expressed between mussel groups, especially in gills where cyp32, π-gst and CuZn-sod mRNA levels could be biomarker candidates. Multivariate analyses confirmed the ability of mRNA levels to highlight site-effects and suggested the use of several combined markers instead of individual ones. These findings support the use of qPCR technology and mRNA levels as early-warning biomarkers in marine monitoring programs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Searching for non-genetic molecular and imaging PTSD risk and resilience markers: Systematic review of literature and design of the German Armed Forces PTSD biomarker study.

Science.gov (United States)

Schmidt, Ulrike; Willmund, Gerd-Dieter; Holsboer, Florian; Wotjak, Carsten T; Gallinat, Jürgen; Kowalski, Jens T; Zimmermann, Peter

2015-01-01

Biomarkers allowing the identification of individuals with an above average vulnerability or resilience for posttraumatic stress disorder (PTSD) would especially serve populations at high risk for trauma exposure like firefighters, police officers and combat soldiers. Aiming to identify the most promising putative PTSD vulnerability markers, we conducted the first systematic review on potential imaging and non-genetic molecular markers for PTSD risk and resilience. Following the PRISMA guidelines, we systematically screened the PubMed database for prospective longitudinal clinical studies and twin studies reporting on pre-trauma and post-trauma PTSD risk and resilience biomarkers. Using 25 different combinations of search terms, we retrieved 8151 articles of which we finally included and evaluated 9 imaging and 27 molecular studies. In addition, we briefly illustrate the design of the ongoing prospective German Armed Forces (Bundeswehr) PTSD biomarker study (Bw-BioPTSD) which not only aims to validate these previous findings but also to identify novel and clinically applicable molecular, psychological and imaging risk, resilience and disease markers for deployment-related psychopathology in a cohort of German soldiers who served in Afghanistan. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of novel biomarkers to monitor β-cell function and enable early detection of type 2 diabetes risk.

Directory of Open Access Journals (Sweden)

Kirstine J Belongie

Full Text Available A decline in β-cell function is a prerequisite for the development of type 2 diabetes, yet the level of β-cell function in individuals at risk of the condition is rarely measured. This is due, in part, to the fact that current methods for assessing β-cell function are inaccurate, prone to error, labor-intensive, or affected by glucose-lowering therapy. The aim of the current study was to identify novel circulating biomarkers to monitor β-cell function and to identify individuals at high risk of developing β-cell dysfunction. In a nested case-control study from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC cohort (n = 1157, proteomics and miRNA profiling were performed on fasting plasma samples from 43 individuals who progressed to impaired glucose tolerance (IGT and 43 controls who maintained normal glucose tolerance (NGT over three years. Groups were matched at baseline for age, gender, body mass index (BMI, insulin sensitivity (euglycemic clamp and β-cell glucose sensitivity (mathematical modeling. Proteomic profiling was performed using the SomaLogic platform (Colorado, USA; miRNA expression was performed using a modified RT-PCR protocol (Regulus Therapeutics, California, USA. Results showed differentially expressed proteins and miRNAs including some with known links to type 2 diabetes, such as adiponectin, but also novel biomarkers and pathways. In cross sectional analysis at year 3, the top differentially expressed biomarkers in people with IGT/ reduced β-cell glucose sensitivity were adiponectin, alpha1-antitrypsin (known to regulate adiponectin levels, endocan, miR-181a, miR-342, and miR-323. At baseline, adiponectin, cathepsin D and NCAM.L1 (proteins expressed by pancreatic β-cells were significantly lower in those that progressed to IGT. Many of the novel prognostic biomarker candidates were within the epithelial-mesenchymal transition (EMT pathway: for example, Noggin, DLL4 and miR-181a. Further

Clinical, functional, behavioural and epigenomic biomarkers of obesity.

Science.gov (United States)

Lafortuna, Claudio L; Tovar, Armando R; Rastelli, Fabio; Tabozzi, Sarah A; Caramenti, Martina; Orozco-Ruiz, Ximena; Aguilar-Lopez, Miriam; Guevara-Cruz, Martha; Avila-Nava, Azalia; Torres, Nimbe; Bertoli, Gloria

2017-06-01

Overweight and obesity are highly prevalent conditions worldwide, linked to an increased risk for death, disability and disease due to metabolic and biochemical abnormalities affecting the biological human system throughout different domains. Biomarkers, defined as indicators of biological processes in health and disease, relevant for body mass excess management have been identified according to different criteria, including anthropometric and molecular indexes, as well as physiological and behavioural aspects. Analysing these different biomarkers, we identified their potential role in diagnosis, prognosis and treatment. Epigenetic biomarkers, cellular mediators of inflammation and factors related to microbiota-host interactions may be considered to have a theranostic value. Though, the molecular processes responsible for the biological phenomenology detected by the other analysed markers, is not clear yet. Nevertheless, these biomarkers possess valuable diagnostic and prognostic power. A new frontier for theranostic biomarkers can be foreseen in the exploitation of parameters defining behaviours and lifestyles linked to the risk of obesity, capable to describe the effects of interventions for obesity prevention and treatment which include also behaviour change strategies.

Seasonal variation in biomarkers in blue mussel (Mytilus edulis), Icelandic scallop (Chlamys islandica) and Atlantic cod (Gadus morhua)-Implications for environmental monitoring in the Barents Sea

Energy Technology Data Exchange (ETDEWEB)

Nahrgang, J., E-mail: jasmine.m.nahrgang@uit.no [Akvaplan-niva, FRAM Centre, NO-9296 Tromso (Norway); Brooks, S.J. [Norwegian Institute for Water Research (NIVA), NO-0349 Oslo (Norway); Evenset, A. [Akvaplan-niva, FRAM Centre, NO-9296 Tromso (Norway); Camus, L. [Akvaplan-niva, FRAM Centre, NO-9296 Tromso (Norway); University Centre In Svalbard (UNIS), NO-9171 Longyearbyen (Norway); Jonsson, M.; Smith, T.J. [Akvaplan-niva, FRAM Centre, NO-9296 Tromso (Norway); Lukina, J. [Akvaplan-niva, FRAM Centre, NO-9296 Tromso (Norway); University of Tromso, Faculty of Biosciences, Fisheries and Economics, Department of Arctic and Marine Biosciences, NO-9037 Tromso (Norway); Frantzen, M. [Akvaplan-niva, FRAM Centre, NO-9296 Tromso (Norway); Giarratano, E. [Centro Nacional Patagonico (CENPAT-CONICET), AR-9120 Puerto Madryn (Argentina); Renaud, P.E. [Akvaplan-niva, FRAM Centre, NO-9296 Tromso (Norway); University Centre In Svalbard (UNIS), NO-9171 Longyearbyen (Norway)

2013-02-15

In the Barents Sea, the limited data on biological relevant indicators and their responses to various anthropogenic stressors have hindered the development of a consistent scientific basis for selecting indicator species and developing practical procedures for environmental monitoring. Accordingly, the main aim of the present study was to develop a common set of baseline values for contaminants and biomarkers in three species, and to identify their strengths and limitations in monitoring of the Barents Sea. Blue mussel (Mytilus edulis), Icelandic scallop (Chlamys islandica) and Atlantic cod (Gadus morhua) were sampled from a north Norwegian fjord in March, June, September and December 2010. Digestive glands from the bivalve species and liver from Atlantic cod were analysed for biomarkers of oxidative stress (catalase [CAT], glutathione peroxidase [GPX], glutathione-S-transferase activities [GST], lipid peroxidation as thiobarbituric reactive substances [TBARS] and total oxyradical scavenging capacity [TOSC]), biotransformation (ethoxyresorufine-O-deethylase activity [EROD]) and general stress (lysosomal membrane stability [LMS]). Concentrations of polycyclic aromatic hydrocarbons (PAHs) and metals in the bivalves and PAH metabolites in fish bile were quantified. Finally, energy reserves (total lipids, proteins and carbohydrates) and electron transport system (ETS) activity in the digestive gland of the bivalves and liver of Atlantic cod provided background information for reproductive cycle and general physiological status of the organisms. Blue mussel and Icelandic scallop showed very similar trends in biological cycle, biomarker expression and seasonality. Biomarker baselines in Atlantic cod showed weaker seasonal variability. However, important biological events may have been undetected due to the large time intervals between sampling occasions. Physiological biomarkers such as energy reserves and ETS activity were recommended as complementary parameters to the

Low molecular weight protein enrichment on mesoporous silica thin films for biomarker discovery.

Science.gov (United States)

Fan, Jia; Gallagher, James W; Wu, Hung-Jen; Landry, Matthew G; Sakamoto, Jason; Ferrari, Mauro; Hu, Ye

2012-04-17

The identification of circulating biomarkers holds great potential for non invasive approaches in early diagnosis and prognosis, as well as for the monitoring of therapeutic efficiency.(1-3) The circulating low molecular weight proteome (LMWP) composed of small proteins shed from tissues and cells or peptide fragments derived from the proteolytic degradation of larger proteins, has been associated with the pathological condition in patients and likely reflects the state of disease.(4,5) Despite these potential clinical applications, the use of Mass Spectrometry (MS) to profile the LMWP from biological fluids has proven to be very challenging due to the large dynamic range of protein and peptide concentrations in serum.(6) Without sample pre-treatment, some of the more highly abundant proteins obscure the detection of low-abundance species in serum/plasma. Current proteomic-based approaches, such as two-dimensional polyacrylamide gel-electrophoresis (2D-PAGE) and shotgun proteomics methods are labor-intensive, low throughput and offer limited suitability for clinical applications.(7-9) Therefore, a more effective strategy is needed to isolate LMWP from blood and allow the high throughput screening of clinical samples. Here, we present a fast, efficient and reliable multi-fractionation system based on mesoporous silica chips to specifically target and enrich LMWP.(10,11) Mesoporous silica (MPS) thin films with tunable features at the nanoscale were fabricated using the triblock copolymer template pathway. Using different polymer templates and polymer concentrations in the precursor solution, various pore size distributions, pore structures, connectivity and surface properties were determined and applied for selective recovery of low mass proteins. The selective parsing of the enriched peptides into different subclasses according to their physicochemical properties will enhance the efficiency of recovery and detection of low abundance species. In combination with mass

Biomarkers to Stratify Risk Groups among Children with Malnutrition in Resource-Limited Settings and to Monitor Response to Intervention.

Science.gov (United States)

McGrath, Christine J; Arndt, Michael B; Walson, Judd L

2017-01-01

Despite global efforts to reduce childhood undernutrition, current interventions have had little impact on stunting and wasting, and the mechanisms underlying growth faltering are poorly understood. There is a clear need to distinguish populations of children most likely to benefit from any given intervention and to develop tools to monitor response to therapy prior to the development of morbid sequelae. In resource-limited settings, environmental enteric dysfunction (EED) is common among children, contributing to malnutrition and increasing childhood morbidity and mortality risk. In addition to EED, early alterations in the gut microbiota can adversely affect growth through nutrient malabsorption, altered metabolism, gut inflammation, and dysregulation of the growth hormone axis. We examined the evidence linking EED and the gut microbiome to growth faltering and explored novel biomarkers to identify subgroups of children at risk of malnutrition due to underlying pathology. These and other biomarkers could be used to identify specific groups of children at risk of malnutrition and monitor response to targeted interventions. © 2017 S. Karger AG, Basel.

In vitro biomarker discovery in the parasitic flatworm Fasciola hepatica for monitoring chemotherapeutic treatment

Directory of Open Access Journals (Sweden)

Russell M. Morphew

2014-06-01

Full Text Available The parasitic flatworm Fasciola hepatica is a global food security risk. With no vaccines, the sustainability of triclabendazole (TCBZ is threatened by emerging resistance. F. hepatica excretory/secretory (ES products can be detected in host faeces and used to estimate TCBZ success and failure. However, there are no faecal based molecular diagnostics dedicated to assessing drug failure or resistance to TCBZ in the field. Utilising in vitro maintenance and sub-proteomic approaches two TCBZ stress ES protein response fingerprints were identified: markers of non-killing and lethal doses. This study provides candidate protein/peptide biomarkers to validate for detection of TCBZ failure and resistance.

A New Serum Biomarker for Lung Cancer - Transthyretin

Directory of Open Access Journals (Sweden)

Liyun LIU

2009-04-01

Full Text Available Background and objective Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI technique. Methods Serumsample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers were identified by ESI/MS-MS and database searching, and further confirmed by immunoprecipitation. The same sets of serum sample from all groups were re-measured by ELISA assay. Results Three protein peaks with the molecular weight 13.78 kDa, 13.90 kDa and 14.07 kDa were found significantlydecreased in lung cancer serum compared to the other groups and were all automatically selected as specific biomarkers by Biomarker Wizard software. The candidate biomarkers obtained from 1-D SDS gel bands by matching the molecular weight with peaks on CM10 chips were identified by Mass spectrometry as the native transthyretin (nativeTTR, cysTTR and glutTTR, and the identity was further validated by immunoprecipitation using commercial TTR antibodies. Downregulated of TTR was found in both ELISA and SELDI analysis. Conclusion TTRs acted as the potentially useful biomarkers for lung cancer by SELDI technique.

Chlamydia trachomatis induces an upregulation of molecular biomarkers podoplanin, Wilms' tumour gene 1, osteopontin and inflammatory cytokines in human mesothelial cells.

Science.gov (United States)

De Filippis, Anna; Buommino, Elisabetta; Domenico, Marina Di; Feola, Antonia; Brunetti-Pierri, Raffaella; Rizzo, Antonietta

2017-05-01

Chlamydia trachomatis is the most prevalent infection of the genital tract in women worldwide. C. trachomatis has a tendency to cause persistent infection and induce a state of chronic inflammation, which has been reported to play a role in carcinogenesis. We report that persistent C. trachomatis infection increases the expression of inflammatory tumour cytokines and upregulates molecular biomarkers such as podoplanin, Wilms' tumour gene 1 and osteopontin in primary cultures of mesothelial cells (Mes1) and human mesothelioma cells (NCI). Infection experiments showed that Mes1 and NCI supported the growth of C. trachomatisin vitro, and at an m.o.i. of 4, the inclusion-forming units/cell showed many intracellular inclusion bodies after 3 days of infection. However, after 7 days of incubation, increased proliferative and invasive activity was also observed in Mes1 cells, which was more evident after 14 days of incubation. ELISA analysis revealed an increase in vascular endothelial growth factor, IL-6, IL-8, and TNF-α release in Mes1 cells infected for a longer period (14 days). Finally, real-time PCR analysis revealed a strong induction of podoplanin, Wilms' tumour gene 1 and osteopontin gene expression in infected Mes1 cells. The aim of the present study was to investigate the inflammatory response elicited by C. trachomatis persistent infection and the role played by inflammation in cell proliferation, secretion of proinflammatory cytokines and molecular biomarkers of cancer. The results of this study suggest that increased molecular biomarkers of cancer by persistent inflammation from C. trachomatis infection might support cellular transformation, thus increasing the risk of cancer.

Molecular biomarkers in extrahepatic bile duct cancer patients undergoing chemoradiotherapy for gross residual disease after surgery

International Nuclear Information System (INIS)

Koh, Hyeon Kang; Kim, Kyu Bo; Chie, Eui Kyu; Ha, Sung W.; Park, Hae Jin

2012-01-01

To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and β-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and β-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and β-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

Molecular biomarkers in extrahepatic bile duct cancer patients undergoing chemoradiotherapy for gross residual disease after surgery

Energy Technology Data Exchange (ETDEWEB)

Koh, Hyeon Kang; Kim, Kyu Bo; Chie, Eui Kyu; Ha, Sung W. [Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Hae Jin [Dept. of Radiation Oncology, Soonchunhyang University Hospital, Seoul (Korea, Republic of)

2012-12-15

To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and {beta}-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and {beta}-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and {beta}-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

Diagnostic and prognostic epigenetic biomarkers in cancer.

Science.gov (United States)

Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

2015-01-01

Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

Biomedical wellness monitoring system based upon molecular markers

Science.gov (United States)

Ingram, Whitney

2012-06-01

We wish to assist caretakers with a sensor monitoring systems for tracking the physiological changes of homealone patients. One goal is seeking biomarkers and modern imaging sensors like stochastic optical reconstruction microscopy (STORM), which has achieved visible imaging at the nano-scale range. Imaging techniques like STORM can be combined with a fluorescent functional marker in a system to capture the early transformation signs from wellness to illness. By exploiting both microscopic knowledge of genetic pre-disposition and the macroscopic influence of epigenetic factors we hope to target these changes remotely. We adopt dual spectral infrared imaging for blind source separation (BSS) to detect angiogenesis changes and use laser speckle imaging for hypertension blood flow monitoring. Our design hypothesis for the monitoring system is guided by the user-friendly, veteran-preferred "4-Non" principles (noninvasive, non-contact, non-tethered, non-stop-to-measure) and by the NIH's "4Ps" initiatives (predictive, personalized, preemptive, and participatory). We augment the potential storage system with the recent know-how of video Compressive Sampling (CSp) from surveillance cameras. In CSp only major changes are saved, which reduces the manpower cost of caretakers and medical analysts. This CSp algorithm is based on smart associative memory (AM) matrix storage: change features and detailed scenes are written by the outer-product and read by the inner product without the usual Harsh index for image searching. From this approach, we attempt to design an effective household monitoring approach to save healthcare costs and maintain the quality of life of seniors.

Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.

Directory of Open Access Journals (Sweden)

Seraina Cooksley-Decasper

Full Text Available To date, no plaque-derived blood biomarker is available to allow diagnosis, prognosis or monitoring of atherosclerotic vascular diseases. In this study, specimens of thrombendarterectomy material from carotid and iliac arteries were incubated in protein-free medium to obtain plaque and control secretomes for subsequent subtractive phage display. The selection of nine plaque secretome-specific antibodies and the analysis of their immunopurified antigens by mass spectrometry led to the identification of 22 proteins. One of them, junction plakoglobin (JUP-81 and its smaller isoforms (referred to as JUP-63, JUP-55 and JUP-30 by molecular weight were confirmed by immunohistochemistry and immunoblotting with independent antibodies to be present in atherosclerotic plaques and their secretomes, coronary thrombi of patients with acute coronary syndrome (ACS and macrophages differentiated from peripheral blood monocytes as well as macrophage-like cells differentiated from THP1 cells. Plasma of patients with stable coronary artery disease (CAD (n = 15 and ACS (n = 11 contained JUP-81 at more than 2- and 14-fold higher median concentrations, respectively, than plasma of CAD-free individuals (n = 13. In conclusion, this proof of principle study identified and verified JUP isoforms as potential plasma biomarkers for atherosclerosis. Clinical validation studies are needed to determine its diagnostic efficacy and clinical utility as a biomarker for diagnosis, prognosis or monitoring of atherosclerotic vascular diseases.

Urinary Biomarkers of Brain Diseases

Directory of Open Access Journals (Sweden)

Manxia An

2015-12-01

Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

Seasonal variation in biomarkers in blue mussel (Mytilus edulis), Icelandic scallop (Chlamys islandica) and Atlantic cod (Gadus morhua)—Implications for environmental monitoring in the Barents Sea

International Nuclear Information System (INIS)

Nahrgang, J.; Brooks, S.J.; Evenset, A.; Camus, L.; Jonsson, M.; Smith, T.J.; Lukina, J.; Frantzen, M.; Giarratano, E.; Renaud, P.E.

2013-01-01

In the Barents Sea, the limited data on biological relevant indicators and their responses to various anthropogenic stressors have hindered the development of a consistent scientific basis for selecting indicator species and developing practical procedures for environmental monitoring. Accordingly, the main aim of the present study was to develop a common set of baseline values for contaminants and biomarkers in three species, and to identify their strengths and limitations in monitoring of the Barents Sea. Blue mussel (Mytilus edulis), Icelandic scallop (Chlamys islandica) and Atlantic cod (Gadus morhua) were sampled from a north Norwegian fjord in March, June, September and December 2010. Digestive glands from the bivalve species and liver from Atlantic cod were analysed for biomarkers of oxidative stress (catalase [CAT], glutathione peroxidase [GPX], glutathione-S-transferase activities [GST], lipid peroxidation as thiobarbituric reactive substances [TBARS] and total oxyradical scavenging capacity [TOSC]), biotransformation (ethoxyresorufine-O-deethylase activity [EROD]) and general stress (lysosomal membrane stability [LMS]). Concentrations of polycyclic aromatic hydrocarbons (PAHs) and metals in the bivalves and PAH metabolites in fish bile were quantified. Finally, energy reserves (total lipids, proteins and carbohydrates) and electron transport system (ETS) activity in the digestive gland of the bivalves and liver of Atlantic cod provided background information for reproductive cycle and general physiological status of the organisms. Blue mussel and Icelandic scallop showed very similar trends in biological cycle, biomarker expression and seasonality. Biomarker baselines in Atlantic cod showed weaker seasonal variability. However, important biological events may have been undetected due to the large time intervals between sampling occasions. Physiological biomarkers such as energy reserves and ETS activity were recommended as complementary parameters to the

Proteomic and metabolomic approaches to biomarker discovery

CERN Document Server

Issaq, Haleem J

2013-01-01

Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

Biomarkers of drug-induced vascular injury

International Nuclear Information System (INIS)

Brott, D.; Gould, S.; Jones, H.; Schofield, J.; Prior, H.; Valentin, J.P; Bjurstrom, S.; Kenne, K.; Schuppe-Koistinen, I.; Katein, A.; Foster-Brown, L.; Betton, G.; Richardson, R.; Evans, G.; Louden, C.

2005-01-01

In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury

Immune biomarkers in the spectrum of childhood noncommunicable diseases

NARCIS (Netherlands)

Skevaki, Chrysanthi; Van Den Berg, Jolice; Jones, Nicholas; Garssen, Johan; Vuillermin, Peter; Levin, Michael; Landay, Alan; Renz, Harald; Calder, Philip C.; Thornton, Catherine A.

2016-01-01

A biomarker is an accurately and reproducibly quantifiable biological characteristic that provides an objective measure of health status or disease. Benefits of biomarkers include identification of therapeutic targets, monitoring of clinical interventions, and development of personalized (or

Nanomaterials based biosensors for cancer biomarker detection

International Nuclear Information System (INIS)

Malhotra, Bansi D; Kumar, Saurabh; Pandey, Chandra Mouli

2016-01-01

Biosensors have enormous potential to contribute to the evolution of new molecular diagnostic techniques for patients suffering with cancerous diseases. A major obstacle preventing faster development of biosensors pertains to the fact that cancer is a highly complex set of diseases. The oncologists currently rely on a few biomarkers and histological characterization of tumors. Some of the signatures include epigenetic and genetic markers, protein profiles, changes in gene expression, and post-translational modifications of proteins. These molecular signatures offer new opportunities for development of biosensors for cancer detection. In this context, conducting paper has recently been found to play an important role towards the fabrication of a biosensor for cancer biomarker detection. In this paper we will focus on results of some of the recent studies obtained in our laboratories relating to fabrication and application of nanomaterial modified paper based biosensors for cancer biomarker detection. (paper)

Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring

Directory of Open Access Journals (Sweden)

Sanjiv Sharma

2017-04-01

Full Text Available The next generation of devices for personal healthcare monitoring will comprise molecular sensors to monitor analytes of interest in the skin compartment. Transdermal devices based on microneedles offer an excellent opportunity to explore the dynamics of molecular markers in the interstitial fluid, however good acceptability of these next generation devices will require several technical problems associated with current commercially available wearable sensors to be overcome. These particularly include reliability, comfort and cost. An essential pre-requisite for transdermal molecular sensing devices is that they can be fabricated using scalable technologies which are cost effective.We present here a minimally invasive microneedle array as a continuous monitoring platform technology. Method for scalable fabrication of these structures is presented. The microneedle arrays were characterised mechanically and were shown to penetrate human skin under moderate thumb pressure. They were then functionalised and evaluated as glucose, lactate and theophylline biosensors. The results suggest that this technology can be employed in the measurement of metabolites, therapeutic drugs and biomarkers and could have an important role to play in the management of chronic diseases. Keywords: Microneedles, Minimally invasive sensors, Continuous glucose monitoring (CGM, Continuous lactate monitoring (CLM, Interstitial therapeutic drug monitoring (iTDM

Quantifying Treatment Benefit in Molecular Subgroups to Assess a Predictive Biomarker.

Science.gov (United States)

Iasonos, Alexia; Chapman, Paul B; Satagopan, Jaya M

2016-05-01

An increased interest has been expressed in finding predictive biomarkers that can guide treatment options for both mutation carriers and noncarriers. The statistical assessment of variation in treatment benefit (TB) according to the biomarker carrier status plays an important role in evaluating predictive biomarkers. For time-to-event endpoints, the hazard ratio (HR) for interaction between treatment and a biomarker from a proportional hazards regression model is commonly used as a measure of variation in TB. Although this can be easily obtained using available statistical software packages, the interpretation of HR is not straightforward. In this article, we propose different summary measures of variation in TB on the scale of survival probabilities for evaluating a predictive biomarker. The proposed summary measures can be easily interpreted as quantifying differential in TB in terms of relative risk or excess absolute risk due to treatment in carriers versus noncarriers. We illustrate the use and interpretation of the proposed measures with data from completed clinical trials. We encourage clinical practitioners to interpret variation in TB in terms of measures based on survival probabilities, particularly in terms of excess absolute risk, as opposed to HR. Clin Cancer Res; 22(9); 2114-20. ©2016 AACR. ©2016 American Association for Cancer Research.

Molecular Imaging: A Promising Tool to Monitor Islet Transplantation

Directory of Open Access Journals (Sweden)

Ping Wang

2011-01-01

Full Text Available Replacement of insulin production by pancreatic islet transplantation has great potential as a therapy for type 1 diabetes mellitus. At present, the lack of an effective approach to islet grafts assessment limits the success of this treatment. The development of molecular imaging techniques has the potential to fulfill the goal of real-time noninvasive monitoring of the functional status and viability of the islet grafts. We review the application of a variety of imaging modalities for detecting endogenous and transplanted beta-cell mass. The review also explores the various molecular imaging strategies for assessing islet delivery, the metabolic effects on the islet grafts as well as detection of immunorejection. Here, we highlight the use of combined imaging and therapeutic interventions in islet transplantation and the in vivo monitoring of stem cells differentiation into insulin-producing cells.

Allergic asthma biomarkers using systems approaches

Directory of Open Access Journals (Sweden)

Gaurab eSircar

2014-01-01

Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

Role of laboratory biomarkers in monitoring and prediction of the effectiveness of treatment of rheumatic diseases using genetically engineered drugs

Directory of Open Access Journals (Sweden)

Elena Nikolayevna Aleksandrova

2014-03-01

Full Text Available Significant progress in treating immunoinflammatory rheumatic diseases (RD is related to the design of a novel family of drugs, genetically engineered (GE drugs. Molecular and cellular biomarkers (antibodies, indicators of acute inflammation, cytokines, chemokines, growth factors, endothelial activation markers, immunoglobulins, cryoglobulins, T- and B-cell subpopulations, products of bone and cartilage metabolism, genetic and metabolic markers that allow one to conduct immunological monitoring and prediction of the effectiveness of RD therapy using tumor necrosis factor α inhibitors (infliximab, adalimumab, golimumab, etanercept, anti-B-cell drugs (rituximab, belimumab, interleukin-6 receptor antagonist (tocilizumab, and T-cell costimulation blocker (abatacept have been detected in blood, synovial fluid, urine, and bioptates of the affected tissues. In addition to the conventional uniplex immunodiagnostics techniques, multiplex analysis of marker, which is based on genetic, transcriptomic and proteomic technologies using DNA and protein microarrays, polymerase chain reaction, and flow cytometry, is becoming increasingly widespread. The search for and validation of immunological predictors of the effective response to GE drug therapy make it possible to optimize and reduce the cost of therapy using these drugs in future.

Role of laboratory biomarkers in monitoring and prediction of the effectiveness of treatment of rheumatic diseases using genetically engineered drugs

Directory of Open Access Journals (Sweden)

Elena Nikolayevna Aleksandrova

2014-01-01

Full Text Available Significant progress in treating immunoinflammatory rheumatic diseases (RD is related to the design of a novel family of drugs, genetically engineered (GE drugs. Molecular and cellular biomarkers (antibodies, indicators of acute inflammation, cytokines, chemokines, growth factors, endothelial activation markers, immunoglobulins, cryoglobulins, T- and B-cell subpopulations, products of bone and cartilage metabolism, genetic and metabolic markers that allow one to conduct immunological monitoring and prediction of the effectiveness of RD therapy using tumor necrosis factor α inhibitors (infliximab, adalimumab, golimumab, etanercept, anti-B-cell drugs (rituximab, belimumab, interleukin-6 receptor antagonist (tocilizumab, and T-cell costimulation blocker (abatacept have been detected in blood, synovial fluid, urine, and bioptates of the affected tissues. In addition to the conventional uniplex immunodiagnostics techniques, multiplex analysis of marker, which is based on genetic, transcriptomic and proteomic technologies using DNA and protein microarrays, polymerase chain reaction, and flow cytometry, is becoming increasingly widespread. The search for and validation of immunological predictors of the effective response to GE drug therapy make it possible to optimize and reduce the cost of therapy using these drugs in future.

Haematological and serum enzymes biomarkers of heavy metals in ...

African Journals Online (AJOL)

Haematological and serum enzymes biomarkers of heavy metals in Chrysichthys Nigrodigitatus and Cynoglossus senegalensis. ... Haematological and serum enzymes activities are predilective biomarkers for the detection and monitoring of aquatic ecosystems pollution. The inclusion of Allium sativum at 1.5g/kg is ...

Biomarker Development for TLR4 Agonists

National Research Council Canada - National Science Library

Persing, David H

2004-01-01

.... To monitor the effectiveness of immunoprophylaxis in human trials, it may become necessary to develop surrogate biomarkers of protection since experimental challenge endpoints are not readily available...

Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

Directory of Open Access Journals (Sweden)

Natalie Turner

2014-03-01

Full Text Available Circulating tumor cell (CTC count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne muscular Dystrophy.

Directory of Open Access Journals (Sweden)

Irina T Zaharieva

Full Text Available Duchenne muscular Dystrophy (DMD is an inherited disease caused by mutations in the dystrophin gene that disrupt the open reading frame, while in frame mutations result in Becker muscular dystrophy (BMD. Ullrich congenital muscular dystrophy (UCMD is due to mutations affecting collagen VI genes. Specific muscle miRNAs (dystromirs are potential non-invasive biomarkers for monitoring the outcome of therapeutic interventions and disease progression. We quantified miR-1, miR-133a,b, miR-206 and miR-31 in serum from patients with DMD, BMD, UCMD and healthy controls. MiR-1, miR-133a,b and miR-206 were upregulated in DMD, but unchanged in UCMD compared to controls. Milder DMD patients had higher levels of dystromirs than more severely affected patients. Patients with low forced vital capacity (FVC values, indicating respiratory muscle weakness, had low levels of serum miR-1 and miR-133b. There was no significant difference in the level of the dystromirs in BMD compared to controls. We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene. The dystromirs were also analysed in muscle biopsies of DMD patients included in a single dose intramuscular eteplirsen clinical trial. Our analysis detected a trend towards normalization of these miRNA between the pre- and post-treatment samples of the systemic trial, which however failed to reach statistical significance. This could possibly be due to the small number of patients and the short duration of these clinical trials. Although longer term studies are needed to clarify the relationship between dystrophin restoration following therapeutic intervention and the level of circulating miRNAs, our results indicate that miR-1 and miR-133 can be considered as exploratory biomarkers for monitoring the progression of muscle weakness

SERS-based inverse molecular sentinel (iMS) nanoprobes for multiplexed detection of microRNA cancer biomarkers in biological samples

Science.gov (United States)

Crawford, Bridget M.; Wang, Hsin-Neng; Fales, Andrew M.; Bowie, Michelle L.; Seewaldt, Victoria L.; Vo-Dinh, Tuan

2017-02-01

The development of sensitive and selective biosensing techniques is of great interest for clinical diagnostics. Here, we describe the development and application of a surface enhanced Raman scattering (SERS) sensing technology, referred to as "inverse Molecular Sentinel (iMS)" nanoprobes, for the detection of nucleic acid biomarkers in biological samples. This iMS nanoprobe involves the use of plasmonic-active nanostars as the sensing platform for a homogenous assay for multiplexed detection of nucleic acid biomarkers, including DNA, RNA and microRNA (miRNA). The "OFF-to-ON" signal switch is based on a non-enzymatic strand-displacement process and the conformational change of stem-loop (hairpin) oligonucleotide probes upon target binding. Here, we demonstrate the development of iMS nanoprobes for the detection of DNA sequences as well as a modified design of the nanoprobe for the detection of short (22-nt) microRNA sequences. The application of iMS nanoprobes to detect miRNAs in real biological samples was performed with total small RNA extracted from breast cancer cell lines. The multiplex capability of the iMS technique was demonstrated using a mixture of the two differently labeled nanoprobes to detect miR-21 and miR-34a miRNA biomarkers for breast cancer. The results of this study demonstrate the feasibility of applying the iMS technique for multiplexed detection of nucleic acid biomarkers, including short miRNAs molecules.

Diagnosing phenotypes of single-sample individuals by edge biomarkers.

Science.gov (United States)

Zhang, Wanwei; Zeng, Tao; Liu, Xiaoping; Chen, Luonan

2015-06-01

Network or edge biomarkers are a reliable form to characterize phenotypes or diseases. However, obtaining edges or correlations between molecules for an individual requires measurement of multiple samples of that individual, which are generally unavailable in clinical practice. Thus, it is strongly demanded to diagnose a disease by edge or network biomarkers in one-sample-for-one-individual context. Here, we developed a new computational framework, EdgeBiomarker, to integrate edge and node biomarkers to diagnose phenotype of each single test sample. By applying the method to datasets of lung and breast cancer, it reveals new marker genes/gene-pairs and related sub-networks for distinguishing earlier and advanced cancer stages. Our method shows advantages over traditional methods: (i) edge biomarkers extracted from non-differentially expressed genes achieve better cross-validation accuracy of diagnosis than molecule or node biomarkers from differentially expressed genes, suggesting that certain pathogenic information is only present at the level of network and under-estimated by traditional methods; (ii) edge biomarkers categorize patients into low/high survival rate in a more reliable manner; (iii) edge biomarkers are significantly enriched in relevant biological functions or pathways, implying that the association changes in a network, rather than expression changes in individual molecules, tend to be causally related to cancer development. The new framework of edge biomarkers paves the way for diagnosing diseases and analyzing their molecular mechanisms by edges or networks in one-sample-for-one-individual basis. This also provides a powerful tool for precision medicine or big-data medicine. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

DNA Methylation Biomarkers: Cancer and Beyond

Directory of Open Access Journals (Sweden)

Thomas Mikeska

2014-09-01

Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

Prognostic value of bone- and vascular-derived molecular biomarkers in hemodialysis and renal transplant patients: a systematic review and meta-analysis.

Science.gov (United States)

Pichler, Gernot; Haller, Maria C; Kainz, Alexander; Wolf, Myles; Redon, Josep; Oberbauer, Rainer

2017-09-01

Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data [hazard Ratio (HR)] or as effect size with a fixed time of follow-up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP-7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association. In hemodialysis patients, FGF23 is a

Carbon sources in suspended particles and surface sediments from the Beaufort Sea revealed by molecular lipid biomarkers and compound-specific isotope analysis

Directory of Open Access Journals (Sweden)

I. Tolosa

2013-03-01

Full Text Available Molecular lipid biomarkers (hydrocarbons, alcohols, sterols and fatty acids and compound-specific isotope analysis of suspended particulate organic matter (SPM and surface sediments of the Mackenzie Shelf and slope (southeast Beaufort Sea, Arctic Ocean were studied in summer 2009. The concentrations of the molecular lipid markers, characteristic of known organic matter sources, were grouped and used as proxies to evaluate the relative importance of fresh algal, detrital algal, fossil, C3 terrestrial plants, bacterial and zooplankton material in the organic matter (OM of this area. Fossil and detrital algal contributions were the major fractions of the freshwater SPM from the Mackenzie River with ~34% each of the total molecular biomarkers. Fresh algal, C3 terrestrial, bacterial and zooplanktonic components represented much lower percentages, 17, 10, 4 and 80%, with a minor contribution of fossil and C3 terrestrial biomarkers. Characterization of the sediments revealed a major sink of refractory algal material mixed with some fresh algal material, fossil hydrocarbons and a small input of C3 terrestrial sources. In particular, the sediments from the shelf and at the mouth of the Amundsen Gulf presented the highest contribution of detrital algal material (60–75%, whereas those from the slope contained the highest proportion of fossil (40% and C3 terrestrial plant material (10%. Overall, considering that the detrital algal material is marine derived, autochthonous sources contributed more than allochthonous sources to the OM lipid pool. Using the ratio of an allochthonous biomarker (normalized to total organic carbon, TOC found in the sediments to those measured at the river mouth water, we estimated that the fraction of terrestrial material preserved in the sediments accounted for 30–40% of the total carbon in the inner shelf sediments, 17% in the outer shelf and Amundsen Gulf and up to 25% in the slope sediments. These estimates are low

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

Science.gov (United States)

Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

2013-05-01

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Identification of the lipid biomarkers from plasma in idiopathic pulmonary fibrosis by Lipidomics.

Science.gov (United States)

Yan, Feng; Wen, Zhensong; Wang, Rui; Luo, Wenling; Du, Yufeng; Wang, Wenjun; Chen, Xianyang

2017-12-06

Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial pulmonary disease featured by high mortality, chronic and progressive course, and poor prognosis with unclear etiology. Currently, more studies have been focusing on identifying biomarkers to predict the progression of IPF, such as genes, proteins, and lipids. Lipids comprise diverse classes of molecules and play a critical role in cellular energy storage, structure, and signaling. The role of lipids in respiratory diseases, including cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD) has been investigated intensely in the recent years. The human serum lipid profiles in IPF patients however, have not been thoroughly understood and it will be very helpful if there are available molecular biomarkers, which can be used to monitor the disease progression or provide prognostic information for IPF disease. In this study, we performed the ultraperformance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and identify biomarker in plasma of IPF patients. The plasma were from 22 IPF patients before received treatment and 18 controls. A total of 507 individual blood lipid species were determined with lipidomics from the 40 plasma samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7 types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By comparing the variations in the lipid metabolite levels in IPF patients, a total of 62 unique lipids were identified by statistical analysis including 24 kinds of glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating lipids were selected as the potential biomarkers, which are able to differentiate between IPF disease and controls with ROC

A review of molecular biomarkers for bladder cancer

African Journals Online (AJOL)

McRoy

Volume 2 Issue 3 September – December 2013 ... methodology were identified but only half of them have shown consistence ... Conclusion: It is envisaged that a combination ... biomarkers for bladder cancer are adopted in the UK standard practice. ... words used for the literature review were ..... Multi centre validation.

Biomarkers in spinal cord compression Ethics and perspectives

Directory of Open Access Journals (Sweden)

Iencean A.St.

2016-09-01

Full Text Available The phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H in serum or in cerebro-spinal fluid (CSF is a specific lesional biomarker for spinal cord injury. The lesional biomarkers and the reaction biomarkers are both presented after several hours post-injury. The specific predictive patterns of lesional biomarkers could be used to aid clinicians with making a diagnosis and establishing a prognosis, and evaluating therapeutic interventions. Diagnosis, prognosis, and treatment guidance based on biomarker used as a predictive indicator can determine ethical difficulties by differentiated therapies in patients with spinal cord compression. At this point based on studies until today we cannot take a decision based on biomarker limiting the treatment of neurological recovery in patients with complete spinal cord injury because we do not know the complexity of the biological response to spinal cord compression.

Possible biomarkers modulating haloperidol efficacy and/or tolerability.

Science.gov (United States)

Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

2016-04-01

Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

Preservation of terrestrial plant biomarkers from Nachukui Formation sediments and their viability for stable isotope analysis

Science.gov (United States)

Kahle, E.; Uno, K. T.; Polissar, P. J.; Lepre, C. J.; deMenocal, P. B.

2013-12-01

Plio-Pleistocene sedimentary records from the Turkana Basin in eastern Africa provide a unique opportunity to compare a high-resolution record of climate and terrestrial vegetation with important changes in the record of human evolution. Molecular biomarkers from terrestrial vegetation can yield stable isotope ratios of hydrogen and carbon that reflect ancient climate and vegetation. However, the preservation of long-chain plant wax biomarkers in these paleosol, fluvial, and lacustrine sediments is not known, and this preservation must be studied to establish their utility for molecular stable isotope studies. We investigated leaf wax biomarkers in Nachukui Formation sediments deposited between 2.3 and 1.7 Ma to assess biomarker preservation. We analyzed n alkane and n alkanoic acid concentrations and, where suitable, molecular carbon and hydrogen isotope ratios. Molecular abundance distributions show a great deal of variance in biomarker preservation and plant-type source as indicated by the carbon preference index and average chain length. This variation suggests that some samples are suitable for isotopic analysis, while other samples lack primary terrestrial plant biomarker signatures. The biomarker signal in many samples contains significant additional material from unidentified sources. For example, the n-alkane distributions contain an unresolved complex mixture underlying the short and mid-chain n-alkanes. Samples from lacustrine intervals include long-chain diacids, hydroxy acids and (ω-1) ketoacids that suggest degradation of the original acids. Degradation of poorly preserved samples and the addition of non-terrestrial plant biomarkers may originate from a number of processes including forest fire or microbial alteration. Isotopic analysis of well-preserved terrestrial plant biomarkers will be presented along with examples where the original biomarker distribution has been altered.

The development and applications of biomarkers

International Nuclear Information System (INIS)

Normandy, J.; Peeters, J.

1994-01-01

This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community

The development and applications of biomarkers

Energy Technology Data Exchange (ETDEWEB)

Normandy, J.; Peeters, J. [eds.

1994-04-15

This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community.

Experience of molecular monitoring techniques in upstream oil and gas operations

Energy Technology Data Exchange (ETDEWEB)

Mitchell, Anthony F.; Anfindsen, Hilde; Liengen, Turid; Molid, Solfrid [Statoil ASA (Denmark)

2011-07-01

For a numbers of years, molecular monitoring tools have been used in upstream oil and gas operations but the results have given only limited added value. This paper discusses the various techniques available for upstream molecular monitoring which provides scope for identification of microbial influenced problems. The methodology, which consists of analyzing solid samples using traditional as well as molecular techniques, is detailed. Two cases were studied with the objective of determining if microbial contamination was contributing to the problem. The first case was a study of amorphous deposits in production wells and mainly iron sulphide was found. The second study was of amorphous deposits in water injection wells and the analysis showed typical components of drilling and completion fluids with some organic material. Two more cases, corrosion of tubing in a water injection well and flow line corrosion, are discussed and the results are given. From the study, it can be concluded that failure can be due to several factors, chemical and biological.

Unraveling the molecular repertoire of tears as a source of biomarkers: beyond ocular diseases.

Science.gov (United States)

Pieragostino, Damiana; D'Alessandro, Michele; di Ioia, Maria; Di Ilio, Carmine; Sacchetta, Paolo; Del Boccio, Piero

2015-02-01

Proteomics and metabolomics investigations of body fluids present several challenges for biomarker discovery of several diseases. The search for biomarkers is actually conducted in different body fluids, even if the ideal biomarker can be found in an easily accessible biological fluid, because, if validated, the biomarker could be sought in the healthy population. In this regard, tears could be considered an optimum material obtained by noninvasive procedures. In the past years, the scientific community has become more interested in the study of tears for the research of new biomarkers not only for ocular diseases. In this review, we provide a discussion on the current state of biomarkers research in tears and their relevance for clinical practice, and report the main results of clinical proteomics studies on systemic and eye diseases. We summarize the main methods for tear samples analyses and report recent advances in "omics" platforms for tears investigations. Moreover, we want to take stock of the emerging field of metabolomics and lipidomics as a new and integrated approach to study protein-metabolites interplay for biomarkers research, where tears represent a still unexplored and attractive field. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systemic, local and imaging biomarkers of brain injury: more needed, and better use of those already established?

Directory of Open Access Journals (Sweden)

Keri Linda Carpenter

2015-02-01

Full Text Available Much progress has been made over the past two decades in the treatment of severe acute brain injury, including traumatic brain injury and subarachnoid haemorrhage, resulting in a higher proportion of patients surviving with better outcomes. This has arisen from a combination of factors. These include improvements in procedures at the scene (pre-hospital and in the hospital emergency department, advances in neuromonitoring in the intensive care unit, both continuously at the bedside and intermittently in scans, evolution and refinement of protocol-driven therapy for better management of patients, and advances in surgical procedures and rehabilitation. Nevertheless, many patients still experience varying degrees of long-term disabilities post-injury with consequent demands on carers and resources, and there is room for improvement. Biomarkers are a key aspect of neuromonitoring. A broad definition of a biomarker is any observable feature that can be used to inform on the state of the patient, e.g. a molecular species, a feature on a scan, or a monitoring characteristic e.g. cerebrovascular pressure reactivity index. Biomarkers are usually quantitative measures, which can be utilised in diagnosis and monitoring of response to treatment. They are thus crucial to the development of therapies and may be utilised as surrogate endpoints in Phase II clinical trials. To date, there is no specific drug treatment for acute brain injury, and many seemingly promising agents emerging from pre-clinical animal models have failed in clinical trials. Large Phase III studies of clinical outcomes are costly, consuming time and resources. It is therefore important that adequate Phase II clinical studies with informative surrogate endpoints are performed employing appropriate biomarkers. In this article we review some of the available systemic, local and imaging biomarkers and technologies relevant in acute brain injury patients, and highlight gaps in the current

Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective.

Science.gov (United States)

Giglio, Anita; Brandmayr, Pietro

2017-08-01

Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers.

Science.gov (United States)

Rantalainen, Mattias; Klevebring, Daniel; Lindberg, Johan; Ivansson, Emma; Rosin, Gustaf; Kis, Lorand; Celebioglu, Fuat; Fredriksson, Irma; Czene, Kamila; Frisell, Jan; Hartman, Johan; Bergh, Jonas; Grönberg, Henrik

2016-11-30

Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data. Non-routine biomarkers, including mutations in BRCA1, BRCA2 and ERBB2(HER2), and additional clinically actionable somatic alterations were also investigated. Concordance with routine diagnostic biomarkers was high for ER status (AUC = 0.95;AUC(replication) = 0.97) and HER2 status (AUC = 0.97;AUC(replication) = 0.92). The transcriptomic grade model enabled classification of histological grade 1 and histological grade 3 tumors with high accuracy (AUC = 0.98;AUC(replication) = 0.94). Clinically actionable mutations in BRCA1, BRCA2 and ERBB2(HER2) were detected in 5.5% of patients, while 53% had genomic alterations matching ongoing or concluded breast cancer studies. Sequencing-based molecular profiling can be applied as an alternative to histopathology to determine ER and HER2 status, in addition to providing improved tumor grading and clinically actionable mutations and molecular subtypes. Our results suggest that sequencing-based breast cancer diagnostics in a near future can replace routine biomarkers.

4-Methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol as a urinary biomarker for monitoring of metofluthrin, a fluorine-containing pyrethroid, in exposed rats.

Science.gov (United States)

Yoshida, Toshiaki

2015-02-01

A fluorine-containing pyrethroid metofluthrin is widely used recently in mosquito repellents. The urinary excretion kinetics of its metabolites was evaluated in rats to establish an optimal biomarker for monitoring metofluthrin exposure of the general population. After metofluthrin had been administered intraperitoneally to rats, the urinary excretion kinetics of the major metofluthrin metabolites was evaluated by moment analysis. The urinary excretion amounts of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol were estimated to be proportional to the absorption amounts over a wide exposure range. Urinary 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol was considered to be an optimal biomarker for metofluthrin exposure.

Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping.

Science.gov (United States)

Scott, Alison J; Jones, Jace W; Orschell, Christie M; MacVittie, Thomas J; Kane, Maureen A; Ernst, Robert K

2014-01-01

Integral to the characterization of radiation-induced tissue damage is the identification of unique biomarkers. Biomarker discovery is a challenging and complex endeavor requiring both sophisticated experimental design and accessible technology. The resources within the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against Radiological Threats (MCART), allow for leveraging robust animal models with novel molecular imaging techniques. One such imaging technique, MALDI (matrix-assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for the direct spatial visualization of lipids, proteins, small molecules, and drugs/drug metabolites-or biomarkers-in an unbiased manner. MALDI-MSI acquires mass spectra directly from an intact tissue slice in discrete locations across an x, y grid that are then rendered into a spatial distribution map composed of ion mass and intensity. The unique mass signals can be plotted to generate a spatial map of biomarkers that reflects pathology and molecular events. The crucial unanswered questions that can be addressed with MALDI-MSI include identification of biomarkers for radiation damage that reflect the response to radiation dose over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI also enable integration of biomarker identification among diverse animal models. Analysis of early, sublethally irradiated tissue injury samples from diverse mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated with histological features of these unique tissues. This paper will discuss the application of MALDI-MSI for use in a larger biomarker discovery pipeline.

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

Science.gov (United States)

Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

The molecular signature of impaired diabetic wound healing identifies serpinB3 as a healing biomarker.

Science.gov (United States)

Fadini, Gian Paolo; Albiero, Mattia; Millioni, Renato; Poncina, Nicol; Rigato, Mauro; Scotton, Rachele; Boscari, Federico; Brocco, Enrico; Arrigoni, Giorgio; Villano, Gianmarco; Turato, Cristian; Biasiolo, Alessandra; Pontisso, Patrizia; Avogaro, Angelo

2014-09-01

Chronic foot ulceration is a severe complication of diabetes, driving morbidity and mortality. The mechanisms underlying delaying wound healing in diabetes are incompletely understood and tools to identify such pathways are eagerly awaited. Wound biopsies were obtained from 75 patients with diabetic foot ulcers. Matched subgroups of rapidly healing (RH, n = 17) and non-healing (NH, n = 11) patients were selected. Proteomic analysis was performed by labelling with isobaric tag for relative and absolute quantification and mass spectrometry. Differentially expressed proteins were analysed in NH vs RH for identification of pathogenic pathways. Individual sample gene/protein validation and in vivo validation of candidate pathways in mouse models were carried out. Pathway analyses were conducted on 92/286 proteins that were differentially expressed in NH vs RH. The following pathways were enriched in NH vs RH patients: apoptosis, protease inhibitors, epithelial differentiation, serine endopeptidase activity, coagulation and regulation of defence response. SerpinB3 was strongly upregulated in RH vs NH wounds, validated as protein and mRNA in individual samples. To test the relevance of serpinB3 in vivo, we used a transgenic mouse model with α1-antitrypsin promoter-driven overexpression of human SERPINB3. In this model, wound healing was unaffected by SERPINB3 overexpression in non-diabetic or diabetic mice with or without hindlimb ischaemia. In an independent validation cohort of 47 patients, high serpinB3 protein content was confirmed as a biomarker of healing improvement. We provide a benchmark for the unbiased discovery of novel molecular targets and biomarkers of impaired diabetic wound healing. High serpinB3 protein content was found to be a biomarker of successful healing in diabetic patients.

Environmental monitoring of molecular tritium

Energy Technology Data Exchange (ETDEWEB)

Ichimasa, M.; Ichimasa, Y.; Akita, Y. (Ibaraki Univ., Mito (Japan). Faculty of Science); Suzuki, M.; Obayashi, H.; Sakuma, Y.

1992-01-01

The oxidation of atmospheric molecular tritium (HT) in vegetation was determined by in vitro experiments for various kinds of woody and herbaceous plant leaves, mosses and lichens taken from a forest and a garden in Ibaraki prefecture and a forest in Gifu prefecture, and comparison of the HT oxidation activity in vegetation was made with those in its neighboring surface soil (0-5cm in depth). The oxidation of HT in woody plant leaves was extremely low, only about 1/10000-1/1000 that in the surface soil as well as herbaceous plant leaves with some exception, whereas HT oxidation in mosses and lichens was 50-500 times that in pine needles. These results suggest the usefulness of mosses and lichens as monitor vegetation for accidental release of HT into the environment. (author).

The current status of biomarkers for predicting toxicity

Science.gov (United States)

Campion, Sarah; Aubrecht, Jiri; Boekelheide, Kim; Brewster, David W; Vaidya, Vishal S; Anderson, Linnea; Burt, Deborah; Dere, Edward; Hwang, Kathleen; Pacheco, Sara; Saikumar, Janani; Schomaker, Shelli; Sigman, Mark; Goodsaid, Federico

2013-01-01

Introduction There are significant rates of attrition in drug development. A number of compounds fail to progress past preclinical development due to limited tools that accurately monitor toxicity in preclinical studies and in the clinic. Research has focused on improving tools for the detection of organ-specific toxicity through the identification and characterization of biomarkers of toxicity. Areas covered This article reviews what we know about emerging biomarkers in toxicology, with a focus on the 2012 Northeast Society of Toxicology meeting titled ‘Translational Biomarkers in Toxicology.’ The areas covered in this meeting are summarized and include biomarkers of testicular injury and dysfunction, emerging biomarkers of kidney injury and translation of emerging biomarkers from preclinical species to human populations. The authors also provide a discussion about the biomarker qualification process and possible improvements to this process. Expert opinion There is currently a gap between the scientific work in the development and qualification of novel biomarkers for nonclinical drug safety assessment and how these biomarkers are actually used in drug safety assessment. A clear and efficient path to regulatory acceptance is needed so that breakthroughs in the biomarker toolkit for nonclinical drug safety assessment can be utilized to aid in the drug development process. PMID:23961847

Molecular biomarkers of resistance to anti-EGFR treatment in metastatic colorectal cancer, from classical to innovation.

Science.gov (United States)

Giampieri, Riccardo; Scartozzi, Mario; Del Prete, Michela; Maccaroni, Elena; Bittoni, Alessandro; Faloppi, Luca; Bianconi, Maristella; Cecchini, Luca; Cascinu, Stefano

2013-11-01

Systematic dissection of the EGFR pathway was considered as the best way to identify putative markers of resistance to anti-EGFR therapies. This kind of approach leaves other, less known but by no means less important, putative mechanisms of resistance. We tried to shed some light on these mechanisms of resistance. We performed a research through Pubmed database of all published articles highlighting mechanisms of resistance to Cetuximab and Panitumumab based therapies, published in 2000-2012 period. We reviewed the "classical" molecular factors, extensively analyzed as predictive factors for efficacy to anti-EGFR therapy, such as K-ras, B-raf, and PI3K-mTOR-Akt, focusing on their predictive or prognostic value and on the controversial aspects of the biomarker analysis for clinical practice. On the second part we will then move on to other less known molecular markers, for the future understanding of biological mechanisms underlying anti-EGFR therapy resistance, such as non-canonical heterodimer candidates, microRNA, IGF1-IGF1R, HGF-cMET and secondary mutations of EGFR. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Biofluid-based microRNA Biomarkers for Parkinsons Disease: an Overview and Update

Directory of Open Access Journals (Sweden)

Sapana Shinde

2015-02-01

Full Text Available Parkinson's disease (PD is a highly debilitating motor disorder and is the second most common neurodegenerative disease after Alzheimer's disease. Its current method of diagnosis mainly relies on subjective clinical rating scales in the presence of clinical motor features. Early detection of PD is a known challenge as neuronal cell death may range from 50% to 80% when a patient is first diagnosed with PD. Therefore, there is an urgent need to identify and develop biomarkers for early detection of this progressive disease. This mini review focuses on the recent developments of biofluid-based microRNAs (miRNAs as molecular biomarkers for PD. A comprehensive list of miRNA biomarkers found in blood, plasma, serum, and cerebral spinal fluid is presented. Challenges and future perspectives of using these PD-related molecular biomarkers in a “real-world” clinical setting are also discussed.

The use of genotoxicity biomarkers in molecular epidemiology: applications in environmental, occupational and dietary studies

Directory of Open Access Journals (Sweden)

Carina Ladeira

2017-08-01

Full Text Available Molecular epidemiology is an approach increasingly used in the establishment of associations between exposure to hazardous substances and development of disease, including the possible modulation by genetic susceptibility factors. Environmental chemicals and contaminants from anthropogenic pollution of air, water and soil, but also originating specifically in occupational contexts, are potential sources of risk of development of disease. Also, diet presents an important role in this process, with some well characterized associations existing between nutrition and some types of cancer. Genotoxicity biomarkers allow the detection of early effects that result from the interaction between the individual and the environment; they are therefore important tools in cancer epidemiology and are extensively used in human biomonitoring studies. This work intends to give an overview of the potential for genotoxic effects assessment, specifically with the cytokinesis blocked micronucleus assay and comet assay in environmental and occupational scenarios, including diet. The plasticity of these techniques allows their inclusion in human biomonitoring studies, adding important information with the ultimate aim of disease prevention, in particular cancer, and so it is important that they be included as genotoxicity assays in molecular epidemiology.

Biomarkers in the clinical development of asthma therapies.

Science.gov (United States)

Staton, Tracy L; Choy, David F; Arron, Joseph R

2016-01-01

Here we review how biomarkers have been used in the design, execution and interpretation of recent clinical studies of therapeutic candidates targeting cytokine-mediated inflammatory pathways in asthma. This review focuses on type 2 inflammation, as there are multiple therapeutics and/or clinical studies that can be compared within that specific pathway. Comparative analyses of data from these clinical studies illustrate the utility of biomarkers to quantify pharmacodynamic effects, clarify mechanism of action and stratify patients, which may facilitate the interpretation of outcomes in the development of molecularly targeted therapies. These case examples provide a basis for biomarker considerations in the design of future studies in the asthma setting.

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

Directory of Open Access Journals (Sweden)

Cesar Reis

2015-05-01

Full Text Available Traumatic brain injury (TBI, defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI, diffusion tensor imaging (DTI, positron emission tomography (PET, and high definition fiber tracking (HDFT show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI.

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

Science.gov (United States)

Reis, Cesar; Wang, Yuechun; Akyol, Onat; Ho, Wing Mann; Applegate II, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

2015-01-01

Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI. PMID:26016501

Emerging Biomarkers and Metabolomics for Assessing Toxic Nephropathy and Acute Kidney Injury (AKI in Neonatology

Directory of Open Access Journals (Sweden)

M. Mussap

2014-01-01

Full Text Available Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called “omics” allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics and proteome (proteomics, including the emerging epigenomics, to those related to metabolites (metabolomics. In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS, proton nuclear magnetic resonance (1H NMR, and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL and kidney injury molecule-1 (KIM-1 are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods.

Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis

Science.gov (United States)

Musumeci, Giuseppe; Castrogiovanni, Paola; Trovato, Francesca Maria; Weinberg, Annelie Martina; Al-Wasiyah, Mohammad K.; Alqahtani, Mohammed H.; Mobasheri, Ali

2015-01-01

Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that may eliminate the cause or, at least, slow down the degenerative processes in OA. The aim of this review was to explore the molecular markers and signals that induce chondrocyte apoptosis in OA. A literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar using the keywords chondrocyte death, apoptosis, osteoarthritis, autophagy and biomarker. Several molecules considered to be markers of chondrocyte apoptosis will be discussed in this brief review. Molecular markers and signalling pathways associated with chondroycte apoptosis may turn out to be therapeutic targets in OA and approaches aimed at neutralizing apoptosis-inducing molecules may at least delay the progression of cartilage degeneration in OA. PMID:26334269

Seasonal changes in stress biomarkers of an exotic coastal species - Chaetopleura angulata (Polyplacophora) - Implications for biomonitoring.

Science.gov (United States)

Madeira, Diana; Vinagre, Catarina; Mendonça, Vanessa; Diniz, Mário Sousa

2017-07-15

Knowledge on baseline values of stress biomarkers in natural conditions is urgent due to the need of reference values for monitoring purposes. Here we assessed the cellular stress response of the chiton Chaetopleura angulata in situ. Biomarkers commonly used in environmental monitoring (heat shock protein 70kDa, total ubiquitin, catalase, glutathione-S-transferase, superoxide-dismutase, lipid peroxidation) were analyzed in the digestive system, gills and muscle of C. angulata, under spring and summer conditions in order to assess seasonal tissue-specific responses. Season had an effect on all targeted organs, especially affecting the digestive system which displayed clear seasonal clusters. The respective Integrated Biomarker Response (IBR) showed a 7.2-fold seasonal difference. Muscle and gills showed similar IBRs between seasons making them appropriate organs to monitor chemical pollution as they were less responsive to seasonal variation. The most stable biomarkers in these organs were ubiquitin and superoxide-dismutase thus being reliable for monitoring purposes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biomarkers for CNS involvement in pediatric lupus

Science.gov (United States)

Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

2015-01-01

CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

Characterization of a genotoxicity biomarker in three-spined stickleback (Gasterosteus aculeatus L.): Biotic variability and integration in a battery of biomarkers for environmental monitoring.

Science.gov (United States)

Santos, Raphael; Joyeux, Aude; Palluel, Olivier; Palos-Ladeiro, Mélissa; Besnard, Aurélien; Blanchard, Christophe; Porcher, Jean Marc; Bony, Sylvie; Devaux, Alain; Sanchez, Wilfried

2016-04-01

As a large array of hazardous substances exhibiting genotoxicity are discharged into surface water, this work aimed at assessing the relevance of adding a genotoxicity biomarker in a battery of biomarkers recently developed in the model fish three-spined stickleback (Gasterosteus aculeatus). First the confounding influence of gender, body length, and season (used as a proxy of age and of the fish reproductive status, respectively) on the level of primary DNA damage in erythrocytes was investigated in wild sticklebacks. Then, the genotoxity biomarker was included in a large battery of biomarkers assessing xenobiotic biotransformation, oxidative stress and neurotoxicity, and implemented in five sites. Gender, age and reproductive status did not influence DNA damage level in fish from the reference site. A significant relationship between the level of primary DNA damage and fish length (as a proxy of age also correlated to the season) was highlighted in the contaminated site. Among all biomarkers investigated in the field, the level of DNA damage was one of the four most discriminating biomarkers with EROD, catalase activity and the level of lipid peroxidation representing together 75.40% of the discriminating power in sampled fish. The level of DNA damage was correlated to the EROD activity and to the level of peroxidation, which mainly discriminated fish from sites under urban pressure. Finally, Integrated Biomarker Response indexes (IBRv2), which were calculated with the whole biomarker response dataset exhibited higher values in the Reveillon (9.62), the Scarpe and Rhonelle contaminated sites (5.11 and 4.90) compared with the two reference sites (2.38 and 2.55). The present work highlights that integration of a genotoxicity biomarker in a multiparametric approach is relevant to assess ecotoxicological risk in freshwater aquatic organisms. © 2014 Wiley Periodicals, Inc.

Human Biological Monitoring of Diisononyl Phthalate and Diisodecyl Phthalate: A Review

Directory of Open Access Journals (Sweden)

Gurusankar Saravanabhavan

2012-01-01

Full Text Available High molecular-weight phthalates, such as diisononyl phthalate (DINP, and diisodecyl phthalate (DIDP, are widely used as plasticizers in the manufacturing of polymers and consumer products. Human biological monitoring studies have employed the metabolites of DINP and DIDP as biomarkers to assess human exposure. In this review, we summarize and analyze publicly available scientific data on chemistry, metabolism, and excretion kinetics, of DINP and DIDP, to identify specific and sensitive metabolites. Human biological monitoring data on DINP and DIDP are scrutinised to assess the suitability of these metabolites as biomarkers of exposure. Results from studies carried out in animals and humans indicate that phthalates are metabolised rapidly and do not bioaccmulate. During Phase-I metabolism, ester hydrolysis of DINP and DIDP leads to the formation of hydrolytic monoesters. These primary metabolites undergo further oxidation reactions to produce secondary metabolites. Hence, the levels of secondary metabolites of DINP and DIDP in urine are found to be always higher than the primary metabolites. Results from human biological monitoring studies have shown that the secondary metabolites of DINP and DIDP in urine were detected in almost all tested samples, while the primary metabolites were detected in only about 10% of the samples. This indicates that the secondary metabolites are very sensitive biomarkers of DINP/DIDP exposure while primary metabolites are not. The NHANES data indicate that the median concentrations of MCIOP and MCINP (secondary metabolites of DINP and DIDP, resp. at a population level are about 5.1 μg/L and 2.7 μg/L, respectively. Moreover, the available biological monitoring data suggest that infants/children are exposed to higher levels of phthalates than adults.

Biomarkers of nanomaterial exposure and effect: current status

Science.gov (United States)

Iavicoli, Ivo; Leso, Veruscka; Manno, Maurizio; Schulte, Paul A.

2014-03-01

Recent advances in nanotechnology have induced a widespread production and application of nanomaterials. As a consequence, an increasing number of workers are expected to undergo exposure to these xenobiotics, while the possible hazards to their health remain not being completely understood. In this context, biological monitoring may play a key role not only to identify potential hazards from and to evaluate occupational exposure to nanomaterials, but also to detect their early biological effects to better assess and manage risks of exposure in respect of the health of workers. Therefore, the aim of this review is to provide a critical evaluation of potential biomarkers of nanomaterial exposure and effect investigated in human and animal studies. Concerning exposure biomarkers, internal dose of metallic or metal oxide nanoparticle exposure may be assessed measuring the elemental metallic content in blood or urine or other biological materials, whereas specific molecules may be carefully evaluated in target tissues as possible biomarkers of biologically effective dose. Oxidative stress biomarkers, such as 8-hydroxy-deoxy-guanosine, genotoxicity biomarkers, and inflammatory response indicators may also be useful, although not specific, as biomarkers of nanomaterial early adverse health effects. Finally, potential biomarkers from "omic" technologies appear to be quite innovative and greatly relevant, although mechanistic, ethical, and practical issues should all be resolved before their routine application in occupational settings could be implemented. Although all these findings are interesting, they point out the need for further research to identify and possibly validate sensitive and specific biomarkers of exposure and effect, suitable for future use in occupational biomonitoring programs. A valuable contribution may derive from the studies investigating the biological behavior of nanomaterials and the factors influencing their toxicokinetics and reactivity. In

Cellular Models for Environmental Toxicant Biomarker Discovery

National Research Council Canada - National Science Library

Halverson, Kelly M; Lewsis, John A; Jackson, David A; Dennis, William; Brennan, Linda; Krakaner, Teresa

2006-01-01

...) is the development of biomarkers of exposure, effect, and susceptibility. As exposure monitoring using environmental sampling equipment can be impractical and doesn't account for differences in individual responses, new methodologies must be sought...

Molecular imaging of EGFR and CD44v6 for prediction and response monitoring of HSP90 inhibition in an in vivo squamous cell carcinoma model

Energy Technology Data Exchange (ETDEWEB)

Spiegelberg, Diana; Mortensen, Anja C.; Stenerloew, Bo [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Selvaraju, Ram K.; Eriksson, Olof [Uppsala University, Preclinical PET Platform, Uppsala (Sweden); Nestor, Marika [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Uppsala University, Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala (Sweden)

2016-05-15

Heat shock protein 90 (HSP90) is essential for the activation and stabilization of numerous oncogenic client proteins. AT13387 is a novel HSP90 inhibitor promoting degradation of oncogenic proteins upon binding, and may also act as a radiosensitizer. For optimal treatment there is, however, the need for identification of biomarkers for patient stratification and therapeutic response monitoring, and to find suitable targets for combination treatments. The aim of this study was to assess the response of surface antigens commonly expressed in squamous cell carcinoma to AT13387 treatment, and to find suitable biomarkers for molecular imaging and radioimmunotherapy in combination with HSP90 inhibition. Cancer cell proliferation and radioimmunoassays were used to evaluate the effect of AT13387 on target antigen expression in vitro. Inhibitor effects were then assessed in vivo in mice-xenografts. Animals were treated with AT13387 (5 x 50 mg/kg), and were imaged with PET using either {sup 18}F-FDG or {sup 124}I-labelled tracers for EGFR and CD44v6, and this was followed by ex-vivo biodistribution analysis and immunohistochemical staining. AT13387 exposure resulted in high cytotoxicity and possible radiosensitization with IC{sub 50} values below 4 nM. Both in vitro and in vivo AT13387 effectively downregulated HSP90 client proteins. PET imaging with {sup 124}I-cetuximab showed a significant decrease of EGFR in AT13387-treated animals compared with untreated animals. In contrast, the squamous cell carcinoma-associated biomarker CD44v6, visualized with {sup 124}I-AbD19384 as well as {sup 18}F-FDG uptake, were not significantly altered by AT13387 treatment. We conclude that AT13387 downregulates HSP90 client proteins, and that molecular imaging of these proteins may be a suitable approach for assessing treatment response. Furthermore, radioimmunotherapy targeting CD44v6 in combination with AT13387 may potentiate the radioimmunotherapy outcome due to radiosensitizing effects of

Study on IL-2 and CA 15-3 level as combined biomarkers in monitoring chemotherapeutic response among invasive breast cancer patients

Science.gov (United States)

Hameed, Ahmed Muthanna Abdul; Hamid, Auni Fatin Abdul; Shahfiza Noor, Nurul; Appalanaido, Gokula Kumar; Bariyah Sahul Hamid, Shahrul

2017-05-01

In Malaysia, breast cancer is the most frequent type of disease among women. This study was designed to determine the clinical usefulness of carbohydrate antigen (CA 15-3) and interleukin 2 (IL-2) levels as combined biomarkers in monitoring breast cancer patient’s response to chemotherapy. Ethical approval was obtained to recruit patients with histologically confirmed invasive ductal carcinoma (IDC) attending Oncology Clinic at Advanced Medical and Dental Institute. Whole blood was collected from 10 IDC breast cancer patients’ pre and post primary chemotherapy. Plasma was separated from the whole blood to determine the CA 15-3 level and IL-2 level using enzyme-linked immunosorbent assay (ELISA) pre and post-treatment. In addition, the histological findings, tumour stage and other patients’ data were obtained from the medical record. Findings showed that IL-2 had borderline significant changes between pre- and post-chemotherapy (p = 0.074) whereas for CA 15-3, there was insignificant differences of CA 15-3 level between pre and post-chemotherapy (p > 0.05). It was noted that only CA 15-3 level had significant correlation with tumour size. This study demonstrates that IL-2 level requires further investigation in a larger sample size to correlate its potential use as combined biomarker with CA 15-3 in monitoring response to chemotherapy.

Fish scale deformation analysis using scanning electron microscope: New potential biomarker in aquatic environmental monitoring of aluminum and iron contamination

Energy Technology Data Exchange (ETDEWEB)

Hidayati, Dewi; Sulaiman, Norela; Othman, Shuhaimi; Ismail, B. S. [School of Environmental and Natural Resource Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia)

2013-11-27

Fish scale has the potential to be a rapid biomarker due to its structure and high possibility to come into contact with any pollutant in the aquatic environment. The scale structure consists of osteoblastic cells and other bone materials such as collagen where it is possible to form a molecular complex with heavy metals such as aluminum and iron. Hence, aluminum and iron in water could possibly destroy the scale material and marked as a scale deformation that quantitatively could be analyzed by comparing it to the normal scale structure. Water sampling and fish cage experiment were performed between June and July 2011 in Porong river which represented the water body that has high aluminum and iron contamination. The filtered water samples were preserved and extracted using the acid-mixture procedure prior to measurement of the aluminum and iron concentrations using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES), while samples for total suspended solid (TSS) analysis were kept at 4 °C in cool-boxes. The scales were cleaned with sterile water, then dehydrated in 30, 50, 70, and 90% ethanol and dried on filter papers. They were then mounted on an aluminum stub and coated with gold in a sputter coater prior to Scanning Electron Microscope (SEM) observation. According to the SEM analysis, it was found that there were several deformations on the scale samples taken from sites that have high concentrations of aluminum and iron i.e. the increasing number of pits, deformation and decreasing number of spherules and ridges while the control scale exhibited the normal features. However, the site with higher TSS and pH indicated lower aluminum effect. A moderate correlation was found between the number of pits with aluminum (r=0.43) and iron (r=0.41) concentrations. Fish scale deformation using SEM analysis can potentially be a rapid biomarker in aquatic monitoring of aluminum and iron contamination. However, the measurement must be accompanied by pH and

Fish scale deformation analysis using scanning electron microscope: New potential biomarker in aquatic environmental monitoring of aluminum and iron contamination

Science.gov (United States)

Hidayati, Dewi; Sulaiman, Norela; Othman, Shuhaimi; Ismail, B. S.

2013-11-01

Fish scale has the potential to be a rapid biomarker due to its structure and high possibility to come into contact with any pollutant in the aquatic environment. The scale structure consists of osteoblastic cells and other bone materials such as collagen where it is possible to form a molecular complex with heavy metals such as aluminum and iron. Hence, aluminum and iron in water could possibly destroy the scale material and marked as a scale deformation that quantitatively could be analyzed by comparing it to the normal scale structure. Water sampling and fish cage experiment were performed between June and July 2011 in Porong river which represented the water body that has high aluminum and iron contamination. The filtered water samples were preserved and extracted using the acid-mixture procedure prior to measurement of the aluminum and iron concentrations using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES), while samples for total suspended solid (TSS) analysis were kept at 4 °C in cool-boxes. The scales were cleaned with sterile water, then dehydrated in 30, 50, 70, and 90% ethanol and dried on filter papers. They were then mounted on an aluminum stub and coated with gold in a sputter coater prior to Scanning Electron Microscope (SEM) observation. According to the SEM analysis, it was found that there were several deformations on the scale samples taken from sites that have high concentrations of aluminum and iron i.e. the increasing number of pits, deformation and decreasing number of spherules and ridges while the control scale exhibited the normal features. However, the site with higher TSS and pH indicated lower aluminum effect. A moderate correlation was found between the number of pits with aluminum (r=0.43) and iron (r=0.41) concentrations. Fish scale deformation using SEM analysis can potentially be a rapid biomarker in aquatic monitoring of aluminum and iron contamination. However, the measurement must be accompanied by pH and

Proposed biomimetic molecular sensor array for astrobiology applications

Science.gov (United States)

Cullen, D. C.; Grant, W. D.; Piletsky, S.; Sims, M. R.

2001-08-01

A key objective of future astrobiology lander missions, e.g. to Mars and Europa, is the detection of biomarkers - molecules whose presence indicates the existence of either current or extinct life. To address limitations of current analytical methods for biomarker detection, we describe the methodology of a new project for demonstration of a robust molecular-recognition sensor array for astrobiology biomarkers. The sensor array will be realised by assembling components that have been demonstrated individually in previous or current research projects. The major components are (1) robust artificial molecular receptors comprised of molecular imprinted polymer (MIP) recognition systems and (2) a sensor array comprised of both optical and electrochemical sensor elements. These components will be integrated together using ink-jet printing technology coupled with in situ photo-polymerisation of MIPs. For demonstration, four model biomarkers are chosen as targets and represent various classes of potential biomarkers. Objectives of the proposed work include (1) demonstration of practical proof-of-concept, (2) identify areas for further development and (3) provide performance and design data for follow-up projects leading to astrobiology missions.

Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

International Nuclear Information System (INIS)

LaCourse, E. James; Hernandez-Viadel, Mariluz; Jefferies, James R.; Svendsen, Claus; Spurgeon, David J.; Barrett, John; John Morgan, A.; Kille, Peter; Brophy, Peter M.

2009-01-01

The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

Energy Technology Data Exchange (ETDEWEB)

LaCourse, E. James, E-mail: james.la-course@liverpool.ac.u [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Hernandez-Viadel, Mariluz; Jefferies, James R. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Svendsen, Claus; Spurgeon, David J. [Centre for Ecology and Hydrology, Huntingdon PE28 2LS (United Kingdom); Barrett, John [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); John Morgan, A.; Kille, Peter [Biosciences, University of Cardiff, Cardiff CF10 3TL (United Kingdom); Brophy, Peter M. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom)

2009-08-15

The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

Computational and Experimental Approaches to Cancer Biomarker Discovery

DEFF Research Database (Denmark)

Krzystanek, Marcin

of a patient’s response to a particular treatment, thus helping to avoid unnecessary treatment and unwanted side effects in non-responding individuals.Currently biomarker discovery is facilitated by recent advances in high-throughput technologies when association between a given biological phenotype...... and the state or level of a large number of molecular entities is investigated. Such associative analysis could be confounded by several factors, leading to false discoveries. For example, it is assumed that with the exception of the true biomarkers most molecular entities such as gene expression levels show...... random distribution in a given cohort. However, gene expression levels may also be affected by technical bias when the actual measurement technology or sample handling may introduce a systematic error. If the distribution of systematic errors correlates with the biological phenotype then the risk...

Quantitative imaging as cancer biomarker

Science.gov (United States)

Mankoff, David A.

2015-03-01

The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine

Severe bronchial asthma in children: a review of novel biomarkers used as predictors of the disease

Directory of Open Access Journals (Sweden)

Uwaezuoke SN

2018-01-01

Full Text Available Samuel N Uwaezuoke, Adaeze C Ayuk, Joy N Eze Department of Pediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria Abstract: Severe asthma or therapy-resistant asthma in children is a heterogeneous disease that affects all age-groups. Given its heterogeneity, precision in diagnosis and treatment has become imperative, in order to achieve better outcomes. If one is thus able to identify specific patient phenotypes and endotypes using the appropriate biomarkers, it will assist in providing the patient with more personalized and appropriate treatment. However, there appears to be a huge diagnostic gap in severe asthma, as there is no single test yet that accurately determines disease phenotype. In this paper, we review the published literature on some of these biomarkers and their possible role in bridging this diagnostic gap. We also highlight the cellular and molecular mechanisms involved in severe asthma, in order to show the basis for the novel biomarkers. Some markers useful for monitoring therapy and assessing airway remodeling in the disease are also discussed. A review of the literature was conducted with PubMed to gather baseline data on the subject. The literature search extended to articles published within the last 40 years. Although biomarkers specific to different severe asthma phenotypes have been identified, progress in their utility remains slow, because of several disease mechanisms, the variation of biomarkers at different levels of inflammation, changes in relying on one test over time (eg, from sputum eosinophilia to blood eosinophilia, and the degree of invasive tests required to collect biomarkers, which limits their applicability in clinical settings. In conclusion, several biomarkers remain useful in recognizing various asthma phenotypes. However, due to disease heterogeneity, identification and utilization of ideal and defined biomarkers in severe asthma are still inconclusive. The development of novel

Biomarkers in the evolution of multiple sclerosis.

Science.gov (United States)

Berger, Thomas

2017-11-01

Nonimaging biomarkers can be applied in differential diagnosis, evaluation of disease progression and therapy monitoring of multiple sclerosis (MS). Presence of oligoclonal IgG bands in cerebrospinal fluid is a diagnostic element and a negative predictor of MS evolution. AQP4 antibodies are pathogenic and diagnostic for neuromyelitis optica spectrum disorder. Antibodies to myelin oligodendrocyte glycoprotein develop in about 50% of predominantly pediatric patients with acute disseminated encephalomyelitis, but their possible role in pathogenesis is unknown. Currently, there are no individualized biomarkers suitable to track disease progression. Neutralizing antibodies against IFN-β, natalizumab and daclizumab arise with variable frequency and reduce treatment efficacy. The anti-John Cunningham virus antibody index has potential as a biomarker for risk of progressive multifocal leukoencephalopathy.

Emerging biomarkers for cancer immunotherapy in melanoma.

Science.gov (United States)

Axelrod, Margaret L; Johnson, Douglas B; Balko, Justin M

2017-09-14

The treatment and prognosis of metastatic melanoma has changed substantially since the advent of novel immune checkpoint inhibitors (ICI), agents that enhance the anti-tumor immune response. Despite the success of these agents, clinically actionable biomarkers to aid patient and regimen selection are lacking. Herein, we summarize and review the evidence for candidate biomarkers of response to ICIs in melanoma. Many of these candidates can be examined as parts of a known molecular pathway of immune response, while others are clinical in nature. Due to the ability of ICIs to illicit dramatic and durable responses, well-validated biomarkers that can be effectively implemented in the clinic will require strong negative predictive values that do not limit patients with who may benefit from ICI therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Calcium-deficiency assessment and biomarker identification by an integrated urinary metabonomics analysis

Science.gov (United States)

2013-01-01

Background Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. Methods The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. Results Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson

Molecular profiling of advanced breast cancer tumors is beneficial in assisting clinical treatment plans.

Science.gov (United States)

Carter, Philip; Alifrangis, Costi; Cereser, Biancastella; Chandrasinghe, Pramodh; Del Bel Belluz, Lisa; Moderau, Nina; Poyia, Fotini; Schwartzberg, Lee S; Tabassum, Neha; Wen, Jinrui; Krell, Jonathan; Stebbing, Justin

2018-04-03

We used data obtained by Caris Life Sciences, to evaluate the benefits of tailoring treatments for a breast carcinoma cohort by using tumor molecular profiles to inform decisions. Data for 92 breast cancer patients from the commercial Caris Molecular Intelligence database was retrospectively divided into two groups, so that the first always followed treatment recommendations, whereas in the second group all patients received at least one drug after profiling that was predicted to lack benefit. The biomarker and drug associations were based on tests including fluorescent in situ hybridization and DNA sequencing, although immunohistochemistry was the main test used. Patients whose drugs matched those recommended according to their tumor profile had an average overall survival of 667 days, compared to 510 days for patients that did not (P=0.0316). In the matched treatment group, 26% of patients were deceased by the last time of monitoring, whereas this was 41% in the unmatched group (P=0.1257). We therefore confirm the ability of tumor molecular profiling to improve survival of breast cancer patients. Immunohistochemistry biomarkers for the androgen, estrogen and progesterone receptors were found to be prognostic for survival.

Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review.

Science.gov (United States)

Nicolaou, Orthodoxia; Kousios, Andreas; Hadjisavvas, Andreas; Lauwerys, Bernard; Sokratous, Kleitos; Kyriacou, Kyriacos

2017-05-01

Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Fusion peptides from oncogenic chimeric proteins as putative specific biomarkers of cancer.

Science.gov (United States)

Conlon, Kevin P; Basrur, Venkatesha; Rolland, Delphine; Wolfe, Thomas; Nesvizhskii, Alexey I; MacCoss, Michael J; Lim, Megan S; Elenitoba-Johnson, Kojo S J

2013-10-01

Chromosomal translocations encoding chimeric fusion proteins constitute one of the most common mechanisms underlying oncogenic transformation in human cancer. Fusion peptides resulting from such oncogenic chimeric fusions, though unique to specific cancer subtypes, are unexplored as cancer biomarkers. Here we show, using an approach termed fusion peptide multiple reaction monitoring mass spectrometry, the direct identification of different cancer-specific fusion peptides arising from protein chimeras that are generated from the juxtaposition of heterologous genes fused by recurrent chromosomal translocations. Using fusion peptide multiple reaction monitoring mass spectrometry in a clinically relevant scenario, we demonstrate the specific, sensitive, and unambiguous detection of a specific diagnostic fusion peptide in clinical samples of anaplastic large cell lymphoma, but not in a diverse array of benign lymph nodes or other forms of primary malignant lymphomas and cancer-derived cell lines. Our studies highlight the utility of fusion peptides as cancer biomarkers and carry broad implications for the use of protein biomarkers in cancer detection and monitoring.

Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers.

Science.gov (United States)

Skotland, Tore; Ekroos, Kim; Kauhanen, Dimple; Simolin, Helena; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

2017-01-01

Exosomes have recently appeared as a novel source of noninvasive cancer biomarkers, since these nanovesicles contain molecules from cancer cells and can be detected in biofluids. We have here investigated the potential use of lipids in urinary exosomes as prostate cancer biomarkers. A high-throughput mass spectrometry quantitative lipidomic analysis was performed to reveal the lipid composition of urinary exosomes in prostate cancer patients and healthy controls. Control samples were first analysed to characterise the lipidome of urinary exosomes and test the reproducibility of the method. In total, 107 lipid species were quantified in urinary exosomes. Several differences, for example, in cholesterol and phosphatidylcholine, were found between urinary exosomes and exosomes derived from cell lines, thus showing the importance of in vivo studies for biomarker analysis. The 36 most abundant lipid species in urinary exosomes were then quantified in 15 prostate cancer patients and 13 healthy controls. Interestingly, the levels of nine lipids species were found to be significantly different when the two groups were compared. The highest significance was shown for phosphatidylserine (PS) 18:1/18:1 and lactosylceramide (d18:1/16:0), the latter also showed the highest patient-to-control ratio. Furthermore, combinations of these lipid species and PS 18:0-18:2 distinguished the two groups with 93% sensitivity and 100% specificity. Finally, in agreement with the reported dysregulation of sphingolipid metabolism in cancer cells, alteration in specific sphingolipid lipid classes were observed. This study shows for the first time the potential use of exosomal lipid species in urine as prostate cancer biomarkers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomarkers to monitor drug-induced phospholipidosis

International Nuclear Information System (INIS)

Baronas, Elizabeth Tengstrand; Lee, Ju-Whei; Alden, Carl; Hsieh, Frank Y.

2007-01-01

Di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) was identified as a promising phospholipidosis (PL) biomarker in rats treated with either amiodarone, gentamicin, or azithromycin. Sprague-Dawley rats received either amiodarone (150 mg/kg), gentamicin (100 mg/kg) or azithromycin (30 mg/kg) once daily for ten consecutive days. Histopathological examination of tissues by transmission electron microscopy (TEM) indicated different degrees of accumulation of phospholipidosis in liver, lung, mesenteric lymph node, and kidney of drug-treated rats but not controls. Liquid chromatography coupled to mass spectrometry (LC/MS) was used to identify levels of endogenous biochemical profiles in rat urine. Urinary levels of di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) correlated with induction of phospholipidosis for amiodarone, gentamicin and azithromycin. Rats treated with gentamicin also had increased urinary levels of several phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) species

Biomarkers of cancer cachexia.

Science.gov (United States)

Loumaye, Audrey; Thissen, Jean-Paul

2017-12-01

Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Guidelines for Biomarker of Food Intake Reviews (BFIRev)

DEFF Research Database (Denmark)

Praticò, Giulia; Gao, Qian; Scalbert, Augustin

2018-01-01

and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while......Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important...... and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health....

MR Imaging Biomarkers to Monitor Early Response to Hypoxia-Activated Prodrug TH-302 in Pancreatic Cancer Xenografts.

Directory of Open Access Journals (Sweden)

Xiaomeng Zhang

Full Text Available TH-302 is a hypoxia-activated prodrug known to activate selectively under the hypoxic conditions commonly found in solid tumors. It is currently being evaluated in clinical trials, including two trials in Pancreatic Ductal Adenocarcinomas (PDAC. The current study was undertaken to evaluate imaging biomarkers for prediction and response monitoring of TH-302 efficacy in xenograft models of PDAC. Dynamic contrast-enhanced (DCE and diffusion weighted (DW magnetic resonance imaging (MRI were used to monitor acute effects on tumor vasculature and cellularity, respectively. Three human PDAC xenografts with known differential responses to TH-302 were imaged prior to, and at 24 h and 48 hours following a single dose of TH-302 or vehicle to determine if imaging changes presaged changes in tumor volumes. DW-MRI was performed at five b-values to generate apparent diffusion coefficient of water (ADC maps. For DCE-MRI, a standard clinically available contrast reagent, Gd-DTPA, was used to determine blood flow into the tumor region of interest. TH-302 induced a dramatic decrease in the DCE transfer constant (Ktrans within 48 hours after treatment in the sensitive tumors, Hs766t and Mia PaCa-2, whereas TH-302 had no effect on the perfusion behavior of resistant SU.86.86 tumors. Tumor cellularity, estimated from ADC, was significantly increased 24 and 48 hours after treatment in Hs766t, but was not observed in the Mia PaCa-2 and SU.86.86 groups. Notably, growth inhibition of Hs766t was observed immediately (day 3 following initiation of treatment, but was not observed in MiaPaCa-2 tumors until 8 days after initiation of treatment. Based on these preclinical findings, DCE-MRI measures of vascular perfusion dynamics and ADC measures of cell density are suggested as potential TH-302 response biomarkers in clinical trials.

MR Imaging Biomarkers to Monitor Early Response to Hypoxia-Activated Prodrug TH-302 in Pancreatic Cancer Xenografts.

Science.gov (United States)

Zhang, Xiaomeng; Wojtkowiak, Jonathan W; Martinez, Gary V; Cornnell, Heather H; Hart, Charles P; Baker, Amanda F; Gillies, Robert

2016-01-01

TH-302 is a hypoxia-activated prodrug known to activate selectively under the hypoxic conditions commonly found in solid tumors. It is currently being evaluated in clinical trials, including two trials in Pancreatic Ductal Adenocarcinomas (PDAC). The current study was undertaken to evaluate imaging biomarkers for prediction and response monitoring of TH-302 efficacy in xenograft models of PDAC. Dynamic contrast-enhanced (DCE) and diffusion weighted (DW) magnetic resonance imaging (MRI) were used to monitor acute effects on tumor vasculature and cellularity, respectively. Three human PDAC xenografts with known differential responses to TH-302 were imaged prior to, and at 24 h and 48 hours following a single dose of TH-302 or vehicle to determine if imaging changes presaged changes in tumor volumes. DW-MRI was performed at five b-values to generate apparent diffusion coefficient of water (ADC) maps. For DCE-MRI, a standard clinically available contrast reagent, Gd-DTPA, was used to determine blood flow into the tumor region of interest. TH-302 induced a dramatic decrease in the DCE transfer constant (Ktrans) within 48 hours after treatment in the sensitive tumors, Hs766t and Mia PaCa-2, whereas TH-302 had no effect on the perfusion behavior of resistant SU.86.86 tumors. Tumor cellularity, estimated from ADC, was significantly increased 24 and 48 hours after treatment in Hs766t, but was not observed in the Mia PaCa-2 and SU.86.86 groups. Notably, growth inhibition of Hs766t was observed immediately (day 3) following initiation of treatment, but was not observed in MiaPaCa-2 tumors until 8 days after initiation of treatment. Based on these preclinical findings, DCE-MRI measures of vascular perfusion dynamics and ADC measures of cell density are suggested as potential TH-302 response biomarkers in clinical trials.

Use of biomarkers in ALS drug development and clinical trials.

Science.gov (United States)

Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert

2015-05-14

The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Diagnostics

OpenAIRE

Choe, Hyonmin; Deirmengian, Carl A.; Hickok, Noreen J.; Morrison, Tiffany N.; Tuan, Rocky S.

2015-01-01

Orthopaedic infections are complex conditions that require immediate diagnosis and accurate identification of the causative organisms to facilitate appropriate management. Conventional methodologies for diagnosis of these infections sometimes lack accuracy or sufficient rapidity. Current molecular diagnostics are an emerging area of bench-to-bedside research in orthopaedic infections. Examples of promising molecular diagnostics include measurement of a specific biomarker in the synovial fluid...

Incorporating biomarkers in ecological risk assessment of chemical contaminants of soils

Directory of Open Access Journals (Sweden)

A. J. Reinecke

2007-09-01

Full Text Available Soil is an important but complex natural resource which is increasingly used as sink for chemicals. The monitoring of soil quality and the assessment of risks posed by contaminants have become crucial. This study deals with the potential use of biomarkers in the monitoring of soils and the assessment of risk resulting from contamination. Apart from an overview of the existing literature on biomarkers, the results of various of our field experiments in South African soils are discussed. Biomarkers may have potential in the assessment of risk because they can indicate at an early stage that exposure has taken place and that a toxic response has been initiated. It is therefore expected that early biomarkers will play an increasing role as diagnostic tools for determining exposure to chemicals and the resulting effects. They may have predictive value that can assist in the prevention or minimising of risks. The aim of this study was to investigate the possibilities of using our results on biomarker responses of soil dwelling organisms to predict changes at higher organisational levels (which may have ecological implications. Our recent experimental results on the evaluation of various biomarkers in both the laboratory and the field are interpreted and placed in perspective within the broader framework of response biology. The aim was further to contribute to the development and application of biomarkers in regulatory risk assessment schemes of soils. This critical review of our own and recent literature on biomarkers in ecotoxicology leads to the conclusion that biomarkers can, under certain conditions, be useful tools in risk assessment. Clear relationships between contamination loads in soil organisms and certain biomarker responses were determined in woodlice, earthworms and terrestrial snails. Clear correlations were also established in field experiments between biomarker responses and changes at the population level. This indicated that, in

Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.

Science.gov (United States)

Ma, Qiu-Lan; Teng, Edmond; Zuo, Xiaohong; Jones, Mychica; Teter, Bruce; Zhao, Evan Y; Zhu, Cansheng; Bilousova, Tina; Gylys, Karen H; Apostolova, Liana G; LaDu, Mary Jo; Hossain, Mir Ahamed; Frautschy, Sally A; Cole, Gregory M

2018-06-01

Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7-8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4 +/+ /FAD +/- ) relative to E4FAD- (non-carrier; APOE4 +/+ /FAD -/- ) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD. Copyright © 2018. Published by Elsevier Inc.

Biomarkers in adult posthemorrhagic hydrocephalus.

Science.gov (United States)

Hua, Cong; Zhao, Gang

2017-08-01

Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.

Time-dependent efficacy of longitudinal biomarker for clinical endpoint.

Science.gov (United States)

Kolamunnage-Dona, Ruwanthi; Williamson, Paula R

2018-06-01

Joint modelling of longitudinal biomarker and event-time processes has gained its popularity in recent years as they yield more accurate and precise estimates. Considering this modelling framework, a new methodology for evaluating the time-dependent efficacy of a longitudinal biomarker for clinical endpoint is proposed in this article. In particular, the proposed model assesses how well longitudinally repeated measurements of a biomarker over various time periods (0,t) distinguish between individuals who developed the disease by time t and individuals who remain disease-free beyond time t. The receiver operating characteristic curve is used to provide the corresponding efficacy summaries at various t based on the association between longitudinal biomarker trajectory and risk of clinical endpoint prior to each time point. The model also allows detecting the time period over which a biomarker should be monitored for its best discriminatory value. The proposed approach is evaluated through simulation and illustrated on the motivating dataset from a prospective observational study of biomarkers to diagnose the onset of sepsis.

Immunohistochemistry for predictive biomarkers in non-small cell lung cancer.

Science.gov (United States)

Mino-Kenudson, Mari

2017-10-01

In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC.

Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

Science.gov (United States)

Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E; Joshi, Lokesh; Kilcoyne, Michelle

2015-01-01

Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques.

Biomarkers as tracers for life on early earth and Mars

Science.gov (United States)

Simoneit, B. R.; Summons, R. E.; Jahnke, L. L.

1998-01-01

Biomarkers in geological samples are products derived from biochemical (natural product) precursors by reductive and oxidative processes (e.g., cholestanes from cholesterol). Generally, lipids, pigments and biomembranes are preserved best over longer geological times and labile compounds such as amino acids, sugars, etc. are useful biomarkers for recent times. Thus, the detailed characterization of biomarker compositions permits the assessment of the major contributing species of extinct and/or extant life. In the case of the early Earth, work has progressed to elucidate molecular structure and carbon isotropic signals preserved in ancient sedimentary rocks. In addition, the combination of bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems permits the modeling of the nature, behavior and preservation potential of primitive microbial communities. This approach uses combined molecular and isotopic analyses to characterize lipids produced by cultured bacteria (representative of ancient strains) and to test a variety of culture conditions which affect their biosynthesis. On considering Mars, the biomarkers from lipids and biopolymers would be expected to be preserved best if life flourished there during its early history (3.5-4 x 10(9) yr ago). Both oxidized and reduced products would be expected. This is based on the inferred occurrence of hydrothermal activity during that time with the concomitant preservation of biochemically-derived organic matter. Both known biomarkers (i.e., as elucidated for early terrestrial samples and for primitive terrestrial microbiota) and novel, potentially unknown compounds should be characterized.

Urinary microRNAs as potential biomarkers of pesticide exposure

International Nuclear Information System (INIS)

Weldon, Brittany A.; Shubin, Sara Pacheco; Smith, Marissa N.; Workman, Tomomi; Artemenko, Alexander; Griffith, William C.; Thompson, Beti; Faustman, Elaine M.

2016-01-01

MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response. - Highlights: • A novel method to identify microRNA biomarkers in urinary samples is proposed. • Six miRNAs have been identified as associated with occupational farm work and pesticide exposure. • An observed seasonal difference suggests transient

Microvesicles/exosomes as potential novel biomarkers of metabolic diseases

Directory of Open Access Journals (Sweden)

Müller G

2012-08-01

Full Text Available Günter MüllerDepartment of Biology 1, Genetics, Ludwig-Maximilians University Munich, Biocenter, Munich, GermanyAbstract: Biomarkers are of tremendous importance for the prediction, diagnosis, and observation of the therapeutic success of common complex multifactorial metabolic diseases, such as type II diabetes and obesity. However, the predictive power of the traditional biomarkers used (eg, plasma metabolites and cytokines, body parameters is apparently not sufficient for reliable monitoring of stage-dependent pathogenesis starting with the healthy state via its initiation and development to the established disease and further progression to late clinical outcomes. Moreover, the elucidation of putative considerable differences in the underlying pathogenetic pathways (eg, related to cellular/tissue origin, epigenetic and environmental effects within the patient population and, consequently, the differentiation between individual options for disease prevention and therapy – hallmarks of personalized medicine – plays only a minor role in the traditional biomarker concept of metabolic diseases. In contrast, multidimensional and interdependent patterns of genetic, epigenetic, and phenotypic markers presumably will add a novel quality to predictive values, provided they can be followed routinely along the complete individual disease pathway with sufficient precision. These requirements may be fulfilled by small membrane vesicles, which are so-called exosomes and microvesicles (EMVs that are released via two distinct molecular mechanisms from a wide variety of tissue and blood cells into the circulation in response to normal and stress/pathogenic conditions and are equipped with a multitude of transmembrane, soluble and glycosylphosphatidylinositol-anchored proteins, mRNAs, and microRNAs. Based on the currently available data, EMVs seem to reflect the diverse functional and dysfunctional states of the releasing cells and tissues along the

Urinary microRNAs as potential biomarkers of pesticide exposure

Energy Technology Data Exchange (ETDEWEB)

Weldon, Brittany A.; Shubin, Sara Pacheco; Smith, Marissa N.; Workman, Tomomi; Artemenko, Alexander; Griffith, William C. [Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA (United States); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Thompson, Beti [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Faustman, Elaine M., E-mail: faustman@uw.edu [Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA (United States); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States)

2016-12-01

MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response. - Highlights: • A novel method to identify microRNA biomarkers in urinary samples is proposed. • Six miRNAs have been identified as associated with occupational farm work and pesticide exposure. • An observed seasonal difference suggests transient

Monitoring bioremediation of atrazine in soil microcosms using molecular tools

International Nuclear Information System (INIS)

Sagarkar, Sneha; Mukherjee, Shinjini; Nousiainen, Aura; Björklöf, Katarina; Purohit, Hemant J.; Jørgensen, Kirsten S.; Kapley, Atya

2013-01-01

Molecular tools in microbial community analysis give access to information on catabolic potential and diversity of microbes. Applied in bioremediation, they could provide a new dimension to improve pollution control. This concept has been demonstrated in the study using atrazine as model pollutant. Bioremediation of the herbicide, atrazine, was analyzed in microcosm studies by bioaugmentation, biostimulation and natural attenuation. Genes from the atrazine degrading pathway atzA/B/C/D/E/F, trzN, and trzD were monitored during the course of treatment and results demonstrated variation in atzC, trzD and trzN genes with time. Change in copy number of trzN gene under different treatment processes was demonstrated by real-time PCR. The amplified trzN gene was cloned and sequence data showed homology to genes reported in Arthrobacter and Nocardioides. Results demonstrate that specific target genes can be monitored, quantified and correlated to degradation analysis which would help in predicting the outcome of any bioremediation strategy. - Highlights: ► Degradation of herbicide, atrazine. ► Comparison of bioremediation via bioaugmentation, biostimulation and natural attenuation. ► Gene profile analysis in all treatments. ► Variation in trzN gene numbers correlated to degradation efficiency. ► Cloning and sequence analysis of trzN gene demonstrates very high homology to reported gene. - This study demonstrates the use of molecular tools in bioremediation to monitor and track target genes; correlates the results with degradation and thereby predicts the efficiency of treatment.

Glucosylsphingosine is a highly sensitive and specific biomarker for primary diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian cohort of Gaucher disease patients.

Directory of Open Access Journals (Sweden)

Arndt Rolfs

Full Text Available Gaucher disease (GD is the most common lysosomal storage disorder (LSD. Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs.Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD.

Risk Factors and Biomarkers of Age-Related Macular Degeneration

Science.gov (United States)

Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

2016-01-01

A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

Pulmonary biomarkers in chronic obstructive pulmonary disease

NARCIS (Netherlands)

Barnes, Peter J.; Chowdhury, Badrul; Kharitonov, Sergei A.; Magnussen, Helgo; Page, Clive P.; Postma, Dirkje; Saetta, Marina

2006-01-01

There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current

Urinary 1-Hydroxypyrene as a Biomarker to Carcinogenic Polycyclic Aromatic Hydrocarbon Exposure

OpenAIRE

Clinton Ifegwu; Kayode Osunjaye; Folasade Fashogbon; Kolawole Oke; Afolabi Adeniyi; Chimezie Anyakora

2012-01-01

In order to capture the extent of exposure to polycyclic aromatic hydrocarbons (PAHs), various biomarkers have been employed. The biomarkers employed for PAHs include PAHs genetoxic end points in lymphocytes, urinary metabolites, PAH-DNA adducts, and PAH-Protein adducts. Of these, excretory 1-hydroxypyene, a metabolite of pyrene, has been used extensively as a biological monitoring indicator of exposure to PAHs. This study attempts to assess the level of this biomarker in the body fluid of 68...

Cerebrospinal fluid biomarkers for Parkinson's disease

DEFF Research Database (Denmark)

Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon

2017-01-01

Diagnosticering af Parkinson's sygdom (PD) er baseret på den kliniske udvikling af sygdommen samt en fysisk undersøgelse af patienten, men fejldiagnosticering sker hyppigt; specielt i tidlige stadier. Biomarkører for PD kan muliggøre en tidligere og mere præcis diagnosticering samt monitorering a...

Optimised Selection of Stroke Biomarker Based on Svm and Information Theory

Directory of Open Access Journals (Sweden)

Wang Xiang

2017-01-01

Full Text Available With the development of molecular biology and gene-engineering technology, gene diagnosis has been an emerging approach for modern life sciences. Biological marker, recognized as the hot topic in the molecular and gene fields, has important values in early diagnosis, malignant tumor stage, treatment and therapeutic efficacy evaluation. So far, the researcher has not found any effective way to predict and distinguish different type of stroke. In this paper, we aim to optimize stroke biomarker and figure out effective stroke detection index based on SVM (support vector machine and information theory. Through mutual information analysis and principal component analysis to complete the selection of biomarkers and then we use SVM to verify our model. According to the testing data of patients provided by Xuanwu Hospital, we explore the significant markers of the stroke through data analysis. Our model can predict stroke well. Then discuss the effects of each biomarker on the incidence of stroke.

Prognostic and predictive potential molecular biomarkers in colon cancer.

Science.gov (United States)

Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

2011-01-01

An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

The Knowledge-Integrated Network Biomarkers Discovery for Major Adverse Cardiac Events

Science.gov (United States)

Jin, Guangxu; Zhou, Xiaobo; Wang, Honghui; Zhao, Hong; Cui, Kemi; Zhang, Xiang-Sun; Chen, Luonan; Hazen, Stanley L.; Li, King; Wong, Stephen T. C.

2010-01-01

The mass spectrometry (MS) technology in clinical proteomics is very promising for discovery of new biomarkers for diseases management. To overcome the obstacles of data noises in MS analysis, we proposed a new approach of knowledge-integrated biomarker discovery using data from Major Adverse Cardiac Events (MACE) patients. We first built up a cardiovascular-related network based on protein information coming from protein annotations in Uniprot, protein–protein interaction (PPI), and signal transduction database. Distinct from the previous machine learning methods in MS data processing, we then used statistical methods to discover biomarkers in cardiovascular-related network. Through the tradeoff between known protein information and data noises in mass spectrometry data, we finally could firmly identify those high-confident biomarkers. Most importantly, aided by protein–protein interaction network, that is, cardiovascular-related network, we proposed a new type of biomarkers, that is, network biomarkers, composed of a set of proteins and the interactions among them. The candidate network biomarkers can classify the two groups of patients more accurately than current single ones without consideration of biological molecular interaction. PMID:18665624

First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

Science.gov (United States)

Van Keer, Severien; Pattyn, Jade; Tjalma, Wiebren A A; Van Ostade, Xaveer; Ieven, Margareta; Van Damme, Pierre; Vorsters, Alex

2017-09-01

Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the

Promising molecular targets and biomarkers for male BPH and LUTS.

Science.gov (United States)

Gharaee-Kermani, Mehrnaz; Macoska, Jill A

2013-12-01

Benign prostatic hyperplasia (BPH) is a major health concern for aging men. BPH is associated with urinary voiding dysfunction and lower urinary tract symptoms (LUTS), which negatively affects quality of life. Surgical resection and medical approaches have proven effective for improving urinary flow and relieving LUTS but are not effective for all men and can produce adverse effects that require termination of the therapeutic regimen. Thus, there is a need to explore other therapeutic targets to treat BPH/LUTS. Complicating the treatment of BPH/LUTS is the lack of biomarkers to effectively identify pathobiologies contributing to BPH/LUTS or to gauge successful response to therapy. This review will briefly discuss current knowledge and will highlight new studies that illuminate the pathobiologies contributing to BPH/LUTS, potential new therapeutic strategies for successfully treating BPH/LUTS, and new approaches for better defining these pathobiologies and response to therapeutics through the development of biomarkers and phenotyping strategies.

MiRNAs of peripheral blood as the biomarker of schizophrenia.

Science.gov (United States)

He, Kuanjun; Guo, Chuang; He, Lin; Shi, Yongyong

2018-01-01

The diagnosis of schizophrenia is currently based on the symptoms and bodily signs rather than on the pathological and physiological markers of the patient. In the search for new molecular targeted therapy medicines, and recurrence of early-warning indicators have become the major focus of contemporary research, because they improve diagnostic accuracy. Biomarkers reflect the physiological, physical and biochemical status of the body, and so have extensive applicability and practical significance. The ascertainment of schizophrenia biomarkers will help diagnose, stratify of disease, and treat of schizophrenia patients. The detection of biomarkers from blood has become a promising area of schizophrenia research. Recently, a series of studies revealed that, MiRNAs play an important role in the genesis of schizophrenia, and their abnormal expressions have the potential to be used as biomarkers of schizophrenia. This article presents and summarizes the value of peripheral blood miRNAs with abnormal expression as the biomarker of schizophrenia.

(68)Ga-DOTA-peptide: A novel molecular biomarker for nasopharyngeal carcinoma.

Science.gov (United States)

Khor, Lih Kin; Loi, Hoi Yin; Sinha, Arvind Kumar; Tong, Kian Ti; Goh, Boon Cher; Loh, Kwok Seng; Lu, Suat-Jin

2016-04-01

-grade uptake of FDG lower than mediastinal blood pool activity were deemed to be reactive/inflammatory and showed low-grade uptake of DOTA-NOC. This study highlights the potential of (68) Ga-DOTA-peptide PET/CT as a new molecular biomarker for newly diagnosed undifferentiated NPC, and less so for recurrent NPC and metastatic nodes. This potentially opens up new diagnostic and therapeutic options in the management of undifferentiated NPC. © 2015 Wiley Periodicals, Inc.

CEP biomarkers as potential tools for monitoring therapeutics.

Directory of Open Access Journals (Sweden)

Kutralanathan Renganathan

Full Text Available Carboxyethylpyrrole (CEP adducts are oxidative modifications derived from docosahexaenoate-containing lipids that are elevated in ocular tissues and plasma in age-related macular degeneration (AMD and in rodents exposed to intense light. The goal of this study was to determine whether light-induced CEP adducts and autoantibodies are modulated by pretreatment with AL-8309A under conditions that prevent photo-oxidative damage of rat retina. AL-8309A is a serotonin 5-HT1A receptor agonist.Albino rats were dark adapted prior to blue light exposure. Control rats were maintained in normal cyclic light. Rats were injected subcutaneously 3x with 10 mg/kg AL-8309A (2 days, 1 day and 0 hours before light exposure for 6 h (3.1 mW/cm(2, λ=450 nm. Animals were sacrificed immediately following light exposure and eyes, retinas and plasma were collected. CEP adducts and autoantibodies were quantified by Western analysis or ELISA.ANOVA supported significant differences in mean amounts of CEP adducts and autoantibodies among the light + vehicle, light + drug and dark control groups from both retina and plasma. Light-induced CEP adducts in retina were reduced ~20% following pretreatment with AL-8309A (n = 62 rats, p = 0.006 and retinal CEP immunoreactivity was less intense by immunohistochemistry. Plasma levels of light-induced CEP adducts were reduced at least 30% (n = 15 rats, p = 0.004 by drug pretreatment. Following drug treatment, average CEP autoantibody titer in light exposed rats (n = 22 was unchanged from dark control levels, and ~20% (p = 0.046 lower than in vehicle-treated rats.Light-induced CEP adducts in rat retina and plasma were significantly decreased by pretreatment with AL-8309A. These results are consistent with and extend previous studies showing AL-8309A reduces light-induced retinal lesions in rats and support CEP biomarkers as possible tools for monitoring the efficacy of select therapeutics.

Validated biomarkers: The key to precision treatment in patients with breast cancer.

Science.gov (United States)

Duffy, Michael J; O'Donovan, Norma; McDermott, Enda; Crown, John

2016-10-01

Recent DNA sequencing and gene expression studies have shown that at a molecular level, almost every case of breast cancer is unique and different from other breast cancers. For optimum management therefore, every patient should receive treatment that is guided by the molecular composition of their tumor, i.e., precision treatment. While such a scenario is still some distance into the future, biomarkers are beginning to play an important role in preparing the way for precision treatment. In particular, biomarkers are increasingly being used for predicting patient outcome and informing as to the most appropriate type of systemic therapy to be administered. Mandatory biomarkers for every newly diagnosed case of breast cancer are estrogen receptors and progesterone receptors in selecting patients for endocrine treatment and HER2 for identifying patients likely to benefit from anti-HER2 therapy. Amongst the best validated prognostic biomarker tests are uPA/PAI-1, MammaPrint and Oncotype DX. Although currently, there are no biomarkers available for predicting response to specific forms of chemotherapy, uPA/PAI-1 and Oncotype DX can aid the identification of lymph node-negative patients that are most likely to benefit from adjuvant chemotherapy, in general. In order to accelerate progress towards precision treatment for women with breast cancer, we need additional predictive biomarkers, especially for enhancing the positive predictive value for endocrine and anti-HER2 therapies, as well as biomarkers for predicting response to specific forms of chemotherapy. The ultimate biomarker test for achieving the goal of precision treatment for patients with breast cancer will likely require a combination of gene sequencing and transcriptomic analysis of every patient's tumor. Copyright © 2016 Elsevier Ltd. All rights reserved.

One-year monitoring of core biomarker and digestive enzyme responses in transplanted zebra mussels (Dreissena polymorpha).

Science.gov (United States)

Palais, F; Dedourge-Geffard, O; Beaudon, A; Pain-Devin, S; Trapp, J; Geffard, O; Noury, P; Gourlay-Francé, C; Uher, E; Mouneyrac, C; Biagianti-Risbourg, S; Geffard, A

2012-04-01

A 12-month active biomonitoring study was performed in 2008-2009 on the Vesle river basin (Champagne-Ardenne, France) using the freshwater mussel Dreissena polymorpha as a sentinel species; allochthonous mussels originating from a reference site (Commercy) were exposed at four sites (Bouy, Sept-Saulx, Fismes, Ardre) within the Vesle river basin. Selected core biomarkers (acetylcholinesterase (AChE) activity, glutathione-S transferase (GST) activity, metallothionein concentration), along with digestive enzyme activities (amylase, endocellulase) and energy reserve concentrations (glycogen, lipids), were monitored throughout the study in exposed mussels. At the Fismes and Ardre sites (downstream basin), metallic and organic contamination levels were low but still high enough to elicit AChE and GST activity induction in exposed mussels (chemical stress); besides, chemical pollutants had no apparent deleterious effects on mussel condition. At the Bouy and Sept-Saulx sites (upstream basin), mussels obviously suffered from adverse food conditions which seriously impaired individual physiological state and survival (nutritional stress); food scarcity had however no apparent effects on core biomarker responses. Digestive enzyme activities responded to both chemical and nutritional stresses, the increase in energy outputs (general adaptation syndrome-downstream sites) or the decrease in energy inputs (food scarcity-upstream sites) leading to mid- or long-term induction of digestive carbohydrase activities in exposed mussels (energy optimizing strategy). Complex regulation patterns of these activities require nevertheless the use of a multi-marker approach to allow data interpretation. Besides, their sensitivity to natural confounding environmental factors remains to be precised.

The rational development of molecularly imprinted polymer-based sensors for protein detection.

Science.gov (United States)

Whitcombe, Michael J; Chianella, Iva; Larcombe, Lee; Piletsky, Sergey A; Noble, James; Porter, Robert; Horgan, Adrian

2011-03-01

The detection of specific proteins as biomarkers of disease, health status, environmental monitoring, food quality, control of fermenters and civil defence purposes means that biosensors for these targets will become increasingly more important. Among the technologies used for building specific recognition properties, molecularly imprinted polymers (MIPs) are attracting much attention. In this critical review we describe many methods used for imprinting recognition for protein targets in polymers and their incorporation with a number of transducer platforms with the aim of identifying the most promising approaches for the preparation of MIP-based protein sensors (277 references).

Guidelines for Biomarker of Food Intake Reviews (BFIRev: how to conduct an extensive literature search for biomarker of food intake discovery

Directory of Open Access Journals (Sweden)

Giulia Praticò

2018-02-01

Full Text Available Abstract Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs. However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

Guidelines for Biomarker of Food Intake Reviews (BFIRev): how to conduct an extensive literature search for biomarker of food intake discovery.

Science.gov (United States)

Praticò, Giulia; Gao, Qian; Scalbert, Augustin; Vergères, Guy; Kolehmainen, Marjukka; Manach, Claudine; Brennan, Lorraine; Pedapati, Sri Harsha; Afman, Lydia A; Wishart, David S; Vázquez-Fresno, Rosa; Lacueva, Cristina Andres; Garcia-Aloy, Mar; Verhagen, Hans; Feskens, Edith J M; Dragsted, Lars O

2018-01-01

Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs). However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

Potential Immune Biomarkers in Diagnosis and Clinical Management for Systemic Lupus Erythematosus

Directory of Open Access Journals (Sweden)

Zecevic Lamija

2018-04-01

Full Text Available Background: There is still no reliable, specific biomarker for precision diagnosis and clinical monitoring of systemic lupus erythematosus. The aim of this study was to investigate the importance of the determination of immunofenotypic profiles (T, B lymphocytes and NK cells and serum cytokine concentrations (IL-17 and IFN-alpha as potential biomarkers for this disease.

Imaging biomarkers in primary brain tumours

Energy Technology Data Exchange (ETDEWEB)

Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

2015-04-01

We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

[What will happen to molecular cell biomarkers of aging in case we cancel its program (of course, if it does exist)?].

Science.gov (United States)

Khokhlov, A N

2013-01-01

Currently, gerontologists, evaluating the effectiveness of various impacts on the aging process, as a rule, use a variety of molecular cell biomarkers of aging. This provides much more rapid results than in the case of the survival curve obtaining. However, in many cases the usefulness of these biomarkers of aging is grounded in works devoted to what is called cellular/cell senescence. Unfortunately, the evolution of the term in recent years has led to the loss, to a large extent, of its original meaning, that is the changes of the cells during their replicative senescence ("on Hayflick's grounds"), similar to the changes of cells in the aging organism. At present, most of the work in this area is related to the induction of the relevant changes in the cells (usually transformed) by various DNA damaging factors. Such an approach, although is very important to define a strategy to fight cancer, but, yet again, takes us away from the study of the real mechanisms of organismal aging. In addition, there are reasons to believe that the biomarkers of aging, proposed by these studies (and in particular, the most popular of them--the activity of senescence-associated beta-galactosidase), are related, as a rule, to the proliferative status of the cells, which in the whole body is generally determined by proper implementing the program of development and differentiation, leading to the emergence of tissues and organs composed of postmitotic or very slowly proliferating cells. Therefore, the possible disabling the aging program, apparently, will not lead to any changes in the age dynamics of those biomarkers of aging. This conclusion brings us back to the need for obtaining the survival curves of experimental animals or humans as the only true (although the most time- and money-consuming) approach to evaluating the effectiveness of the modification of the aging process.

Heterogeneity as Biomarker in Tumour Imaging (abstract only)

NARCIS (Netherlands)

Alić, L.; Veenland, J.F.

2013-01-01

PURPOSE: Tumour heterogeneity could be a valuable biomarker for differentiation, grading, response monitoring and outcome prediction. Many quantification techniques have been described, however in clinical practice these methods are scarcely used. The aim of this study is to evaluate the performance

BIOMarkers for occupational diesel exhaust exposure monitoring (BIOMODEM) - a study in underground mining

DEFF Research Database (Denmark)

Scheepers, P.T.J.; Coggon, D.; Knudsen, Lisbeth E.

2002-01-01

Methods for the assessment of exposures to diesel exhaust were evaluated, including various biomarkers of internal exposure and early biological effects. The impact of possible biomarkers of susceptibility was also explored. Underground workers (drivers of diesel-powered excavators) at an oil sha...... bulky DNA adducts determined by 32P-postlabelling, or in DNA damage. The study indicated that smoking, diet and residential indoor air pollution are important non-occupational factors to consider when interpreting biomonitoring results....

Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

Science.gov (United States)

Htun, Nay Min; Peter, Karlheinz

2014-10-01

Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity?

Science.gov (United States)

Mohan, Chandra; Assassi, Shervin

2015-11-26

Serological and proteomic biomarkers can help clinicians diagnose rheumatic diseases earlier and assess disease activity more accurately. These markers have been incorporated into the recently revised classification criteria of several diseases to enable early diagnosis and timely initiation of treatment. Furthermore, they also facilitate more accurate subclassification and more focused monitoring for the detection of certain disease manifestations, such as lung and renal involvement. These biomarkers can also make the assessment of disease activity and treatment response more reliable. Simultaneously, several new serological and proteomic biomarkers have become available in the routine clinical setting--for example, a protein biomarker panel for rheumatoid arthritis and a myositis antibody panel for dermatomyositis and polymyositis. This review will focus on commercially available antibody and proteomic biomarkers in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis and polymyositis, and axial spondyloarthritis (including ankylosing spondylitis). It will discuss how these markers can facilitate early diagnosis as well as more accurate subclassification and assessment of disease activity in the clinical setting. The ultimate goal of current and future biomarkers in rheumatic diseases is to enable early detection of these diseases and their clinical manifestations, and to provide effective monitoring and treatment regimens that are tailored to each patient's needs and prognosis. © BMJ Publishing Group Ltd 2015.

Metabolomics for Biomarker Discovery: Moving to the Clinic

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun

2015-01-01

To improve the clinical course of diseases, more accurate diagnostic and assessment methods are required as early as possible. In order to achieve this, metabolomics offers new opportunities for biomarker discovery in complex diseases and may provide pathological understanding of diseases beyond traditional technologies. It is the systematic analysis of low-molecular-weight metabolites in biological samples and has become an important tool in clinical research and the diagnosis of human disease and has been applied to discovery and identification of the perturbed pathways. It provides a powerful approach to discover biomarkers in biological systems and offers a holistic approach with the promise to clinically enhance diagnostics. When carried out properly, it could provide insight into the understanding of the underlying mechanisms of diseases, help to identify patients at risk of disease, and predict the response to specific treatments. Currently, metabolomics has become an important tool in clinical research and the diagnosis of human disease and becomes a hot topic. This review will highlight the importance and benefit of metabolomics for identifying biomarkers that accurately screen potential biomarkers of diseases. PMID:26090402

Crevicular fluid biomarkers and periodontal disease progression.

Science.gov (United States)

Kinney, Janet S; Morelli, Thiago; Oh, Min; Braun, Thomas M; Ramseier, Christoph A; Sugai, Jim V; Giannobile, William V

2014-02-01

Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Student award for outstanding research winner in the Ph.D. category for the 2017 society for biomaterials annual meeting and exposition, april 5-8, 2017, Minneapolis, Minnesota: Characterization of protein interactions with molecularly imprinted hydrogels that possess engineered affinity for high isoelectric point biomarkers.

Science.gov (United States)

Clegg, John R; Zhong, Justin X; Irani, Afshan S; Gu, Joann; Spencer, David S; Peppas, Nicholas A

2017-06-01

Molecularly imprinted polymers (MIPs) with selective affinity for protein biomarkers could find extensive utility as environmentally robust, cost-efficient biomaterials for diagnostic and therapeutic applications. In order to develop recognitive, synthetic biomaterials for prohibitively expensive protein biomarkers, we have developed a molecular imprinting technique that utilizes structurally similar, analogue proteins. Hydrogel microparticles synthesized by molecular imprinting with trypsin, lysozyme, and cytochrome c possessed an increased affinity for alternate high isoelectric point biomarkers both in isolation and plasma-mimicking adsorption conditions. Imprinted and non-imprinted P(MAA-co-AAm-co-DEAEMA) microgels containing PMAO-PEGMA functionalized polycaprolactone nanoparticles were net-anionic, polydisperse, and irregularly shaped. MIPs and control non-imprinted polymers (NIPs) exhibited regions of Freundlich and BET isotherm adsorption behavior in a range of non-competitive protein solutions, where MIPs exhibited enhanced adsorption capacity in the Freundlich isotherm regions. In a competitive condition, imprinting with analogue templates (trypsin, lysozyme) increased the adsorption capacity of microgels for cytochrome c by 162% and 219%, respectively, as compared to a 122% increase provided by traditional bulk imprinting with cytochrome c. Our results suggest that molecular imprinting with analogue protein templates is a viable synthetic strategy for enhancing hydrogel-biomarker affinity and promoting specific protein adsorption behavior in biological fluids. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1565-1574, 2017. © 2017 Wiley Periodicals, Inc.

Placenta-derived exosomes: potential biomarkers of preeclampsia.

Science.gov (United States)

Pillay, Preenan; Moodley, Kogi; Moodley, Jagidesa; Mackraj, Irene

2017-01-01

Preeclampsia remains a leading cause of maternal and fetal mortality, due to ineffective treatment and diagnostic strategies, compounded by the lack of clarity on the etiology of the disorder. Although several clinical and biological markers of preeclampsia have been evaluated, they have proven to be ineffective in providing a definitive diagnosis during the various stages of the disorder. Exosomes have emerged as ideal biomarkers of pathological states, such as cancer, and have more recently gained interest in pregnancy-related complications, due to their role in cellular communication in normal and complicated pregnancies. This occurs as a result of the specific placenta-derived exosomal molecular cargo, which may be involved in normal pregnancy-associated immunological events, such as the maintenance of maternal-fetal tolerance. This review provides perspectives on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis of preeclampsia. Using keywords, online databases were searched to identify relevant publications to review the potential use of placenta-derived exosomes as biomarkers of preeclampsia.

The use of biomarkers in occupational health research, practice, and policy.

Science.gov (United States)

Schulte, P A; Hauser, J E

2012-08-13

Biomarkers are potentially useful tools for occupational health and safety research, practice, and policy. However, the full realization of this potential has not been achieved. In this paper, the progress made in these three usage areas is reviewed to identify what efforts can be taken to realize the full promise of biomarkers. Biomarker uses are described by a diverse taxonomy that builds on the categories of exposure, effect and susceptibility, and the continuum between exposure and disease prognosis. The most significant uses of biomarkers in occupational health have been in biological monitoring of workers. Other important uses have been in enhancing research and assessing mechanisms of action of occupational toxicants at low exposures. Seven critical areas will influence the extent to which the potential of biomarkers in occupational health and safety is realized. These include: (1) adequate investment in validation; (2) obtaining international agreement on exposure guidelines; (3) exploring the utility of biomarkers in regulation; (4) applying biomarkers to critical occupational safety and health questions; (5) developing the exposome; (6) utilizing biomarkers to address emerging occupational health issues; and (7) continuing to address the ethical and social justice issues related to biomarkers. Overall, if biomarkers are to make a major contribution to occupational health and safety then a more holistic approach to bringing them from the laboratory to practice will be needed. Published by Elsevier Ireland Ltd.

Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

Science.gov (United States)

Chauhan, Ranjit; Lahiri, Nivedita

2016-01-01

Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Ranjit Chauhan

2016-01-01

Full Text Available Hepatocellular carcinoma (HCC, one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

Effects of dietary restriction on adipose mass and biomarkers of healthy aging in human.

Science.gov (United States)

Lettieri-Barbato, Daniele; Giovannetti, Esmeralda; Aquilano, Katia

2016-11-29

In developing countries the rise of obesity and obesity-related metabolic disorders, such as cardiovascular diseases and type 2 diabetes, reflects the changes in lifestyle habits and wrong dietary choices. Dietary restriction (DR) regimens have been shown to extend health span and lifespan in many animal models including primates. Identifying biomarkers predictive of clinical benefits of treatment is one of the primary goals of precision medicine. To monitor the clinical outcomes of DR interventions in humans, several biomarkers are commonly adopted. However, a validated link between the behaviors of such biomarkers and DR effects is lacking at present time. Through a systematic analysis of human intervention studies, we evaluated the effect size of DR (i.e. calorie restriction, very low calorie diet, intermittent fasting, alternate day fasting) on health-related biomarkers. We found that DR is effective in reducing total and visceral adipose mass and improving inflammatory cytokines profile and adiponectin/leptin ratio. By analysing the levels of canonical biomarkers of healthy aging, we also validated the changes of insulin, IGF-1 and IGFBP-1,2 to monitor DR effects. Collectively, we developed a useful platform to evaluate the human responses to dietary regimens low in calories.

Evaluation of high density lipoprotein as a circulating biomarker of Gaucher disease activity

Science.gov (United States)

Stein, Philip; Yang, Ruhua; Liu, Jun; Pastores, Gregory M.; Mistry, Pramod K.

2011-01-01

Circulating biomarkers are important surrogates for monitoring disease activity in type I Gaucher disease (GD1). We and others have reported low high-density lipoprotein (HDL) in GD1. We assessed HDL cholesterol as a biomarker of GD1, with respect to its correlation with indicators of disease severity and its response to imiglucerase enzyme replacement therapy (ERT). In 278 consecutively evaluated GD1 patients, we correlated HDL cholesterol, chitotriosidase, and angiotensin-converting enzyme (ACE) with indicators of disease severity. Additionally, we measured the response of these biomarkers to ERT. HDL cholesterol was negatively correlated with spleen volume, liver volume, and GD severity score index; the magnitude of this association of disease severity with HDL cholesterol was similar to that for ACE and for chitotriosidase. Within individual patients monitored over many years, there was a strikingly strong correlation of HDL with liver and spleen volumes; there was a similarly strong correlation of chitotriosidase and ACE with disease severity in individual patients monitored serially over many years (chitotriosidase r=0.96 to 0.98, ACE r =0.88 to 0.94, and HDL r=−0.84 to −0.94, p<0.001). ERT for 3 years resulted in a striking increase of HDL while serum levels of chitotriosidase and ACE decreased. Our results reveal markedly low HDL cholesterol in untreated GD1, a correlation with indicators of disease severity in GD1, and a rise towards normal after ERT. These findings suggest HDL cholesterol merits inclusion within the “biomarker basket” for monitoring of patients with GD1. PMID:21290183

Association between regular molecular monitoring and tyrosine kinase inhibitor therapy adherence in chronic myelogenous leukemia in the chronic phase.

Science.gov (United States)

Guérin, Annie; Chen, Lei; Dea, Katherine; Wu, Eric Q; Goldberg, Stuart L

2014-07-01

Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence. This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring. Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1-2 tests, and 27.1% had 3-4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3-4 qPCR tests cohort had an average MPR that was 10.22 (p sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence. These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence. Frequent molecular monitoring (3-4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.

MRM screening/biomarker discovery with linear ion trap MS: a library of human cancer-specific peptides

International Nuclear Information System (INIS)

Yang, Xu; Lazar, Iulia M

2009-01-01

The discovery of novel protein biomarkers is essential in the clinical setting to enable early disease diagnosis and increase survivability rates. To facilitate differential expression analysis and biomarker discovery, a variety of tandem mass spectrometry (MS/MS)-based protein profiling techniques have been developed. For achieving sensitive detection and accurate quantitation, targeted MS screening approaches, such as multiple reaction monitoring (MRM), have been implemented. MCF-7 breast cancer protein cellular extracts were analyzed by 2D-strong cation exchange (SCX)/reversed phase liquid chromatography (RPLC) separations interfaced to linear ion trap MS detection. MS data were interpreted with the Sequest-based Bioworks software (Thermo Electron). In-house developed Perl-scripts were used to calculate the spectral counts and the representative fragment ions for each peptide. In this work, we report on the generation of a library of 9,677 peptides (p < 0.001), representing ~1,572 proteins from human breast cancer cells, that can be used for MRM/MS-based biomarker screening studies. For each protein, the library provides the number and sequence of detectable peptides, the charge state, the spectral count, the molecular weight, the parameters that characterize the quality of the tandem mass spectrum (p-value, DeltaM, Xcorr, DeltaCn, Sp, no. of matching a, b, y ions in the spectrum), the retention time, and the top 10 most intense product ions that correspond to a given peptide. Only proteins identified by at least two spectral counts are listed. The experimental distribution of protein frequencies, as a function of molecular weight, closely matched the theoretical distribution of proteins in the human proteome, as provided in the SwissProt database. The amino acid sequence coverage of the identified proteins ranged from 0.04% to 98.3%. The highest-abundance proteins in the cellular extract had a molecular weight (MW)<50,000. Preliminary experiments have

Guidelines for Biomarker of Food Intake Reviews (BFIRev)

NARCIS (Netherlands)

Praticò, Giulia; Gao, Qian; Scalbert, Augustin; Vergères, Guy; Kolehmainen, Marjukka; Manach, Claudine; Brennan, Lorraine; Pedapati, Sri Harsha; Afman, Lydia A.; Wishart, David S.; Vázquez-Fresno, Rosa; Lacueva, Cristina Andres; Garcia-Aloy, Mar; Verhagen, Hans; Feskens, Edith J.M.; Dragsted, Lars O.

2018-01-01

Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important

Functional MRI and CT biomarkers in oncology

Energy Technology Data Exchange (ETDEWEB)

Winfield, J.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom); Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Sutton (United Kingdom); Payne, G.S.; DeSouza, N.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom)

2015-04-01

Imaging biomarkers derived from MRI or CT describe functional properties of tumours and normal tissues. They are finding increasing numbers of applications in diagnosis, monitoring of response to treatment and assessment of progression or recurrence. Imaging biomarkers also provide scope for assessment of heterogeneity within and between lesions. A wide variety of functional parameters have been investigated for use as biomarkers in oncology. Some imaging techniques are used routinely in clinical applications while others are currently restricted to clinical trials or preclinical studies. Apparent diffusion coefficient, magnetization transfer ratio and native T{sub 1} relaxation time provide information about structure and organization of tissues. Vascular properties may be described using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, transverse relaxation rate (R{sub 2}*), vessel size index and relative blood volume, while magnetic resonance spectroscopy may be used to probe the metabolic profile of tumours. This review describes the mechanisms of contrast underpinning each technique and the technical requirements for robust and reproducible imaging. The current status of each biomarker is described in terms of its validation, qualification and clinical applications, followed by a discussion of the current limitations and future perspectives. (orig.)

Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

Directory of Open Access Journals (Sweden)

Martha V. Douglas-Escobar

2012-11-01

Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

Biomarker Research in Parkinson's Disease Using Metabolite Profiling

DEFF Research Database (Denmark)

Havelund, Jesper F; Heegaard, Niels H H; Færgeman, Nils J K

2017-01-01

Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifa......) and purine metabolism (uric acid) are also altered in most metabolite profiling studies in PD......., the potential as a biomarker and the significance of understanding the pathophysiology of PD. Many of the studies report alterations in alanine, branched-chain amino acids and fatty acid metabolism, all pointing to mitochondrial dysfunction in PD. Aromatic amino acids (phenylalanine, tyrosine, tryptophan...

Carbonic Anhydrase as Pollution Biomarker: An Ancient Enzyme with a New Use

Directory of Open Access Journals (Sweden)

Trifone Schettino

2012-11-01

Full Text Available The measurement of cellular and sub-cellular responses to chemical contaminants (referred to as biomarkers in living organisms represents a recent tool in environmental monitoring. The review focuses on carbonic anhydrase, a ubiquitous metalloenzyme which plays key roles in a wide variety of physiological processes involving CO2 and HCO3−. In the last decade a number of studies have demonstrated the sensitivity of this enzyme to pollutants such as heavy metals and organic chemicals in both humans and wildlife. The review analyses these studies and discusses the potentiality of this enzyme as novel biomarker in environmental monitoring and assessment.

Conceptual strategy for design, implementation, and validation of a biomarker-based biomonitoring capability

Energy Technology Data Exchange (ETDEWEB)

McCarthy, J.F.; Halbrook, R.S.; Shugart, L.R.

1991-12-01

This document describes a strategy for defining specific objectives for biomarker studies and for designing and implementing a biomonitoring study that focuses on these objectives. In researching this subject, it became clear to the authors that the subject of biomarkers created a great deal of interest among scientists and regulators but that general acceptance of biomarkers as a tool for environmental protection was hampered by lack of a clear notion of how to develop and apply this approach. We intend this document to be a user's guide'' that lays out a logical scheme for applying biomarkers in environmental monitoring. In addition, laboratory and field research components needed to develop and validate fundamental understanding and interpretation of biomarker responses are also described, as is a strategy for evolution of a biomarker-based biomonitoring capability. The document is divided into sections intended to lead the reader to an understanding of how biomarkers can be developed and applied.

Conceptual strategy for design, implementation, and validation of a biomarker-based biomonitoring capability

Energy Technology Data Exchange (ETDEWEB)

McCarthy, J.F.; Halbrook, R.S.; Shugart, L.R.

1991-12-01

This document describes a strategy for defining specific objectives for biomarker studies and for designing and implementing a biomonitoring study that focuses on these objectives. In researching this subject, it became clear to the authors that the subject of biomarkers created a great deal of interest among scientists and regulators but that general acceptance of biomarkers as a tool for environmental protection was hampered by lack of a clear notion of how to develop and apply this approach. We intend this document to be a ``user`s guide`` that lays out a logical scheme for applying biomarkers in environmental monitoring. In addition, laboratory and field research components needed to develop and validate fundamental understanding and interpretation of biomarker responses are also described, as is a strategy for evolution of a biomarker-based biomonitoring capability. The document is divided into sections intended to lead the reader to an understanding of how biomarkers can be developed and applied.

Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

DEFF Research Database (Denmark)

Kofoed, K.

This PhD-thesis is based on work performed at Clinical Research Centre and Department of Infectious Diseases at Copenhagen University Hospital, Hvidovre, and includes a review, a method development study, and two clinical studies. The background of the thesis is, that timely and accurate diagnosis...... of sepsis is of great importance for choice of treatment, level of monitoring and prognosis. In this biomarkers could be a significant aid, and thus the search for and application of "new" sepsis biomarkers is of great importance. The thesis reviews the definitions and the epidemiology, and gives...

Zooming into Molecular Biomarker Distribution through Spatially Resolved Mass Spectrometry on Intact Sediment Sections

Science.gov (United States)

Wörmer, L.; Fuchser, J.; Alfken, S.; Elvert, M.; Schimmelmann, A.; Hinrichs, K. U.

2016-02-01

Marine microorganisms adapt to their habitat by structural modification of their membrane lipids. After sedimentation, and due to their persistence in the sedimentary record, the information archived in them remains available on geological time-scales. Thereby sedimentary lipid biomarkers become important informants of past environments. Conventional biomarker analysis is labor-intensive and requires cm-sized samples, temporal resolution is consequently low. We here present an approach, based on laser desorption ionization (LDI) coupled to ultra high resolution mass spectrometry, that avoids wet-chemical sample preparation and enables analysis directly on sediment sections at sub-mm spatial resolution. Our initial study targeted archaeal glycerol dialkyl glycerol tetraethers (GDGTs). GDGTS are ubiquitous and persistent components in marine sediments, and used in several, widely recognized paleoenvironmental proxies. Applied to an Eastern Mediterranean Sapropel layer, GDGT-profiles with previously unachieved temporal resolution were obtained, and pointed to a strong influence of high frequency cycles on sea-surface temperature and planktonic archaeal ecology. Spatial information furthermore revealed a new view on the fine-scale patchiness of lipid distribution. Following these pioneering studies, major developments are under way. A dedicated facility has been set up at MARUM/University of Bremen, which combines lipid biomarker and elemental analysis at sub-mm resolution (down to 50 µm). We present methods for other comprehensive lipid biomarkers (e.g. alkenones or sterols) that are currently being targeted; and the application of spatially resolved biomarker analysis to recent laminated sediments (Santa Barbara Basin), yielding informative profiles with subannual resolution. We also discuss criteria for analyte and sample selection, as well as the main potentialities and constraints of this new approach.

Geriatric medicine, Japanese Alzheimer's disease neuroimaging initiative and biomarker development

International Nuclear Information System (INIS)

Arai, Hiroyuki; Furukawa, Katsutoshi; Okamura, Nobuyuki; Kudo, Yukitsuka

2010-01-01

Due to a change in disease spectrum in aged countries, the primary role of geriatricians should be directed to an appropriate management and prevention of cognitive decline and dementia, swallowing and aspiration pneumonia and falls and fractures. Management of dementia constitutes a central part in the practice of geriatric medicine in order to support independence of life in elderly people. The current paradigm of cognitive function-based testing for the diagnosis and treatment of Alzheimer's disease (AD) is going to drastically shift to a biomarker-based test approach, a shift that will correspond to the emergence of disease-modifying drugs. In addition, a new molecular imaging technique that visualizes neuronal protein deposits or pathological features has been developed in Japan and the U.S.A. Based on these achievements, the Alzheimer's Disease Neuroimaging Initiative (ADNI) was proposed and initiated in 2005. The ADNI is a long-term observational study being conducted in the U.S.A., Europe, Australia, and Japan using identical protocols. The objectives of ADNI are: to establish methodology which will allow standard values related to long-term changes in imaging data, such as MRI and positron emission tomography (PET), in patients with AD and mild cognitive impairment and normal elderly persons; to obtain clinical indices, psychological test data, and blood/cerebrospinal fluid biomarkers to demonstrate the validity of image-based surrogate markers; and to establish optimum methods to monitor the therapeutic effects of disease-modifying drugs for AD. Patient enrollment in the Japanese ADNI has begun in July 2008. Imaging of AD pathology not only acts as a reliable biomarker with which to assay curative drug development by novel pharmaceutical companies, but it also helps health promotion toward AD prevention. (author)

Biomarkers in Diabetic Retinopathy.

Science.gov (United States)

Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

2015-01-01

There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

Validation of Heat Shock Protein 70 as a Tumor-Specific Biomarker for Monitoring the Outcome of Radiation Therapy in Tumor Mouse Models

Energy Technology Data Exchange (ETDEWEB)

Bayer, Christine; Liebhardt, Michael E.; Schmid, Thomas E. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Trajkovic-Arsic, Marija [II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Hube, Kathrin; Specht, Hanno M. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Schilling, Daniela [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Clinical Kooperation Group, Innate Immunity in Tumor Biology, HelmholtzZentrum München, Munich (Germany); Gehrmann, Mathias; Stangl, Stefan [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Siveke, Jens T. [II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Wilkens, Jan J. [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Multhoff, Gabriele, E-mail: Gabriele.multhoff@lrz.tum.de [Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Clinical Kooperation Group, Innate Immunity in Tumor Biology, HelmholtzZentrum München, Munich (Germany)

2014-03-01

Purpose: Tumor cells, in contrast to normal cells, frequently overexpress heat shock protein 70 (Hsp70) in the cytosol, present it on their cell surface, and actively release it. Therefore, soluble Hsp70 (sHsp70) was investigated as a potential tumor biomarker for monitoring the outcome of radiation therapy. Methods and Materials: Plasma from mice bearing membrane Hsp70 (mHsp70)-positive FaDu human squamous cell carcinoma of the head and neck and spontaneous pancreatic ductal adenocarcinoma (PDAC) was investigated. A cohort of mice with FaDu tumors (0.32 cm{sup 3}) was irradiated with 30 Gy, and plasma was collected 24 hours after irradiation, after the tumors had shrunk to 50% of their starting volume and after complete remission. sHsp70 levels in the plasma were quantified by enzyme-linked immunosorbent assay. Results: sHsp70 levels were significantly higher in the blood of tumor-bearing mice than that of control animals. A correlation between increasing sHsp70 plasma levels and tumor volume in the range of 0.01 cm{sup 3} to 0.66 cm{sup 3} was observed. Radiation-induced regression of the tumors was associated with significantly decreased sHsp70 levels, which returned to the level of control animals after complete remission. Conclusion: We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients.

A brief review and evaluation of earthworm biomarkers in soil pollution assessment.

Science.gov (United States)

Shi, Zhiming; Tang, Zhiwen; Wang, Congying

2017-05-01

Earthworm biomarker response to pollutants has been widely investigated in the assessment of soil pollution. However, whether and how the earthworm biomarker-approach can be actually applied to soil pollution assessment is still a controversial issue. This review is concerned about the following points: 1. Despite much debate, biomarker is valuable to ecotoxicology and biomarker approach has been properly used in different fields. Earthworm biomarker might be used in different scenarios such as large-scale soil pollution survey and soil pollution risk assessment. Compared with physicochemical analysis, they can provide more comprehensive and straightforward information about soil pollution at low cost. 2. Although many earthworm species from different ecological categories have been tested, Eisenia fetida/andrei is commonly used. Many earthworm biomarkers have been screened from the molecular to the individual level, while only a few biomarkers, such as avoidance behavior and lysosomal membrane stability, have been focused on. Other aspects of the experimental design were critically reviewed. 3. More studies should focus on determining the reliability of various earthworm biomarkers in soil pollution assessment in future research. Besides, establishing a database of a basal level of each biomarker, exploring biomarker response in different region/section/part of earthworm, and other issues are also proposed. 4. A set of research guideline for earthworm biomarker studies was recommended, and the suitability of several earthworm biomarkers was briefly evaluated with respect to their application in soil pollution assessment. This review will help to promote further studies and practical application of earthworm biomarker in soil pollution assessment.

Perspectives in Molecular Imaging Using Staging Biomarkers and Immunotherapies in Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Benoît Leclerc

2013-01-01

Full Text Available Sporadic Alzheimer’s disease (AD is an emerging chronic illness characterized by a progressive pleiotropic pathophysiological mode of actions triggered during the senescence process and affecting the elderly worldwide. The complex molecular mechanisms of AD not only are supported by cholinergic, beta-amyloid, and tau theories but also have a genetic basis that accounts for the difference in symptomatology processes activation among human population which will evolve into divergent neuropathological features underlying cognitive and behaviour alterations. Distinct immune system tolerance could also influence divergent responses among AD patients treated by immunotherapy. The complexity in nature increases when taken together the genetic/immune tolerance with the patient’s brain reserve and with neuropathological evolution from early till advance AD clinical stages. The most promising diagnostic strategies in today’s world would consist in performing high diagnostic accuracy of combined modality imaging technologies using beta-amyloid 42 peptide-cerebrospinal fluid (CSF positron emission tomography (PET, Pittsburgh compound B-PET, fluorodeoxyglucose-PET, total and phosphorylated tau-CSF, and volumetric magnetic resonance imaging hippocampus biomarkers for criteria evaluation and validation. Early diagnosis is the challenge task that needs to look first at plausible mechanisms of actions behind therapies, and combining them would allow for the development of efficient AD treatment in a near future.

Measurement of DNA strand breaks as a biomarker of genotoxic pollutants

Digital Repository Service at National Institute of Oceanography (India)

Sarkar, A.; Patil, S.S.; Holkar, P.K.R.

This paper deals with the development of a molecular biomarker technique by measurement of DNA integrity in marine organisms for biomonitoring of pollution due to genotoxic compounds. The marine environment is continuously being polluted...

Targeted and Untargeted Lipidomics of Emiliania huxleyi Viral Infection and Life Cycle Phases Highlights Molecular Biomarkers of Infection, Susceptibility, and Ploidy

Directory of Open Access Journals (Sweden)

Jonathan Eliott Hunter

2015-10-01

Full Text Available Marine viruses that infect phytoplankton strongly influence the ecology and evolution of their hosts. Emiliania huxleyi is characterized by a biphasic life cycle composed of a diploid (2N and haploid (1N phase; diploid cells are susceptible to infection by specific coccolithoviruses, yet haploid cells are resistant. Glycosphingolipids (GSLs play a role during infection, but their molecular distribution in haploid cells is unknown. We present mass spectrometric analyses of lipids from cultures of uninfected diploid, infected diploid, and uninfected haploid E. huxleyi. Known viral GSLs were present in the infected diploid cultures as expected, but surprisingly, trace amounts of viral GSLs were also detected in the uninfected haploid cells. Sialic-acid GSLs have been linked to viral susceptibility in diploid cells, but were found to be absent in the haploid cultures, suggesting a mechanism of haploid resistance to infection. Additional untargeted high-resolution mass spectrometry data processed via multivariate analysis unveiled a number of novel biomarkers of infected, non-infected, and haploid cells. These data expand our understanding on the dynamics of lipid metabolism during E. huxleyi host/virus interactions and highlight potential novel biomarkers for infection, susceptibility, and ploidy.

Mass Spectrometry-based Assay for High Throughput and High Sensitivity Biomarker Verification

Energy Technology Data Exchange (ETDEWEB)

Guo, Xuejiang; Tang, Keqi

2017-06-14

Searching for disease specific biomarkers has become a major undertaking in the biomedical research field as the effective diagnosis, prognosis and treatment of many complex human diseases are largely determined by the availability and the quality of the biomarkers. A successful biomarker as an indicator to a specific biological or pathological process is usually selected from a large group of candidates by a strict verification and validation process. To be clinically useful, the validated biomarkers must be detectable and quantifiable by the selected testing techniques in their related tissues or body fluids. Due to its easy accessibility, protein biomarkers would ideally be identified in blood plasma or serum. However, most disease related protein biomarkers in blood exist at very low concentrations (<1ng/mL) and are “masked” by many none significant species at orders of magnitude higher concentrations. The extreme requirements of measurement sensitivity, dynamic range and specificity make the method development extremely challenging. The current clinical protein biomarker measurement primarily relies on antibody based immunoassays, such as ELISA. Although the technique is sensitive and highly specific, the development of high quality protein antibody is both expensive and time consuming. The limited capability of assay multiplexing also makes the measurement an extremely low throughput one rendering it impractical when hundreds to thousands potential biomarkers need to be quantitatively measured across multiple samples. Mass spectrometry (MS)-based assays have recently shown to be a viable alternative for high throughput and quantitative candidate protein biomarker verification. Among them, the triple quadrupole MS based assay is the most promising one. When it is coupled with liquid chromatography (LC) separation and electrospray ionization (ESI) source, a triple quadrupole mass spectrometer operating in a special selected reaction monitoring (SRM) mode

Di- or polysulphide-bound biomarkers in sulphur-rich geomacromolecules as revealed by selective chemolysis

Science.gov (United States)

Kohnen, Math E. l.; Sinninghe Damsté, Jaap S.; Kock-van Dalen, A. c.; Jan, W. De Leeuw

1991-05-01

Three types of sulphur-rich high-molecular-weight material in the alkylsulphide, the polar, and the asphaltene fractions isolated from the bitumen of an immature bituminous shale from the Vena del Gesso basin (Italy) were desulphurised using Raney Ni and were treated with MeLi/MeI, a chemical degradation method which cleaves selectively and quantitatively di- or polysulphide linkages. The products formed were characterised by gas chromatography-mass spectrometry. Raney Ni desulphurisation revealed that these S-rich macromolecules are in substantial part composed of sulphur-linked biomarkers with linear, branched, isoprenoid, steroid, hopanoid, and carotenoid carbon skeletons. MeLi/Mel treatment provided evidence that a major part of the total amount of macromolecularly bound biomarkers are linked via di- or polysulphide moieties to the macromolecular network. Since the di- or polysulphide linkages are attached at specific positions of the bound biomarkers it is proposed that they are formed by intermolecular incorporation reactions of HS x- into low-molecular-weight functionalised biological lipids during early diagenesis. The different properties (solubility and molecular weight) of the sulphur-rich macromolecules in the alkylsulphide, the resin, and the asphaltene fractions can be explained simply by differences in degree of sulphur cross-linking.

Suppression of Proinflammatory and Prosurvival Biomarkers in Oral Cancer Patients Consuming a Black Raspberry Phytochemical-Rich Troche.

Science.gov (United States)

Knobloch, Thomas J; Uhrig, Lana K; Pearl, Dennis K; Casto, Bruce C; Warner, Blake M; Clinton, Steven K; Sardo-Molmenti, Christine L; Ferguson, Jeanette M; Daly, Brett T; Riedl, Kenneth; Schwartz, Steven J; Vodovotz, Yael; Buchta, Anthony J; Schuller, David E; Ozer, Enver; Agrawal, Amit; Weghorst, Christopher M

2016-02-01

Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and noninvolved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of prosurvival genes (AURKA, BIRC5, EGFR) and proinflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated grade 3-4 toxicities or adverse events, and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark antiapoptotic and proinflammatory molecular biomarkers were overexpressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. As these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention. ©2015 American Association for Cancer

Towards a biological monitoring guidance value for acrylamide.

Science.gov (United States)

Sams, C; Jones, K; Warren, N; Cocker, J; Bell, S; Bull, P; Cain, M

2015-08-19

Acrylamide is classified as a potential human carcinogen and neurotoxicant. Biological monitoring is a useful tool for monitoring worker exposure. However, other sources of exposure to acrylamide (including cigarette smoke and diet) also need to be considered. This study has performed repeat measurements of the urinary mercapturic acids of acrylamide (AAMA) and its metabolite glycidamide (GAMA) and determined globin adducts in 20 production-plant workers at a UK acrylamide production facility. The relationship between biomarker levels and environmental monitoring data (air levels and hand washes) was investigated. Good correlations were found between all of the biomarkers (r(2)=0.86-0.91) and moderate correlations were found between the biomarkers and air levels (r(2) = 0.56-0.65). Our data show that urinary AAMA is a reliable biomarker of acrylamide exposure. Occupational hygiene data showed that acrylamide exposure at the company was well within the current UK Workplace Exposure Limit. The 90th percentile of urinary AAMA in non-smoking production-plant workers (537 μmol/mol creatinine (n = 59 samples)) is proposed as a possible biological monitoring guidance value. This 90th percentile increased to 798 μmol/mol if smokers were included (n = 72 samples). These values would be expected following an airborne exposure of less than 0.07 mg/m(3), well below the current UK workplace exposure limit of 0.3mg/m(3). Comparison of biomarker levels in non-occupationally exposed individuals suggests regional variations (between UK and Germany), possibly due to differences in diet. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Validation of beverage intake methods vs. hydration biomarker: a short review

OpenAIRE

Nissensohn, Mariela; Ruano, Cristina; Serra-Majem, Lluis

2013-01-01

Introduction: Fluid intake is difficult to monitor. Biomarkers of beverage intake are able to assess dietary intake / hydration status without the bias of self-reported dietary intake errors and also the intra-individual variability. Various markers have been proposed to assess hydration, however, to date; there is a lack of universally accepted biomarker that reflects changes of hydration status in response to changes in beverage intake. Aim: We conduct a review to find out the questionnaire...

Identification of protein biomarkers in Dupuytren's contracture using surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS).

Science.gov (United States)

O'Gorman, David; Howard, Jeffrey C; Varallo, Vincenzo M; Cadieux, Peter; Bowley, Erin; McLean, Kris; Pak, Brian J; Gan, Bing Siang

2006-06-01

To study the protein expression profiles associated with Dupuytren's contracture (DC) to identify potential disease protein biomarkers (PBM) using a proteomic technology--Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). Normal and disease palmar fascia from DC patients were analyzed using Ciphergen's SELDI-TOF-MS Protein Biological System II (PBSII) ProteinChip reader. Analysis of the resulting SELDI-TOF spectra was carried out using the peak cluster analysis program (BioMarker Wizard, Ciphergen). Common peak clusters were then filtered using a bootstrap algorithm called SAM (Significant Analysis of Microarrays) for increased fidelity in our analysis. Several differentially expressed low molecular weight (mass standard deviation for both methods of biomarker-rich low molecular weight region of the human proteome. Application of such novel technology may help clinicians to focus on specific molecular abnormalities in diseases with no known molecular pathogenesis, and uncover therapeutic and/or diagnostic targets.

Platelet RNA as a circulating biomarker trove for cancer diagnostics.

Science.gov (United States)

Best, M G; Vancura, A; Wurdinger, T

2017-07-01

Platelets are multifunctional cell fragments, circulating in blood in high abundance. Platelets assist in thrombus formation, sensing of pathogens entering the blood stream, signaling to immune cells, releasing vascular remodeling factors, and, negatively, enhancing cancer metastasis. Platelets are 'educated' by their environment, including in patients with cancer. Cancer cells appear to initiate intraplatelet signaling, resulting in splicing of platelet pre-mRNAs, and enhance secretion of cytokines. Platelets can induce leukocyte and endothelial cell modeling factors, for example, through adenine nucleotides (ATP), thereby facilitating extravasation of cancer cells. Besides releasing factors, platelets can also sequester RNAs and proteins released by cancer cells. Thus, platelets actively respond to queues from local and systemic conditions, thereby altering their transcriptome and molecular content. Platelets contain a rich repertoire of RNA species, including mRNAs, small non-coding RNAs and circular RNAs; although studies regarding the functionality of the various platelet RNA species require more attention. Recent advances in high-throughput characterization of platelet mRNAs revealed 10 to > 1000 altered mRNAs in platelets in the presence of disease. Hence, platelet RNA appears to be dynamically affected by pathological conditions, thus possibly providing opportunities to use platelet RNA as diagnostic, prognostic, predictive, or monitoring biomarkers. In this review, we cover the literature regarding the platelet RNA families, processing of platelet RNAs, and the potential application of platelet RNA as disease biomarkers. © 2017 International Society on Thrombosis and Haemostasis.

Real-Time Molecular Monitoring of Chemical Environment in ObligateAnaerobes during Oxygen Adaptive Response

Energy Technology Data Exchange (ETDEWEB)

Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David. A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

2009-02-25

Determining the transient chemical properties of the intracellular environment canelucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms which enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier Transform Infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bonding in their cellular water. We observed a sequence of wellorchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses.

A review of molecular biomarkers for bladder cancer | Miakhil ...

African Journals Online (AJOL)

Background: Numerous molecular markers for bladder cancer have been identified and investigated with various laboratory techniques. Molecular markers are isolated from tissue, serum and urine. They fall into proteomic, genetic and epigenetic categories. Some of molecular markers show promising results in terms of ...

MIP-Based Sensors: Promising New Tools for Cancer Biomarker Determination

Directory of Open Access Journals (Sweden)

Giulia Selvolini

2017-03-01

Full Text Available Detecting cancer disease at an early stage is one of the most important issues for increasing the survival rate of patients. Cancer biomarker detection helps to provide a diagnosis before the disease becomes incurable in later stages. Biomarkers can also be used to evaluate the progression of therapies and surgery treatments. In recent years, molecularly imprinted polymer (MIP based sensors have been intensely investigated as promising analytical devices in several fields, including clinical analysis, offering desired portability, fast response, specificity, and low cost. The aim of this review is to provide readers with an overview on recent important achievements in MIP-based sensors coupled to various transducers (e.g., electrochemical, optical, and piezoelectric for the determination of cancer biomarkers by selected publications from 2012 to 2016.

Data from a targeted proteomics approach to discover biomarkers in saliva for the clinical diagnosis of periodontitis

Directory of Open Access Journals (Sweden)

V. Orti

2018-06-01

Full Text Available This study focused on the search for new biomarkers based on liquid chromatography-multiple reaction monitoring (LC-MRM proteomics profiling of whole saliva from patients with periodontitis compared to healthy subjects. The LC-MRM profiling approach is a new and innovative method that has already been validated for the absolute and multiplexed quantification of biomarkers in several diseases. The dataset for this study was produced using LC-MRM to monitor protein levels in a multiplex assay, it provides clinical information on salivary biomarkers of periodontitis. The data presented here is an extension of our recently published research article (Mertens et al., 2017 [1]. Keywords: Clinical chemistry, Mass spectrometry, Proteomics, Saliva biochemistry, Oral disease, Periodontitis

Role of biomarkers in understanding and treating children with asthma: towards personalized care

Directory of Open Access Journals (Sweden)

Lang JE

2013-08-01

Full Text Available Jason E Lang,1 Kathryn V Blake21Division of Pulmonary and Sleep Medicine, Nemours Children's Hospital, Orlando, FL, USA; 2Center for Pharmacogenomics and Translational Research, Nemours Children's Clinic, Jacksonville, FL, USA Both authors contributed equally to this workAbstract: Asthma is one of the most common chronic diseases affecting children. Despite publicized expert panels on asthma management and the availability of high-potency inhaled corticosteroids, asthma continues to pose an enormous burden on quality of life for children. Research into the genetic and molecular origins of asthma are starting to show how distinct disease entities exist within the syndrome of "asthma". Biomarkers can be used to diagnose underlying molecular mechanisms that can predict the natural course of disease or likely response to drug treatment. The progress of personalized medicine in the care of children with asthma is still in its infancy. We are not yet able to apply stratified asthma treatments based on molecular phenotypes, although that time may be fast approaching. This review discusses some of the recent advances in asthma genetics and the use of current biomarkers that can help guide improved treatment. For example, the fraction of expired nitric oxide and serum Immunoglobulin E (IgE (including allergen-specific IgE, when evaluated in the context of recurrent asthma symptoms, are general predictors of allergic airway inflammation. Biomarker assays for secondhand tobacco smoke exposure and cysteinyl leukotrienes are both promising areas of study that can help personalize management, not just for pharmacologic management, but also education and prevention efforts.Keywords: asthma, biomarkers, children, management

Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation?

Science.gov (United States)

Baron, Morgane; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

2012-07-01

Cardiovascular diseases remain an important cause of morbi-mortality. Atherosclerosis, which predisposes to cardiovascular disorders such as myocardial infarction and stroke, develops silently over several decades. Identification of circulating biomarkers to evaluate cardiovascular event risk and pathology prognosis is of particular importance. Microparticles (MPs) are small vesicles released from cells upon apoptosis or activation. Microparticles are present in blood of healthy individuals. Studies showing a modification of their concentrations in patients with cardiovascular risk factors and after cardiovascular events identify MPs as potential biomarkers of disease. Moreover, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological compounds, used in the treatment of cardiovascular disease, can reduce plasma MP concentrations. Nevertheless, numerous issues remain to be solved before MP measurement can be applied as routine biological tests to improve cardiovascular risk prediction. In particular, prospective studies to identify the predictive values of MPs in pathologies such as cardiovascular diseases are needed to demonstrate whether MPs are useful biomarkers for the early detection of the disease and its progression. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

RNA Biomarkers: Frontier of Precision Medicine for Cancer

Directory of Open Access Journals (Sweden)

Xiaochen Xi

2017-02-01

Full Text Available As an essential part of central dogma, RNA delivers genetic and regulatory information and reflects cellular states. Based on high‐throughput sequencing technologies, cumulating data show that various RNA molecules are able to serve as biomarkers for the diagnosis and prognosis of various diseases, for instance, cancer. In particular, detectable in various bio‐fluids, such as serum, saliva and urine, extracellular RNAs (exRNAs are emerging as non‐invasive biomarkers for earlier cancer diagnosis, tumor progression monitor, and prediction of therapy response. In this review, we summarize the latest studies on various types of RNA biomarkers, especially extracellular RNAs, in cancer diagnosis and prognosis, and illustrate several well‐known RNA biomarkers of clinical utility. In addition, we describe and discuss general procedures and issues in investigating exRNA biomarkers, and perspectives on utility of exRNAs in precision medicine.

Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers

Science.gov (United States)

Chen, Qiuying; Deeb, Ruba S.; Ma, Yuliang; Staudt, Michelle R.; Crystal, Ronald G.; Gross, Steven S.

2015-01-01

COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US. Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease. Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD. A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentially-expressed in COPD-smokers vs. healthy-smokers. These 23 putative biomarkers were differentially-correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8% sensitivity and 86.5% specificity. In an independent validation set, this model correctly predicted COPD in 8/10 individuals. These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels. Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways. Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD. PMID:26674646

Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers.

Directory of Open Access Journals (Sweden)

Ping Yip

Full Text Available FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC=0.933 and CA-125 (AUC=0.907 were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800. To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912. Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the

Cetuximab and biomarkers in non-small-cell lung carcinoma

Directory of Open Access Journals (Sweden)

Patil N

2012-07-01

Full Text Available Nitin Patil, Mohammed Abba, Heike AllgayerDepartment of Experimental Surgery, Medical Faculty Mannheim, University of Heidelberg and Molecular Oncology of Solid Tumors Unit, German Cancer Research Center (DKFZ, Heidelberg, GermanyAbstract: Cancer progression is a highly complex process that is driven by a constellation of deregulated signaling pathways and key molecular events. In non-small-cell lung cancer (NSCLC, as in several other cancer types, the epidermal growth factor receptor (EGFR and its downstream signaling components represent a key axis that has been found not only to trigger cancer progression but also to support advanced disease leading to metastasis. Two major therapeutic approaches comprising monoclonal antibodies and small molecule tyrosine kinase inhibitors have so far been used to target this pathway, with a combination of positive, negative, and inconsequential results, as judged by patient survival indices. Since these drugs are expensive and not all patients derive benefits from taking them, it has become both pertinent and paramount to identify biomarkers that can predict not only beneficial response but also resistance. This review focuses on the chimeric monoclonal antibody, cetuximab, its application in the treatment of NSCLC, and the biomarkers that may guide its use in the clinical setting. A special emphasis is placed on the EGFR, including its structural and mechanistic attributes.Keywords: NSCLC, cetuximab, biomarker, cancer progression

Biomarkers in Sports and Exercise: Tracking Health, Performance, and Recovery in Athletes.

Science.gov (United States)

Lee, Elaine C; Fragala, Maren S; Kavouras, Stavros A; Queen, Robin M; Pryor, John Luke; Casa, Douglas J

2017-10-01

Biomarker discovery and validation is a critical aim of the medical and scientific community. Research into exercise and diet-related biomarkers aims to improve health, performance, and recovery in military personnel, athletes, and lay persons. Exercise physiology research has identified individual biomarkers for assessing health, performance, and recovery during exercise training. However, there are few recommendations for biomarker panels for tracking changes in individuals participating in physical activity and exercise training programs. Our approach was to review the current literature and recommend a collection of validated biomarkers in key categories of health, performance, and recovery that could be used for this purpose. We determined that a comprehensive performance set of biomarkers should include key markers of (a) nutrition and metabolic health, (b) hydration status, (c) muscle status, (d) endurance performance, (e) injury status and risk, and (f) inflammation. Our review will help coaches, clinical sport professionals, researchers, and athletes better understand how to comprehensively monitor physiologic changes, as they design training cycles that elicit maximal improvements in performance while minimizing overtraining and injury risk.

Tissue is alive: New technologies are needed to address the problems of protein biomarker pre-analytical variability.

Science.gov (United States)

Espina, Virginia; Mueller, Claudius; Edmiston, Kirsten; Sciro, Manuela; Petricoin, Emanuel F; Liotta, Lance A

2009-08-01

Instability of tissue protein biomarkers is a critical issue for molecular profiling. Pre-analytical variables during tissue procurement, such as time delays during which the tissue remains stored at room temperature, can cause significant variability and bias in downstream molecular analysis. Living tissue, ex vivo, goes through a defined stage of reactive changes that begin with oxidative, hypoxic and metabolic stress, and culminate in apoptosis. Depending on the delay time ex vivo, and reactive stage, protein biomarkers, such as signal pathway phosphoproteins will be elevated or suppressed in a manner which does not represent the biomarker levels at the time of excision. Proteomic data documenting reactive tissue protein changes post collection indicate the need to recognize and address tissue stability, preservation of post-translational modifications, and preservation of morphologic features for molecular analysis. Based on the analysis of phosphoproteins, one of the most labile tissue protein biomarkers, we set forth tissue procurement guidelines for clinical research. We propose technical solutions for (i) assessing the state of protein analyte preservation and specimen quality via identification of a panel of natural proteins (surrogate stability markers), and (ii) using multi-purpose fixative solution designed to stabilize, preserve and maintain proteins, nucleic acids, and tissue architecture.

UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry.

Science.gov (United States)

Zhao, Ying-Yong; Cheng, Xian-Long; Vaziri, Nosratola D; Liu, Shuman; Lin, Rui-Chao

2014-10-01

Metabonomics is a powerful and promising analytic tool that allows assessment of global low-molecular-weight metabolites in biological systems. It has a great potential for identifying useful biomarkers for early diagnosis, prognosis and assessment of therapeutic interventions in clinical practice. The aim of this review is to provide a brief summary of the recent advances in UPLC-based metabonomic approach for biomarker discovery in a variety of diseases, and to discuss their significance in clinical chemistry. All the available information on UPLC-based metabonomic applications for discovering biomarkers of diseases were collected via a library and electronic search (using Web of Science, Pubmed, ScienceDirect, Springer, Google Scholar, etc.). Metabonomics has been used in clinical chemistry to identify and evaluate potential biomarkers and therapeutic targets in various diseases affecting the liver (hepatocarcinoma and liver cirrhosis), lung (lung cancer and pneumonia), gastrointestinal tract (colorectal cancer) and urogenital tract (prostate cancer, ovarian cancer and chronic kidney disease), as well as metabolic diseases (diabetes) and neuropsychiatric disorders (Alzheimer's disease and schizophrenia), etc. The information provided highlights the potential value of determination of endogenous low-molecular-weight metabolites and the advantages and potential drawbacks of the application of UPLC-based metabonomics in clinical setting. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Potentials of single-cell biology in identification and validation of disease biomarkers.

Science.gov (United States)

Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

2016-09-01

Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Children's exposure to environmental pollutants and biomarkers of genetic damage. I. Overview and critical issues

DEFF Research Database (Denmark)

Neri, Monica; Bonassi, Stefano; Knudsen, Lisbeth E

2005-01-01

In the last decade, molecular epidemiological studies have provided new perspectives on studying environmental risks in pediatric populations, based on the growing understanding that children may be more susceptible to toxicants than adults. Protecting children's health is a social priority...... of the information provided, and the need to warrant controlled access to sensitive information. The use of incentives such as gifts and payment to ensure the participation of school-aged children is specifically discussed. Examples of field studies that are focused on the effects of pesticides, air pollution...... biomarker results into intervention strategies and for integrating them with environmental monitoring and health data, (iv) optimal ways to obtain consent and provide information to children and/or their parents participating in the studies and (v) techniques for the effective communication with policy...

TIP-1 translocation onto the cell plasma membrane is a molecular biomarker of tumor response to ionizing radiation.

Directory of Open Access Journals (Sweden)

Hailun Wang

2010-08-01

Full Text Available Tumor response to treatment has been generally assessed with anatomic and functional imaging. Recent development of in vivo molecular and cellular imaging showed promise in time-efficient assessment of the therapeutic efficacy of a prescribed regimen. Currently, the in vivo molecular imaging is limited with shortage of biomarkers and probes with sound biological relevance. We have previously shown in tumor-bearing mice that a hexapeptide (HVGGSSV demonstrated potentials as a molecular imaging probe to distinguish the tumors responding to ionizing radiation (IR and/or tyrosine kinase inhibitor treatment from those of non-responding tumors.In this study we have studied biological basis of the HVGGSSV peptide binding within the irradiated tumors by use of tumor-bearing mice and cultured cancer cells. The results indicated that Tax interacting protein 1 (TIP-1, also known as Tax1BP3 is a molecular target that enables the selective binding of the HVGGSSV peptide within irradiated xenograft tumors. Optical imaging and immunohistochemical staining indicated that a TIP-1 specific antibody demonstrated similar biodistribution as the peptide in tumor-bearing mice. The TIP-1 antibody blocked the peptide from binding within irradiated tumors. Studies on both of human and mouse lung cancer cells showed that the intracellular TIP-1 relocated to the plasma membrane surface within the first few hours after exposure to IR and before the onset of treatment associated apoptosis and cell death. TIP-1 relocation onto the cell surface is associated with the reduced proliferation and the enhanced susceptibility to the subsequent IR treatment.This study by use of tumor-bearing mice and cultured cancer cells suggested that imaging of the radiation-inducible TIP-1 translocation onto the cancer cell surface may predict the tumor responsiveness to radiation in a time-efficient manner and thus tailor radiotherapy of cancer.

Competitive Reporter Monitored Amplification (CMA) - Quantification of Molecular Targets by Real Time Monitoring of Competitive Reporter Hybridization

Science.gov (United States)

Ullrich, Thomas; Ermantraut, Eugen; Schulz, Torsten; Steinmetzer, Katrin

2012-01-01

Background State of the art molecular diagnostic tests are based on the sensitive detection and quantification of nucleic acids. However, currently established diagnostic tests are characterized by elaborate and expensive technical solutions hindering the development of simple, affordable and compact point-of-care molecular tests. Methodology and Principal Findings The described competitive reporter monitored amplification allows the simultaneous amplification and quantification of multiple nucleic acid targets by polymerase chain reaction. Target quantification is accomplished by real-time detection of amplified nucleic acids utilizing a capture probe array and specific reporter probes. The reporter probes are fluorescently labeled oligonucleotides that are complementary to the respective capture probes on the array and to the respective sites of the target nucleic acids in solution. Capture probes and amplified target compete for reporter probes. Increasing amplicon concentration leads to decreased fluorescence signal at the respective capture probe position on the array which is measured after each cycle of amplification. In order to observe reporter probe hybridization in real-time without any additional washing steps, we have developed a mechanical fluorescence background displacement technique. Conclusions and Significance The system presented in this paper enables simultaneous detection and quantification of multiple targets. Moreover, the presented fluorescence background displacement technique provides a generic solution for real time monitoring of binding events of fluorescently labelled ligands to surface immobilized probes. With the model assay for the detection of human immunodeficiency virus type 1 and 2 (HIV 1/2), we have been able to observe the amplification kinetics of five targets simultaneously and accommodate two additional hybridization controls with a simple instrument set-up. The ability to accommodate multiple controls and targets into a

Competitive reporter monitored amplification (CMA--quantification of molecular targets by real time monitoring of competitive reporter hybridization.

Directory of Open Access Journals (Sweden)

Thomas Ullrich

Full Text Available BACKGROUND: State of the art molecular diagnostic tests are based on the sensitive detection and quantification of nucleic acids. However, currently established diagnostic tests are characterized by elaborate and expensive technical solutions hindering the development of simple, affordable and compact point-of-care molecular tests. METHODOLOGY AND PRINCIPAL FINDINGS: The described competitive reporter monitored amplification allows the simultaneous amplification and quantification of multiple nucleic acid targets by polymerase chain reaction. Target quantification is accomplished by real-time detection of amplified nucleic acids utilizing a capture probe array and specific reporter probes. The reporter probes are fluorescently labeled oligonucleotides that are complementary to the respective capture probes on the array and to the respective sites of the target nucleic acids in solution. Capture probes and amplified target compete for reporter probes. Increasing amplicon concentration leads to decreased fluorescence signal at the respective capture probe position on the array which is measured after each cycle of amplification. In order to observe reporter probe hybridization in real-time without any additional washing steps, we have developed a mechanical fluorescence background displacement technique. CONCLUSIONS AND SIGNIFICANCE: The system presented in this paper enables simultaneous detection and quantification of multiple targets. Moreover, the presented fluorescence background displacement technique provides a generic solution for real time monitoring of binding events of fluorescently labelled ligands to surface immobilized probes. With the model assay for the detection of human immunodeficiency virus type 1 and 2 (HIV 1/2, we have been able to observe the amplification kinetics of five targets simultaneously and accommodate two additional hybridization controls with a simple instrument set-up. The ability to accommodate multiple controls

Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer.

Science.gov (United States)

Nedaeinia, R; Manian, M; Jazayeri, M H; Ranjbar, M; Salehi, R; Sharifi, M; Mohaghegh, F; Goli, M; Jahednia, S H; Avan, A; Ghayour-Mobarhan, M

2017-02-01

The most important biological function of exosomes is their possible use as biomarkers in clinical diagnosis. Compared with biomarkers identified in conventional specimens such as serum or urine, exosomal biomarkers provide the highest amount of sensitivity and specificity, which can be attributed to their excellent stability. Exosomes, which harbor different types of proteins, nucleic acids and lipids, are present in almost all bodily fluids. The molecular constituents of exosomes, especially exosomal proteins and microRNAs (miRNAs), are promising as biomarkers in clinical diagnosis. This discovery that exosomes also contain messenger RNAs and miRNAs shows that they could be carriers of genetic information. Although the majority of RNAs found in exosomes are degraded RNA fragments with a length of exosomal miRNAs have been found to be associated with certain diseases. Several studies have pointed out miRNA contents of circulating exosomes that are similar to those of originating cancer cells. In this review, the recent advances in circulating exosomal miRNAs as biomarkers in gastrointestinal cancers are discussed. These studies indicated that miRNAs can be detected in exosomes isolated from body fluids such as saliva, which suggests potential advantages of using exosomal miRNAs as noninvasive novel biomarkers.

Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

Science.gov (United States)

Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

2014-06-01

Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics

Science.gov (United States)

Kocevar, Nina; Komel, Radovan

2014-01-01

Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. PMID:24550697

Biomarker fingerprinting : application and limitations for source identification and correlation of oils and petroleum products

International Nuclear Information System (INIS)

Wang, Z.; Fingas, M.F.; Yang, C.; Hollebone, B.

2004-01-01

Biological markers or biomarkers are complex molecules originating from formerly living organisms. They are among the most important hydrocarbon groups in petroleum because every crude oil exhibits an essentially unique biomarker or fingerprint due to the wide variety of geological conditions under which oil is formed. When found in crude oils, rocks and sediments, biomarkers have the same structures as their parent organic molecules. Therefore, chemical analysis of source-characteristic and environmentally persistent biomarkers can provide valuable information in determining the source of spilled oil. Biomarkers can also be used to differentiate oils and to monitor the degradation process and the weathering state of oils under a range of conditions. The use of biomarker techniques to study oil spills has increased significantly in recent years. This paper provided case studies to demonstrate: (1) biomarker distribution in weathered oil and in petroleum products with similar chromatographic profiles, (2) sesquiterpenes and diamondoid biomarkers in oils and light petroleum products, (3) unique biomarker compounds in oils, (4) diagnostic ratios of biomarkers, and (5) biodegradation of biomarkers. It was noted that the trend to use biomarkers to study oil spills will continue. Continuous advances in analytical methods will further improve the application of oil hydrocarbon fingerprinting for environmental studies. 36 refs., 5 tabs., 12 figs

Biomarkers in Diabetic Retinopathy

Science.gov (United States)

Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

2015-01-01

There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

Biomarkers for bladder cancer management: present and future

Science.gov (United States)

Ye, Fei; Wang, Li; Castillo-Martin, Mireia; McBride, Russell; Galsky, Matthew D; Zhu, Jun; Boffetta, Paolo; Zhang, David Y; Cordon-Cardo, Carlos

2014-01-01

Accurate and sensitive detection of bladder cancer is critical to diagnose this deadly disease at an early stage, estimate prognosis, predict response to treatment, and monitor recurrence. In past years, laboratory diagnosis and surveillance of urinary bladder cancer have improved significantly. Although urine cytology remains the gold standard test, many new urinary biomarkers have been identified. Furthermore, recent advances in genomic studies of bladder cancer have helped to refine our understanding of the pathogenesis of the disease, the biological basis for outcome disparities, and to inform more efficient treatment and surveillance strategies. In this article, the established diagnostic tests, newly identified biomarkers and genomic landscape of bladder cancer will be reviewed. PMID:25374904

Molecular biomarkers for weight control in obese individuals subjected to a multi-phase dietary intervention

DEFF Research Database (Denmark)

Bolton, Jennifer L; Montastier, Emilie; Carayol, Jérôme

2017-01-01

Context: While calorie restriction has proven beneficial for weight loss, long-term weight control is variable between individuals. Objective: To identify biomarkers of successful weight control during a dietary intervention (DI). Design, Setting, and Participants: Adipose tissue (AT) transcripto......-controllers. Interestingly, ASPN is a TGFβ1 inhibitor. Conclusions: We found circulating biomarkers associated with weight control, which could influence weight management strategies, and genes that may be prognostic for successful weight control....

The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers

DEFF Research Database (Denmark)

Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan

2011-01-01

. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.......The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories...

Analyses of plant biomarkers in modern ecosystems to improve vegetation reconstructions at hominid sites

Science.gov (United States)

Uno, K. T.; Boisserie, J. R.; Cerling, T. E.; Polissar, P. J.

2017-12-01

Reconstructing vegetation at hominid localities in eastern Africa remains a significant challenge for examining the role of climate and environment in human evolution. Plant wax biomarker approaches, particularly carbon isotopes of n-alkyl lipids, have been increasingly used to estimate the proportion of C3 and C4­ vegetation in past environments. Identifying new biomarkers indicative of vegetation type, specifically those that can be used to identify (C3) grasses prior to the late Miocene C4 expansion, will enable vegetation reconstructions during the first half of the Neogene, where much remains to be learned about hominid environments. Here, we begin to look beyond carbon isotopes from n-alkyl lipids by analyzing molecular distributions and screening for new plant biomarkers that can be used to identify plant functional types or possibly, more specific taxonomic information. We evaluate molecular distributions, carbon isotope ratios, and pentacyclic triterpenoid methyl esters (PTMEs) in modern soils from a wide range of ecosystems in Ethiopia and Kenya where vegetation types, fraction woody cover, and climatic conditions are known. Preliminary data suggest PTMEs are associated with grassy ecosystems but absent from forested ones. We also find that woody cover can be estimated using n-alkane molecular distributions. This non-isotopic approach to reconstructing woody cover opens the door to reconstructing Neogene vegetation provided the molecular distributions of C3 grasses in the past are similar to those of modern C4 grasses.

Some aspects of cancer biomarkers and their clinical application in solid tumors – revisited

Directory of Open Access Journals (Sweden)

Isaac D

2017-07-01

Full Text Available Cancer biomarkers can be used for a variety of purposes related to screening, prediction, stratification, detection, diagnosis, prognosis, treatment design, and monitoring of a therapeutic response. One of the most important characteristics of a given biomarker includes ease of collection allowing for a non-invasive approach and frequent sampling. Such samples may be obtained from serum or plasma, sputum, bronchoalveolar lavage, saliva, nipple discharge, pleural, or peritoneal effusions. Validation of different biomarkers is considered a mandatory method for useful evaluation. In this review, we highlight the clinical applicability of some cancer biomarkers, as well as future approaches for their development and collection, which may help guide clinicians and researchers. The role of liquid biopsies will also be summarized. Further studies using liquid biopsies are needed to elucidate the significance of various sources of biomarkers suitable for clinical application.

Prostate Cancer Detection by Molecular Urinalysis

Science.gov (United States)

2011-04-01

subjected to physical manipulation, thus creating the potential for their non- invasive detection in either urine or expressed prostatic fluid ( EPF ...samples or EPF . The recent application of molecular techniques to the study of PC has led to the identification of several novel molecular alterations...focused on detecting such molecular changes in the urine or EPF [7-12,15]. Paralleling the advances in biomarker discovery, sig- nificant advances in

Ionizing radiation biomarkers for potential use in epidemiological studies

International Nuclear Information System (INIS)

Pernot, Eileen; Cardis, Elisabeth; Hall, Janet; Baatout, Sarah; El Saghire, Houssein; Mohammed Abderrafi Benotmane; Roel Quintens; Blanchardon, Eric; Bouffler, Simon; Gomolka, Maria; Guertler, Anne; Kreuzer, Michaela; Harms-Ringdahl, Mats; Jeggo, Penny; Laurier, Dominique; Lindholm, Carita; Mkacher, Radhia; Sabatier, Laure; Tapio, Soile; De Vathaire, Florent

2012-01-01

Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100 mSv and/or 0.1 mSv min -1 ) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of

A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

Directory of Open Access Journals (Sweden)

Kjell Oberg

2016-09-01

Full Text Available The complexity of the clinical management of neuroendocrine neoplasia (NEN is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin; monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33 assessed current imaging strategies and biomarkers in NEN management. Consensus (>75% was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

Metallothionein from Wild Populations of the African Catfish Clarias gariepinus: From Sequence, Protein Expression and Metal Binding Properties to Transcriptional Biomarker of Metal Pollution

Directory of Open Access Journals (Sweden)

Ethel M’kandawire

2017-07-01

Full Text Available Anthropogenic pollution with heavy metals is an on-going concern throughout the world, and methods to monitor release and impact of heavy metals are of high importance. With a view to probe its suitability as molecular biomarker of metal pollution, this study has determined a coding sequence for metallothionein of the African sharptooth catfish Clarias gariepinus. The gene product was recombinantly expressed in Escherichia coli in presence of Zn(II, Cd(II, or Cu, and characterised by Electrospray Ionisation Mass Spectrometry and elemental analysis. C. gariepinus MT displays typical features of fish MTs, including 20 conserved cysteines, and seven bound divalent cations (Zn(II or Cd(II when saturated. Livers from wild C. gariepinus fish collected in all three seasons from four different sites on the Kafue River of Zambia were analysed for their metal contents and for MT expression levels by quantitative PCR. Significant correlations were found between Zn and Cu levels and MT expression in livers, with MT expression clearly highest at the most polluted site, Chililabombwe, which is situated in the Copperbelt region. Based on our findings, hepatic expression of MT from C. gariepinus may be further developed as a major molecular biomarker of heavy metal pollution resulting from mining activities in this region.

Metallothionein from Wild Populations of the African Catfish Clarias gariepinus: From Sequence, Protein Expression and Metal Binding Properties to Transcriptional Biomarker of Metal Pollution.

Science.gov (United States)

M'kandawire, Ethel; Mierek-Adamska, Agnieszka; Stürzenbaum, Stephen R; Choongo, Kennedy; Yabe, John; Mwase, Maxwell; Saasa, Ngonda; Blindauer, Claudia A

2017-07-18

Anthropogenic pollution with heavy metals is an on-going concern throughout the world, and methods to monitor release and impact of heavy metals are of high importance. With a view to probe its suitability as molecular biomarker of metal pollution, this study has determined a coding sequence for metallothionein of the African sharptooth catfish Clarias gariepinus . The gene product was recombinantly expressed in Escherichia coli in presence of Zn(II), Cd(II), or Cu, and characterised by Electrospray Ionisation Mass Spectrometry and elemental analysis. C. gariepinus MT displays typical features of fish MTs, including 20 conserved cysteines, and seven bound divalent cations (Zn(II) or Cd(II)) when saturated. Livers from wild C. gariepinus fish collected in all three seasons from four different sites on the Kafue River of Zambia were analysed for their metal contents and for MT expression levels by quantitative PCR. Significant correlations were found between Zn and Cu levels and MT expression in livers, with MT expression clearly highest at the most polluted site, Chililabombwe, which is situated in the Copperbelt region. Based on our findings, hepatic expression of MT from C. gariepinus may be further developed as a major molecular biomarker of heavy metal pollution resulting from mining activities in this region.

Biomarkers and Genetics in Peripheral Artery Disease.

Science.gov (United States)

Hazarika, Surovi; Annex, Brian H

2017-01-01

Peripheral artery disease (PAD) is highly prevalent and there is considerable diversity in the initial clinical manifestation and disease progression among individuals. Currently, there is no ideal biomarker to screen for PAD, to risk stratify patients with PAD, or to monitor therapeutic response to revascularization procedures. Advances in human genetics have markedly enhanced the ability to develop novel diagnostic and therapeutic approaches across a host of human diseases, but such developments in the field of PAD are lagging. In this article, we will discuss the epidemiology, traditional risk factors for, and clinical presentations of PAD. We will discuss the possible role of genetic factors and gene-environment interactions in the development and/or progression of PAD. We will further explore future avenues through which genetic advances can be used to better our understanding of the pathophysiology of PAD and potentially find newer therapeutic targets. We will discuss the potential role of biomarkers in identifying patients at risk for PAD and for risk stratifying patients with PAD, and novel approaches to identification of reliable biomarkers in PAD. The exponential growth of genetic tools and newer technologies provides opportunities to investigate and identify newer pathways in the development and progression of PAD, and thereby in the identification of newer biomarkers and therapies. © 2016 American Association for Clinical Chemistry.

Miniaturized Bio-and Chemical-Sensors for Point-of-Care Monitoring of Chronic Kidney Diseases.

Science.gov (United States)

Tricoli, Antonio; Neri, Giovanni

2018-03-22

This review reports the latest achievements in point-of-care (POC) sensor technologies for the monitoring of ammonia, creatinine and urea in patients suffering of chronic kidney diseases (CKDs). Abnormal levels of these nitrogen biomarkers are found in the physiological fluids, such as blood, urine and sweat, of CKD patients. Delocalized at-home monitoring of CKD biomarkers via integration of miniaturized, portable, and low cost chemical- and bio-sensors in POC devices, is an emerging approach to improve patients' health monitoring and life quality. The successful monitoring of CKD biomarkers, performed on the different body fluids by means of sensors having strict requirements in term of size, cost, large-scale production capacity, response time and simple operation procedures for use in POC devices, is reported and discussed.

Molecular profiling of childhood cancer: Biomarkers and novel therapies

Directory of Open Access Journals (Sweden)

Federica Saletta

2014-06-01

General significance: The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

Application of molecular methods for monitoring transmission stages of malaria parasites

International Nuclear Information System (INIS)

Babiker, Hamza A; Schneider, Petra

2008-01-01

Recent technical advances in malaria research have allowed specific detection of mRNA of genes that are expressed exclusively in sexual stages (gametocytes) of malaria parasites. The specificity and sensitivity of these techniques were validated on cultured laboratory clones of both human malaria parasites (Plasmodium falciparum) and rodent parasites (P. chabaudi). More recently, quantitative molecular techniques have been developed to quantify these sexual stages and used to monitor gametocyte dynamics and their transmission to mosquitoes. Molecular techniques showed that the infectious reservoir for malaria is larger than expected from previous microscopic studies; individual parasite genotypes within an infection can simultaneously produce infectious gametocytes; gametocyte production can be sustained for several months, and is modulated by environmental factors. The above techniques have empowered approaches for in-depth analysis of the biology of the transmission stages of the parasite and epidemiology of malaria transmission

Biomarkers of a Low-Latitude Neoproterozoic Glaciation

Science.gov (United States)

Olcott, A. N.; Sessions, A. L.; Corsetti, F. A.; Kaufman, A. J.

2005-12-01

Neoproterozoic low-latitude glaciations are often considered times of great biologic limitation because of the hypothesized presence of thick, global sea ice. Alternatively, climate models have suggested that tropical oceans could have remained ice-free, or covered by only thin sea ice, allowing life to continue unimpeded throughout the glaciations. The analysis of organic remains from synglacial sediments provides an approach to address the debate. Here we describe molecular, isotopic, and petrographic analyses of organic rich strata (up to 3.0 percent TOC) deposited in southeastern Brazil during Neoproterozoic low-latitude glaciation ca. 700 Ma. These strata contain extractable biomarkers, including 2-α-methyl hopanes, 2,3,6-trimethylarylisoprenoids, C29-C31 hopanes, and C27-C29 steranes. The preserved biomarkers reflect the presence of a complex and productive ecosystem comprised of both aerobic and anaerobic phototrophs, heterotrophs, and eukaryotes. The biomarker data indicate euxinia extending into the photic zone, providing evidence that the oceans were strongly stratified. Significantly, the occurrence of photosynthetic cyanobacteria and green sulfur bacteria at this time indicates that sea-ice cover at this location was thin to nonexistent, and is incompatible with models for snowball Earth that envision kilometers of ice thickness.

Deciphering metabonomics biomarkers-targets interactions for psoriasis vulgaris by network pharmacology.

Science.gov (United States)

Gu, Jiangyong; Li, Li; Wang, Dongmei; Zhu, Wei; Han, Ling; Zhao, Ruizhi; Xu, Xiaojie; Lu, Chuanjian

2018-06-01

Psoriasis vulgaris is a chronic inflammatory and immune-mediated skin disease. 44 metabonomics biomarkers were identified by high-throughput liquid chromatography coupled to mass spectrometry in our previous work, but the roles of metabonomics biomarkers in the pathogenesis of psoriasis is unclear. The metabonomics biomarker-enzyme network was constructed. The key metabonomics biomarkers and enzymes were screened out by network analysis. The binding affinity between each metabonomics biomarker and target was calculated by molecular docking. A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways. Long-chain fatty acids, phospholipids, Estradiol and NADH were the most important metabonomics biomarkers. Most key enzymes belonged hydrolase, thioesterase and acyltransferase. Six proteins (TNF-alpha, MAPK3, iNOS, eNOS, COX2 and mTOR) were extensively involved in inflammatory reaction, immune response and cell proliferation, and might be drug targets for psoriasis. PI3K-Akt signaling pathway and five other pathways had close correlation with the pathogenesis of psoriasis and could deserve further research. The inflammatory reaction, immune response and cell proliferation are mainly involved in psoriasis. Network pharmacology provide a new insight into the relationships between metabonomics biomarkers and the pathogenesis of psoriasis. KEY MESSAGES   • Network pharmacology was adopted to identify key metabonomics biomarkers and enzymes.   • Six proteins were screened out as important drug targets for psoriasis.   • A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways.

Mass Spectrometry-Based Serum Proteomics for Biomarker Discovery and Validation.

Science.gov (United States)

Bhosale, Santosh D; Moulder, Robert; Kouvonen, Petri; Lahesmaa, Riitta; Goodlett, David R

2017-01-01

Blood protein measurements are used frequently in the clinic in the assessment of patient health. Nevertheless, there remains the need for new biomarkers with better diagnostic specificities. With the advent of improved technology for bioanalysis and the growth of biobanks including collections from specific disease risk cohorts, the plasma proteome has remained a target of proteomics research toward the characterization of disease-related biomarkers. The following protocol presents a workflow for serum/plasma proteomics including details of sample preparation both with and without immunoaffinity depletion of the most abundant plasma proteins and methodology for selected reaction monitoring mass spectrometry validation.

Molecular diagnostics in the management of rhabdomyosarcoma.

Science.gov (United States)

Arnold, Michael A; Barr, Fredric G

2017-02-01

A classification of rhabdomyosarcoma (RMS) with prognostic relevance has primarily relied on clinical features and histologic classification as either embryonal or alveolar RMS. The PAX3-FOXO1 and PAX7-FOXO1 gene fusions occur in 80% of cases with the alveolar subtype and are more predictive of outcome than histologic classification. Identifying additional molecular hallmarks that further subclassify RMS is an active area of research. Areas Covered: The authors review the current state of the PAX3-FOXO1 and PAX7-FOXO1 fusions as prognostic biomarkers. Emerging biomarkers, including mRNA expression profiling, MYOD1 mutations, RAS pathway mutations and gene fusions involving NCOA2 or VGLL2 are also reviewed. Expert commentary: Strategies for modifying RMS risk stratification based on molecular biomarkers are emerging with the potential to transform the clinical management of RMS, ultimately improving patient outcomes by tailoring therapy to predicted patient risk and identifying targets for novel therapies.

Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease—From Brain Starch to Bench and Bedside

Directory of Open Access Journals (Sweden)

Matthias Pawlowski

2017-07-01

Full Text Available Alzheimer’s disease is the most common cause of dementia. Over the last three decades, research has advanced dramatically and provided a detailed understanding of the molecular events underlying the pathogenesis of Alzheimer’s disease. In parallel, assays for the detection of biomarkers that reflect the typical Alzheimer’s disease-associated pathology have been developed and validated in myriads of clinical studies. Such biomarkers complement clinical diagnosis and improve diagnostic accuracy. The use of biomarkers will become even more important with the advent of disease-modifying therapies. Such therapies will likely be most beneficial when administered early in the disease course. Here, we summarise the development of the core Alzheimer’s disease cerebrospinal fluid biomarkers: amyloid-β and tau. We provide an overview of their role in cellular physiology and Alzheimer’s disease pathology, and embed their development as cerebrospinal fluid biomarkers into the historical context of Alzheimer’s disease research. Finally, we summarise recommendations for their use in clinical practice, and outline perspectives for novel cerebrospinal fluid candidate biomarkers.

Bioresponsive probes for molecular imaging : Concepts and in vivo applications

NARCIS (Netherlands)

van Duijnhoven, S.M.J.; Robillard, M.S.; Langereis, S.; Grüll, H.

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of

Bioresponsive probes for molecular imaging: concepts and in vivo applications

NARCIS (Netherlands)

Duijnhoven, S.M. van; Robillard, M.S.; Langereis, S.; Grull, H.

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of

Biomarkers and Environmental Stress: Relevance of Cellular Responses in Determining Adverse Outcomes

Science.gov (United States)

Biomarkers are measurable changes in a biological system indicative of an interaction with a chemical, physical, or biological agent. Such changes can be molecular, biochemical, physiological, or histological and can be reflective of either xenobiotic exposures or effects. Molecu...

Limitations of an ocular surface inflammatory biomarker in impression cytology specimens.

Science.gov (United States)

Yafawi, Rolla; Ko, Mira; Sace, Frederick P; John-Baptiste, Annette

2013-03-01

A number of ocular conditions, such as dry eye, are associated with inflammation on the surface of the eye leading to irritation and ocular pain. Many drugs such as chemotherapeutics, beta blockers, angiotensin-converting enzymes and so forth also cause dry eye but currently there are no validated ocular surface biomarkers available. We evaluated sample stability, assay sensitivity, reproducibility and overall performance of impression cytology (IC) utilizing the cellular surface biomarker human leukocyte antigen DR-1 (HLA-DR) as an ocular surface inflammatory biomarker by flow cytometry in a fit-for-purpose validation study. Additionally, subjects classified as normal or having various degrees of dry eye were evaluated to determine if HLA-DR could demonstrate a clear separation between normal and dry eye samples. The assay demonstrated high dynamic range detecting a broad range of fluorescent intensities in healthy donors. Additionally, inter, intra and stability assay results demonstrated strong concordance and low variability. Overall CV% for both assays were less than 25% for all measured parameters. However, high variability was observed for donor samples assayed beyond day 10 post IC sample collection (4.2-110.8 CV%). HLA-DR expression demonstrated a progressive increase in patients with mild to severe levels of dry eye disease providing sufficient evidence it is sensitive enough to monitor inflammatory effects of dry eye when coupled with additional biomarkers and/or methodologies such as cytokine analysis or ICAM-1. This biomarker can be used to monitor ocular surface disorders in patients and to evaluate potential treatment options during drug development. Although our results demonstrate this methodology is reproducible for routine evaluation, limitations around sample integrity exist. The ocular cell surface inflammatory biomarker, HLA-DR coupled with impression cytology is a simple non-invasive robust, specific and reproducible assay that can be

Amyloid Biomarkers in Conformational Diseases at Face Value: A Systematic Review

Directory of Open Access Journals (Sweden)

Maria Fernanda Avila-Vazquez

2017-12-01

Full Text Available Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, β-cells, etc. represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and presents the future possibilities it opens up. The nuclear diagnosis methods are immunoassays: ELISA, immunodot, western blot, etc., while the therapeutic approach is focused on pharmaco- and molecular chaperones.

MortalityPredictors.org: a manually-curated database of published biomarkers of human all-cause mortality.

Science.gov (United States)

Peto, Maximus V; De la Guardia, Carlos; Winslow, Ksenia; Ho, Andrew; Fortney, Kristen; Morgen, Eric

2017-08-31

Biomarkers of all-cause mortality are of tremendous clinical and research interest. Because of the long potential duration of prospective human lifespan studies, such biomarkers can play a key role in quantifying human aging and quickly evaluating any potential therapies. Decades of research into mortality biomarkers have resulted in numerous associations documented across hundreds of publications. Here, we present MortalityPredictors.org , a manually-curated, publicly accessible database, housing published, statistically-significant relationships between biomarkers and all-cause mortality in population-based or generally healthy samples. To gather the information for this database, we searched PubMed for appropriate research papers and then manually curated relevant data from each paper. We manually curated 1,576 biomarker associations, involving 471 distinct biomarkers. Biomarkers ranged in type from hematologic (red blood cell distribution width) to molecular (DNA methylation changes) to physical (grip strength). Via the web interface, the resulting data can be easily browsed, searched, and downloaded for further analysis. MortalityPredictors.org provides comprehensive results on published biomarkers of human all-cause mortality that can be used to compare biomarkers, facilitate meta-analysis, assist with the experimental design of aging studies, and serve as a central resource for analysis. We hope that it will facilitate future research into human mortality and aging.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

Science.gov (United States)

Figueiredo, Ceu; Camargo, M C; Leite, Marina; Fuentes-Pananá, Ezequiel M; Rabkin, Charles S; Machado, José C

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Autologous Blood Transfusion in Sports: Emerging Biomarkers.

Science.gov (United States)

Salamin, Olivier; De Angelis, Sara; Tissot, Jean-Daniel; Saugy, Martial; Leuenberger, Nicolas

2016-07-01

Despite being prohibited by the World Anti-Doping Agency, blood doping through erythropoietin injection or blood transfusion is frequently used by athletes to increase oxygen delivery to muscles and enhance performance. In contrast with allogeneic blood transfusion and erythropoietic stimulants, there is presently no direct method of detection for autologous blood transfusion (ABT) doping. Blood reinfusion is currently monitored with individual follow-up of hematological variables via the athlete biological passport, which requires further improvement. Microdosage is undetectable, and suspicious profiles in athletes are often attributed to exposure to altitude, heat stress, or illness. Additional indirect biomarkers may increase the sensitivity and specificity of the longitudinal approach. The emergence of "-omics" strategies provides new opportunities to discover biomarkers for the indirect detection of ABT. With the development of direct quantitative methods, transcriptomics based on microRNA or messenger RNA expression is a promising approach. Because blood donation and blood reinfusion alter iron metabolism, quantification of proteins involved in metal metabolism, such as hepcidin, may be applied in an "ironomics" strategy to improve the detection of ABT. As red blood cell (RBC) storage triggers changes in membrane proteins, proteomic methods have the potential to identify the presence of stored RBCs in blood. Alternatively, urine matrix can be used for the quantification of the plasticizer di(2-ethyhexyl)phthalate and its metabolites that originate from blood storage bags, suggesting recent blood transfusion, and have an important degree of sensitivity and specificity. This review proposes that various indirect biomarkers should be applied in combination with mathematical approaches for longitudinal monitoring aimed at improving ABT detection. Copyright © 2016 Elsevier Inc. All rights reserved.

Sparse feature selection identifies H2A.Z as a novel, pattern-specific biomarker for asymmetrically self-renewing distributed stem cells

Directory of Open Access Journals (Sweden)

Yang Hoon Huh

2015-03-01

Full Text Available There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow. Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify such useful and specific DSC biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells, with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ.

Evaluation of early changes of cartilage biomarkers following arthroscopic meniscectomy in young Egyptian adults

Directory of Open Access Journals (Sweden)

Hamdy Khamis Koryem

2015-09-01

Conclusion: Cartilage volume loss by MRI combined with changes in cartilage matrix turnover detected by molecular biomarkers may reflect the initial changes associated with cartilage degeneration that account for early OA.

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.

Science.gov (United States)

Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

2014-09-01

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. © FASEB.

Advances in gene therapy of myocardial ischemia and the monitoring with molecular imaging

International Nuclear Information System (INIS)

Zhang Guopeng; Zhang Yongxue

2008-01-01

Cardiovascular diseases are harmful for people. Recent advances in understanding the molecular basis of cardiovascular diseases, together with some studies of the gene therapy on cardiovascular disorders, have offered possibilities for new treatments. Gene therapies have demonstrated potential usefulness in treating myocardial ischemia. Therefore, the monitoring of the expression of therapy gene and therapeutic efficacy has become an important issue. (authors)

Evaluation of a Serum Lung Cancer Biomarker Panel.

Science.gov (United States)

Mazzone, Peter J; Wang, Xiao-Feng; Han, Xiaozhen; Choi, Humberto; Seeley, Meredith; Scherer, Richard; Doseeva, Victoria

2018-01-01

A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results.

Miniaturized Bio-and Chemical-Sensors for Point-of-Care Monitoring of Chronic Kidney Diseases

Directory of Open Access Journals (Sweden)

Antonio Tricoli

2018-03-01

Full Text Available This review reports the latest achievements in point-of-care (POC sensor technologies for the monitoring of ammonia, creatinine and urea in patients suffering of chronic kidney diseases (CKDs. Abnormal levels of these nitrogen biomarkers are found in the physiological fluids, such as blood, urine and sweat, of CKD patients. Delocalized at-home monitoring of CKD biomarkers via integration of miniaturized, portable, and low cost chemical- and bio-sensors in POC devices, is an emerging approach to improve patients’ health monitoring and life quality. The successful monitoring of CKD biomarkers, performed on the different body fluids by means of sensors having strict requirements in term of size, cost, large-scale production capacity, response time and simple operation procedures for use in POC devices, is reported and discussed.

Bio-markers: traceability in food safety issues.

Science.gov (United States)

Raspor, Peter

2005-01-01

Research and practice are focusing on development, validation and harmonization of technologies and methodologies to ensure complete traceability process throughout the food chain. The main goals are: scale-up, implementation and validation of methods in whole food chains, assurance of authenticity, validity of labelling and application of HACCP (hazard analysis and critical control point) to the entire food chain. The current review is to sum the scientific and technological basis for ensuring complete traceability. Tracing and tracking (traceability) of foods are complex processes due to the (bio)markers, technical solutions and different circumstances in different technologies which produces various foods (processed, semi-processed, or raw). Since the food is produced for human or animal consumption we need suitable markers to be stable and traceable all along the production chain. Specific biomarkers can have a function in technology and in nutrition. Such approach would make this development faster and more comprehensive and would make possible that food effect could be monitored with same set of biomarkers in consumer. This would help to develop and implement food safety standards that would be based on real physiological function of particular food component.

Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS

Energy Technology Data Exchange (ETDEWEB)

Garabedian, Alyssa; Benigni, Paolo; Ramirez, Cesar; Baker, Erin M.; Liu, Tao; Smith, Richard D.; Fernandez-Lima, Francisco

2018-05-01

Abstract. In the present work, the potential of trapped ion mobility spectrometry coupled to TOF mass spectrometry (TIMS-TOF MS) for discovery and targeted monitoring of peptide biomarkers from human-in-mouse xenograft tumor tissue was evaluated. In particular, a TIMS-MS workflow was developed for the detection and quantification of peptide biomarkers using internal heavy analogs, taking advantage of the high mobility resolution (R = 150–250) prior to mass analysis. Five peptide biomarkers were separated, identified, and quantified using offline nanoESI-TIMSCID- TOF MS; the results were in good agreement with measurements using a traditional LC-ESI-MS/MS proteomics workflow. The TIMS-TOF MS analysis permitted peptide biomarker detection based on accurate mobility, mass measurements, and high sequence coverage for concentrations in the 10–200 nM range, while simultaneously achieving discovery measurements

The role of toxicology to characterize biomarkers for agrochemicals with potential endocrine activities.

Science.gov (United States)

Mantovani, Alberto; Maranghi, Francesca; La Rocca, Cinzia; Tiboni, Gian Mario; Clementi, Maurizio

2008-09-01

The paper discusses current knowledge and possible research priorities on biomarkers of exposure, effect and susceptibility for potential endocrine activities of agrochemicals (dicarboximides, ethylene bisdithiocarbammates, triazoles, etc.). Possible widespread, multiple-pathway exposure to agrochemicals highlights the need to assess internal exposure of animals or humans, which is the most relevant exposure measure for hazard and risk estimation; however, exposure data should be integrated by early indicators predictive of possible health effects, particularly for vulnerable groups such as mother-child pairs. Research need include: non-invasive biomarkers for children biomonitoring; novel biomarkers of total exposure to measure whole endocrine disrupter-related burden; characterization of biomarkers of susceptibility, including the role of markers of nutritional status; anchoring early molecular markers to established toxicological endpoints to support their predictivity; integrating "omics"-based approaches in a system-toxicology framework. As biomonitoring becomes increasingly important in the environment-and-health scenario, toxicologists can substantially contribute both to the characterization of new biomarkers and to the predictivity assessment and improvement of the existing ones.

Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

Science.gov (United States)

Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

2017-03-07

Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the

Ambient temperature and cardiovascular biomarkers in a repeated-measure study in healthy adults: A novel biomarker index approach.

Science.gov (United States)

Wu, Shaowei; Yang, Di; Pan, Lu; Shan, Jiao; Li, Hongyu; Wei, Hongying; Wang, Bin; Huang, Jing; Baccarelli, Andrea A; Shima, Masayuki; Deng, Furong; Guo, Xinbiao

2017-07-01

Associations of ambient temperature with cardiovascular morbidity and mortality have been well documented in numerous epidemiological studies, but the underlying pathways remain unclear. We investigated whether systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function may be the mechanistic pathways associated with ambient temperature. Forty study participants underwent repeated blood collections for 12 times in Beijing, China in 2010-2011. Ambient temperature and air pollution data were measured in central monitors close to student residences. We created five indices as the sum of weighted biomarker percentiles to represent the overall levels of 15 cardiovascular biomarkers in five pathways (systemic inflammation: hs-CRP, TNF-α and fibrinogen; coagulation: fibrinogen, PAI-1, tPA, vWF and sP-selectin; systemic oxidative stress: Ox-LDL and sCD36: antioxidant activity: EC-SOD and GPX1; and endothelial function: ET-1, E-selectin, ICAM-1 and VCAM-1). We used generalized mixed-effects models to estimate temperature effects controlling for air pollution and other covariates. There were significant decreasing trends in the adjusted means of biomarker indices over the lowest to the highest quartiles of daily temperatures before blood collection. A 10°C decrease at 2-d average daily temperature were associated with increases of 2.5% [95% confidence interval (CI): 0.7, 4.2], 1.6% (95% CI: 0.1, 3.1), 2.7% (95% CI: 0.5, 4.8), 5.5% (95% CI: 3.8, 7.3) and 2.0% (95% CI: 0.3, 3.8) in the indices for systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function, respectively. In contrast, the associations between ambient temperature and individual biomarkers had substantial variation in magnitude and strength. The altered cardiovascular biomarker profiles in healthy adults associated with ambient temperature changes may help explain the temperature-related cardiovascular morbidity

Can the Growth/Differentiation Factor-15 Be a Surrogate Target in Chronic Heart Failure Biomarker-Guided Therapy?

Directory of Open Access Journals (Sweden)

Alexander E. Berezin

2017-03-01

Full Text Available Heart failure (HF biomarker-guided therapy is a promising method, which directs to the improvement of clinical status, attenuation of admission/readmission to the hospital and reduction in mortality rate. Many biological markers, like inflammatory cytokines, are under consideration as a surrogate target for HF treatment, while there are known biomarkers with established predictive value, such as natriuretic peptides. However, discovery of new biomarkers reflecting various underlying mechanisms of HF and appearing to be surrogate targets for biomarker-guided therapy is fairly promising. Nowadays, growth/differentiation factor 15 (GDF-15 is suggested a target biomarker for HF treatment. Although elevated level of GDF-15 is associated with HF development, progression, and prognosis, there is no represented evidence regarding the direct comparison of this biomarker with other clinical risk predictors and biomarkers. Moreover, GDF-15 might serve as a contributor to endothelial progenitor cells (EPC dysfunction by inducing EPC death/autophagy and limiting their response to angiopoetic and reparative effects. The short communication was discussed whether GDF-15 is good molecular target for HF biomarker-guided therapy.

Potential biomarker panels in overall breast cancer management: advancements by multilevel diagnostics.

Science.gov (United States)

Girotra, Shantanu; Yeghiazaryan, Kristina; Golubnitschaja, Olga

2016-09-01

Breast cancer (BC) prevalence has reached an epidemic scale with half a million deaths annually. Current deficits in BC management include predictive and preventive approaches, optimized screening programs, individualized patient profiling, highly sensitive detection technologies for more precise diagnostics and therapy monitoring, individualized prediction and effective treatment of BC metastatic disease. To advance BC management, paradigm shift from delayed to predictive, preventive and personalized medical services is essential. Corresponding step forwards requires innovative multilevel diagnostics procuring specific panels of validated biomarkers. Here, we discuss current instrumental advancements including genomics, proteomics, epigenetics, miRNA, metabolomics, circulating tumor cells and cancer stem cells with a focus on biomarker discovery and multilevel diagnostic panels. A list of the recommended biomarker candidates is provided.

Suppression of pro-inflammatory and pro-survival biomarkers in oral cancer patients consuming a black raspberry phytochemical-rich troche

Science.gov (United States)

Knobloch, Thomas J.; Uhrig, Lana K.; Pearl, Dennis K.; Casto, Bruce C.; Warner, Blake M.; Clinton, Steven K.; Sardo-Molmenti, Christine L.; Ferguson, Jeanette M.; Daly, Brett T.; Riedl, Kenneth; Schwartz, Steven J.; Vodovotz, Yael; Buchta, Anthony J.; Schuller, David E.; Ozer, Enver; Agrawal, Amit; Weghorst, Christopher M.

2016-01-01

Black raspberries (BRBs) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce pro-inflammatory and anti-apoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCCs) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and non-involved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of pro-survival genes (AURKA, BIRC5, EGFR) and pro-inflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated Grade 3–4 toxicities or adverse events and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark anti-apoptotic and pro-inflammatory molecular biomarkers were over-expressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. Since these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention. PMID:26701664

Using exposure windows to explore an elusive biomarker: blood manganese.

Science.gov (United States)

Baker, Marissa G; Stover, Bert; Simpson, Christopher D; Sheppard, Lianne; Seixas, Noah S

2016-05-01

We sought to understand the time course between exposure to manganese (Mn) and uptake into the blood, to allow a more meaningful interpretation of exposure biomarker data, and to determine the utility of blood as a biomarker of Mn exposure. Welder trainees were monitored over the course of a five-quarter training program. Each quarter, trainees gave eight blood samples and had personal air monitoring four times. A mixed model was fit to obtain estimates of airborne exposure by welding type (fixed effect), adjusted for subject (random effect). Considering weekends and days absent as zero exposure, estimated exposures were summed over various exposure windows and related to measured blood manganese (MnB) using a mixed model. A relationship consistent with zero was found between MnB and modeled 1 or 7 days of exposure. After 30 days of preceding exposure, a 1 mg-days/m(3) increase in air Mn is associated with a 0.57 ng/mL increase in MnB (95% CI -0.04, 1.19). Considering a 90-day exposure window and a cumulative exposure window, a 1 mg-days/m(3) increase in air Mn is associated with a 0.26 (95% CI 0.005, 0.51) and 0.09 (95% CI 0.006, 0.17) ng/mL increase in MnB, respectively. From this analysis, MnB may begin to act as a biomarker of Mn exposure over longer time periods, or at higher levels of exposure. This novel study design allowed investigation of how MnB relates to different time windows of exposure, representing the most robust Mn exposure assessment in the biomarker literature.

Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis.

Science.gov (United States)

Yarmola, Elena G; Shah, Yash; Arnold, David P; Dobson, Jon; Allen, Kyle D

2016-04-01

Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker--the c-terminus telopeptide of type II collagen (CTXII)--magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide-containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 μL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed tenfold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat.

MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

Directory of Open Access Journals (Sweden)

Tarek Shalaby

2014-11-01

Full Text Available Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5–10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets.

Evaluating Chagas disease progression and cure through blood-derived biomarkers: a systematic review.

Science.gov (United States)

Requena-Méndez, Ana; López, Manuel Carlos; Angheben, Andrea; Izquierdo, Luis; Ribeiro, Isabela; Pinazo, Maria-Jesús; Gascon, Joaquim; Muñoz, José

2013-09-01

This article reviews the usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage. The authors used a search strategy based on MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS databases. Out of 1716 screened articles, only 166 articles were eligible for final inclusion. The authors classified the biomarkers according to their biochemical structure and primary biological activity in four groups: i) markers of inflammation and cellular injury, ii) metabolic biomakers, iii) prothrombotic biomarkers and iv) markers derived from specific antigens of the parasite. Several potential biomarkers might have clinical potential for the detection of early cardiopathy. Such capacity is imperative in order to detect high-risk patients who require intensive monitoring and earlier therapy. Prospective studies with longer follow-ups are needed for the appraisal of biomarkers assessing clinical or microbiological cure after therapy. At the same time, studies evaluating more than one biomarker are useful to compare the efficacy among them given the lack of a recognized gold standard.

An Update on Genetic and Serotoneric Biomarker Findings in Bulimia Nervosa

DEFF Research Database (Denmark)

Sjögren, Magnus

2017-01-01

support in understanding the pathophysiology of BN, and potentially in diagnosing, and monitoring of effects of treatment. This review describes genetic and serotonergic biomarkers for BN. Method: A literature search using PUBMED (20 June 2017) was done using the following search terms: 1) “Bulimia...

Development of protein biomarkers in cerebrospinal fluid for secondary progressive multiple sclerosis using selected reaction monitoring mass spectrometry (SRM-MS

Directory of Open Access Journals (Sweden)

Jia Yan

2012-07-01

Full Text Available Abstract Background Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system (CNS. It involves damage to the myelin sheath surrounding axons and to the axons themselves. MS most often presents with a series of relapses and remissions but then evolves over a variable period of time into a slowly progressive form of neurological dysfunction termed secondary progressive MS (SPMS. The reasons for this change in clinical presentation are unclear. The absence of a diagnostic marker means that there is a lag time of several years before the diagnosis of SPMS can be established. At the same time, understanding the mechanisms that underlie SPMS is critical to the development of rational therapies for this untreatable stage of the disease. Results Using high performance liquid chromatography-coupled mass spectrometry (HPLC; we have established a highly specific and sensitive selected reaction monitoring (SRM assay. Our multiplexed SRM assay has facilitated the simultaneous detection of surrogate peptides originating from 26 proteins present in cerebrospinal fluid (CSF. Protein levels in CSF were generally ~200-fold lower than that in human sera. A limit of detection (LOD was determined to be as low as one femtomol. We processed and analysed CSF samples from a total of 22 patients with SPMS, 7 patients with SPMS treated with lamotrigine, 12 patients with non-inflammatory neurological disorders (NIND and 10 healthy controls (HC for the levels of these 26 selected potential protein biomarkers. Our SRM data found one protein showing significant difference between SPMS and HC, three proteins differing between SPMS and NIND, two proteins between NIND and HC, and 11 protein biomarkers showing significant difference between a lamotrigine-treated and untreated SPMS group. Principal component analysis (PCA revealed that these 26 proteins were correlated, and could be represented by four principal components. Overall, we established an

ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock.

Science.gov (United States)

Aletti, Federico; Conti, Costanza; Ferrario, Manuela; Ribas, Vicent; Bollen Pinto, Bernardo; Herpain, Antoine; Post, Emiel; Romay Medina, Eduardo; Barlassina, Cristina; de Oliveira, Eliandre; Pastorelli, Roberta; Tedeschi, Gabriella; Ristagno, Giuseppe; Taccone, Fabio S; Schmid-Schönbein, Geert W; Ferrer, Ricard; De Backer, Daniel; Bendjelid, Karim; Baselli, Giuseppe

2016-01-28

The ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock. Ninety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1  5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses. ShockOmics will provide new insights into the pathophysiological mechanisms underlying shock as well as new biomarkers for the timely diagnosis of cardiac dysfunction in shock and quantitative indices for assisting the therapeutic management of shock patients.

Use of Saliva Biomarkers to Monitor Efficacy of Vitamin C in Exercise-Induced Oxidative Stress

Directory of Open Access Journals (Sweden)

Levi W. Evans

2017-01-01

Full Text Available Saliva is easily obtainable for medical research and requires little effort or training for collection. Because saliva contains a variety of biological compounds, including vitamin C, malondialdehyde, amylase, and proteomes, it has been successfully used as a biospecimen for the reflection of health status. A popular topic of discussion in medical research is the potential association between oxidative stress and negative outcomes. Systemic biomarkers that represent oxidative stress can be found in saliva. It is unclear, however, if saliva is an accurate biospecimen as is blood and/or plasma. Exercise can induce oxidative stress, resulting in a trend of antioxidant supplementation to combat its assumed detriments. Vitamin C is a popular antioxidant supplement in the realm of sports and exercise. One potential avenue for evaluating exercise induced oxidative stress is through assessment of biomarkers like vitamin C and malondialdehyde in saliva. At present, limited research has been done in this area. The current state of research involving exercise-induced oxidative stress, salivary biomarkers, and vitamin C supplementation is reviewed in this article.

In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device

NARCIS (Netherlands)

De Lima Braga Lopes Cordeiro, Carlos; de Vries, M.G.; Ngabi, W; Oomen, P.E.; Cremers, T.I.F.H.; Westerink, B.H.C.

2015-01-01

Enzyme-based amperometric biosensors are widely used for monitoring key biomarkers. In experimental neuroscience there is a growing interest in in vivo continuous and simultaneous monitoring of metabolism-related biomarkers, like glucose, lactate and pyruvate. The use of multiplex biosensors will

Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis.

Directory of Open Access Journals (Sweden)

Tong Zhou

Full Text Available Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis. Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n = 39 from healthy controls (n = 35, 86% classification accuracy and which served as a molecular signature for complicated sarcoidosis (n = 17. As aberrancies in T cell receptor (TCR signaling, JAK-STAT (JS signaling, and cytokine-cytokine receptor (CCR signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1. In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis.

Molecular biomarkers for sources of organic matter in lacustrine sediments in a subtropical lake in China.

Science.gov (United States)

Wang, Yan-Hua; Yang, Hao; Chen, Xia; Zhang, Ji-Xiang; Ou, Jie; Xie, Biao; Huang, Chang-Chun

2013-05-01

N-alkanes distributions and stable isotopic compositions (δ(13)C and δ(15)N) in the lacustrine sediments of Shijiu lake were measured to assess whether biological source information was recorded in the molecular biomarker. Results showed regular unimodal n-alkanes distribution in range of C16-C33 with strong predominance of odd-numbered n-alkanes, maximizing at C29. The δ(15)N for SON were uniformly low, ranging from -6.7‰ to 3.8‰ and C/N ratios ranged from 6.6 to 10.0, suggesting that most of organic matter was influenced by terrestrial characteristics of the watershed. The δ(13)C for C27 to C31n-alkanes and for SOC varied from -32.9‰ to -26.6‰ and -23.4‰ to -21.6‰, respectively, falling within the range of corresponding n-alkanes in leaves mainly from C3 land plants. The values of C/N, CPI, OEP, ACL and C27/C31 exhibit similar temporal changes with the primary production, showing enhanced eutrophication resulted from increased anthropogenic activities in Shijiu lake from 1852 to 2010. Copyright © 2013 Elsevier Ltd. All rights reserved.

Epithelial membrane protein-1 is a biomarker of gefitinib resistance.

Science.gov (United States)

Jain, Anjali; Tindell, Charles A; Laux, Isett; Hunter, Jacob B; Curran, John; Galkin, Anna; Afar, Daniel E; Aronson, Nina; Shak, Steven; Natale, Ronald B; Agus, David B

2005-08-16

We describe a molecular resistance biomarker to gefitinib, epithelial membrane protein-1 (EMP-1). Gefitinib is a small-molecule inhibitor that competes for the ATP-binding site on EGF receptor (EGFR) and has been approved for patients with advanced lung cancers. Treatment with gefitinib has resulted in clinical benefit in patients, and, recently, heterozygous somatic mutations within the EGFR catalytic domain have been identified as a clinical correlate to objective response to gefitinib. However, clinical resistance to gefitinib limits the utility of this therapeutic to a fraction of patients, and objective clinical responses are rare. We aimed to assess the molecular phenotype and mechanism of in vivo gefitinib resistance in xenograft models and in patient samples. We generated in vivo gefitinib-resistance models in an adenocarcinoma xenograft model by serially passaging tumors in nude mice in presence of gefitinib until resistance was acquired. EMP-1 was identified as a surface biomarker whose expression correlated with acquisition of gefitinib resistance. EMP-1 expression was further correlated with lack of complete or partial response to gefitinib in lung cancer patient samples as well as clinical progression to secondary gefitinib resistance. EMP-1 expression and acquisition of gefitinib clinical resistance was independent of gefitinib-sensitizing EGFR somatic mutations. This report suggests the role of the adhesion molecule, EMP-1, as a biomarker of gefitinib clinical resistance, and further suggests a probable cross-talk between this molecule and the EGFR signaling pathway.

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

Science.gov (United States)

Kao, Amy H.; Manzi, Susan; Ahearn, Joseph M.

2013-01-01

The search for lupus biomarkers to diagnose, monitor, stratify, and predict individual response to therapy is currently more intense than ever before. This effort is essential for several reasons. First, epidemic overdiagnosis and underdiagnosis of lupus, even by certified rheumatologists, leads to errors in therapy with concomitant side effects which may be more serious than the disease itself. Second, identification of lupus flares remains as much an art as it is a science. Third, the capacity to stratify patients so as to predict those who will develop specific patterns of organ involvement is not currently possible but would potentially lead to preventive therapeutic strategies. Fourth, only one new drug for the treatment of lupus has been approved by the US Food and Drug Administration in over 50 years. A major obstacle in this pipeline is the dearth of biomarkers available to prove a patient has responded to an experimental therapeutic intervention. This review will summarize the challenges faced in the discovery and validation of lupus biomarkers, the most promising lupus biomarkers identified to date, and the promise of future directions. PMID:23904865

Biomarker development for presymptomatic molecular diagnosis of preeclampsia: feasible, useful or even unnecessary?

Science.gov (United States)

Hahn, Sinuhe; Lapaire, Olav; Than, Nandor Gabor

2015-05-01

The past decade saw the advent of a number of promising biomarkers to detect pregnancies at risk for preeclampsia (PE), the foremost being those associated with an imbalance of angiogenic factors. In late pregnancy, these are useful for the detection of imminent cases of PE, while earlier they were more predictive for early- than late-onset PE. This suggests that there may be fundamental differences between the underlying pathology of these two PE forms. Therefore, it is possible that such a biological premise may limit the development of biomarkers that will permit the efficacious detection of both early- and late-onset PE via an analysis of first-trimester maternal blood samples. Consequently, a significant increase in our understanding of the underlying pathology of PE, using a variety of approaches ranging from systems biology to animal models, will be necessary in order to overcome this obstacle.

Combination of biomarkers

DEFF Research Database (Denmark)

Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger

2012-01-01

The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

[Strategy for molecular testing in pulmonary carcinoma].

Science.gov (United States)

Penault-Llorca, Frédérique; Tixier, Lucie; Perrot, Loïc; Cayre, Anne

2016-01-01

Nowadays, the analysis of theranostic molecular markers is central in the management of lung cancer. As those tumors are diagnosed in two third of the cases at an advanced stage, molecular screening is frequently performed on "small samples". The screening strategy starts by an accurate histopathological characterization, including on biopsies or cytological specimens. WHO 2015 provided a new classification for small biopsy and cytology, defining categories such as non-small cell carcinoma (NSCC), favor adenocarcinoma (TTF1 positive), or favor squamous cell carcinoma (p40 positive). Only the NSCC tumors, non-squamous, are eligible to molecular testing. A strategy aiming at tissue sparing for the small biopsies has to be organized. Tests corresponding to available drugs are prioritized. Blank slides will be prepared for immunohistochemistry and in situ hybridization based tests such as ALK. DNA will then be extracted for the other tests, EGFR mutation screening first associated or not to KRAS. Then, the emerging biomarkers (HER2, ROS1, RET, BRAF…) as well as potentially other markers in case of clinical trials, can been tested. The spread of next generation sequencing technologies, with a very sensitive all-in-one approach will allow the identification of minority clones. Eventually, the development of liquid biopsies will provide the opportunity to monitor the apparition of resistance clones during treatment. This non-invasive approach allows patients with a contraindication to perform biopsy or with non-relevant biopsies to access to molecular screening. Copyright © 2016. Published by Elsevier Masson SAS.

Evaluation of a biomarker of Cd(II) exposure on Limnoperna fortunei

International Nuclear Information System (INIS)

Mariano, Belaich; Cristian, Oliver; Marcela, Pilloff; Porta, Andres

2006-01-01

The use of organisms to monitor contamination allows the access to information that cannot be acquired by chemical methods. Limnoperna fortunei, mussel frequently found in Rio de la Plata estuary, fulfils the requirements to be used as a biomonitoring organism. In this work we report that a polypeptide of 22 kDa of molecular weight (LF22) is induced when L. fortunei is exposed to Cd (II), Cu(II) and Hg(II) sublethal levels. To characterize LF22, mussels were sampled from a non-polluted region and whole soft tissue was homogenized, with and without previous exposure to 100 μg/L of Cd(II). The cytosolic proteins were evaluated by mono and bidimensional SDS-PAGE, and size exclusion chromatography. All the methods showed that LF22 triples its concentration in presence of Cd(II). Purification of LF22 was achieved by fractioned precipitation, salting-out, ionic exchange and size exclusion chromatography. We conclude that LF22 is a useful biomarker of heavy metal exposure. - Limnoperna fortunei induces a 22 kDa polypeptide in sublethal exposure to Cd(II)

Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

Science.gov (United States)

Hainfellner, J A; Heinzl, H

2010-01-01

Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

Emerging biomarkers in the diagnosis of prostate cancer

Directory of Open Access Journals (Sweden)

Filella X

2018-05-01

Full Text Available Xavier Filella, Esther Fernández-Galan, Rosa Fernández Bonifacio, Laura Foj Department of Biochemistry and Molecular Genetics (CDB, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain Abstract: Prostate cancer (PCa is the second most common cancer in men worldwide. A large proportion of PCa are latent, never destined to progress or affect the patients’ life. It is of utmost importance to identify which PCa are destined to progress and which would benefit from an early radical treatment. Prostate-specific antigen (PSA remains the most used test to detect PCa. Its limited specificity and an elevated rate of overdiagnosis are the main problems associated with PSA testing. New PCa biomarkers have been proposed to improve the accuracy of PSA in the management of early PCa. Commercially available biomarkers such as PCA3 score, Prostate Health Index (PHI, and the four-kallikrein panel are used with the purpose of reducing the number of unnecessary biopsies and providing information related to the aggressiveness of the tumor. The relationship with PCa aggressiveness seems to be confirmed by PHI and the four-kallikrein panel, but not by the PCA3 score. In this review, we also summarize new promising biomarkers, such as PSA glycoforms, TMPRSS2:ERG fusion gene, microRNAs, circulating tumor cells, androgen receptor variants, and PTEN gene. All these emerging biomarkers could change the management of early PCa, offering more accurate results than PSA. Nonetheless, large prospective studies comparing these new biomarkers among them are required to know their real value in PCa detection and prognosis. Keywords: prostate cancer, PSA, PHI, four-kallikrein panel, PCA3, miRNAs

Placenta-derived exosomes: potential biomarkers of preeclampsia

Directory of Open Access Journals (Sweden)

Pillay P

2017-10-01

Full Text Available Preenan Pillay,1,2 Kogi Moodley,1 Jagidesa Moodley,3 Irene Mackraj3 1Discipline of Human Physiology, Nelson R Mandela School of Medicine, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; 2Pearson Institute of Higher Education, Midrand, South Africa; 3Women’s Health and HIV Research Group, Nelson R Mandela School of Medicine, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: Preeclampsia remains a leading cause of maternal and fetal mortality, due to ineffective treatment and diagnostic strategies, compounded by the lack of clarity on the etiology of the disorder. Although several clinical and biological markers of preeclampsia have been evaluated, they have proven to be ineffective in providing a definitive diagnosis during the various stages of the disorder. Exosomes have emerged as ideal biomarkers of pathological states, such as cancer, and have more recently gained interest in pregnancy-related complications, due to their role in cellular communication in normal and complicated pregnancies. This occurs as a result of the specific placenta-derived exosomal molecular cargo, which may be involved in normal pregnancy-associated immunological events, such as the maintenance of maternal–fetal tolerance. This review provides perspectives on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis of preeclampsia. Using keywords, online databases were searched to identify relevant publications to review the potential use of placenta-derived exosomes as biomarkers of preeclampsia. Keywords: placenta-derived exosomes, preeclampsia, biomarkers

A distinct urinary biomarker pattern characteristic of female Fabry patients that mirrors response to enzyme replacement therapy.

Directory of Open Access Journals (Sweden)

Andreas D Kistler

Full Text Available Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naïve female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naïve Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy.

Biological monitoring of occupational exposure to dust among aluminium foundry workers

Directory of Open Access Journals (Sweden)

Ali Choupani

2018-05-01

Conclusion ― Determination of AL concentration in urine is not enough to serve as a biomarker. Estimation of AL nanoparticles in the air and biomarkers that determine the actual absorption rate seems to be an adequate method for occupational exposure monitoring of AL.

Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of distal airway and blood biomarkers that predict FEV1 decline

Science.gov (United States)

Weiden, Michael D.; Kwon, Sophia; Caraher, Erin; Berger, Kenneth I.; Reibman, Joan; Rom, William N.; Prezant, David J.; Nolan, Anna

2016-01-01

Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung’s normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after World Trade Center (WTC) exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1biomarkers of WTC-LI. We have identified biomarkers of Inflammation, metabolic derangement, protease/antiprotease balance and vascular injury expressed in serum within 6 months of WTC exposure that were predictive of their FEV1 up to 7 years after their WTC exposure. Predicting future risk of airway injury after particulate exposures can focus monitoring and early treatment on a subset of patients in greatest need of these services. PMID:26024341

III: Use of biomarkers as Risk Indicators in Environmental Risk Assessment of oil based discharges offshore.

Science.gov (United States)

Sanni, Steinar; Lyng, Emily; Pampanin, Daniela M

2017-06-01

Offshore oil and gas activities are required not to cause adverse environmental effects, and risk based management has been established to meet environmental standards. In some risk assessment schemes, Risk Indicators (RIs) are parameters to monitor the development of risk affecting factors. RIs have not yet been established in the Environmental Risk Assessment procedures for management of oil based discharges offshore. This paper evaluates the usefulness of biomarkers as RIs, based on their properties, existing laboratory biomarker data and assessment methods. Data shows several correlations between oil concentrations and biomarker responses, and assessment principles exist that qualify biomarkers for integration into risk procedures. Different ways that these existing biomarkers and methods can be applied as RIs in a probabilistic risk assessment system when linked with whole organism responses are discussed. This can be a useful approach to integrate biomarkers into probabilistic risk assessment related to oil based discharges, representing a potential supplement to information that biomarkers already provide about environmental impact and risk related to these kind of discharges. Copyright © 2016 Elsevier Ltd. All rights reserved.

A critical assessment of some biomarker approaches linked with dietary intake

DEFF Research Database (Denmark)

Crews, H.; Alink, G.; Andersen, Rikke

2001-01-01

interactions and the role of measuring total antioxidant capacity is considered in some detail. In contrast to most nutrients, there is a marked lack of biomarkers of either exposure or effect for most non-nutrients. The role of biological effect monitoring is considered for dietary contaminants, fumonisins...

MicroRNA Biomarkers in Neurodegenerative Diseases and Emerging Nano-Sensors Technology

Directory of Open Access Journals (Sweden)

Pratik Shah

2017-01-01

Full Text Available MicroRNAs (miRNAs are essential small RNA molecules (20–24 nt that negatively regulate the expression of target genes at the post-transcriptional level. Due to their roles in a variety of biological processes, the aberrant expression profiles of miRNAs have been identified as biomarkers for many diseases, such as cancer, diabetes, cardiovascular disease and neurodegenerative diseases. In order to precisely, rapidly and economically monitor the expression of miRNAs, many cutting-edge nanotechnologies have been developed. One of the nanotechnologies, based on DNA encapsulated silver nanoclusters (DNA/AgNCs, has increasingly been adopted to create nanoscale bio-sensing systems due to its attractive optical properties, such as brightness, tuneable emission wavelengths and photostability. Using the DNA/AgNCs sensor methods, the presence of miRNAs can be detected simply by monitoring the fluorescence alteration of DNA/AgNCs sensors. We introduce these DNA/ AgNCs sensor methods and discuss their possible applications for detecting miRNA biomarkers in neurodegenerative diseases.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort.

Science.gov (United States)

Lam, Raymond W; Milev, Roumen; Rotzinger, Susan; Andreazza, Ana C; Blier, Pierre; Brenner, Colleen; Daskalakis, Zafiris J; Dharsee, Moyez; Downar, Jonathan; Evans, Kenneth R; Farzan, Faranak; Foster, Jane A; Frey, Benicio N; Geraci, Joseph; Giacobbe, Peter; Feilotter, Harriet E; Hall, Geoffrey B; Harkness, Kate L; Hassel, Stefanie; Ismail, Zahinoor; Leri, Francesco; Liotti, Mario; MacQueen, Glenda M; McAndrews, Mary Pat; Minuzzi, Luciano; Müller, Daniel J; Parikh, Sagar V; Placenza, Franca M; Quilty, Lena C; Ravindran, Arun V; Salomons, Tim V; Soares, Claudio N; Strother, Stephen C; Turecki, Gustavo; Vaccarino, Anthony L; Vila-Rodriguez, Fidel; Kennedy, Sidney H

2016-04-16

Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants

Identification and Quantitation of Biomarkers for Radiation-Induced Injury via Mass Spectrometry

Science.gov (United States)

Jones, Jace W.; Scott, Alison J.; Tudor, Gregory; Xu, Pu-Ting; Jackson, Isabel L.; Vujaskovic, Zeljko; Booth, Catherine; MacVittie, Thomas J.; Ernst, Robert K.; Kane, Maureen A.

2013-01-01

Biomarker identification and validation for radiation exposure is a rapidly expanding field encompassing the need for well-defined animal models and advanced analytical techniques. The resources within the consortium, Medical Countermeasures Against Radiological Threats (MCART), provide a unique opportunity for accessing well-defined animal models that simulate the key sequelae of the acute radiation syndrome and the delayed effects of acute radiation exposure. Likewise, the use of mass spectrometry-based analytical techniques for biomarker discovery and validation enables a robust analytical platform that is amenable to a variety of sample matrices and considered the benchmark for bio-molecular identification and quantitation. Herein, we demonstrate the use of two targeted mass spectrometry approaches to link established MCART animal models to identified metabolite biomarkers. Circulating citrulline concentration was correlated to gross histological gastrointestinal tissue damage and retinoic acid production in lung tissue was established to be reduced at early and late time points post high dose irradiation. Going forward, the use of mass spectrometry-based metabolomics coupled to well-defined animal models provides the unique opportunity for comprehensive biomarker discovery. PMID:24276554

Preservation of Lipid Biomarkers Under Prolonged and Extreme Hyperaridity in Atacama Desert Soils

Science.gov (United States)

Wilhelm, M. B.; Davila, A. F.; Eigenbrode, J. L.; Parenteau, M. N.; Jahnke, L. L.; Summons, R. E.; Liu, X.; Wray, J. J.; Stamos, B.; O'Reilly, S. S.; Williams, A. J.

2015-12-01

Molecular biomarkers are the most direct biosignatures of life on early Earth and a key target in the search for life on Mars. Lipid biomarkers are of particular interest given their ability to survive oxidative degradation and record microbial presence and activity of microorganisms that occurred billions of years ago (Eigenbrode, 2008). Environmental conditions that suspend biotic and abiotic degradative processes prior to lithification can lead to enhanced biomolecular preservation over geological time-scales. The hyperarid core of the Atacama Desert in northern Chile offers a unique environment to investigate lipid biomarker taphonomy under extreme and prolonged dryness. We investigated the accumulation and degree of preservation of lipid biomarkers in million-year-old hyperarid soils where primarily abiotic conditions influence their taphonomy. Soils were extracted and free and membrane bound lipids were analyzed across a vertical profile of 2.5 meters in the Yungay hyper-arid core of the Atacama Desert. Due to the extremely low inventory of biomass in Atacama soils, samples were collected by scientists wearing cleanroom suits to minimize anthropogenic contamination during sampling. Fatty acids were found to be well preserved in Yungay soils, and were most abundant in the clay-rich soils at ~2 m depth (~750 ng of fatty acid methyl ester/g of soil). These buried clays layers were fluvially deposited approximately 2 million years ago, and have been excluded from exposure to rainwater and modern surficial processes since their emplacement (Ewing et al., 2008). Monocarboxylic fatty acid, monohydroxy fatty acid, glycerol tetraether, and n-alkane hydrocarbon content was found to change with depth. Lipid biomarker content in deeper soil layers is suggestive of soils having been formed at a time when environmental conditions were capable of supporting active microbial communities and plants. In short, total lipid extracts reveal a remarkable degree of lipid biomarker

Preservation of Lipid Biomarkers Under Prolonged and Extreme Hyperaridity in Atacama Desert Soils

Science.gov (United States)

Wilhelm, Mary Beth

2015-01-01

Molecular biomarkers are the most direct biosignatures of life on early Earth and a key target in the search for life on Mars. Lipid biomarkers are of particular interest given their ability to survive oxidative degradation and record microbial presence and activity of microorganisms that occurred billions of years ago (Eigenbrode, 2008). Environmental conditions that suspend biotic and abiotic degradative processes prior to lithification can lead to enhanced biomolecular preservation over geological time-scales. The hyperarid core of the Atacama Desert in northern Chile offers a unique environment to investigate lipid biomarker taphonomy under extreme and prolonged dryness. We investigated the accumulation and degree of preservation of lipid biomarkers in million-year-old hyperarid soils where primarily abiotic conditions influence their taphonomy. Soils were extracted and free and membrane bound lipids were analyzed across a vertical profile of 2.5 meters in the Yungay hyper-arid core of the Atacama Desert. Due to the extremely low inventory of biomass in Atacama soils, samples were collected by scientists wearing cleanroom suits to minimize anthropogenic contamination during sampling. Fatty acids were found to be well preserved in Yungay soils, and were most abundant in the clay-rich soils at approx.2 m depth (approx.750 ng of fatty acid methyl ester/g of soil). These buried clays layers were fluvially deposited approximately 2 million years ago, and have been excluded from exposure to rainwater and modern surficial processes since their emplacement (Ewing et al., 2008). Monocarboxylic fatty acid, monohydroxy fatty acid, glycerol tetraether, and n-alkane hydrocarbon content was found to change with depth. Lipid biomarker content in deeper soil layers is suggestive of soils having been formed at a time when environmental conditions were capable of supporting active microbial communities and plants. In short, total lipid extracts reveal a remarkable degree of

Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers

Science.gov (United States)

Goel, Ajay; Tovar-Camargo, Oscar A; Toden, Shusuke

2016-01-01

Diagnostic strategies, particularly non-invasive blood-based screening approaches, are gaining increased attention for the early detection and attenuation of mortality associated with colorectal cancer (CRC). However, the majority of current screening approaches are inadequate at replacing the conventional CRC diagnostic procedures. Yet, due to technological advances and a better understanding of molecular events underlying human cancer, a new category of biomarkers are on the horizon. Recent evidence indicates that cells release a distinct class of small vesicles called ‘exosomes’, which contain nucleic acids and proteins that reflect and typify host-cell molecular architecture. Intriguingly, exosomes released from cancer cells have a distinct genetic and epigenetic makeup, which allows them to undertake their tumorigenic function. From a clinical standpoint, these unique cancer-specific fingerprints present in exosomes appear to be detectable in a small amount of blood, making them very attractive substrates for developing cancer biomarkers, particularly noninvasive diagnostic approaches. PMID:26892862

The extracellular domain of Her2 in serum as a biomarker of breast cancer.

Science.gov (United States)

Perrier, Alexandre; Gligorov, Joseph; Lefèvre, Guillaume; Boissan, Mathieu

2018-02-28

Breast cancer is a major health problem worldwide. In ~15% of breast cancers, the epidermal growth factor receptor HER2, a transmembrane protein, is overexpressed. This HER2 overexpression is associated with an aggressive form of the disease and a poor clinical prognosis. The extracellular domain (ECD) of HER2 is released into the blood by a proteolytic mechanism known as "ECD shedding". This proteolytic shedding leaves a constitutively active truncated receptor in the membrane that is 10-100-fold more oncogenic than the full-length receptor and promotes the growth and survival of cancer cells. Shedding of the HER2 ECD is increased during metastasis: whereas 15% of primary breast cancer patients have elevated levels of serum HER2 ECD (sHER2 ECD), the levels reach 45% in patients with metastatic disease. Thus, sHER2 ECD has been proposed as a promising biomarker for cancer recurrence and for monitoring the disease status of patients overexpressing HER2. Nevertheless, in 2016, the American Society of Clinical Oncology advises clinicians not to use soluble HER2 levels to guide their choice of adjuvant therapy for patients with HER2-positive breast cancer, because the evidence was considered not strong enough. Currently, biomarkers such as carcinoembryonic antigen and cancer antigen 15-3 are widely used to monitor metastatic breast cancer disease even if the level of evidence of clinical impact of this monitoring is poor. In this article, we review the evidence that sHER2 ECD might be used in some situations as a biomarker for breast cancer. Although this serum biomarker will not replace the direct measurement of tumor HER2 status for diagnosis of early-stage tumors; it might be especially useful in metastatic disease for prognosis, as an indicator of cancer progression and of therapy response, particularly to anti-HER2 therapies. Owing to these data, sHER2 ECD should be considered as a promising biomarker to detect cancer recurrence and metastasis.

Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges.

Science.gov (United States)

Root, Alex; Allen, Peter; Tempst, Paul; Yu, Kenneth

2018-03-07

Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but interdisciplinary

Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges

Directory of Open Access Journals (Sweden)

Alex Root

2018-03-01

Full Text Available Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but

Crystallins are regulated biomarkers for monitoring topical therapy of glaucomatous optic neuropathy.

Directory of Open Access Journals (Sweden)

Verena Prokosch

Full Text Available Optic nerve atrophy caused by abnormal intraocular pressure (IOP remains the most common cause of irreversible loss of vision worldwide. The aim of this study was to determine whether topically applied IOP-lowering eye drugs affect retinal ganglion cells (RGCs and retinal metabolism in a rat model of optic neuropathy. IOP was elevated through cauterization of episcleral veins, and then lowered either by the daily topical application of timolol, timolol/travoprost, timolol/dorzolamide, or timolol/brimonidine, or surgically with sectorial iridectomy. RGCs were retrogradely labeled 4 days prior to enucleation, and counted. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE, matrix-assisted laser desorption ionization mass spectrometry, Western blotting, and immunohistochemistry allowed the identification of IOP-dependent proteomic changes. Genomic changes were scrutinized using microarrays and qRT-PCR. The significant increase in IOP induced by episcleral vein cauterization that persisted until 8 weeks of follow-up in control animals (p<0.05 was effectively lowered by the eye drops (p<0.05. As anticipated, the number of RGCs decreased significantly following 8 weeks of elevated IOP (p<0.05, while treatment with combination compounds markedly improved RGC survival (p<0.05. 2D-PAGE and Western blot analyses revealed an IOP-dependent expression of crystallin cry-βb2. Microarray and qRT-PCR analyses verified the results at the mRNA level. IHC demonstrated that crystallins were expressed mainly in the ganglion cell layer. The data suggest that IOP and either topically applied antiglaucomatous drugs influence crystallin expression within the retina. Neuronal crystallins are thus suitable biomarkers for monitoring the progression of neuropathy and evaluating any neuroprotective effects.

Non-Small Cell Carcinoma Biomarker Testing: The Pathologist's Perspective.

Directory of Open Access Journals (Sweden)

Elisa eBrega

2014-07-01

Full Text Available Biomarker testing has become standard of care for patients diagnosed with non-small cell lung cancer. Although it can be successfully performed in circulating tu-mor cells, at present, the vast majority of investigations are carried out using di-rect tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically signifi-cant, particularly in cases of lung adenocarcinomas (ADC, which in turn, has prompted a new proposal for the histologic classification of such pulmonary neo-plasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist’s role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire pro-cess happens in a timely fashion. Therefore, it is part of the pathologist’s respon-sibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play NSCLC bi-omarker testing, as well as to provide a summarized review of the main NSCLC bi-omarkers of

Biomarkers in patients treated with BCG: an update.

Science.gov (United States)

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2014-08-01

Bacillus Calmette-Guerin (BCG) instillations are the recommended treatment for non-muscle invasive bladder cancer but high recurrence and progression rates remain after treatment. Despite patients risk stratification, BCG effectiveness remains unpredictable. A close, invasive and expensive follow up is mandatory. To improve or even replace this heavy surveillance in this high risk population, validated biomarkers were developed. To identify the useful tools for the urologist in monitoring bladder cancer patients, we reviewed the literature focusing on plasma and urinary biomarkers of BCG-therapy outcome. Articles dated from 1988 to 2013 including specific keywords (urinary bladder neoplasm, biological markers, intravesical administration, recurrence) were examined and relevant papers were selected. Before treatment initiation, genetic polymorphisms of multiple agents (cytokines, matrix-metalloproteinases) were found to become very useful to tailor therapy and monitoring. Those biomarkers belong to personalized medicine which is a topic of great interest today, but still need to be validated in cohorts from different ethnicities. During instillations, cytokines (IL-2, IL-8, IL-6/IL-10) were reported to be reliable to determine treatment response and efficacy. Further studies are needed to confirm results and standardize thresholds. After treatment, UroVysion, the FDA-approved fluorescence in situ hybridization (FISH), appeared to be the most robust marker of all the clinical parameters reviewed; but is not yet validated for BCG-treated patients. No recommendations for everyday practice can be established today, but a combination of several markers and clinicopathological characteristics may be the future. As bladder cancer diagnosis and management are evolving, practicing urologists should be aware of and utilize bladder cancer markers in clinical practice.

Plasma low-molecular-weight proteome profiling identified neuropeptide-Y as a prostate cancer biomarker polypeptide.

Science.gov (United States)

Ueda, Koji; Tatsuguchi, Ayako; Saichi, Naomi; Toyama, Atsuhiko; Tamura, Kenji; Furihata, Mutsuo; Takata, Ryo; Akamatsu, Shusuke; Igarashi, Masahiro; Nakayama, Masato; Sato, Taka-Aki; Ogawa, Osamu; Fujioka, Tomoaki; Shuin, Taro; Nakamura, Yusuke; Nakagawa, Hidewaki

2013-10-04

In prostate cancer diagnosis, PSA test has greatly contributed to the early detection of prostate cancer; however, expanding overdiagnosis and unnecessary biopsies have emerged as serious issues. To explore plasma biomarkers complementing the specificity of PSA test, we developed a unique proteomic technology QUEST-MS (Quick Enrichment of Small Targets for Mass Spectrometry). The QUEST-MS method based on 96-well formatted sequential reversed-phase chromatography allowing efficient enrichment of <20 kDa proteins quickly and reproducibly. Plasma from 24 healthy controls, 19 benign prostate hypertrophy patients, and 73 prostate cancer patients were purified with QUEST-MS and analyzed by LC/MS/MS. Among 153 057 nonredundant peptides, 189 peptides showed prostate cancer specific detection pattern, which included a neurotransmitter polypeptide neuropeptide-Y (NPY). We further validated the screening results by targeted multiple reaction monitoring technology using independent sample set (n = 110). The ROC curve analysis revealed that logistic regression-based combination of NPY, and PSA showed 81.5% sensitivity and 82.2% specificity for prostate cancer diagnosis. Thus QUEST-MS technology allowed comprehensive and high-throughput profiling of plasma polypeptides and had potential to effectively uncover very low abundant tumor-derived small molecules, such as neurotransmitters, peptide hormones, or cytokines.

Using MALDI-IMS and MRM to stablish a pipeline for discovery and validation of tumor neovasculature biomarker candidates. — EDRN Public Portal

Science.gov (United States)

In an effort to circumvent the limitations associated with biomarker discovery workflows involving cell lines and cell cultures, histology-directed MALDI protein profiling and imaging mass spectrometry will be used for identification of vascular endothelial biomarkers suitable for early prostate cancer detection by CEUS targeted molecular imaging

Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

International Nuclear Information System (INIS)

Kuremsky, Jeffrey G.; Tepper, Joel E.; McLeod, Howard L. Phar

2009-01-01

Locally advanced rectal cancer (LARC) is currently treated with neoadjuvant chemoradiation. Although approximately 45% of patients respond to neoadjuvant therapy with T-level downstaging, there is no effective method of predicting which patients will respond. Molecular biomarkers have been investigated for their ability to predict outcome in LARC treated with neoadjuvant chemotherapy and radiation. A literature search using PubMed resulted in the initial assessment of 1,204 articles. Articles addressing the ability of a biomarker to predict outcome for LARC treated with neoadjuvant chemotherapy and radiation were included. Six biomarkers met the criteria for review: p53, epidermal growth factor receptor (EGFR), thymidylate synthase, Ki-67, p21, and bcl-2/bax. On the basis of composite data, p53 is unlikely to have utility as a predictor of response. Epidermal growth factor receptor has shown promise as a predictor when quantitatively evaluated in pretreatment biopsies or when EGFR polymorphisms are evaluated in germline DNA. Thymidylate synthase, when evaluated for polymorphisms in germline DNA, is promising as a predictive biomarker. Ki-67 and bcl-2 are not useful in predicting outcome. p21 needs to be further evaluated to determine its usefulness in predicting outcome. Bax requires more investigation to determine its usefulness. Epidermal growth factor receptor, thymidylate synthase, and p21 should be evaluated in larger prospective clinical trials for their ability to guide preoperative therapy choices in LARC.

Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

Directory of Open Access Journals (Sweden)

Giovanni Nardo

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC, a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%, and from patients with neurological disorders that may resemble ALS (91%, between two levels of disease severity (90%, and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms.

Molecular pathology of prostate cancer.

Science.gov (United States)

Cazares, L H; Drake, R R; Esquela-Kirscher, A; Lance, R S; Semmes, O J; Troyer, D A

2010-01-01

This chapter includes discussion of the molecular pathology of tissue, blood, urine, and expressed prostatic secretions. Because we are unable to reliably image the disease in vivo, a 12 core method that oversamples the peripheral zone is widely used. This generates large numbers of cores that need to be carefully processed and sampled. In spite of the large number of tissue cores, the amount of tumor available for study is often quite limited. This is a particular challenge for research, as new biomarker assays will need to preserve tissue architecture intact for histopathology. Methods of processing and reporting pathology are discussed. With the exception of ductal variants, recognized subtypes of prostate cancer are largely confined to research applications, and most prostate cancers are acinar. Biomarker discovery in urine and expressed prostatic secretions would be useful since these are readily obtained and are proximate fluids. The well-known challenges of biomarker discovery in blood and urine are referenced and discussed. Mediators of carcinogenesis can serve as biomarkers as exemplified by mutations in PTEN and TMPRSS2:ERG fusion. The use of proteomics in biomarker discovery with an emphasis on imaging mass spectroscopy of tissues is discussed. Small RNAs are of great interest, however, their usefulness as biomarkers in clinical decision making remains the subject of ongoing research. The chapter concludes with an overview of blood biomarkers such as circulating nucleic acids and tumor cells and bound/free isoforms of prostate specific antigen (PSA).

Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS

Science.gov (United States)

Garabedian, Alyssa; Benigni, Paolo; Ramirez, Cesar E.; Baker, Erin S.; Liu, Tao; Smith, Richard D.; Fernandez-Lima, Francisco

2017-09-01

In the present work, the potential of trapped ion mobility spectrometry coupled to TOF mass spectrometry (TIMS-TOF MS) for discovery and targeted monitoring of peptide biomarkers from human-in-mouse xenograft tumor tissue was evaluated. In particular, a TIMS-MS workflow was developed for the detection and quantification of peptide biomarkers using internal heavy analogs, taking advantage of the high mobility resolution (R = 150-250) prior to mass analysis. Five peptide biomarkers were separated, identified, and quantified using offline nanoESI-TIMS-CID-TOF MS; the results were in good agreement with measurements using a traditional LC-ESI-MS/MS proteomics workflow. The TIMS-TOF MS analysis permitted peptide biomarker detection based on accurate mobility, mass measurements, and high sequence coverage for concentrations in the 10-200 nM range, while simultaneously achieving discovery measurements of not initially targeted peptides as markers from the same proteins and, eventually, other proteins. [Figure not available: see fulltext.

Validation of New Cancer Biomarkers

DEFF Research Database (Denmark)

Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

2015-01-01

BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

Multi-dimensional discovery of biomarker and phenotype complexes

Directory of Open Access Journals (Sweden)

Huang Kun

2010-10-01

Full Text Available Abstract Background Given the rapid growth of translational research and personalized healthcare paradigms, the ability to relate and reason upon networks of bio-molecular and phenotypic variables at various levels of granularity in order to diagnose, stage and plan treatments for disease states is highly desirable. Numerous techniques exist that can be used to develop networks of co-expressed or otherwise related genes and clinical features. Such techniques can also be used to create formalized knowledge collections based upon the information incumbent to ontologies and domain literature. However, reports of integrative approaches that bridge such networks to create systems-level models of disease or wellness are notably lacking in the contemporary literature. Results In response to the preceding gap in knowledge and practice, we report upon a prototypical series of experiments that utilize multi-modal approaches to network induction. These experiments are intended to elicit meaningful and significant biomarker-phenotype complexes spanning multiple levels of granularity. This work has been performed in the experimental context of a large-scale clinical and basic science data repository maintained by the National Cancer Institute (NCI funded Chronic Lymphocytic Leukemia Research Consortium. Conclusions Our results indicate that it is computationally tractable to link orthogonal networks of genes, clinical features, and conceptual knowledge to create multi-dimensional models of interrelated biomarkers and phenotypes. Further, our results indicate that such systems-level models contain interrelated bio-molecular and clinical markers capable of supporting hypothesis discovery and testing. Based on such findings, we propose a conceptual model intended to inform the cross-linkage of the results of such methods. This model has as its aim the identification of novel and knowledge-anchored biomarker-phenotype complexes.

Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments.

Science.gov (United States)

Alifrangis, Costi; Carter, Philip; Cereser, Biancastella; Chandrasinghe, Pramodh; Belluz, Lisa Del Bel; Lim, Eric; Moderau, Nina; Poyia, Fotini; Tabassum, Neha; Zhang, Hua; Krell, Jonathan; Stebbing, Justin

2018-02-27

In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group's drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor's molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not ( P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group ( P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival.

Circulating epigenetic biomarkers in lung malignancies: From early diagnosis to therapy

Czech Academy of Sciences Publication Activity Database

Tomasetti, M.; Amati, M.; Neužil, Jiří; Santarelli, L.

2017-01-01

Roč. 107, May 2017 (2017), s. 65-72 ISSN 0169-5002 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Malignant mesothelioma * Epigenetic biomarkers * Lung cancer * Circulating methylated DNA Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 4.294, year: 2016

Biomarkers in Autism

Directory of Open Access Journals (Sweden)

Robert eHendren

2014-08-01

Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

Bioresponsive probes for molecular imaging:Concepts and in vivo applications

OpenAIRE

Duijnhoven, van, SMJ Sander; Robillard, MS Marc; Langereis, S Sander; Grüll, H Holger

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecular imaging probes, known as bioresponsive molecular probes, has been developed. These probes generally benefit from signal enhancement at the site of interaction with its target. There are mainly ...

Have biomarkers made their mark? A brief review of dental biomarkers

Directory of Open Access Journals (Sweden)

Mohammed Kaleem Sultan

2014-01-01

Full Text Available Biomarkers are substances that are released into the human body by tumor cells or by other cells in response to tumor. A high level of a tumor marker is considered a sign of certain cancer, which makes biomarker the subject of many testing methods for the diagnosis of cancers. In recent times, these biomarkers have been successfully isolated to diagnose dental-related tumors, benign and malignant conditions. This article is a brief review of literature for various biomarkers used in the field of dentistry.

Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease

NARCIS (Netherlands)

Kester, M.I.; Teunissen, C.E.; Crimmins, D.L.; Herries, E.M.; Ladenson, J.H.; Scheltens, P.; van der Flier, W.M.; Morris, J.C.; Holtzman, D.M.; Fagan, A.M.

2015-01-01

IMPORTANCE: Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. OBJECTIVE: To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of

Calling Biomarkers in Milk Using a Protein Microarray on Your Smartphone

Science.gov (United States)

Ludwig, Susann K. J.; Tokarski, Christian; Lang, Stefan N.; van Ginkel, Leendert A.; Zhu, Hongying; Ozcan, Aydogan; Nielen, Michel W. F.

2015-01-01

Here we present the concept of a protein microarray-based fluorescence immunoassay for multiple biomarker detection in milk extracts by an ordinary smartphone. A multiplex immunoassay was designed on a microarray chip, having built-in positive and negative quality controls. After the immunoassay procedure, the 48 microspots were labelled with Quantum Dots (QD) depending on the protein biomarker levels in the sample. QD-fluorescence was subsequently detected by the smartphone camera under UV light excitation from LEDs embedded in a simple 3D-printed opto-mechanical smartphone attachment. The somewhat aberrant images obtained under such conditions, were corrected by newly developed Android-based software on the same smartphone, and protein biomarker profiles were calculated. The indirect detection of recombinant bovine somatotropin (rbST) in milk extracts based on altered biomarker profile of anti-rbST antibodies was selected as a real-life challenge. RbST-treated and untreated cows clearly showed reproducible treatment-dependent biomarker profiles in milk, in excellent agreement with results from a flow cytometer reference method. In a pilot experiment, anti-rbST antibody detection was multiplexed with the detection of another rbST-dependent biomarker, insulin-like growth factor 1 (IGF-1). Milk extract IGF-1 levels were found to be increased after rbST treatment and correlated with the results obtained from the reference method. These data clearly demonstrate the potential of the portable protein microarray concept towards simultaneous detection of multiple biomarkers. We envisage broad application of this ‘protein microarray on a smartphone’-concept for on-site testing, e.g., in food safety, environment and health monitoring. PMID:26308444

Calling Biomarkers in Milk Using a Protein Microarray on Your Smartphone.

Directory of Open Access Journals (Sweden)

Susann K J Ludwig

Full Text Available Here we present the concept of a protein microarray-based fluorescence immunoassay for multiple biomarker detection in milk extracts by an ordinary smartphone. A multiplex immunoassay was designed on a microarray chip, having built-in positive and negative quality controls. After the immunoassay procedure, the 48 microspots were labelled with Quantum Dots (QD depending on the protein biomarker levels in the sample. QD-fluorescence was subsequently detected by the smartphone camera under UV light excitation from LEDs embedded in a simple 3D-printed opto-mechanical smartphone attachment. The somewhat aberrant images obtained under such conditions, were corrected by newly developed Android-based software on the same smartphone, and protein biomarker profiles were calculated. The indirect detection of recombinant bovine somatotropin (rbST in milk extracts based on altered biomarker profile of anti-rbST antibodies was selected as a real-life challenge. RbST-treated and untreated cows clearly showed reproducible treatment-dependent biomarker profiles in milk, in excellent agreement with results from a flow cytometer reference method. In a pilot experiment, anti-rbST antibody detection was multiplexed with the detection of another rbST-dependent biomarker, insulin-like growth factor 1 (IGF-1. Milk extract IGF-1 levels were found to be increased after rbST treatment and correlated with the results obtained from the reference method. These data clearly demonstrate the potential of the portable protein microarray concept towards simultaneous detection of multiple biomarkers. We envisage broad application of this 'protein microarray on a smartphone'-concept for on-site testing, e.g., in food safety, environment and health monitoring.

A Review of the “Omics” Approach to Biomarkers of Oxidative Stress in Oryza sativa

Directory of Open Access Journals (Sweden)

Su Shiung Lam

2013-04-01

Full Text Available Physiological and ecological constraints that cause the slow growth and depleted production of crops have raised a major concern in the agriculture industry as they represent a possible threat of short food supply in the future. The key feature that regulates the stress signaling pathway is always related to the reactive oxygen species (ROS. The accumulation of ROS in plant cells would leave traces of biomarkers at the genome, proteome, and metabolome levels, which could be identified with the recent technological breakthrough coupled with improved performance of bioinformatics. This review highlights the recent breakthrough in molecular strategies (comprising transcriptomics, proteomics, and metabolomics in identifying oxidative stress biomarkers and the arising opportunities and obstacles observed in research on biomarkers in rice. The major issue in incorporating bioinformatics to validate the biomarkers from different omic platforms for the use of rice-breeding programs is also discussed. The development of powerful techniques for identification of oxidative stress-related biomarkers and the integration of data from different disciplines shed light on the oxidative response pathways in plants.

Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma

DEFF Research Database (Denmark)

Rasmussen, Gregers Brünnich; Håkansson, Katrin E; Vogelius, Ivan R

2017-01-01

.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063). CONCLUSIONS: The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has......OBJECTIVE: To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. PATIENT AND METHODS: Tissue microarray blocks of 196 head and neck squamous...... cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional...

Phonologically-based biomarkers for major depressive disorder

Science.gov (United States)

Trevino, Andrea Carolina; Quatieri, Thomas Francis; Malyska, Nicolas

2011-12-01

Of increasing importance in the civilian and military population is the recognition of major depressive disorder at its earliest stages and intervention before the onset of severe symptoms. Toward the goal of more effective monitoring of depression severity, we introduce vocal biomarkers that are derived automatically from phonologically-based measures of speech rate. To assess our measures, we use a 35-speaker free-response speech database of subjects treated for depression over a 6-week duration. We find that dissecting average measures of speech rate into phone-specific characteristics and, in particular, combined phone-duration measures uncovers stronger relationships between speech rate and depression severity than global measures previously reported for a speech-rate biomarker. Results of this study are supported by correlation of our measures with depression severity and classification of depression state with these vocal measures. Our approach provides a general framework for analyzing individual symptom categories through phonological units, and supports the premise that speaking rate can be an indicator of psychomotor retardation severity.

Biomarkers for Lupus Nephritis: A Critical Appraisal

Directory of Open Access Journals (Sweden)

Chi Chiu Mok

2010-01-01

Full Text Available Kidney disease is one of the most serious manifestations of systemic lupus erythematosus (SLE. Despite the improvement in the medical care of SLE in the past two decades, the prognosis of lupus nephritis remains unsatisfactory. Besides exploring more effective but less toxic treatment modalities that will further improve the remission rate, early detection and treatment of renal activity may spare patients from intensive immunosuppressive therapies and reduce renal damage. Conventional clinical parameters such as creatinine clearance, proteinuria, urine sediments, anti-dsDNA, and complement levels are not sensitive or specific enough for detecting ongoing disease activity in the lupus kidneys and early relapse of nephritis. Thus, novel biomarkers are necessary to enhance the diagnostic accuracy and sensitivity of lupus renal disease, prognostic stratification, monitoring of treatment response, and detection of early renal flares. This paper reviews promising biomarkers that have recently been evaluated in longitudinal studies of lupus nephritis.

Assessment of the impact of xenobiotic pollutants on the marine organisms: Molecular biomarker approach

Digital Repository Service at National Institute of Oceanography (India)

Sarkar, A.

of the organisms to xenobiotic compounds being transformed into reactive oxygen species. Most importantly, the occurrence of DNA strand breaks in marine organisms leading to the loss of DNA integrity is a significant biomarker of marine pollution. The measurement...

Household air pollution: a call for studies into biomarkers of exposure and predictors of respiratory disease.

Science.gov (United States)

Rylance, Jamie; Gordon, Stephen B; Naeher, Luke P; Patel, Archana; Balmes, John R; Adetona, Olorunfemi; Rogalsky, Derek K; Martin, William J

2013-05-01

Household air pollution (HAP) from indoor burning of biomass or coal is a leading global cause of morbidity and mortality, mostly due to its association with acute respiratory infection in children and chronic respiratory and cardiovascular diseases in adults. Interventions that have significantly reduced exposure to HAP improve health outcomes and may reduce mortality. However, we lack robust, specific, and field-ready biomarkers to identify populations at greatest risk and to monitor the effectiveness of interventions. New scientific approaches are urgently needed to develop biomarkers of human exposure that accurately reflect exposure or effect. In this Perspective, we describe the global need for such biomarkers, the aims of biomarker development, and the state of development of tests that have the potential for rapid transition from laboratory bench to field use.

Transparency of Reporting in Molecular Diagnostics

Directory of Open Access Journals (Sweden)

Stephen Bustin

2013-07-01

Full Text Available The major advances made over the past few years in molecular and cell biology are providing a progressively more detailed understanding of the molecular pathways that control normal processes and become dysregulated in disease [1]. This has resulted in the documentation of numerous genetic, epigenetic, transcriptomic, proteomic and metabolomic biomarkers that promise earlier disease detection, more accurate patient stratification and better prognosis [2–5]. Furthermore, molecular fingerprinting of diseases can be predictive of drug response and so assist with specific targeting of drugs against disease-associated molecules and function [6]. [...

[Microdose clinical trial--impact of PET molecular imaging].

Science.gov (United States)

Yano, Tsuneo; Watanabe, Yasuyoshi

2010-10-01

Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

Proteomics for discovery of candidate colorectal cancer biomarkers

Science.gov (United States)

Álvarez-Chaver, Paula; Otero-Estévez, Olalla; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S

2014-01-01

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers. PMID:24744574

Synthesis of eukaryotic lipid biomarkers in the bacterial domain

Science.gov (United States)

Welander, P. V.; Banta, A. B.; Lee, A. K.; Wei, J. H.

2017-12-01

Lipid biomarkers are organic molecules preserved in sediments and sedimentary rocks that can function as geological proxies for certain microbial taxa or for specific environmental conditions. These molecular fossils provide a link between organisms and their environments in both modern and ancient settings and have afforded significant insight into ancient climatic events, mass extinctions, and various evolutionary transitions throughout Earth's history. However, the proper interpretation of lipid biomarkers is dependent on a broad understanding of their diagenetic precursors in modern systems. This includes understanding the taphonomic transformations that these molecules undergo, their biosynthetic pathways, and the ecological conditions that affect their cellular production. In this study, we focus on one group of lipid biomarkers - the sterols. These are polycyclic isoprenoidal lipids that have a high preservation potential and play a critical role in the physiology of most eukaryotes. However, the synthesis and function of these lipids in the bacterial domain has not been fully explored. Here we utilize a combination of bioinformatics, microbial genetics, and biochemistry to demonstrate that bacterial sterol producers are more prevalent in environmental metagenomic samples than in the genomic databases of cultured organisms and to identify novel proteins required to synthesize and modify sterols in bacteria. These proteins represent a distinct pathway for sterol synthesis exclusive to bacteria and indicate that sterol synthesis in bacteria may have evolved independently of eukaryotic sterol biosynthesis. Taken together, these results demonstrate how studies in extant bacteria can provide insight into the biological sources and the biosynthetic pathways of specific lipid biomarkers and in turn may allow for more robust interpretation of biomarker signatures.

Dysregulated microRNAs in neural system: Implication in pathogenesis and biomarker development in Parkinson's disease.

Science.gov (United States)

Lu, Jiangkun; Xu, Yan; Quan, Zhenzhen; Chen, Zixuan; Sun, Zhenzhen; Qing, Hong

2017-12-04

Parkinson's disease is a debilitating neurodegenerative movement disorder, characterized by the progressive and selective loss of dopaminergic neurons located in the substantia nigra, leading to clinical motor symptoms. The factors involved in PD are rather multifaceted. There are many cellular pathways contributing to its neuro-pathogenesis, which include abnormal protein aggregation, impaired ubiquitin proteasome system, autophagy, and neuroinflammation. However, despite years of investigation, still little is known about early events in the molecular pathogenesis. MicroRNAs are small non-coding RNAs that can regulate post-transcriptional expression of mRNAs. Since they somewhat modulate many mRNA targets simultaneously, many cellular pathways may be affected by one individual miRNA. Moreover, miRNAs can stably circulate in cerebrospinal fluid and blood, and their expression pattern can reflect the molecular pathophysiology, thus making them promising biomarkers in PD diagnosis and prognosis. In this review, we will review the recent progress on miRNA's mechanism in PD pathogenesis and discuss the possibilities of miRNAs as PD molecular biomarkers. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

The current state of serum biomarkers of hepatotoxicity.

Science.gov (United States)

Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

2008-03-20

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in

The current state of serum biomarkers of hepatotoxicity

International Nuclear Information System (INIS)

Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

2008-01-01

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early

Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization.

Science.gov (United States)

Amur, S; LaVange, L; Zineh, I; Buckman-Garner, S; Woodcock, J

2015-07-01

The discovery, development, and use of biomarkers for a variety of drug development purposes are areas of tremendous interest and need. Biomarkers can become accepted for use through submission of biomarker data during the drug approval process. Another emerging pathway for acceptance of biomarkers is via the biomarker qualification program developed by the Center for Drug Evaluation and Research (CDER, US Food and Drug Administration). Evidentiary standards are needed to develop and evaluate various types of biomarkers for their intended use and multiple stakeholders, including academia, industry, government, and consortia must work together to help develop this evidence. The article describes various types of biomarkers that can be useful in drug development and evidentiary considerations that are important for qualification. A path forward for coordinating efforts to identify and explore needed biomarkers is proposed for consideration. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Early Detection of Breast Cancer Using Molecular Beacons

National Research Council Canada - National Science Library

Yang, Lily

2008-01-01

.... We proposed to use molecular beacon technology to detect the level of expression of several biomarker genes that are highly expressed in breast cancer cells but not in normal breast epithelial cells...

Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data.

Science.gov (United States)

Martyanov, Viktor; Whitfield, Michael L

2016-01-01

The goal of this review is to summarize recent advances into the pathogenesis and treatment of systemic sclerosis (SSc) from genomic and proteomic studies. Intrinsic gene expression-driven molecular subtypes of SSc are reproducible across three independent datasets. These subsets are a consistent feature of SSc and are found in multiple end-target tissues, such as skin and esophagus. Intrinsic subsets as well as baseline levels of molecular target pathways are potentially predictive of clinical response to specific therapeutics, based on three recent clinical trials. A gene expression-based biomarker of modified Rodnan skin score, a measure of SSc skin severity, can be used as a surrogate outcome metric and has been validated in a recent trial. Proteome analyses have identified novel biomarkers of SSc that correlate with SSc clinical phenotypes. Integrating intrinsic gene expression subset data, baseline molecular pathway information, and serum biomarkers along with surrogate measures of modified Rodnan skin score provides molecular context in SSc clinical trials. With validation, these approaches could be used to match patients with the therapies from which they are most likely to benefit and thus increase the likelihood of clinical improvement.

PAH biomarkers in common eelpout (Zoarces viviparus) from Danish waters

DEFF Research Database (Denmark)

Tairova, Zhanna; Strand, Jakob; Chevalier, Julie

2012-01-01

Eelpouts (Zoarces viviparus) sampled at surveillance stations during the fall of 2007 and spring 2008 in different Danish coastal areas, were studied for biomarkers of polycyclic aromatic hydrocarbons (PAHs) exposure and effects. Two analytical techniques, synchronous fluorescence spectrometry (SFS......) and high-performance liquid chromatography with fluorescence detection (HPLC/F), were applied for detecting PAH metabolites in bile and urine. CYP1A activity, in this study regarded as potential biomarker of effect, was measured as 7-ethoxyresorufin-O-deethylase (EROD) activity in liver of eelpouts from...... different stations. Biliary PAH metabolite measurements were used for monitoring the environmental PAH load at the surveillance stations. There was found significant difference in biliary PAH metabolite content between sexes with male fish containing higher concentrations of PAH metabolites than females...

A biomarker-responsive T2ex MRI contrast agent.

Science.gov (United States)

Daryaei, Iman; Randtke, Edward A; Pagel, Mark D

2017-04-01

This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T 2 exchange (T 2ex ) properties after interacting with a molecular biomarker. The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O 2 . The R 1 and R 2 relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r 2ex relaxivities. The reaction of Tm-DO3A-oAA with NO and O 2 caused a 6.4-fold increase in the r 2 relaxivity of the agent, whereas r 1 relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T 2ex agent. The effects of pH and temperature on the r 2 relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand. T 2ex MRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665-1670, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Marine pollution detection through biomarkers in marine bivalves

Digital Repository Service at National Institute of Oceanography (India)

Verlecar, X.N.; Pereira, N.; Desai, S.R.; Jena, K.B.; Snigdha

ous physiological and biochemical parameters in resident b i ota. Use of the so - called ?biomarker? has been adopted from i demiology? or ?molecular toxicology? by free - radical biologists to describe changes in biolog i cal molec ules out... of attack by free radicals like oxygen, nitrogen or ha l- ide species, in dealing with aquatic toxico l ogy 6 . In this context, the cytochrome P450 - linked mixed function ox y- genase (MFO) enzyme system has been extensively stu d ied 7...

Knowledge-based identification of soluble biomarkers: hepatic fibrosis in NAFLD as an example.

Science.gov (United States)

Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Petricoin, Emanuel; Younossi, Zobair; Chandhoke, Vikas; Baranova, Ancha

2013-01-01

The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.

Knowledge-based identification of soluble biomarkers: hepatic fibrosis in NAFLD as an example.

Directory of Open Access Journals (Sweden)

Sandra Page

Full Text Available The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1 NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2 biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.

Oxyfluorfen toxic effect on S. obliquus evaluated by different photosynthetic and enzymatic biomarkers.

Science.gov (United States)

Geoffroy, L; Dewez, D; Vernet, G; Popovic, R

2003-11-01

The effect of oxyfluorfen was investigated when alga Scenedesmus obliquus has been exposed to different concentrations (7.5, 15, and 22.5 microg x L(-1)) at 12, 24, and 48 hours of exposure. Toxicity test was done by using 13 biomarkers concerning growth rate, chlorophyll content and indicators of photosynthetic and antioxidant enzyme activities. The change of the 13 parameters showed a great variation of sensitivity indicating differences in parameters' suitability to be used as biomarkers when alga culture was exposed to oxyfluorfen toxicity. The order of sensitivity between those biomarkers was: Antenna size (ABS/RC) > Chlorophyll content > Catalase (CAT) > Operational PSII quantum yield (phiS(PSII)) > Glutathione S-transferase (GST) > Functional plastoquinone pool (Q(PQ)) > Glutathione reductase (GR) > Growth rate > Nonphotochemical quenching (QN) > Proton gradient quenching (Q(Emax)) > Ascorbate peroxidase (APX) > Photochemical quenching (Q(p)) > Maximum PSII quantum yield (Phi(PSII)). The effect of oxyfluorfen on the changes of those parameters was interpreted as a result of herbicide mode of action at molecular level of alga cellular system. This study indicated for some photosynthetic and enzymatic biomarkers to be useful indicators of toxicity effect induced in non-target alga species. Determination of biomarkers' sensitivity order may facilitate their selection to be used in environmental risk assessment of polluted water.

Genotoxic monitoring of nurses handling cytotoxic drugs

Directory of Open Access Journals (Sweden)

Anna Tompa

2016-01-01

Full Text Available Objective: Several biomarkers may be used to detect harmful exposure and individual susceptibility to cancer. Monitoring of biomarkers related to exposure may have a significant effect on early detection of cell transformation, thereby aiding the primary prevention of various chronic and malignant diseases. Nurses who handle cytotoxic drugs are exposed to carcinogenic agents, which have the potential to interrupt the cell cycle and to induce chromosomal aberrations. The presence of high chromosomal aberrations indicates the need for intervention even when exposure to these carcinogens is low. Methods: Nationally representative samples of 552 nurses were investigated by a follow-up monitoring system. The measured biomarkers were clinical laboratory routine tests, completed with genotoxicological (chromosome aberrations [CAs] and sister chromatid exchanges [SCEs] and immunotoxicological monitoring (ratio of lymphocyte subpopulations and lymphocyte activation markers measured on peripheral blood lymphocytes. Results were compared to the data of 140 healthy, age-matched controls. Results: In nurses exposed to cytostatics, we observed a significantly increased frequency of CAs and SCEs compared with those in the controls. Cytostatic drug exposure also manifested itself in an increased frequency of helper T lymphocytes. Genotoxicological and immunotoxicological changes, as well as negative health effects (i.e., iron deficiency, anemia, and thyroid diseases, increased among cytostatic exposed subjects. Conclusions: These results raised concerns about the protection of nursing staff from chemical carcinogens in the working environment.

Biomarkers of Atrial Cardiopathy and Atrial Fibrillation Detection on Mobile Outpatient Continuous Telemetry After Embolic Stroke of Undetermined Source.

Science.gov (United States)

Sebasigari, Denise; Merkler, Alexander; Guo, Yang; Gialdini, Gino; Kummer, Benjamin; Hemendinger, Morgan; Song, Christopher; Chu, Antony; Cutting, Shawna; Silver, Brian; Elkind, Mitchell S V; Kamel, Hooman; Furie, Karen L; Yaghi, Shadi

2017-06-01

Biomarkers of atrial dysfunction or "cardiopathy" are associated with embolic stroke risk. However, it is unclear if this risk is mediated by undiagnosed paroxysmal atrial fibrillation or flutter (AF). We aim to determine whether atrial cardiopathy biomarkers predict AF on continuous heart-rhythm monitoring after embolic stroke of undetermined source (ESUS). This was a single-center retrospective study including all patients with ESUS undergoing 30 days of ambulatory heart-rhythm monitoring to look for AF between January 1, 2013 and December 31, 2015. We reviewed medical records for clinical, radiographic, and cardiac variables. The primary outcome was a new diagnosis of AF detected during heart-rhythm monitoring. The primary predictors were atrial biomarkers: left atrial diameter on echocardiography, P-wave terminal force in electrocardiogram (ECG) lead V1, and P wave - R wave (PR) interval on ECG. A multiple logistic regression model was used to assess the relationship between atrial biomarkers and AF detection. Among 196 eligible patients, 23 (11.7%) were diagnosed with AF. In unadjusted analyses, patients with AF were older (72.4 years versus 61.4 years, P atrial diameter (39.2 mm versus 35.7 mm, P = .03). In a multivariable model, the only predictor of AF was age ≥ 60 years (odds ratio, 3.0; 95% CI, 1.06-8.5; P = .04). Atrial biomarkers were weakly associated with AF after ESUS. This suggests that previously reported associations between these markers and stroke may reflect independent cardiac pathways leading to stroke. Prospective studies are needed to investigate these mechanisms. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Onchocerca volvulus-neurotransmitter tyramine is a biomarker for river blindness.

Science.gov (United States)

Globisch, Daniel; Moreno, Amira Y; Hixon, Mark S; Nunes, Ashlee A K; Denery, Judith R; Specht, Sabine; Hoerauf, Achim; Janda, Kim D

2013-03-12

Onchocerciasis, also known as "river blindness", is a neglected tropical disease infecting millions of people mainly in Africa and the Middle East but also in South America and Central America. Disease infectivity initiates from the filarial parasitic nematode Onchocerca volvulus, which is transmitted by the blackfly vector Simulium sp. carrying infectious third-stage larvae. Ivermectin has controlled transmission of microfilariae, with an African Program elimination target date of 2025. However, there is currently no point-of-care diagnostic that can distinguish the burden of infection--including active and/or past infection--and enable the elimination program to be effectively monitored. Here, we describe how liquid chromatography-MS-based urine metabolome analysis can be exploited for the identification of a unique biomarker, N-acetyltyramine-O,β-glucuronide (NATOG), a neurotransmitter-derived secretion metabolite from O. volvulus. The regulation of this tyramine neurotransmitter was found to be linked to patient disease infection, including the controversial antibiotic doxycycline treatment that has been shown to both sterilize and kill adult female worms. Further clues to its regulation have been elucidated through biosynthetic pathway determination within the nematode and its human host. Our results demonstrate that NATOG tracks O. volvulus metabolism in both worms and humans, and thus can be considered a host-specific biomarker for onchocerciasis progression. Liquid chromatography-MS-based urine metabolome analysis discovery of NATOG not only has broad implications for a noninvasive host-specific onchocerciasis diagnostic but provides a basis for the metabolome mining of other neglected tropical diseases for the discovery of distinct biomarkers and monitoring of disease progression.

Biomarker responses and PAH ratios in fish inhabiting an estuarine urban waterway.

Science.gov (United States)

Duarte, Rafael Mendonça; Sadauskas-Henrique, Helen; de Almeida-Val, Vera Maria Fonseca; Val, Adalberto Luis; Nice, Helen Elizabeth; Gagnon, Marthe Monique

2017-10-01

Many cities worldwide are established adjacent to estuaries and their catchments resulting in estuarine contamination due to intense anthropogenic activities. The aim of this study was to evaluate if fish living in an estuarine urban waterway were affected by contamination, via the measurement of a suite of biomarkers of fish health. Black bream (Acanthopagrus butcheri) were sampled in a small urban embayment and a suite of biomarkers of fish health measured. These were condition factor (CF), liver somatic index (LSI), gonadosomatic index (GSI), hepatic EROD activity, polycyclic aromatic hydrocarbon (PAH) biliary metabolites, serum sorbitol dehydrogenase (s-SDH) and branchial enzymes cytochrome C oxidase (CCO), and lactate dehydrogenase (LDH) activities. The biomarkers of exposure EROD activity, and pyrene- and B(a)P-type biliary metabolites confirmed current or recent exposure of the fish and that fish were metabolizing contaminants. Relative to a reference site, LSI was higher in fish collected in the urban inlet as was the metabolic enzyme LDH activity. CF, GSI, s-SDH, CCO, and naphthalene-type metabolites were at similar levels in the urban inlet relative to the reference site. PAH biliary metabolite ratios of high-molecular-weight to low-molecular-weight suggest that fish from the urban inlet were exposed to pyrogenic PAHs, likely from legacy contamination and road runoff entering the embayment. Similarly, the sediment PAH ratios and the freshness indices suggested legacy contamination of a pyrogenic source, likely originating from the adjacent historic gasworks site and a degree of contamination of petrogenic nature entering the inlet via storm water discharge. Biomarkers of exposure and effect confirmed that black bream collected in the Claisebrook Cove inlet, Western Australia, are currently exposed to contamination and are experiencing metabolic perturbations not observed in fish collected at a nearby reference site. © 2017 Wiley Periodicals, Inc.

The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity

International Nuclear Information System (INIS)

Amacher, David E.

2010-01-01

Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in

Leveling the playing field: bringing development of biomarkers and molecular diagnostics up to the standards for drug development.

Science.gov (United States)

Poste, George; Carbone, David P; Parkinson, David R; Verweij, Jaap; Hewitt, Stephen M; Jessup, J Milburn

2012-03-15

Molecular diagnostics are becoming increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, and to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify the pharmacogenetic risk of adverse drug reactions. The articles in this CCR Focus section on molecular diagnosis describe the development and use of markers to guide medical decisions regarding cancer patients. They define sources of preanalytic variability that need to be minimized, as well as the regulatory and financial challenges involved in developing diagnostics and integrating them into clinical practice. They also outline a National Cancer Institute program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation, with sensitivity, specificity, and validity comparable to those required for the development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome-sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval can be achieved. One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts.

Preparation of the low molecular weight serum proteome for mass spectrometry analysis.

Science.gov (United States)

Waybright, Timothy J; Chan, King C; Veenstra, Timothy D; Xiao, Zhen

2013-01-01

The discovery of viable biomarkers or indicators of disease states is complicated by the inherent complexity of the chosen biological specimen. Every sample, whether it is serum, plasma, urine, tissue, cells, or a host of others, contains thousands of large and small components, each interacting in multiple ways. The need to concentrate on a group of these components to narrow the focus on a potential biomarker candidate becomes, out of necessity, a priority, especially in the search for immune-related low molecular weight serum biomarkers. One such method in the field of proteomics is to divide the sample proteome into groups based on the size of the protein, analyze each group, and mine the data for statistically significant items. This chapter details a portion of this method, concentrating on a method for fractionating and analyzing the low molecular weight proteome of human serum.

Recent mass spectrometry-based proteomics for biomarker discovery in lung cancer, COPD, and asthma.

Science.gov (United States)

Fujii, Kiyonaga; Nakamura, Haruhiko; Nishimura, Toshihide

2017-04-01

Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. Areas covered: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma. Expert commentary: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.

Mass spectrometry for biomarker development

Energy Technology Data Exchange (ETDEWEB)

Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

2015-06-19

Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

Biomarkers of brain injury in the premature infant

Directory of Open Access Journals (Sweden)

Martha V. Douglas-Escobar

2013-01-01

Full Text Available The term encephalopathy of prematurity encompasses not only the acute brain injury (such as intraventricular hemorrhage but also complex disturbance on the infant’s subsequent brain development. In premature infants, the most frequent recognized source of brain injury is intraventricular hemorrhage (IVH and periventricular leukomalacia (PVL. Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9 and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after post-hemorrhagic ventricular dilation. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

Science.gov (United States)

Goldman, Jennifer G.; Alcalay, Roy N.; Xie, Tao; Tuite, Paul; Henchcliffe, Claire; Hogarth, Penelope; Amara, Amy W.; Frank, Samuel; Rudolph, Alice; Casaceli, Cynthia; Andrews, Howard; Gwinn, Katrina; Sutherland, Margaret; Kopil, Catherine; Vincent, Lona; Frasier, Mark

2016-01-01

ABSTRACT Background Identifying PD‐specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well‐characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross‐sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort's clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined off and on states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from off state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD's broad and heterogeneous spectrum. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:27113479

Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

Directory of Open Access Journals (Sweden)

Jose A Santiago

Full Text Available Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level.Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP, previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS and the Prognostic Biomarker Study (PROBE, revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients.These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first

Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

Science.gov (United States)

Santiago, Jose A; Potashkin, Judith A

2013-01-01

Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that

Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells

OpenAIRE

Nardo, Giovanni; Pozzi, Silvia; Pignataro, Mauro; Lauranzano, Eliana; Spano, Giorgia; Garbelli, Silvia; Mantovani, Stefania; Marinou, Kalliopi; Papetti, Laura; Monteforte, Marta; Torri, Valter; Paris, Luca; Bazzoni, Gianfranco; Lunetta, Christian; Corbo, Massimo

2011-01-01

Background Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments. Methodology/Principal Findings We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel...